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Repairing spinal cord injuries with a protein that regulates axon regeneration – FierceBiotech

By daniellenierenberg

When the axons that extend from neurons break during a spinal cord injury, the result is often a lifelong loss of motor functioning, because vital connections from the brain to other body parts cannot be restored. Now, researchers from Temple Universitys Lewis Katz School of Medicine say they may have found a way to recover some functions lost to axon breaks.

The researchers discovered that boosting levels of a protein called Lin28 in injured spinal cords of mice prompts the regrowth of axons and repairs communication between the brain and body. Lin28 also helped repair injured optic nerves in the animals, they reported in the journal Molecular Therapy.

The Temple team zeroed in on Lin28 because its a known regulator of stem cells, meaning it controls their ability to differentiate into various cells in the body. The researchers examined the effects of Lin28 on spinal cord and optic nerve injuries using two mouse models: one that was engineered to express extra Lin28 and another that was normal and was given the protein after injury via a viral vector.

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All of the mice experienced axon regeneration, the researchers reported. But they found that the best results occurred in the normal mice that received Lin28 injections post-injury. In fact, in animals with optic nerve injuries, the axons regrew to the point where they filled the entire tract of the nerve.

Lin28 treatment after injury improved coordination and sensation in the mice, the researchers reported.

"We observed a lot of axon regrowth, which could be very significant clinically, since there currently are no regenerative treatments for spinal cord injury or optic nerve injury," said senior author Shuxin Li, M.D., Ph.D., professor of anatomy and cell biology at the Lewis Katz School of Medicine, in a statement.

RELATED: Gene therapy with 'off switch' restores hand movement in rats with spinal cord injury

Lin28 is already a target of interest, though it has garnered the most attention so far in cancer research. Startup Twentyeight-Seven Therapeutics is developing a small molecule that inhibits the protein in the hopes that doing so will boost Let-7, a cancer-suppressing microRNA. The company raised more than $82 million in a series A financing last year.

Several new approaches for repairing spinal cord injuries are under investigation, most notably gene therapy. King's College researchers are working on a gene therapy that repairs axons by prompting the production of the enzyme chondroitinase. A UT Southwestern team is targeting the gene LZK to increase levels of supportive nervous system cells called astrocytes in response to spinal injuries.

The Temple team has a two-pronged approach to further developing their Lin28-directed treatment. They hope to develop a vector that can be safely delivered by injection and that would deliver the therapy directly to damaged neurons. They also plan to study other molecules in the Lin28 signaling pathway.

"Lin28 associates closely with other growth signaling molecules, and we suspect it uses multiple pathways to regulate cell growth," Li said, potentially revealing other therapeutic molecules that could further boost neuron repair.

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Adoption of Spinal Cord Trauma Treatment Market to Increase During the COVID-19 Period on back of Increased Consumer Demand – Jewish Life News

By daniellenierenberg

Spinal Cord Trauma Treatment Market: Global Industry Analysis 2012 2016 and Forecast 2017 2025is the recent report of Persistence Market Research that throws light on the overall market scenario during the period of eight years, i.e. 2017-2025. According to this report, Globalspinal cord trauma treatment marketis expected to witness significant growth during the forecast period.

This growth is expected to be primarily driven by increasing incidence of spinal cord trauma, and increasing government support to reduce the burden of spinal cord injuries. Additionally, development of nerve cells growth therapy is expected to boost the market in near future.

Report Highlights:

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Company Profiles

Get To Know Methodology of Report @ https://www.persistencemarketresearch.com/methodology/17353

The global market for spinal cord trauma treatment is is estimated to be valued at US$ 2,276.3 Mn in terms of value by the end of 2017. The global spinal cord trauma treatment market is expected to expand at a CAGR of 3.7% over the forecast period to reach a value of US$ 3,036.2 Mn by 2025end.

Global Spinal Cord Trauma Treatment Market: Trends

Global Spinal Cord Trauma Treatment Market: Forecast by End User

On the basis of end user, the global spinal cord trauma treatment market is segmented into hospitals and trauma centers. Hospitals segment dominated the global spinal cord trauma treatment market in revenue terms in 2016 and is projected to continue to do so throughout the forecast period.

Hospitals and trauma centers segments are expected to approximately similar attractive index. Hospitals segment accounted for 53.2% value share in 2017 and is projected to account for 52.5% share by 2025 end.

Access Full Report @ https://www.persistencemarketresearch.com/checkout/17353

Global Spinal Cord Trauma Treatment Market: Forecast by Injury Type

On the basis of injury type, the global spinal cord trauma treatment market is segmented into complete spinal cord injuries and partial spinal cord injuries.

Partial spinal cord trauma treatment segment is expected to show better growth than the completed spinal cord treatment segment due to higher growth in the incidence rate of partial spinal cord trauma than the complete spinal cord trauma. With US$ 1,870.3 Mn market value in 2025, this segment is likely to expand at CAGR 3.8% throughout the projected period.

Global Spinal Cord Trauma Treatment Market: Forecast by Treatment Type

On the basis of treatment type, the global spinal cord trauma treatment market is segmented into corticosteroid, surgery, and spinal traction segments.

Surgery segment dominated the global spinal cord trauma treatment market in revenue terms in 2016 and is projected to continue to do so throughout the forecast period. Surgery segment is the most attractive segment, with attractiveness index of 2.6 over the forecast period.

Global Spinal Cord Trauma Treatment Market: Forecast by Region

This market is segmented into five regions such as North America, Latin America, Europe, APAC and MEA. Asia-Pacific account for the largest market share in the global spinal cord trauma treatment market.

Large patient population due to the high rate of road accidents and crime is making the Asia Pacific region most attractive market for spinal cord trauma treatment. On the other hand, MEA and Latin America is expected to be the least attractive market for spinal cord trauma treatment, with attractiveness index of 0.3 and 0.5 respectively over the forecast period.

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Study Reveals New Role of Astrocytes in Brain Function | Neuroscience – Sci-News.com

By daniellenierenberg

Astrocytes play a direct role in the regulation of neuronal circuits involved in learning and memory, according to new research from Baylor College of Medicine and M.D. Anderson Cancer Center.

Huang et al reveal region-specific transcriptional dependencies for astrocytes and identify astrocytic NFIA as a key transcriptional regulator of hippocampal circuits. Image credit: Huang et al, doi: 10.1016/j.neuron.2020.03.025.

Astrocytes are star-shaped glial cells in the brain and spinal cord.

They have unique cellular, molecular and functional properties and outnumber neurons by over fivefold. They occupy distinct brain regions, indicating regional specialization.

There is evidence suggesting that transcription factors proteins involved in controlling gene expression regulate astrocyte diversity.

A team led by Professor Benjamin Deneen from Baylor College of Medicine looked to get a better understanding of the role transcription factor NFIA, a known regulator of astrocyte development, played in adult mouse brain functions.

The researchers worked with a mouse model they had genetically engineered to lack the NFIA gene specifically in adult astrocytes in the entire brain.

They analyzed several brain regions, looking for alterations in astrocyte morphology, physiology and gene expression signatures.

We found that NFIA-deficient astrocytes presented defective shapes and altered functions, Professor Deneen said.

Surprisingly, although the NFIA gene was eliminated in all brain regions, only the astrocytes in the hippocampus were severely altered. Other regions, such as the cortex and the brain stem, were not affected.

Astrocytes in the hippocampus also had less calcium activity calcium is an indicator of astrocyte function as well as a reduced ability to detect neurotransmitters released from neurons.

NFIA-deficient astrocytes also were not as closely associated with neurons as normal astrocytes.

Importantly, all these morphological and functional alterations were linked to defects in the animals ability to learn and remember, providing the first evidence that astrocytes are to some extent controlling the neuronal circuits that mediate learning and memory.

Astrocytes in the brain are physically close to and communicate with neurons. Neurons release molecules that astrocytes can detect and respond to, Professor Deneen said.

We propose that NFIA-deficient astrocytes are not able to listen to neurons as well as normal astrocytes, and, therefore, they cannot respond appropriately by providing the support needed for efficient memory circuit function and neuronal transmission. Consequently, the circuit is disrupted, leading to impaired learning and memory.

The findings were published online in the journal Neuron.

_____

Anna Yu-Szu Huang et al. Region-Specific Transcriptional Control of Astrocyte Function Oversees Local Circuit Activities. Neuron, published online April 21, 2020; doi: 10.1016/j.neuron.2020.03.025

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Safety Stem Cells in Spinal Cord Injury – Full Text View …

By daniellenierenberg

This phase I clinical study is an open clinical trial to investigate the safety of the intrathecal application of Neuro-Cells in the treatment of end stage (chronic), traumatic complete (AIS grade A) and incomplete (AIS grade B/C) SCI patients. To that purpose, after inclusion in this study >1 year and less than 5 years after their SCI-event, 10 patients will be included. All patients are invited to visit the trial hospital every month during this 3-months study for appreciation of their possible (S)AEs and/or SUSARs, for physical examination and a biochemical analysis of their blood/urine. Day 0 and day 90 they also undergo a comprehensive neurological examination, the AISIAms, ASIAss and Pain perception.

Finally, the participants are also invited to undergo neurological examinations at day 360 and 720. The purpose of this neurological assessment is to explore in patients if a late administration of Neuro-Cells may have some beneficial effects on the neurological condition of the chronic SCI patient.

All patients undergo a BM harvesting at the start of their participation in the study and will undergo one LP, performed to administer Neuro-Cells. The study is open and descriptive, and no randomization takes place. All patients are followed up until approximately 3 months after the time of administration. After these 3 months, the safety part of this study ends. Patients are invited for a neurological assessment 9 months later (day 360) to explore if Neuro-Cells may have a beneficial effect when given to end stage patients with a traumatic SCI.

The safety part of the study is completed when the last patient finishes his/her visit at day 90. The explorative part of the study ends approximately one year after the time of inclusion at day 720.

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Spinal Cord Trauma Treatment Market to Grow at Stellar CAGR 3.7% During the Forecast Period 2025 – MENAFN.COM

By daniellenierenberg

(MENAFN - iCrowdNewsWire) Apr 23, 2020

' Spinal Cord Trauma Treatment Market: Global Industry Analysis 2012 2016 and Forecast 2017 2025' is the recent report of Persistence Market Research that throws light on the overall market scenario during the period of eight years, i.e. 2017-2025. According to this report, Global spinal cord trauma treatment market is expected to witness significant growth during the forecast period.

This growth is expected to be primarily driven by increasing incidence of spinal cord trauma, and increasing government support to reduce the burden of spinal cord injuries. Additionally, development of nerve cells growth therapy is expected to boost the market in near future.

Get To Know Methodology of Report @ https://www.persistencemarketresearch.com/methodology/17353

Company Profiles

Get Sample Copy of Report @ https://www.persistencemarketresearch.com/samples/17353

The global market for spinal cord trauma treatment is is estimated to be valued at US$ 2,276.3 Mn in terms of value by the end of 2017. The global spinal cord trauma treatment market is expected to expand at a CAGR of 3.7% over the forecast period to reach a value of US$ 3,036.2 Mn by 2025end.

Global Spinal Cord Trauma Treatment Market: Trends

Global Spinal Cord Trauma Treatment Market: Forecast by End User

On the basis of end user, the global spinal cord trauma treatment market is segmented into hospitals and trauma centers. Hospitals segment dominated the global spinal cord trauma treatment market in revenue terms in 2016 and is projected to continue to do so throughout the forecast period.

Hospitals and trauma centers segments are expected to approximately similar attractive index. Hospitals segment accounted for 53.2% value share in 2017 and is projected to account for 52.5% share by 2025 end.

Access Full Report @ https://www.persistencemarketresearch.com/checkout/17353

Global Spinal Cord Trauma Treatment Market: Forecast by Injury Type

On the basis of injury type, the global spinal cord trauma treatment market is segmented into complete spinal cord injuries and partial spinal cord injuries.

Partial spinal cord trauma treatment segment is expected to show better growth than the completed spinal cord treatment segment due to higher growth in the incidence rate of partial spinal cord trauma than the complete spinal cord trauma. With US$ 1,870.3 Mn market value in 2025, this segment is likely to expand at CAGR 3.8% throughout the projected period.

Global Spinal Cord Trauma Treatment Market: Forecast by Treatment Type

On the basis of treatment type, the global spinal cord trauma treatment market is segmented into corticosteroid, surgery, and spinal traction segments.

Surgery segment dominated the global spinal cord trauma treatment market in revenue terms in 2016 and is projected to continue to do so throughout the forecast period. Surgery segment is the most attractive segment, with attractiveness index of 2.6 over the forecast period.

Global Spinal Cord Trauma Treatment Market: Forecast by Region

This market is segmented into five regions such as North America, Latin America, Europe, APAC and MEA. Asia-Pacific account for the largest market share in the global spinal cord trauma treatment market.

Large patient population due to the high rate of road accidents and crime is making the Asia Pacific region most attractive market for spinal cord trauma treatment. On the other hand, MEA and Latin America is expected to be the least attractive market for spinal cord trauma treatment, with attractiveness index of 0.3 and 0.5 respectively over the forecast period.

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Molecular Diagnostics Market Segmentation by Key Players Novartis AG, Roche Diagnostics, QIAGEN, Siemens Healthcare, Abbott Laboratories, Inc., Gen-Probe, Inc. (Hologic Inc.), Cepheid, Inc., Beckman Coulter, Inc., Becton, Dickinson & Company, Myriad Genetics, Inc., and bioMerieux.

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Spinal Cord Trauma Treatment Market to Grow at Stellar CAGR 3.7% During the Forecast Period 2025 - MENAFN.COM

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A Tribute to Max Randell, Gene Therapy Pioneer – PLoS Blogs

By daniellenierenberg

I awoke on Monday morning to the sad news that Max Randell had passed away on April 18. He would have been 23 on October 9.

Maxie wasnt expected to live past the age of 8, or even much past toddlerhood, according to some doctors. But gene therapy, and his incredible family, had something to say about that. COVID-19 didnt claim him his body just tired of fighting.

Max Randells legacy is one of hope, to the rare disease community whose family members step up to participate in the clinical trials that lead to treatments. In this time of the pandemic, attention has, understandably, turned somewhat away from the many people who live with medical limitations all the time. Ill explore that story next week.

A Devastating Diagnosis

Max was diagnosed at 4 months of age with Canavan disease, an inherited neuromuscular disease that never touched his mind nor his ability to communicate with his eyes, even though his body increasingly limited what he could do. Fewer than a thousand people in the US have the condition.

Canavan disease is an enzyme deficiency that melts away the myelin that insulates brain neurons. Gene therapy provides working copies of the affected gene, ASPA.

Babies with Canavan disease are limp and listless. Most never speak, walk, or even turn over. Yet their facial expressions and responses indicate an uncanny awareness. A child laughs when his dad makes a fart-like noise; a little girl flutters her fingers as if they are on a keyboard when a friend plays piano. Theyre smart.

Today, with excellent speech, occupational, and physical therapy and earlier diagnosis, people with Canavan disease can live into their teens or twenties. Those with mild mutations live even longer.

Maxs passing is a tragedy, but he taught researchers about gene therapy to the brain. And that may help others.

Gene Therapy for Canavan

Max had his first gene therapy at 11 months of age and a second a few years later, after slight backsliding when clinical trials halted in the wake of the death of Jesse Gelsingerin a gene therapy trial for a different disease.

Ive written about Maxs journey through many editions of my human genetics textbook, in my book ongene therapy, and in several DNA Science posts, listed at the end.

Ive had the honor to attend two of Maxs birthday parties, which celebrate Canavan kids and the organization that his family founded, Canavan Research Illinois. At one party I brought along birthday cards that students whod read my gene therapy book made for him. And his grandma Peggy, who emailed me of his passing this past Monday, showed me how Max communicated with eyeblinks of differing duration and direction.

Heres what his mom Ilyce wrote about one yearly gathering:

This year will be the 20th Annual Canavan Charity Ball. Each year as I plan this event Im faced with the undeniable reality that theres a chance Maxie wont be here by the time the day rolls around. With each passing year this fear grows stronger and it becomes increasingly difficult to put into print that our annual event is in honor of Maxies birthday. Ive been talking to Maxie a lot lately about his life. He feels happy, strong, loved, content, productive, and fulfilled and he is looking forward to his upcoming 21st birthday. Im excited to celebrate this incredible milestone.

Maxs parents and brother Alex have had the unusual experience of time, of being able to watch their loved one as the years unfolded following gene therapy. They were able to see more subtle improvements than can the parents whose children have more recently had gene therapy to treat a brain disease. Parents watch and wait and hope that language will return, or that a child will become more mobile or less hyperactive, depending on the treated condition. The changes may be subtle, or slow, or restricted and thats what Max taught the world.

For him, the viruses that ferried the healing genes into his brain seem to have gathered at his visual system. His parents noticed improvements in the short term, just before his first birthday, as well as long term.

Within two to three weeks, he started tracking with his eyes, and he got glasses. He became more verbal and his motor skills improved. His vision is still so good that his ophthalmologist only sees him once a year, like any other kid with glasses. She calls him Miracle Max, Ilyce told me in 2010.

In 2016 I heard from Ilyce again:

I wanted to give you an update on Maxie. Hes going to be 19 on October 9th. He graduated from high school in June and is beginning a work program on Monday. Its been very exciting to watch him grow into a young man!

Max had an appointment with his ophthalmologist this week and his vision continues to improve. His doctor said that the gene is still active in his brain because his optic nerve shows absolutely no signs of degeneration and looks the same each year. I wish we could have been able to express the gene throughout more of his brain, but I am grateful for the treatments because of the progress hes made.

Even though gene therapy wasnt a cure for Max, the things we are experiencing definitely give me a lot of hope that once the delivery system is perfected, I can see a potential cure for Canavan disease in the future. Just knowing that the gene is still there 15 years later gives me confidence that a one-time gene transfer would actually work!

Maxs gene therapy circa 2002 targeted less than 1% of brain cells, with fewer viral vectors than are used to deliver healing genes in todays clinical trials. But it looks like some of the vectors may have made their way beyond the optic nerves, judging by the interest in math he had in high school and his critical thinking skills.

A Choice of Gene-Based Therapies

When the Randell family decided to pursue gene therapy, it was pretty much the only game in town. Thats changed.

Only two gene therapies have been approvedin the U.S. But a search at clinicaltrials.gov yielded 602 entriesdeploying the technology. The list still rounds up the usual suspects of years past mostly immune deficiencies, eye disorders, or blood conditions, with a few inborn errors of metabolism.

But one clinical trial mentions the gene-editing tool CRISPR, which can replace a mutant gene, not just add working copies as classical gene therapy does. TheCRISPRtrial is an experiment on stem cells removed from patients with Kabuki syndrome, which affects many body systems.

Spinal muscular atrophy now has two FDA-approved treatments, one an antisense therapy (Spinraza) that silences a mutation and the other (Zolgensma) a gene therapy that infuses copies of the functioning gene. Without treatment, the destruction of motor neurons in the spinal cord is usually lethal by age two.

In 2018, FDA approved the first drug based on RNA interference (RNAi), yet another biotechnology. It silences gene expression, which is at the RNA rather than the DNA level of the other approaches. Onpattro treats the tingling, tickling, and burning sensations from the rare condition hereditary transthyretin-mediated amyloidosis.

When I wrote my book on gene therapy in 2012, the technology was pretty much the only choice of research to pursue besides protein-based therapies like enzyme replacement. Now families raising funds for treatments for single-gene diseases can add antisense, RNAi, and CRISPR gene editing to the list of possibilities.

In any battle, a diversity of weapons ups the odds of defeating the enemy.

RIP Max Randell.

DNA Science posts:

Fighting Canavan: Honoring Rare Disease Week

A Brothers Love Fights Genetic Disease

Gene Therapy for Canavan Disease: Maxs Story

Celebrating the Moms of Gene Therapy

To support research:Canavan Research Illinois

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Demand for Spinal Cord Trauma Treatment Market to Increase from End-use Industries During COVID-19 Pandemic and Substantially Surge Revenues in the…

By daniellenierenberg

Spinal Cord Trauma Treatment Market: Global Industry Analysis 2012 2016 and Forecast 2017 2025is the recent report of Persistence Market Research that throws light on the overall market scenario during the period of eight years, i.e. 2017-2025. According to this report, Globalspinal cord trauma treatment marketis expected to witness significant growth during the forecast period.

This growth is expected to be primarily driven by increasing incidence of spinal cord trauma, and increasing government support to reduce the burden of spinal cord injuries. Additionally, development of nerve cells growth therapy is expected to boost the market in near future.

Get Sample Copy of Report @ https://www.persistencemarketresearch.com/samples/17353

Company Profiles

Get To Know Methodology of Report @ https://www.persistencemarketresearch.com/methodology/17353

The global market for spinal cord trauma treatment is is estimated to be valued at US$ 2,276.3 Mn in terms of value by the end of 2017. The global spinal cord trauma treatment market is expected to expand at a CAGR of 3.7% over the forecast period to reach a value of US$ 3,036.2 Mn by 2025end.

Global Spinal Cord Trauma Treatment Market: Trends

Global Spinal Cord Trauma Treatment Market: Forecast by End User

On the basis of end user, the global spinal cord trauma treatment market is segmented into hospitals and trauma centers. Hospitals segment dominated the global spinal cord trauma treatment market in revenue terms in 2016 and is projected to continue to do so throughout the forecast period.

Hospitals and trauma centers segments are expected to approximately similar attractive index. Hospitals segment accounted for 53.2% value share in 2017 and is projected to account for 52.5% share by 2025 end.

Access Full Report @ https://www.persistencemarketresearch.com/checkout/17353

Global Spinal Cord Trauma Treatment Market: Forecast by Injury Type

On the basis of injury type, the global spinal cord trauma treatment market is segmented into complete spinal cord injuries and partial spinal cord injuries.

Partial spinal cord trauma treatment segment is expected to show better growth than the completed spinal cord treatment segment due to higher growth in the incidence rate of partial spinal cord trauma than the complete spinal cord trauma. With US$ 1,870.3 Mn market value in 2025, this segment is likely to expand at CAGR 3.8% throughout the projected period.

Global Spinal Cord Trauma Treatment Market: Forecast by Treatment Type

On the basis of treatment type, the global spinal cord trauma treatment market is segmented into corticosteroid, surgery, and spinal traction segments.

Surgery segment dominated the global spinal cord trauma treatment market in revenue terms in 2016 and is projected to continue to do so throughout the forecast period. Surgery segment is the most attractive segment, with attractiveness index of 2.6 over the forecast period.

Global Spinal Cord Trauma Treatment Market: Forecast by Region

This market is segmented into five regions such as North America, Latin America, Europe, APAC and MEA. Asia-Pacific account for the largest market share in the global spinal cord trauma treatment market.

Large patient population due to the high rate of road accidents and crime is making the Asia Pacific region most attractive market for spinal cord trauma treatment. On the other hand, MEA and Latin America is expected to be the least attractive market for spinal cord trauma treatment, with attractiveness index of 0.3 and 0.5 respectively over the forecast period.

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Co-delivery of IL-10 and NT-3 to Enhance Spinal Cord Injury Repair – Mirage News

By daniellenierenberg

-Spinal cord injury (SCI) creates a complex microenvironment that is not conducive to repair; growth factors are in short supply, whereas factors that inhibit regeneration are plentiful. In a new report, researchers have developed a structural bridge material that simultaneously stimulates IL-10 and NT-3 expression using a single bi-cistronic vector to alter the microenvironment and enhance repair. The article is reported in Tissue Engineering, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. Click here to read the article for free on the Tissue Engineering website through May 17, 2020.

In Polycistronic Delivery of IL-10 and NT-3 Promotes Oligodendrocyte Myelination and Functional Recovery in a Mouse Spinal Cord Injury Model, Lonnie D. Shea, PhD, University of Michigan, and coauthors report the development of a new poly(lactide-co-glycolide) (PLG) bridge with an incorporated polycistronic IL-3/NT-3 lentiviral construct. This material was used to stimulate repair in a mouse SCI model. IL-10 was included to successfully stimulate a regenerative phenotype in recruited macrophages, while NT-3 was used to promote axonal survival and elongation. The combined expression was successful; axonal density and myelination were increased, and locomotor functional recovery in mice was improved.

Inflammation plays a vital role in tissue repair and regeneration, and the use of a PLG bridge to take advantage of the inflammatory response to promote SCI repair is an elegant way to take advantage of these natural processes to improve SCI healing, says Tissue Engineering Co-Editor-in-Chief Antonios G. Mikos, PhD, Louis Calder Professor at Rice University, Houston, TX.

About the Journal

Tissue Engineering is an authoritative peer-reviewed journal published monthly online and in print in three parts: Part A, the flagship journal published 24 times per year; Part B: Reviews, published bimonthly, and Part C: Methods, published 12 times per year. Led by Co-Editors-in-Chief Antonios G. Mikos, PhD, Louis Calder Professor at Rice University, Houston, TX, and John P. Fisher, PhD, Fischell Family Distinguished Professor & Department Chair, and Director of the NIH Center for Engineering Complex Tissues at the University of Maryland, the Journal brings together scientific and medical experts in the fields of biomedical engineering, material science, molecular and cellular biology, and genetic engineering. Leadership of Tissue Engineering Parts B (Reviews) and Part C (Methods) is provided by Katja Schenke-Layland, PhD, Eberhard Karls University, Tbingen, Heungsoo Shin, PhD, Hanyang University; and John A. Jansen, DDS, PhD, Radboud University, and Xiumei Wang, PhD, Tsinghua University respectively. Tissue Engineering is the official journal of the Tissue Engineering & Regenerative Medicine International Society (TERMIS). Complete tables of content and a sample issue may be viewed on the Tissue Engineering website.

About the Publisher

Mary Ann Liebert, Inc., publishers is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research, including Stem Cells and Development, Human Gene Therapy, and Advances in Wound Care. Its biotechnology trade magazine, GEN (Genetic Engineering & Biotechnology News), was the first in its field and is today the industrys most widely read publication worldwide. A complete list of the firms 90 journals, books, and newsmagazines is available on the e Mary Ann Liebert, Inc., publishers website.

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What are the underlying conditions causing more serious illness from coronavirus? – WPBF West Palm Beach

By daniellenierenberg

We've heard that elderly people and those with underlying health conditions are most at risk if they're infected with coronavirus, but those can seem like really general terms. Who does that include? And why can they face more serious illness?"According to the , some of the underlying conditions that may put you at higher risk include: chronic lung disease and asthma, heart disease and undergoing cancer treatment," said CNN Chief Medical Correspondent Dr. Sanjay Gupta. Anyone with diabetes, kidney failure or liver failure may also be at higher risk.The role of the immune system is to protect against disease or other potentially damaging pathogens. A strong one is needed to help stave off coronavirus infection."Think of it like this," Dr. Gupta suggested. "In your everyday life, you're always fighting off pathogens. Most of the time you don't even realize it. If you have an underlying condition, it makes it more challenging to fight off a virus like this. You may develop a fever, shortness of breath or a cough more easily than someone who doesn't have a preexisting illness."Additionally, there are more specific reasons why each condition has its own vulnerabilities. Here's a guide to underlying conditions affected by coronavirus and why, and how you can protect yourself or an at-risk loved one.Older adultsEight out of 10 deaths reported in the U.S. have been in adults ages 65 and older, according to the CDC. Older adults have also been more likely to require hospitalization and admission to an intensive care unit.Older adults are more likely to have long-term health problems that can increase their risk for infection and serious disease. And, our immune systems usually weaken with age, making it more difficult for people to fight off infections, according to Johns Hopkins Medicine.The quality of our lung tissue also declines over time, becoming more elastic and making respiratory diseases such as COVID-19 of important concern because of the potential for lung damage.Inflammation in older adults can be more intense, leading to organ damage.Those with lung disease, asthma or heart conditionsPeople with chronic airway and lung diseases such as chronic obstructive pulmonary disease, asthma, pulmonary fibrosis and interstitial lung disease can lay the foundations for more severe infection with coronavirus because of the inflammation, scarring and lung damage those conditions cause, Johns Hopkins Medicine reported.COVID-19 affects a person's airway and lungs, but those organs work together to provide the body with oxygen. When the lungs are overburdened with an infection, the heart has to work harder, which exacerbates the challenges of people already living with heart disease.The immunocompromisedAccording to the CDC, many conditions can cause a person to be immunocompromised, including cancer treatment, smoking, bone marrow or organ transplantation and immune deficiencies. Poorly controlled HIV or AIDS and prolonged use of man-made steroid hormones or other immune-weakening medications can also hamper a person's immune function.Cancer can weaken immunity by spreading into the bone marrow, which makes blood cells that help fight infection, according to Cancer Research UK. Cancer prevents bone marrow from making enough blood cells.Some cancer treatments can temporarily weaken the immune system, too. Because cancer treatments such as chemotherapy, cancer drugs, radiotherapy or steroids are targeted toward cancer cells, they can also diminish the number of white blood cells created in the bone marrow.A 2017 study found cigarette smoking can harm the immune system by either causing extreme immune responses to pathogens or rendering the body less effective at fighting disease. This may occur by smoking, negatively altering the cellular and molecular mechanisms responsible for keeping an immune system strong.When a person undergoes a bone marrow transplant using stem cells from a donor, or they receive an organ, a doctor may prescribe medications to prevent graft-versus-host disease and mitigate the immune system's reaction by suppressing its function. After the operation, it takes time for your immune system to be up and running again.HIV and AIDS attack the body's immune system, specifically the body's T cells, which help the immune system fight off infection. When the diseases are untreated, HIV reduces the number of those cells, making the person more likely to contract other infections or infection-related cancer, according to the CDC.Severe obesityPeople with severe obesity, or a body mass index of 40 or higher, are at higher risk of serious disease."Obesity shares with most chronic diseases the presence of an inflammatory component," a 2012 study said. Inflammatory responses were linked between the immune system and body fat. Obesity is known to impair immune function by altering white blood cell count as well as the cells that control immune responses.DiabetesPeople with type 1 or type 2 diabetes face an increased risk of getting really sick with COVID-19, as both cause a blood sugar spike. If blood sugar is poorly managed, viral diseases can be more dangerous as high blood sugar may give viruses a place to thrive, according to Diabetes in Control, a news and information resource for medical professionals.Higher levels of inflammation have been discovered in the bodies of people with diabetes, weakening the immune system and making it more difficult for those affected to stave off sickness in general.Kidney and liver diseaseThe kidneys produce several hormones that affect immune responses. Having kidney disease and failure can weaken your immune system, making it easier for infections to take hold. According to the National Kidney Foundation, doctors and researchers have found that most infections are worse in people with kidney disease.The liver is an integral member of the body's line of defense, helping to regulate the number of white blood cells utilized in immune responses and defend against harmful pathogens. Someone with liver disease is experiencing abnormalities in the function of the immune system, giving rise to more serious illness.Neurodevelopmental conditionsNeurological and neurodevelopmental conditions may also increase the risk of serious COVID-19 for people of any age.These include disorders of the brain, spinal cord, peripheral nerve and muscle such as cerebral palsy, epilepsy, stroke and intellectual disability, according to the CDC. Those with moderate to severe developmental delay, muscular dystrophy or spinal cord injury are also more at-risk.People with neurological conditions may not be more at risk due to solely their condition, but because medications they might take to control their condition could hamper their immune system. However, some neurological conditions, such as Parkinson's, have been recognized to have inflammatory components, which may harm the immune system.Others including muscular dystrophy, multiple sclerosis or amyotrophic lateral sclerosis (ALS) could cause paralysis to the diaphragm, which leaves those affected very at risk for respiratory failure if they were to be sick with COVID-19.Staying safe when you're more at riskIf you see yourself on the list of those at higher risk for severe illness, there are several things you can do to protect yourself. First, make sure you are contact your doctor or doctors about your risk level. Second, be extra vigilant about the recommendations that most people are being asked to follow.Stay home whenever possible and avoid close contact with people, the CDC suggests. Wash your hands often to prevent transferring the virus from a surface to your face, and try to clean and disinfect frequently touched surfaces as often as you can.If you don't have an underlying condition, doing your part by practicing these cautionary measures can help protect not only you, but your loved ones with existing conditions.

We've heard that elderly people and those with underlying health conditions are most at risk if they're infected with coronavirus, but those can seem like really general terms. Who does that include? And why can they face more serious illness?

"According to the [Centers for Disease Control and Prevention], some of the underlying conditions that may put you at higher risk include: chronic lung disease and asthma, heart disease and undergoing cancer treatment," said CNN Chief Medical Correspondent Dr. Sanjay Gupta. Anyone with diabetes, kidney failure or liver failure may also be at higher risk.

The role of the immune system is to protect against disease or other potentially damaging pathogens. A strong one is needed to help stave off coronavirus infection.

"Think of it like this," Dr. Gupta suggested. "In your everyday life, you're always fighting off pathogens. Most of the time you don't even realize it. If you have an underlying condition, it makes it more challenging to fight off a virus like this. You may develop a fever, shortness of breath or a cough more easily than someone who doesn't have a preexisting illness."

Additionally, there are more specific reasons why each condition has its own vulnerabilities. Here's a guide to underlying conditions affected by coronavirus and why, and how you can protect yourself or an at-risk loved one.

Eight out of 10 deaths reported in the U.S. have been in adults ages 65 and older, according to the CDC. Older adults have also been more likely to require hospitalization and admission to an intensive care unit.

Older adults are more likely to have long-term health problems that can increase their risk for infection and serious disease. And, our immune systems usually weaken with age, making it more difficult for people to fight off infections, according to Johns Hopkins Medicine.

The quality of our lung tissue also declines over time, becoming more elastic and making respiratory diseases such as COVID-19 of important concern because of the potential for lung damage.

Inflammation in older adults can be more intense, leading to organ damage.

People with chronic airway and lung diseases such as chronic obstructive pulmonary disease, asthma, pulmonary fibrosis and interstitial lung disease can lay the foundations for more severe infection with coronavirus because of the inflammation, scarring and lung damage those conditions cause, Johns Hopkins Medicine reported.

COVID-19 affects a person's airway and lungs, but those organs work together to provide the body with oxygen. When the lungs are overburdened with an infection, the heart has to work harder, which exacerbates the challenges of people already living with heart disease.

According to the CDC, many conditions can cause a person to be immunocompromised, including cancer treatment, smoking, bone marrow or organ transplantation and immune deficiencies. Poorly controlled HIV or AIDS and prolonged use of man-made steroid hormones or other immune-weakening medications can also hamper a person's immune function.

Cancer can weaken immunity by spreading into the bone marrow, which makes blood cells that help fight infection, according to Cancer Research UK. Cancer prevents bone marrow from making enough blood cells.

Some cancer treatments can temporarily weaken the immune system, too. Because cancer treatments such as chemotherapy, cancer drugs, radiotherapy or steroids are targeted toward cancer cells, they can also diminish the number of white blood cells created in the bone marrow.

A 2017 study found cigarette smoking can harm the immune system by either causing extreme immune responses to pathogens or rendering the body less effective at fighting disease. This may occur by smoking, negatively altering the cellular and molecular mechanisms responsible for keeping an immune system strong.

When a person undergoes a bone marrow transplant using stem cells from a donor, or they receive an organ, a doctor may prescribe medications to prevent graft-versus-host disease and mitigate the immune system's reaction by suppressing its function. After the operation, it takes time for your immune system to be up and running again.

HIV and AIDS attack the body's immune system, specifically the body's T cells, which help the immune system fight off infection. When the diseases are untreated, HIV reduces the number of those cells, making the person more likely to contract other infections or infection-related cancer, according to the CDC.

People with severe obesity, or a body mass index of 40 or higher, are at higher risk of serious disease.

"Obesity shares with most chronic diseases the presence of an inflammatory component," a 2012 study said. Inflammatory responses were linked between the immune system and body fat. Obesity is known to impair immune function by altering white blood cell count as well as the cells that control immune responses.

People with type 1 or type 2 diabetes face an increased risk of getting really sick with COVID-19, as both cause a blood sugar spike. If blood sugar is poorly managed, viral diseases can be more dangerous as high blood sugar may give viruses a place to thrive, according to Diabetes in Control, a news and information resource for medical professionals.

Higher levels of inflammation have been discovered in the bodies of people with diabetes, weakening the immune system and making it more difficult for those affected to stave off sickness in general.

The kidneys produce several hormones that affect immune responses. Having kidney disease and failure can weaken your immune system, making it easier for infections to take hold. According to the National Kidney Foundation, doctors and researchers have found that most infections are worse in people with kidney disease.

The liver is an integral member of the body's line of defense, helping to regulate the number of white blood cells utilized in immune responses and defend against harmful pathogens. Someone with liver disease is experiencing abnormalities in the function of the immune system, giving rise to more serious illness.

Neurological and neurodevelopmental conditions may also increase the risk of serious COVID-19 for people of any age.

These include disorders of the brain, spinal cord, peripheral nerve and muscle such as cerebral palsy, epilepsy, stroke and intellectual disability, according to the CDC. Those with moderate to severe developmental delay, muscular dystrophy or spinal cord injury are also more at-risk.

People with neurological conditions may not be more at risk due to solely their condition, but because medications they might take to control their condition could hamper their immune system. However, some neurological conditions, such as Parkinson's, have been recognized to have inflammatory components, which may harm the immune system.

Others including muscular dystrophy, multiple sclerosis or amyotrophic lateral sclerosis (ALS) could cause paralysis to the diaphragm, which leaves those affected very at risk for respiratory failure if they were to be sick with COVID-19.

If you see yourself on the list of those at higher risk for severe illness, there are several things you can do to protect yourself. First, make sure you are contact your doctor or doctors about your risk level. Second, be extra vigilant about the recommendations that most people are being asked to follow.

Stay home whenever possible and avoid close contact with people, the CDC suggests. Wash your hands often to prevent transferring the virus from a surface to your face, and try to clean and disinfect frequently touched surfaces as often as you can.

If you don't have an underlying condition, doing your part by practicing these cautionary measures can help protect not only you, but your loved ones with existing conditions.

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What are the underlying conditions causing more serious illness from coronavirus? - WPBF West Palm Beach

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A Quarantine Trendsetter – Long Island Weekly News

By daniellenierenberg

Coronavirus (Image source: U.S. Department of State)

In my February column, I wrote about the fact that I had a stem cell transplant in early December 2019, about a month before I heard for the first time about the coronavirus.

The transplant entailed getting an unrelated donors stem cells to replace mine; then, if all went according to plan, these cells would grow into a new immune system to seek and destroy my cancer cells.

As a result of the transplant, all of my childhood vaccinations became ineffective. I was instructed to stay in isolation for at least four months in order to avoid infectious and possibly deadly diseases like influenza. Consequently, I have been quarantined since December.

Just a day before writing this, a friend told me that Im a trendsetter.

I knew very little about viruses before the coronavirus came alongonly that they were microscopic infectious organisms that invade living cells and then reproduce. In an effort to review what I had been (mostly unconsciously) protected from before transplant, I Googled the Centers for Disease Control and Prevention (CDC) and found a piece entitled, Vaccines for children: Diseases you almost forgot about.

I was reminded that most of us had vaccines as children for some of the nastiest viruses, including polio, which invades the brain and spinal cord and leads to paralysis; tetanus, a potentially fatal disease that causes lockjaw; whooping cough, which can lead to violent coughing that makes it difficult to breathe; and many more.

Most older adults are familiar with chicken pox, mumps and measles. I had two of them as a young teenager. One that I forgot about is diphtheria, which affects breathing or swallowing and can lead to heart failure, paralysis and death. There are several more.

I imagined the panic that parents must have felt and the pain that young children must have experienced before vaccines were discovered to prevent these horrible infectious diseases.

For the time being, I cannot replace my old vaccines. I must wait for at least one year while my new immune system gets stronger.

The idea of being in isolation and maintaining a safe social distance for a few months post-transplant made sense to me. I was well prepared by doctors and nurses and I knew my wife would be a great caregiver, so I thought I could do the time.

And then, the coronavirus came along.

For me, being quarantined was an old hat by the time a national emergency was declared and everything started to shut down. I learned that this new virus main target was the lungs and people older than 60 years with underlying health conditions were its primary targets.

I fit the bill and knew that Id have to do more time: at least another three months, my transplant doctor told me. The only difference is that this time, hundreds of millions of people would be joining me.

I was well-prepared before and after my transplant. I knew why I had to self-isolate and for how long. No one, including me, was prepared for COVID-19 and the mass quarantine that it now requiresnot only to protect oneself and ones family, but also to protect strangers. Mostly older strangers like me.

Scientists and other health professionals were the heroes of viral epidemics gone by. I do believe we will get through this, with people like immunologist Dr. Anthony Fauci leading the way.

Still, the unknown is what is most frightening. We all want answers, yet some remain illusive at the moment. This is an opportunity for all of us to strengthen our tolerance for ambiguity.

When will this end? No clue. Will it come back? No idea.

Although my new immune system needs more time to protect me, I just found out after a PET scan that Im in complete remission from my cancer.

Will it come back? No idea.

We are all in the same boat, living in uncertainty, whether young or old, healthy or unwell. As Plato said, Be kind, for everyone you meet is fighting a harder battle.

Andrew Malekoff is the executive director of North Shore Child and Family Guidance Center. To find out more, call 516-626-1971 or visit http://www.northshorechildguidance.org.

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Stem Cell Assay Market Highlights On Future Development 2025 – Science In Me

By daniellenierenberg

Stem Cell Assay Market: Snapshot

Stem cell assay refers to the procedure of measuring the potency of antineoplastic drugs, on the basis of their capability of retarding the growth of human tumor cells. The assay consists of qualitative or quantitative analysis or testing of affected tissues and tumors, wherein their toxicity, impurity, and other aspects are studied.

With the growing number of successful stem cell therapy treatment cases, the global market for stem cell assays will gain substantial momentum. A number of research and development projects are lending a hand to the growth of the market. For instance, the University of Washingtons Institute for Stem Cell and Regenerative Medicine (ISCRM) has attempted to manipulate stem cells to heal eye, kidney, and heart injuries. A number of diseases such as Alzheimers, spinal cord injury, Parkinsons, diabetes, stroke, retinal disease, cancer, rheumatoid arthritis, and neurological diseases can be successfully treated via stem cell therapy. Therefore, stem cell assays will exhibit growing demand.

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Another key development in the stem cell assay market is the development of innovative stem cell therapies. In April 2017, for instance, the first participant in an innovative clinical trial at the University of Wisconsin School of Medicine and Public Health was successfully treated with stem cell therapy. CardiAMP, the investigational therapy, has been designed to direct a large dose of the patients own bone-marrow cells to the point of cardiac injury, stimulating the natural healing response of the body.

Newer areas of application in medicine are being explored constantly. Consequently, stem cell assays are likely to play a key role in the formulation of treatments of a number of diseases.

Global Stem Cell Assay Market: Overview

The increasing investment in research and development of novel therapeutics owing to the rising incidence of chronic diseases has led to immense growth in the global stem cell assay market. In the next couple of years, the market is expected to spawn into a multi-billion dollar industry as healthcare sector and governments around the world increase their research spending.

The report analyzes the prevalent opportunities for the markets growth and those that companies should capitalize in the near future to strengthen their position in the market. It presents insights into the growth drivers and lists down the major restraints. Additionally, the report gauges the effect of Porters five forces on the overall stem cell assay market.

Global Stem Cell Assay Market: Key Market Segments

For the purpose of the study, the report segments the global stem cell assay market based on various parameters. For instance, in terms of assay type, the market can be segmented into isolation and purification, viability, cell identification, differentiation, proliferation, apoptosis, and function. By kit, the market can be bifurcated into human embryonic stem cell kits and adult stem cell kits. Based on instruments, flow cytometer, cell imaging systems, automated cell counter, and micro electrode arrays could be the key market segments.

In terms of application, the market can be segmented into drug discovery and development, clinical research, and regenerative medicine and therapy. The growth witnessed across the aforementioned application segments will be influenced by the increasing incidence of chronic ailments which will translate into the rising demand for regenerative medicines. Finally, based on end users, research institutes and industry research constitute the key market segments.

The report includes a detailed assessment of the various factors influencing the markets expansion across its key segments. The ones holding the most lucrative prospects are analyzed, and the factors restraining its trajectory across key segments are also discussed at length.

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Global Stem Cell Assay Market: Regional Analysis

Regionally, the market is expected to witness heightened demand in the developed countries across Europe and North America. The increasing incidence of chronic ailments and the subsequently expanding patient population are the chief drivers of the stem cell assay market in North America. Besides this, the market is also expected to witness lucrative opportunities in Asia Pacific and Rest of the World.

Global Stem Cell Assay Market: Vendor Landscape

A major inclusion in the report is the detailed assessment of the markets vendor landscape. For the purpose of the study the report therefore profiles some of the leading players having influence on the overall market dynamics. It also conducts SWOT analysis to study the strengths and weaknesses of the companies profiled and identify threats and opportunities that these enterprises are forecast to witness over the course of the reports forecast period.

Some of the most prominent enterprises operating in the global stem cell assay market are Bio-Rad Laboratories, Inc (U.S.), Thermo Fisher Scientific Inc. (U.S.), GE Healthcare (U.K.), Hemogenix Inc. (U.S.), Promega Corporation (U.S.), Bio-Techne Corporation (U.S.), Merck KGaA (Germany), STEMCELL Technologies Inc. (CA), Cell Biolabs, Inc. (U.S.), and Cellular Dynamics International, Inc. (U.S.).

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Synaptic silencing of fast muscle is compensated by rewired innervation of slow muscle – Science Advances

By daniellenierenberg

/ AChR subunit KO zebrafish lines

We generated a subunit gene KO zebrafish (KO) using CRISPR-Cas9 (Fig. 1A) and an subunit gene KO zebrafish (KO) using transcription activatorlike effector nucleases (TALEN) (Fig. 1A). The KO zebrafish did not show obvious phenotypes during development and matured in a fashion indistinguishable from wild-type (WT) siblings (fig. S1). In contrast, KO fish generally failed to form swim bladders, and most of them died prematurely within 2 weeks after fertilization. However, a fraction of KO fish (approximately 25%) survived to adulthood. A double KO (DKO) line was generated by crossing KO and K lines. DKO larvae also failed to form swim bladders (Fig. 1B) and died within 2 weeks after fertilization.

(A) Schematic diagram of targeted genes. Arrowheads indicate targeted regions of genome editing. Each box and line indicates an exon and an intron, respectively. Alignment of genomic DNA sequences of WT and KO lines showed a 7base pair (bp) insertion in the AChR subunit gene chrng and a 1-bp insertion in the AChR subunit gene chrne. (B) Photograph showing WT and / DKO larva at 6 dpf. Notice the lack of swim bladder (arrowheads) in DKO. Scale bar, 1 mm. (C) Trunk regions of a WT larva (6 dpf) and a DKO larva (6 dpf) were stained with -BTX conjugated with Alexa Fluor 488 (green). In WT, AChRs were distributed in myoseptal regions (arrows) and in punctae in middle regions (arrowhead). DKO had -BTX signals only in myoseptal regions. Scale bars, 100 m.

We histologically analyzed the expression of AChRs in the trunk region of 6 days post-fertilization (dpf) larvae by using -bungarotoxin (-BTX) conjugated with Alexa Fluor 488, a toxin that specifically binds to the assembled AChR (Fig. 1C). AChR clusters in DKOs were observed only in boundary regions between body segments (Fig. 1C), where slow muscles form NMJs (16). We initially expected that AChRs in fast muscles of DKO larvae would convert to the slow muscletype AChRs, comprising only , , and subunits. This conversion of subunit composition would not cause a change in AChR distribution visualized by -BTX, because both types of AChRs bind to -BTX. However, -BTX signals were absent in fast muscles, which suggested that fast muscles could not express AChRs composed of , , and subunits.

To correlate the AChR expression pattern observed by the -BTX staining with the synaptic function, we analyzed synaptic activities of fast and slow muscles in the DKO line at 6 dpf. We recorded spontaneous synaptic currents from muscle cells using the whole-cell patch clamp technique (Fig. 2, A to C). Traces show miniature endplate currents (mEPCs) from muscles of WT or DKO larvae (Fig. 2A). Slow muscles in the DKO line exhibited mEPCs. The frequency (14.5 3.1 Hz in WT, 15.5 3.2 Hz in DKO) and the amplitude of slow muscle mEPCs (260.0 74.1 pA in WT, 491.7 105.2 pA in DKO) showed no differences between WT and DKO lines (Fig. 2, B and C). However, fast muscles in DKO failed to produce mEPCs. To confirm that the lack of mEPCs is caused by the absence of functional receptors, we recorded currents in muscles generated by puff application of ACh (Fig. 2D). While fast muscles in WT larvae showed ACh-induced currents (756.4 138.6 pA), those in DKO larvae failed to show any response (0 0 pA). These results, in conjunction with the -BTX staining (Fig. 1C), showed that fast muscles of DKO larvae do not express any AChRs and receive no synaptic input.

(A) mEPC traces from fast or slow muscles of WT and DKO larvae (6 dpf) by whole-cell patch-clamp recordings. Fast muscle cells in DKO failed to exhibit mEPCs. (B and C) Frequencies (B) and amplitudes (C) of mEPCs were plotted for each muscle (n = 8 cells). (D) Representative traces of voltage-clamped slow and fast muscles in DKO larvae in response to the application of 30 M ACh. Calibration: 1 s, 500 pA. Amplitudes of ACh-induced currents in slow (n = 7 cells) and fast muscles (n = 7 cells) are shown. Each dot represents a muscle cell. (E) Construct used for Ca2+ imaging. Top: The GCaMP7a coding sequence was fused to the promoter region of the -actin promoter pact. Bottom: Schematic illustration showing the experimental procedure. The gene construct was injected into eggs of DKO at the one cell stage. Ca2+ response was analyzed at 6 dpf. Representative traces showing the increase of F/F in a fast muscle (black line) and a slow muscle (red line) during spontaneous contractions. (F) Overexpression of the subunit fused with an EGFP (-EGFP) in WT (3 dpf). Top panels: -EGFPs were expressed under the control of a slow musclespecific promoter, psmyhc. EGFP signals (green), expressed in the superficial slow muscles, filled the cytoplasm and did not colocalize with -BTX (magenta) signals. Bottom panels: -EGFPs were expressed under the regulation of pact. In deeper layer fast muscles, the clusters of EGFP and -BTX colocalized (arrowheads). Scale bars, 50 m.

We performed in vivo Ca2+ imaging in the DKO larvae at 6 dpf to further support the result of synaptic current recordings. We designed a gene construct in which a pan-muscle promoter, -actin promoter, drives the expression of a Ca2+ indicator, GCaMP7a (17), and injected the construct into fertilized eggs (Fig. 2E). In DKOs, we recorded Ca2+ response associated with spontaneous locomotion activities, induced by the application of N-methyl-d-aspartate (50 M) (18). The results showed that slow muscle cells exhibited Ca2+ transients, while fast muscle cells did not generate any Ca2+ response.

Considering that fast muscles do not allow composition of , , and subunits, we next examined whether slow muscles conversely allow incorporation of subunits in the AChR pentamer, by overexpressing the subunit in slow muscles. We designed a gene construct that expressed an subunit fused with enhanced green fluorescent protein (-EGFP) under the regulation of a slow musclespecific promoter, psmyhc (19). We injected the construct into fertilized WT eggs and observed the expression of EGFP at 3 to 4 dpf. EGFP signals typically filled the cytoplasm of the slow muscle cells and never colocalized with -BTX signals (Fig. 2F). In a control experiment, in which -EGFP was driven by the pan-muscle promoter (-actin promoter), the -EGFP signals made clusters in fast muscles, colocalizing with -BTX signals in deeper layers of the trunk region where fast muscles form NMJs. Together, fast muscles and slow muscles express specific types of AChR, and the alternate composition of subunits is prohibited.

To examine how silencing of synapses in fast muscles affect locomotion, we next analyzed swimming of WT and DKO larvae at 6 dpf. We induced escape responses by gentle tactile stimuli. Locomotion was recorded with a high-speed camera, and we measured angles between head and tail trajectories throughout each escape response (Fig. 3A and movie S1). WT fish turned their heads 120 to 140 in the initial stage of escape. The typical startle response of teleosts generally begins with a large turn of the head (termed C-bend), followed by a robust forward propulsion as described in previous studies (20).

(A) Escape behaviors in WT and DKO lines at 6 dpf in response to tactile stimuli. Images of representative larva on the left show superimposed frames of the complete escape response (the duration of movement is indicated in the top right corner). Scale bars, 2 mm. Kinematics for representative traces of 10 larvae are shown for the initial 50 ms of the response. Middle panels represent averaged traces. In the right panels, each trace represents a different larva. Body angles are shown in degrees, with 0 indicating a straight body, and positive and negative values indicating body bends in opposite directions. Scale bars, 10 ms. (B to D) Maximum turn angles, time to reach the maximum angle, and post-startle swimming speed were calculated for each group of fish (6 dpf). In DKO, the turn angle and the swimming speed were notably reduced, and it took longer to reach maximum angles (n = 10 fish). (E and F) Analyses of spontaneous locomotion. Images of representative larva (left) for WT or DKO showed superimposed frames of spontaneous swim bouts (the duration of movement indicated in the bottom right corner). Swimming speed was calculated for WT (n = 5 fish) and DKO (n = 5 fish), which showed no significant difference. Scale bars, 2 mm.

The initial turns of the DKO larvae were in sharp contrast to WT. Averaged maximum head turn angles in DKOs were markedly smaller compared to WT larvae (116.0 5.8 in WT, 20.2 4.0 in DKO; P < 0.001) (Fig. 3B), and time to reach the maximum angle was increased (8.7 0.2 ms in WT, 15.8 0.8 ms in DKO; P < 0.001) (Fig. 3C). In addition to the absence of C-bends, the post-startle swimming speed of the DKO line was also notably slower (84.9 8.1 mm/s in WT, 12.8 1.3 mm/s in DKO; P < 0.001) (Fig. 3D).

In addition to the escape response, we also analyzed spontaneous locomotion, which corresponds to the slow swim described by Budick and OMalley (21) or scoot reported by Burgess and Granato (22) (Fig. 3, E and F). Significant difference in swimming speed was not observed between WT and DKO (16.1 1.60 mm/s in WT, 13.2 0.9 mm/s in DKO; P = 0.20) (Fig. 3F). Thus, the contribution of fast muscles in spontaneous swimming is relatively small. These results strongly suggest that fast muscles in larval zebrafish play a key role in executing quick escape responses including the C-bend and fast forward propulsion behaviors, which corroborate earlier studies (23).

DKO fish die prematurely and do not develop into adults. However, KOs that reached the adult stage are expected to lack both and subunits, because subunit expression terminates early in development.

To dismiss the possibility of compensatory up-regulation of the subunit in adult KOs, we analyzed the expression of subunit mRNA with digital droplet polymerase chain reaction (ddPCR). Subunit mRNA was not detected in adult KOs, which were 3 to 5 months old (Fig. 4A). Interestingly, subunit mRNA was strongly up-regulated in larval KOs (Fig. 4B), which may account for functional escape response behavior at 6 dpf (fig. S1). Thus, our findings suggest that compensation by the subunit expression occurs only in larval KOs and not in adults.

(A) Quantification of or subunit mRNA in adult muscles. Subunit was not detected in WT. or subunit mRNA was not detected in KO (n = 6 fish in WT, n = 5 fish in KO). Sample numbers are shown in parentheses. (B) mRNA expression of subunit in 1-dpf larvae. Subunit was highly up-regulated in the KO (n = 5 fish) compared to WT (n = 5 fish). Sample numbers are shown in parentheses. (C) Schematic illustration of a transverse section of the trunk region. The area shown in micropictograms is indicated with a box. The distribution of AChRs in adults, WT or KO, was visualized by -BTX conjugated with Alexa Fluor 488 (green). Broken lines indicate the boundary of fast muscle area (arrowheads). Fast muscles in the KO fish lack -BTX signals. (D) Sections of adult fast muscles of WT and KO, stained with the fast musclespecific F310 antibody. Fast muscles in KO fish did not display atrophy. In the right panel, diameters of fast muscles in WT and KO were calculated (87 fibers, n = 3 fish). There was no significant difference. Scale bars, 100 m.

The expression of AChR in adult KO fish, visualized by -BTX, was consistent with the lack of compensation (Fig. 4C). Transverse sections of the trunk region were labeled with -BTX. Slow, intermediate, and fast muscles are spatially segregated (11). Slow muscles are located closest to the surface. WT fish displayed universally distributed, positive -BTX signals. In sharp contrast, -BTX signals in the KO fish were detected only in shallow, lateral regions, and fast muscles of the adult KO lacked AChR expression.

In spite of the absence of -BTXpositive signals, fast muscle fibers in KO fish unexpectedly lacked signs of prominent atrophy (24). A fast musclespecific F310 antibody used via immunohistochemistry allowed the visualization and diameter measurements of fast muscle fibers. Statistical analysis revealed no difference between KO and WT fiber size (58.7 0.5 m in WT, 58.3 0.7 m in KO; P = 0.945) (Fig. 4D).

We observed escape responses induced by objects dropping on water and subsequently analyzed C-bend angles and the swimming speed during escape (Fig. 5A) (25). We compared the maximum C-bend angles between the focal genetic lines. Similar to WT larvae (Fig. 3), WT adults start the escape response with the initial extreme head turn. Unexpectedly, we found that KO adult fish also display robust C-bends (Fig. 5, A and B). Although smaller in amplitude (103.0 7.5 in WT, 53.4 2.5 in KO), their time course did not exhibit any delay compared to WT. This is in sharp contrast to the complete loss of C-bend behavior observed in larval DKOs (Fig. 3). The duration of first turn also showed no significant difference between WTs and KOs (38.9 3.8 ms in WT, 46.6 4.9 ms in KO).

(A) Escape behaviors in WT and KO adults (3 to 4 months old). The startle response was induced by dropping objects on water. Images of representative fish to the left show superimposed frames of the complete escape response (the duration of movement is indicated in the bottom right corner). Kinematics for representative traces from 10 or 9 fish are shown for the initial 50 ms of response. Middle panels represent averaged traces. In right panels, each trace represents a different fish. Body angles are shown in degrees, with 0 indicating a straight body. Positive and negative values indicate body bends in opposite directions. (B) First turn angles were calculated for each group of fish (n = 10 fish in WT, n = 9 fish in KO). Turn angles were reduced in the KO fish. Sample numbers are shown in parentheses. (C) Post-startle swimming speed and total distance traveled were calculated for the first 120 ms. There was no significant difference between WT (n = 10 fish) and KO (n = 9 fish) adults.

Furthermore, the forward propulsion during escape of the KO adult zebrafish was almost intact. When the distance traveled was plotted against the time after stimulation, the curves for WT and KO nearly overlapped (Fig. 5C). The swimming speed (31.7 1.3 cm/s in WT, 25.5 3.0 cm/s in KO; P = 0.08) and total distance traveled (4.0 0.2 cm in WT, 3.2 0.4 cm in KO; P = 0.08) were similar between WT and KO adults.

Suspecting that compensation of locomotion occurred at the level of neural projection, we examined the projections of motor neurons by retrograde labeling using a fluorescent tracer, dextran conjugated with Alexa Fluor 488 (Fig. 6, A to C). We injected the tracer into muscles of WT and K fish following a method described in a previous report (26). Spinal motor neurons in adult zebrafish are classified on the basis of morphological features. Dorsomedial motor neurons with larger cell somas, which are called primary motor neurons (pMNs), specifically innervate fast muscles. Ventrolateral motor neurons with smaller somas, called secondary motor neurons (sMNs), are grouped in distinct populations depending on the innervation target: fast, intermediate, and slow muscles (2729). We analyzed the location of motor neuron somas in the spinal cord (Fig. 6B) by measuring the distance from the center of spinal cord to cell somas. In WT adults, fast muscles were innervated mainly by dorsomedial motor neurons (located close to the center), and slow muscles were innervated by ventrolateral motor neurons (Fig. 6, A and B).

(A) Schematic illustration of a transverse section of the trunk region showing the sites of dye injections. Right panels showing cell bodies of labeled motor neurons (arrowheads) in spinal cords. Broken lines indicating outlines of spinal cords. Scale bars, 50 m. (B) A graph showing the distance from the center of the spinal cord to cell bodies of motor neurons. In WT, motor neurons located close to the center innervate fast muscles, and ventrolateral motor neurons innervate slow muscles. In KO, slow muscles were innervated by motor neurons located close to the center. Numbers of labeled cells are shown in parentheses. (C) Graph showing the size of cell somas of motor neurons. In WT, large motor neurons innervate fast muscles, and smaller neurons innervate slow muscles. In KO, slow muscles were innervated by large motor neurons. (D) Schematic illustration of a transverse section of the trunk region showing the locations of the DiI crystal insertion. The right panel displays cell body of labeled pMN (arrowhead) in the spinal cord. The broken line indicates the outline of the spinal cord. Scale bar, 50 m. (E) Presynaptic structures were visualized by SV2A antibody. Broken lines indicate the boundary of slow muscle area (left side). Note the reduced signal in the fast muscles of the KO fish. Scale bars, 100 m. (F and G) Fast musclespecific myosins labeled by F310 antibody in WT (F) and KO (G). In (G), the boxed area is enlarged in the right panel. Broken lines indicate the boundary of slow muscle area (left side). Arrowheads indicate muscle cells with F310 signals in the slow muscle region. While a small number of slow muscle cells in WT sometimes showed immunoreactivity, the cell number was markedly increased in KO. Scale bars, 100 m. (H and I) Glycolytic muscle fibers were visualized by GPD staining in WT (H) and KO (I). Black broken lines indicate the boundary between slow and intermediate muscles, and the red broken line indicates the boundary between intermediate and fast muscles. Fast, intermediate, and slow muscle areas are labeled with F, I, and S, respectively. Note that the intermediate muscle region in KO is hard to distinguish from the fast muscle region, blurring the boundary (I). Arrowheads in the right panel indicate muscle cells with GPD signals in the slow muscle region. Scale bars, 100 m. (J) Schematic illustration showing the rerouted innervation of pMNs. In KO adults, synaptic silencing of fast muscles led to the innervation of fast musclespecific pMNs on slow muscle. This reinnervation caused conversion of slow to fast muscles. The projections of sMNs that innervate fast muscles may not change.

Both the location and the size of motor neuron somas suggested that slow muscles in KO adults were innervated by large motor neurons, which innervate only fast muscles in WT adults (Fig. 6C). Ventrolateral neurons did not seem to innervate slow muscles in KOs, as they were absent in retrograde labeling (Fig. 6, B and C). When we injected the tracer into fast muscles of KO adults, pMNs were not labeled (fig. S2). Motor neurons labeled in these preparations were presumably fast sMNs (26).

To rule out the possibility that pMN axons are inadvertently damaged by dye injections into slow muscles of KO adults, we used another method of retrograde labeling using a lipophilic tracer DiI (or DiIC18), which has a minimal possibility of causing pressure injection damage (30). After gently placing crystals of DiI onto slow muscles of KO adults, we found that pMNs were labeled in spinal cords of KO adults (Fig. 6D). We also analyzed the presynaptic input in muscles of WT and KO adults using SV2A antibody to visualize presynaptic proteins (Fig. 6E). The results showed that positive signals within fast muscles were reduced in KO compared to WT adults. Thus, fewer motor neurons innervated fast muscles in KO fish.

The muscle cell type is determined by the motor neuron input (31). Suspecting the signals from pMNs may convert the properties of slow muscles into those of fast muscles in adult KO fish, we examined the characteristics of slow muscle fibers. To do so, we analyzed the F310 antibody immunohistochemistry in adult KO fish, which labels fast musclespecific myosin (Fig. 6, F and G) (19). We also examined the -glycerophosphate dehydrogenase (-GPD) activity, which is a well-established method to visualize glycolytic muscles, i.e., fast muscles (Fig. 6, H and I) (32). Some tissue located in slow muscle regions stained positive for F310 (n = 3 fish; Fig. 6G) and -GPD signals (n = 3 fish; Fig. 6I), suggesting that some slow muscles expressed the fast muscletype isoform of myosin light chain and obtained glycolytic ability. Intermediate muscle fibers in KO also showed higher glycolytic ability compared to WT (Fig. 6, H and I). Thus, a subpopulation of slow and intermediate muscles was converted to fast muscles, presumably due to the innervation of fast muscle motor neurons (31).

In summary, the absence of AChRs in developing KOs is presumed to drive motor neuron axon innervation of fast muscles to instead reroute to slow muscles. These rewired pMNs presumably predominate over original axons in slow muscles, as a result of synaptic competition, and convert some slow and intermediate muscles to fast muscles (Fig. 6J).

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Synaptic silencing of fast muscle is compensated by rewired innervation of slow muscle - Science Advances

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Blood cancer treatment added to PBS – Newcastle Herald

By daniellenierenberg

news, national

Nearly a decade after doctors told him he had up to six years to live, Ian Fox's blood cancer is in remission. He was part of an early trial of Revlimid, one of a handful of drugs added to the Pharmaceutical Benefits Scheme on Wednesday. "It was a bit scary because right from the start they said, 'Look, there's not a cure for this'," the 65-year-old told AAP. He was placed on a trial for the drug in 2012 after he got stem cell treatment and he's happy he could help researchers, with doctors telling him the cancer was in remission in 2015. "I'm rapt ... I'm on a maintenance program now, still taking a minimum dose," he said. Before his diagnosis, Mr Fox noticed cooking smells were making him nauseous. But it wasn't until he donated blood that he was referred to a GP, with doctors finally diagnosing him with myeloma. Mr Fox said he couldn't have gotten through the past 10 years without his wife Lesley and his kids Cameron and Maddy. Now the retired web designer is working on his vintage cars, having had to give up his motorcycle collection due to peripheral neuropathy in his feet - damage to the nerve cells that carry messages to and from the brain and spinal cord - a side-effect of myeloma treatment. "That's why I'm sort of directing my energies into the classic cars, because they're a bit more stable," Mr Fox said. Revlimid targets blood cancer cells while boosting the immune system. Its addition to the PBS is expected to save Australians $194,000 in out-of-pocket costs over the course of their treatment. More than 1000 people each year are expected to benefit from the change, with about 18,000 Australians living with myeloma. The government has also added Kadcyla, a breast cancer treatment; Symtuza, a treatment for people living with HIV; and Briviact, an epilepsy drug. Health Minister Greg Hunt said the drugs would give patients a better quality of life and boost their chances of recovery. Australian Associated Press

https://nnimgt-a.akamaihd.net/transform/v1/crop/frm/silverstone-feed-data/5926065c-ff01-4d99-b2de-a02d418090f4.jpg/r0_74_800_526_w1200_h678_fmax.jpg

Nearly a decade after doctors told him he had up to six years to live, Ian Fox's blood cancer is in remission.

He was part of an early trial of Revlimid, one of a handful of drugs added to the Pharmaceutical Benefits Scheme on Wednesday.

"It was a bit scary because right from the start they said, 'Look, there's not a cure for this'," the 65-year-old told AAP.

He was placed on a trial for the drug in 2012 after he got stem cell treatment and he's happy he could help researchers, with doctors telling him the cancer was in remission in 2015.

"I'm rapt ... I'm on a maintenance program now, still taking a minimum dose," he said.

Before his diagnosis, Mr Fox noticed cooking smells were making him nauseous.

But it wasn't until he donated blood that he was referred to a GP, with doctors finally diagnosing him with myeloma.

Mr Fox said he couldn't have gotten through the past 10 years without his wife Lesley and his kids Cameron and Maddy.

Now the retired web designer is working on his vintage cars, having had to give up his motorcycle collection due to peripheral neuropathy in his feet - damage to the nerve cells that carry messages to and from the brain and spinal cord - a side-effect of myeloma treatment.

"That's why I'm sort of directing my energies into the classic cars, because they're a bit more stable," Mr Fox said.

Revlimid targets blood cancer cells while boosting the immune system.

Its addition to the PBS is expected to save Australians $194,000 in out-of-pocket costs over the course of their treatment.

More than 1000 people each year are expected to benefit from the change, with about 18,000 Australians living with myeloma.

The government has also added Kadcyla, a breast cancer treatment; Symtuza, a treatment for people living with HIV; and Briviact, an epilepsy drug.

Health Minister Greg Hunt said the drugs would give patients a better quality of life and boost their chances of recovery.

Australian Associated Press

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The science of hope: Why tomorrows world will be better than todays – Irish Examiner

By daniellenierenberg

Rita de Brn gathers 20 of the best innovations that will make life better for all of us.

IF ever hope was needed, its now, during the coronavirus outbreak.

Cocooning, self-isolation, and lock-down are not conducive to positive thinking.

Nor are pandemics. But we can choose to focus our thoughts elsewhere.

Every day, universities and laboratories across the globe announce heartening observations, discoveries, breakthroughs, and cures that will save and enrich life on this planet.

Scientists havent yet succeeded in creating an invisible woman.

But whenever they do, her cloak may be waiting at the University of Rochester.

There, researchers can make objects disappear from view by strategically placing light beams to create a blind spot between them.

Compounds that can kill malaria parasites have been developed by Australian and US researchers.

Drugs based on these compounds should shortly enter phase one of clinical trials.

The birth, this year, of a baby born from eggs matured and frozen in a laboratory was a happy event that gives hope to women made infertile by chemotherapy.

The mother had treatment for breast cancer five years previously.

Researchers at Imperial College London have developed a wearable sensor that can track and monitor vital signs through fur and clothing.

The device will help sniffer dogs in their work, and monitor the health of companion animals.

University of Canterbury scientists are studying the brain networks that produce speech.

The research should benefit everyone who has a stutter or other speech disorder.

Esketamine has recently been licenced in the UK for use in the treatment of depression. The drugs antidepressant impact can take effect within hours.

Academic studies have long shown that dark night skies are crucial for plant life, wildlife, and human mental health.

Growing awareness of this has led to the Polynesian island of Niue becoming the worlds first dark-sky nation.

Washington University scientists have cured type 1 diabetes in mice, using pluripotent stem cells to efficiently create insulin-producing beta cells.

Their success brings hope of a cure one step closer for the 422m people the World Health Organisation estimates have the condition.

Videos from the European Space Agency and satellite images from NASA show air pollution clearing dramatically over Italy and China.

Economic slowdown, due to the COVID-19 outbreak, is thought to play a role.

A massive reduction in tourists to the Italian city, in recent weeks, has sharply reduced boat and cruise ship traffic.

As a result, the canal water is much cleaner, with swimming fish clearly visible, a phenomenon that has not been witnessed for decades.

Scientists have developed contact lenses that correct deuteranomaly, which is reduced sensitivity to green light.

Colour blindness affects approximately six percent of males.

The condition can make it difficult to recognise an unripe banana by its colour.

The FDA has recently approved Romosozumab, a drug that combines the benefits of earlier osteoporosis treatment drugs, while building more bone than was previously possible and helping prevent fractures.

The prospect of a single-dose vaccine, which offers long-lasting protection against multiple strains of influenza, is closer than ever.

The FDA has approved Aimmune Therapeutics peanut allergen powder.

The new immunotherapy is now being administered in US medical centres to youngsters aged between 4 and 17 years who are presenting with peanut allergies.

Making hydrogen fuel a commercially viable option in the energy market has proved elusive.

But the discovery by Tokyo-based scientists that Fe-OOH, a form of rust, is an efficient catalyst in the process, is viewed by environmentalists to be game-changing.

By combining water with plant-based cellulose nanocrystals, scientists have created a powerful, non-toxic adhesive.

Spinal-cord stimulation is a common treatment for chronic back and leg pain, outcomes for which are often disappointing.

A recent innovation, in the form of a closed-loop, spinal-cord stimulation system, delivers superior pain relief for up to 12 months after implant.

For the first time, mitral heart valves have been repaired in beating-heart surgery.

While the patient in this procedure was a dog, the surgical victory augurs well for humans aged 75 and over, roughly ten percent of whom have faulty mitral valves.

The lives of ten COVID-19 patients were recently saved in Italy,when 3D printers were successfully used to create breathing-valve spare parts for respirators.

Airbus is now taking bookings for low-Earth orbit payload slots on the International Space Stations new Bartolomeo platform.

It offers the ISSs only unobstructed view towards Earth and into outer space.

The mission is devoted to addressing sustainable development goals.

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Mayo Clinic research is a step toward hope for spinal cord …

By daniellenierenberg

Early research published in Mayo Clinic Proceedings examines the first case at Mayo Clinic of stem cell therapy tested in humans for spinal cord injury. The case study found stem cell intervention, which took place after standard surgery, and physical and occupational therapy, restored some function in a patient with spinal cord injury. The report, "Celltop Clinical Trial: First Report From a Phase I Trial of Autologous Adipose-Derived Mesenchymal Stem Cells in the Treatment of Paralysis Due to Traumatic Spinal Cord Injury" is published in the Nov. 27, 2019 edition of Mayo Clinic Proceedings.

The research discusses the experience related to the first case in a phase I safety study of mesenchymal stem cell treatment for spinal cord injury. Mohamad Bydon, M.D., a Mayo Clinic neurologic surgeon and the lead author, cautions that each patient is different, so it's too early to consider stem cell therapies as a treatment or cure for paralysis from spinal cord injury. Dr. Bydon adds that much like early trials in general, the stem cell trials are going to show variable response rates.

"Whilein this case, the first subject was a superresponder, others may not respond inthe same manner. We do not yet understand all of the necessary biology neededto achieve neurological recovery in paralyzed individuals," says Dr.Bydon. "One of our objectives in this study and future studies is tobetter delineate who will be a responder and why patients respond differently."

The research

The research centers on a 53-year-old man who suffered a spinal cord injury in a surfing accident that left him paralyzed below the neck. The patient had immediate improvements with standard therapy, but plateaued at six months post-injury. Researchers enrolled the patient in the study at Mayo Clinic nine months after the accident and injected the patient with stem cells 11 months after injury. After the stem cell injection, the patient significantly improved motor and sensory function.

Thecase study focuses on feasibility, safety and dosing of stem cell therapy. Thestudy team derived mesenchymal stem cells from the patient's fat cells andinjected them into the lower back in a procedure known as lumbar puncture.

Dr.Bydon; Wenchun Qu,M.D., Ph.D.,a physical medicine and rehabilitation physician; and Allan Dietz,Ph.D.,a transfusion medicine physician, led the multidisciplinary research team atMayo Clinic.

"Severespinal cord injury is a devastating condition for which scientists andphysicians are trying to find a cure. For the first time, we are inspiring hopethat people may receive better recovery in their function and quality of life,"says Dr. Qu. "Mayo Clinic has been taking the lead in translating thefruits of decades of research and treating neurological conditions, among whichhave been very important clinical trials where we evaluate the safety,feasibility and efficacy of adult stem cells for severe spinal cord injuries."

"This work both demonstrates the ability of cells to initiate repair and capitalizes on more than 10 years of work in the Immune, Progenitor and Cell Therapeutics Lab at Mayo Clinic. While there is still much to learn about the amazing ability of cells to heal tissue, this trial is an important step in advancing cell-based therapies toward clinical practice," says Dr. Dietz.

Investigatorscollected cerebrospinal fluid to look for new biological markers that mightgive clues to healing. Biological markers are important because they can helpidentify the critical processes that lead to spinal cord injury at a cellularlevel and could lead to new regenerative therapies.

Furtherstudy is needed to understand the effectiveness of stem cell lumbar injectionsand why patients may respond differently.

Currently,there is no way to reverse the devastating life-changing effects of paralysisfrom spinal cord injuries. Today, the only treatment is supportive care, suchas surgery and physical and occupational therapy.

Dr.Bydon says his early findings give hope that new regenerative therapies are onthe horizon for spinal cord injuries.

"Thehope is that we will have novel treatments for spinal cord injuries in the comingyears that will be different from what we have today. These will be therapies thatdo not rely upon supportive care, but therapies that rely on science to createa regenerative process for the spinal cord," says Dr. Bydon.

This research was made possible by funding from Mayo Clinic Transform the Practice Initiative and Regenerative Medicine Minnesota with support from the Mayo Clinic Center for Regenerative Medicine and the Department of Laboratory Medicine and Pathology Immune, Progenitor and Cell Therapeutics lab. The Transform the Practice Initiative aims to foster multidisciplinary teams of clinicians and researchers who align discovery and translational science, create new capacities and achieve solutions that improve the practice and address the unmet needs of patients.

###

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Tags: #Mayo Clinic Proceedings, #Spinal cord injury research, #stem cell lumbar puncture, #stem cell research, Dr. Allan Dietz, Dr. Mohamad Bydon, Dr. Wenchun Qu, Mayo Clinic Center for Regenerative Medicine, Regenerative Medicine Minnesota, Research, spinal cord injury

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Coronavirus treatment research is delayed by Trumps ban on the use of fetal tissue – Vox.com

By daniellenierenberg

President Donald Trump has repeatedly said that the US is working to develop a vaccine for Covid-19, the disease caused by the novel coronavirus, as quickly as possible. But one of his own administrations policies appears to be standing in the way of at least one scientist.

According to a report by the Washington Posts Amy Goldstein, Kim Hasenkrug, an immunologist at the National Institutes of Healths Rocky Mountain Laboratories in Montana, wants to test potential treatments for Covid-19 in mice with humanized lungs. But as the Post first reported, the work is being held up by officials at the Department of Health and Human Services due to a 2019 ban on NIH scientists using donated fetal tissue from abortions in their research.

While fetal tissue isnt typically used to develop actual therapies or treatments, it has one particularly key use for researchers: the ability to create mice with human tissue suitable for medical testing. Mice, generally, have similar immune systems to humans, making them particularly useful for early medical testing.

Humanized mice have been key to developing several important medical treatments for diseases like the Zika virus or HIV/AIDS, which was Hasenkrugs previous research focus. The calculation is simple. You cant test certain treatments without humanized mice, and you cant get humanized mice without fetal tissue.

There are, of course, many avenues of research using other kinds of tissue, but fetal cells can rapidly divide, grow, and adapt to new environments in ways that make them the gold standard for some disease research. And in other research areas, we dont yet know if there is anything that could substitute, R. Alta Charo, professor of law and bioethics at the University of Wisconsin at Madison, wrote in the New England Journal of Medicine in 2015.

And as the Posts Goldstein noted, scientists have already shown that humanized mice could make good test subjects for coronavirus treatments specifically:

Just months ago, before the new coronavirus began to infect people around the world, other U.S. scientists made two highly relevant discoveries. They found that specialized mice could be transplanted with human fetal tissue that develops into lungs the part of the body the new coronavirus invades. These humanized mice, they also found, could then be infected with coronaviruses to which ordinary mice are not susceptible closely related to the one that causes the new disease, Covid-19.

Outside researchers have offered the mice to Hasenkrug for coronavirus research. But so far, Hasenkrug and other government researchers havent been allowed to obtain the mice they need to perform testing, the Post reported, thanks to a June 2019 HHS directive banning fetal tissue research for those employed by the government.

Caitlin Oakley, a HHS spokesperson, told the Post that no decision has been made about Hasenkrugs request. A separate HHS spokesperson confirmed that in a statement to Vox.

The spokesperson also pointed to an HHS statement from last June detailing the administrations policy on fetal tissue research. Promoting the dignity of human life from conception to natural death is one of the very top priorities of President Trumps administration, reads the statement.

Hasenkrug, and the potentially millions of Americans who may benefit from his research, now find themselves caught in a deeply divisive political issue thats been years in the making.

The US government had funded fetal tissue research efforts since the 1950s and for nearly as long, anti-abortion activists have opposed the practice.

In the Trump era, they finally found an administration ready to listen.

In 2018, the US government spent $115 million on about 173 research projects utilizing fetal tissue, a third of which were devoted to developing therapies for HIV/AIDS.

Research using fetal tissue has led to the development of vaccines such as those for polio, rubella, and measles, the International Society for Stem Cell Research (ISSCR) said in a statement last September. Fetal tissue is still helping advance science, with research underway using cells from fetal tissue to evaluate conditions including Parkinsons disease, ALS, and spinal cord injury. Fetal tissue is also necessary for the development of potential treatments for Zika virus and HIV/AIDS.

But anti-abortion activists argue it incentivizes abortion providers to perform more abortions in order to procure more tissue they could sell to third-party companies, which then provide the tissue directly to researchers. Fetal tissue procurement has been heavily regulated since enactment of the NIH Revitalization Act of 1993, which states that profits cannot be made in the transfer or acceptance of fetal tissue for research purposes.

That hasnt stopped anti-abortion activists from continuing to call into question the ethics of abortion providers or procurement companies. In 2000, the anti-abortion rights group Life Dynamics seemingly began the practice of releasing false or deceptively edited videos targeting the fetal tissue sales process. The main source in their videos was found to be not credible.

The George W. Bush administration did not take action against fetal tissue research, instead enacting restrictions on stem cell research derived from embryos in an August 2001 executive order. Those restrictions were later rolled back by an executive order from President Barack Obama in 2009.

More recently, the anti-abortion rights group Center for Medical Progress, run by activist David Daleiden, infamously released heavily edited videos appearing to show a Planned Parenthood employee negotiating prices for fetal tissue, and CMP accused the abortion care provider of illegally profiting from sales.

The videos caught the attention of Republican lawmakers. Investigations by the House Energy and Commerce, House Judiciary, and Oversight and Government Reform committees found no wrongdoing. Further investigations into Planned Parenthood and fetal tissue transfer proceeded with the creation of the Select Investigative Panel on Infant Lives in October 2015, chaired by Rep. Marsha Blackburn (R-TN), leading to $1.59 million in spending and a 471-page final report making numerable anti-abortion recommendations.

Among those requests was a call for the government to ban fetal tissue research by government scientists, which Barack Obamas administration, which favored the practice, ultimately ignored.

Democrats on the committee released their own report, disputing the conclusions of their Republican colleagues. At the end of their crusade, the conclusion was undeniable: There was no wrongdoing on behalf of fetal tissue researchers, including Advanced Bioscience Resources, or anyone else in the fetal tissue research space, said Rep. Jan Schakowksy (D-IL), who served as the ranking Democrat on the select committee, in a statement to Rewire.News in October 2018.

Anti-abortion activists saw an opportunity to advance their agenda on fetal tissue research when President Donald Trump won election in 2016, but it took a conservative media freakout in 2018 to enact new restrictions.

Over the summer of 2018, conservative media focused on several transactions by Advanced Bioscience Resources, a company that procured fetal tissue from abortion providers and shipped it to researchers for use. ABR was also one of the subjects of the 2015 select committee investigation.

HHS decided to cancel the governments contract with ABR in late September 2018 and began a review of the agencys rules and processes for procuring fetal tissue for research. That review concluded last summer, with HHS announcing in June that it would ban any fetal tissue studies by in-house NIH scientists, like Hasenkrug. It also introduced strict paperwork requirements for any outside scientists conducting research funded by the government.

The decision came as welcome news to anti-abortion activists. The language is trying to hold an ethical standard for the research proposals and the research that might be done. The policy is not just about science. Its also about ethics, David Prentice, vice president and research director at the anti-abortion Charlotte Lozier Institute, told Science magazine last July.

For his part, Hasenkrug has reportedly asked the Trump administration several times for permission to begin working with UNCs humanized mice for a coronavirus cure, but is still waiting on permission. Per the Post:

On Feb. 19, two people said, Hasenkrug wrote to a senior NIH official, asking for permission to use those mice and run experiments related to covid-19. He eventually was told that his request had been passed on to senior HHS officials.

Since then, he has written repeatedly to NIH, laying out in greater detail the experiments he wants to undertake and why several alternatives to the fetal tissue-implanted mice would not be as useful. In one appeal to NIH, Hasenkrug wrote that the mice he was offered are more than a year old and have a relatively short time remaining to live, so they should be used quickly, according to Kerry Lavender, a Canadian researcher familiar with the correspondence.

Hasenkrugs request has reportedly been forwarded to the White House Domestic Policy Council, which is chaired by Trump himself, but the government has not made a decision on the research as of yet.

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Why computers won’t be reading your mind any time soon – Wired.co.uk

By daniellenierenberg

Edward Chang can't read your thoughts. Whenever the neuroscientist's lab at the University of California publishes a new piece of research, there's always a familiar refrain: that he's created "mind-reading technology" or can "read your thoughts". He's not alone, it's a phrase that follows much of the research into brain-computer interfaces and speech decoding.

And no wonder, when Elon Musk's startup Neuralink claims it will eventually enable "consensual telepathy" and Facebook one of the funders of Chang's lab said it wants to let people send messages by just thinking the words, rather than tapping them out on a phone, an example of a brain-computer interface (BCI).

But Chang isn't trying to read minds; he's decoding speech in people who otherwise can't speak. "We're not really talking about reading someone's thoughts," Chang says. "Every paper or project we've done has been focusing on understanding the basic science of how the brain controls our ability to speak and understand speech. But not what we're thinking, not inner thoughts." Such research would have significant ethical implications, but it's not really possible right now anyway and may never be.

Even decoding speech isn't easy. His most recent paper, in Nature last year, aimed to translate brain signals produced by speech into words and sentences read aloud by a machine; the aim is to help people with diseases such as amyotrophic lateral sclerosis (ALS) a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. "The paper describes the ability to take brain activity in people who are speaking normally and use that to create speech synthesis it's not reading someone's thoughts," he says. "It's just reading the signals that are speaking."

The technology worked to an extent. Patients with electrodes embedded in their brains were read a question and spoke an answer. Chang's system could accurately decipher what they heard 76 per cent of the time and what they said 61 per cent of the time by looking at their motor cortex to see how the brain fired up to move their mouth and tongue. But there are caveats. The potential answers were limited to a selection, making the algorithm's job a bit easier. Plus, the patients were in hospital having brain scans for epilepsy, and could therefore speak normally; it's not clear how this translates to someone who can't speak at all.

"Our goal is to translate this technology to people who are paralysed," he says. "The big challenge is understanding somebody who's not speaking. How do you train an algorithm to do that?" It's one thing to train a model using someone you can ask to read out sentences; you scan their brain signals while they read out sentences. But how do you do that if someone can't speak?

Chang's lab is currently in the middle of a clinical trial attempting to address that "formidable challenge", but it's as yet unclear how speech signals change for those unable to speak, or if different areas of the brain need to be considered. "There are these fairly substantial issues that we have to address in terms of our scientific knowledge," he says.

Decoding such signals is challenging in part because of how little we understand about how our own brains work. And while systems can be more easily trained to move a cursor left or right, speech is complicated. "The main challenges are the huge vocabulary that characterise this task, the need of a very good signal quality achieved only by very invasive technologies and the lack of understanding on how speech is encoded in the brain," says David Valeriani of Harvard Medical School. "This latter aspect is a challenge across many BCI fields. We need to know how the brain works before being able to use it to control other technologies, such as a BCI."

And we simply don't have enough data, says Mariska van Steensel, assistant professor at UMC Utrecht. It's difficult to install brain implants, so it's not frequently done; Chang used epilepsy patients because they were already having implants to track their seizures. Sitting around waiting for a seizure to strike, a handful were willing to take part in his research out of boredom. "On these types of topics, the number of patients that are going to be implanted will stay low, because it is very difficult research and very time consuming," she says, noting that fewer than 30 people have been implanted with a BCI worldwide; her own work is based on two implants. "That is one of the reasons why progress is relatively slow," she added, suggesting a database of work could be brought together to help share information.

There's another reason this is difficult: our brains don't all respond the same. Van Steensel has two patients with implants, allowing them to make a mouse click with brain signals by thinking about moving their hands. In the first patient, with ALS, it worked perfectly. But it didn't in the second, a patient with a brain-stem stroke. "Her signals were different and less optimal for this to b e reliable," she says. "Even a single mouse click to get reliable in all situations is already difficult."

This work is different than that of startups such as NextMind and CTRL-Labs that use external, non-invasive headsets to read brain signals, but they lack the precision of an implant. "If you stay outside a concert hall, you will hear a very distorted version of what's playing inside this is one of the problems of non-invasive BCIs," says Ana Matran-Fernandez, artificial intelligence industry fellow at the University of Essex. "You will get an idea of the general tempo... of the piece that's being played, but you can't pinpoint specifically each of the instruments being played. This is the same with a BCI. At best, we will know which areas of the brain are the most active playing louder, if you will but we won't know why, and we don't necessarily know what that means for a specific person."

Still, tech industry efforts including Neuralink and Facebook aren't misplaced, says Chang, but they're addressing different problems. Those projects are looking at implant or headset technology, not the hard science that's required to make so-called mind reading possible. "I think it's important to have all of these things happening," he says. "My caveat is that's not the only part of making these things work. There's still fundamental knowledge of the brain that we need to have before any of this will work."

Until then, we won't be able to read speech, let alone inner thoughts. "Even if we were perfectly able to distinguish words someone tries to say from brain signals, this is not even close to mind reading or thought reading," van Steensel says. "We're only looking at the areas that are relevant for the motor aspects of speech production. We're not looking at thoughts I don't even think that's possible."

Edward Chang will be one of the speakers at WIRED Health in London on March 25, 2020. For more details, and to book your ticket, click here

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Exploring future spinal cord injury therapies – Drug Target Review

By daniellenierenberg

Drug Target Review explores five of the latest research developments in the field of spinal cord injury (SCI) repair.

MRIs of Lumbar & Thoracic spine showing how a fracture of thoracic spine gets worse over time.

Researchers have shown that increasing energy supply to injured spinal cord neurons can promote axon regrowth and motor function restoration after a spinal cord injury (SCI).

We are the first to show that spinal cord injury results in an energy crisis that is intrinsically linked to the limited ability of damaged axons to regenerate, said Dr Zu-Hang Sheng, study co-senior author, senior principal investigator at the US National Institute of Neurological Disorders and Stroke (NINDS).

According to the team, energy levels are damaged because the mitochondria that produce adenosine triphosphate (ATP) for neurons are located in the axons. When damaged, the mitochondria are unable to produce ATP at the same level.

Nerve repair requires a significant amount of energy, said Dr Sheng. Our hypothesis is that damage to mitochondria following injury severely limits the available ATP and this energy crisis is what prevents the regrowth and repair of injured axons.

The scientists suggest that this is compounded by the anchoring of mitochondria in adult cells alongside the axons, so once damaged they are hard to replace.

Using a murine model, called a Syntaphilin knockout, where mitochondria are free to move along the axons, the researchers showed that when mitochondria are more mobile, mice have significantly more axon regrowth across the site of SCI compared to control animals. The paper also demonstrated that newly-grown axons made appropriate connections beyond the injury site, leading to functional recovery of motor tasks.

They hypothesised that increasing mitochondrial transport and thus the available energy to the injury site could enable repair of damaged nerve fibres.

When fed creatine, a compound that enhances the formation of ATP, both the control and knockout mice had increased axon regrowth following injury, compared to mice fed saline instead. More robust nerve regrowth was seen in the knockout mice that received creatine.

We were very encouraged by these results, said Dr Sheng. The regeneration that we see in our knockout mice is very significant and these findings support our hypothesis that an energy deficiency is holding back the ability of both central and peripheral nervous systems to repair after injury.

Dr Sheng highlighted that despite the promising results of the study published in Cell Metabolism, genetic manipulation was required for the best regrowth as creatine produced only modest regeneration. He concluded that further research is required to develop therapeutic compounds that are more effective in entering the nervous system and increasing energy production for the treatment of SCI.

Experiments exploring the role of immune and glial cells in wound healing and neural repair has revealed that Plexin-B2, an axon guidance protein, is essential for their organisation after SCI.

The researchers suggest their findings could aid in the development of therapies that target axon guidance pathways for treatment of SCI.

An artists impression of a macrophage.

The paper published in Nature Neuroscience reveals that Plexin-B2 on macrophages and microglia is essential for the process of corralling, where microglia and macrophages are mobilised and form a protective barrier around the site of SCI, separating healthy and necrotic tissue. In this study, researchers found that corralling begins early in the healing process and requires the ability of Plexin-B2 to steer immune cells away from colliding cells.

When they deleted Plexin-B2 from the microglia and macrophages in tissues, it led to tissue damage, inflammatory spillover and hindered axonal regeneration.

The lead investigator Dr Hongyan Jenny Zou, Professor of Neurosurgery and Neuroscience at the Icahn School of Medicine at Mount Sinai, US, said the results were quite unexpected.

She concluded that understanding the signalling pathways and interactions of glial cells with each other and the injury environment is fundamental to improving neural repair after a traumatic brain or spinal cord injury.

Another studyexploring the interactions of macrophages and microglia has revealed that in the central nervous system (CNS), microglia interfere with macrophages preventing them from moving out of damaged regions of the CNS.

We expected the macrophages would be present in the area of injury, but what surprised us was that microglia actually encapsulated those macrophages and surrounded them almost like police at a riot. It seemed like the microglia were preventing them from dispersing into areas they should not be, said Jason Plemel, a medical researcher at Canadas University of Alberta and a member of the Neuroscience and Mental Health Institute.

A microglial cell stained with Rio Hortegas silver carbonate method under the microscope.

Plemel said that more research is required to ascertain why this is happening, but they found that both the immune cells that protect the CNS, microglia and the immune cells of the peripheral immune system, macrophages, are present early after demyelination and microglia continue to accumulate at the expense of macrophages.

When we removed the microglia to understand what their role was, the macrophages entered into uninjured tissue. This suggests that when there is injury, the microglia interfere with the macrophages in our CNS and act as a barrier preventing their movement.

The scientists said that this observation was only possible because they were able to distinguish between microglia and macrophages, which has historically not been possible. Using this technique, they established than one type of microglia responded to demyelination. The results were published in Science Advances.

The indication of at least two different populations of microglia is an exciting confirmation for us, said Plemel. We are continuing to study these populations and hopefully, in time, we can learn what makes them unique in terms of function. The more we know, the closer we get to understanding what is going on (or wrong) when there is neurodegeneration or injury and being able to hypothesise treatment and prevention strategies.

Researchers suggest subpially-injecting neural precursor cells (NSCs) may reduce the risk of further injury associated with current spinal cell delivery techniques.

NSCs have the potential to differentiate into many neural cell types depending on the environment and have been the subject of investigation in both the field of SCI repair and neurodegenerative disease therapies.

subpially-injected cells are likely to accelerate and improve treatment potency in cell-replacement therapies for several spinal neurodegenerative disorders

However, the senior author of this study Dr Martin Marsala, professor in the Department of Anesthesiology at University of California (UC) San Diego School of Medicine, US, explained the current delivery techniques involve direct needle injection into the spinal parenchyma the primary cord of nerve fibres running through the vertebral column, so there is an inherent risk of (further) spinal tissue injury or intraparenchymal bleeding.

The novel technique Dr Marsala proposed in a paper published in Stem Cells Translational Medicine, is to inject these cells into the spinal subpial space an area between the pial membrane and the superficial layers of the spinal cord.

This injection technique allows the delivery of high cell numbers from a single injection, Dr Marsala explained. Cells with proliferative properties, such as glial progenitors, then migrate into the spinal parenchyma and populate over time in multiple spinal segments as well as the brain stem. Injected cells acquire the functional properties consistent with surrounding host cells.

The research collaborators suggest that subpially-injected cells are likely to accelerate and improve treatment potency in cell-replacement therapies for several spinal neurodegenerative disorders. This may include spinal traumatic injury, amyotrophic lateral sclerosis and multiple sclerosis, said study senior author Dr Joseph Ciacci, a neurosurgeon at UC San Diego Health.

The team now intend to move their experiments from rats to larger pre-clinical animal models, more anatomically similar to humans. The goal is to define the optimal cell dosing and timing of cell delivery after spinal injury, which is associated with the best treatment effect, concluded Dr Marsala.

Dr Mohamad Khazaei is the recipient of the STEM CELLS Translational Medicines (SCTM) Young Investigator Award for his work on SCI.

The award recognises advancements in the field of stem cells and regenerative medicine made by young researchers. The recipient is the principal author of an article published in SCTM that, over the course of a year, is deemed to have the most impact.

Dr Khazaeis work focuses on bringing cell-based strategies, such as NSC transplantation, into the therapeutic pipeline through generating and differentiating novel cell types using genetic and cell engineering approaches.

While we currently lack effective regenerative medicine treatment options for spinal cord injuries, Dr Khazaeis work to create a cell transplantation therapy utilising neural precursor cells is novel and provides a promising approach, said Dr Anthony Atala, Editor-in-Chief of SCTM and director of the Wake Forest Institute for Regenerative Medicine.

His winning paper details how Dr Khazaei and his team used neurons and oligodendrocytes to obtain better functional recovery after SCI.

Related topicsCell Regeneration, CNS, Disease research, Drug Delivery, Drug Discovery, Drug Targets, Neurons, Neurosciences, Regenerative Medicine, Research & Development, Therapeutics

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Online Extra: London case appears to be second HIV cure – Bay Area Reporter, America’s highest circulation LGBT newspaper

By daniellenierenberg

Adam Castillejo revealed himself to be the London Patient. Photo: Courtesy Adam Castillejo/Facebook

A London man who still has undetectable virus 30 months after stopping antiretroviral treatment is likely the second person ever cured of HIV, according to a report presented this week at the Conference on Retroviruses and Opportunistic Infections.

Two days before the conference was set to open in Boston, organizers decided to make the meeting virtual due to concerns about the coronavirus. Researchers gave their presentations via webcasts.

At last year's CROI, Dr. Ravindra Gupta of University College London reported that the so-called London Patient, who received a bone marrow transplant using stem cells from a donor with natural resistance to HIV, had no detectable virus in his blood plasma or T cells 18 months after stopping treatment.

At this week's meeting, Gupta said that an additional year of more extensive testing had found no functional HIV in the man's blood, lymph nodes, semen, gut tissue or cerebrospinal fluid.

"After 2.5 years off antiretrovirals and lack of evidence for any active virus, this almost certainly represents cure," Gupta told the Bay Area Reporter.

A day before Gupta's presentation, the New York Times revealed that the man, Adam Castillejo, 40, had decided to go public as the London Patient. Castillejo, who grew up in Venezuela, moved to London in 2002 and was diagnosed with HIV a year later. He is now leading a healthy and active life.

"My message to everyone out there living and coping with HIV is to not give up hope," Castillejo told the B.A.R. "I do hope that me going public will give some encouragement and empower people to keep breaking the stigma associated with HIV."

Resistant T cellsLike former San Francisco resident Timothy Ray Brown, known as the Berlin Patient the only other person known to be cured of HIV Castillejo underwent a bone marrow transplant to treat advanced cancer. According to the Times story, he spoke with Brown repeatedly before deciding to reveal his identity.

In both cases, doctors searched an international registry to find donors with double copies of an uncommon genetic mutation known as CCR5-delta-32, which makes T cells resistant to most types of HIV.

Brown received two stem cell transplants to treat leukemia in 2006, first undergoing strong chemotherapy and radiation to kill off his cancerous immune cells. He stopped antiretroviral therapy at the time of his first transplant, but his viral load did not rebound as expected. Over years of testing, researchers have found no functional virus anywhere in his body. Brown has now been free of HIV for more than 13 years.

Castillejo was diagnosed with lymphoma in 2011. After five years of grueling treatment, he underwent a bone marrow transplant in May 2016. But he received less aggressive chemotherapy than Brown and was able to stay on antiretroviral therapy.

The transplant led to complete remission of his lymphoma. Post-transplant tests showed that most of his T cells now lacked the CCR5 receptors HIV uses to enter the cells. In September 2017, with no evidence of viable HIV in his blood, he stopped his antiretrovirals in a closely monitored analytic treatment interruption.

When Castillejo was last tested on March 4, his plasma viral load remained undetectable using an ultrasensitive assay. Viral load was also undetectable in his semen and cerebrospinal fluid surrounding the brain and spinal cord. Biopsies showed no evidence of functional HIV in a lymph node or in his large or small intestine. Some bits of HIV genetic material were detected in long-lived memory T cells, but Gupta said these are probably "fossils" that cannot trigger active viral replication.

If this does prove to be a second cure, experts caution that the high-risk procedure will not be an option for people with HIV who do not need the treatment for cancer. But researchers are working on ways to mimic the same effect using gene therapy to delete CCR5 receptors from T cells or stem cells that give rise to all immune cells.

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10 things to know about stem cell therapy – Outlook India

By daniellenierenberg

10 things to know about stem cell therapy

New Delhi, March 3 (IANSlife) The usage of stem cells to cure or treat a disease or repair the injured tissue is defined as stem cell therapy. The best example of the stem cell treatment is seen in patients suffering from restoring the vision of the damaged eyes, grafting of the skin in severe burnt conditions. Stem cell treatments for brain or neural diseases like Parkinson''s and Alzheimer''s disease, multiple sclerosis, preventing heart strokes, curing diabetes, kidney disorders, autism, and spinal cord injuries are progressively making their way. Vipul Jain, CEO of Advancells and also a Serial entrepreneur, explains in detail the treatment, its uses, cost and effectiveness.

Q: What are stem cells?

Undifferentiated cells that are able to differentiate and transform into any type of cells of the body when and where needed. They have an enormous potential to repair, heal and regenerate. Stem cells come from blood, bone marrow, umbilical cord blood and adipose tissue.

Types of stem cell therapy

Autologous stem cell therapy: Patient receives stem cells from his/her own body

Allogeneic stem cell therapy: Patient receives the stem cells donated by another individual

Autologous stem cell therapy is better than allogeneic stem cell therapy as chances of mismatching are not there and they pose the minimum risk of immune rejection. Also, no side effects or adverse effects are seen as a person''s own blood cells are used. They start the healing process immediately in a natural way.

What is stem cell therapy?

The usage of stem cells to cure or treat a disease or repair the injured tissue is defined as stem cell therapy. Stem cells can be obtained from the bone marrow, adipose tissues etc. Due to their tremendous potential to prevent and to treat various health conditions and to repair the injured tissues global research investigation is continuously being done as to explore the maximum advantage of these cell lines.

The best example of the stem cell treatment is seen in patients suffering from restoring the vision of the damaged eyes, grafting of the skin in severe burnt conditions. Stem cell treatments for brain or neural diseases like Parkinson''s and Alzheimer''s disease, multiple sclerosis, preventing heart strokes, curing diabetes, kidney disorders, autism, and spinal cord injuries are progressively making their way.

What are the sources of stem cell?

Depending upon the disease, different stem cell source can be used in a specific condition. The procedure may involve the extraction of stem cells from adipose tissue-derived stem cells with the combination of PRP (Platelet-rich plasma) or can be obtained from bone marrow that can differentiate into progenitor cells that differentiate into various other tissues which can help in the therapy.

Procedure of stem cell therapy

The stem cells are isolated from the bone marrow or adipose tissues followed by their processing and enrichment under sterile conditions. These activated stem cells are placed back into the patient''s body at the target site for repairing the damaged tissue. It is necessary that the stem cells are injected in the specific area of injury as only then the desired results will be achieved.

Adipose stem cells are preferred over bone marrow stem cells as they are easy to isolate and contain a higher number of stem cells.

Stem cells injection

The stem cells injections are gaining much interest because it is devoid of the painful procedure, takes less time in comparison to a surgery, there are no host and recipient rejections as stem cells are harvested from the patient''s body itself and a targeted delivery system is available.

The stem cells obtained are processed in a sophisticated stem cell lab and after activation are inserted back into the host with the help of intravenous, intramuscular, intra-arterial, intradermal and intrathecal injections as per the requirement of the treatment process.

What is the use of anesthetics and why? Usually, local anesthetics are used during a stem cell procedure to numb the area but sometimes general anesthesia is also given while extracting the stem cells from bone marrow. But it is necessary to find out what anesthetic your doctor uses during orthopedic stem cell treatments.

A number of anesthetics have been found to kill the stem cells thus; the treatment''s end result will greatly depend on the use of anesthetics. Some anesthetics very well sync with the stem cell and hence, aid in the treatment.

How good are the processing techniques in the onsite labs?

Stem cells are to be extracted and processed in a clean room, under aseptic conditions maintaining a controlled environment. The doctor should explain the entire process and the number of viable stem cells infused into the patient during the process. Also, the precision of the injections to provide good quality of stem cells at the site of injury will help in better and faster recovery of the patient''s damaged area.

Duration and cost of the therapy

Cost of the treatment and its duration varies from one patient to another. The disease which needs to be cured, the severity, age factor, health condition, etc, define the duration of the therapy. One may respond during the treatment phase itself while the other may show results after a few sessions or weeks. Depending upon the disease diagnosed, the stem cells extracted, duration of the therapy, other adjuvants used in the process, the cost of the stem cell therapy can vary.

Follow-up visits

It is essential that after the stem cell therapy the patient should visit the stem cell doctor for recuperation therapies. The primary goals of such therapy is the prevention of secondary complications, analysis of recovery of motor, sensory and all the bodily functioning, psychological support/counseling for depression, mood swings or anxiety etc. and reintegration into the community.

There can be different sets of precautions which need to be followed at various steps for the recovery of the damaged tissues. The treatment and post treatment conditions may vary from person to person depending upon the disease and the severity.

Success rate of stem cell therapy

Stem cell therapy has shown results in treating serious ailments like leukemia, grafting tissues, autism, orthopedic conditions and skin problems etc. Stem Cell Therapy has been successfully used in the treatment of around 80 serious disorders.

Survival rates among patients who received stem cell treatment are significantly high, whether the cell donors are related or unrelated to them. With the ongoing research around the world, scientists are exploring new possibilities in which a number of life threatening diseases can be prevented and cured hence, the stem cells have proved to be promising in the near future as many aspects are yet to be revealed.

--IANS

pg/adr/

Disclaimer :- This story has not been edited by Outlook staff and is auto-generated from news agency feeds. Source: IANS

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