After Lives Fraught With Pain, Housing That Says ‘You’re Worthy’

Women who went to prison for killing their abusive partners are starting over at Home Free, an apartment complex created by design volunteers in San Francisco.Nestled on her Chesterfield sofa, her electric wheelchair close at hand, Rosemary Dyer surveyed the glittering peacock figurines she had snapped up on her first solo trip to San Francisco’s Chinatown after leaving prison, and admired the bright tablecloth with silk flowers in her new living room.Dyer, an effervescent woman with a mischievous sense of humor, brought these and other prized possessions to Home Free, a new complex of transitional apartments in San Francisco. It was designed for women who have been imprisoned for killing her abusive partner or being at the scene of a crime under the coercion of an abusive spouse or boyfriend. Dyer was convicted of murder and sentenced to life in prison without parole in 1988 for the 1985 shooting death of her husband of eight years, who had abused and tortured her, in an era when evidence of domestic violence was not allowed in court in California.The insidious viciousness that defined her life included being repeatedly beaten, and sodomized with a loaded handgun. Her husband had dug a grave in the backyard, saying he intended to bury her alive.The interior design for the apartments on Treasure Island, the former home of a naval base, was the work of students at the Academy of Art University in San Francisco and other volunteers. Retailers donated furniture and linens to the renovated units.Talia Herman for The New York TimesIn an apartment ready for re-entry, paintings were donated by students of the Academy of Art University.Talia Herman for The New York TimesHome Free — where Dyer’s 2020 commutation from Gov. Gavin Newsom hangs proudly on the wall — was created by Five Keys Schools and Programs, a statewide nonprofit that provides education, vocational training, therapeutic programs and housing for incarcerated people and the newly released. The complex of five two-bedroom apartments is the result of years of advocacy by survivors of intimate-partner violence, and organizations working with them. Their efforts allowed women like Dyer to achieve release through clemency or by retroactively introducing evidence of their abuse to the state parole board or the courts.“That women who had unspeakable violence committed against them were not allowed to bring in evidence of the abuse is the quintessential injustice,” said Sunny Schwartz, the founder of Five Keys. “We were committed to making a vibrant, dignified and safe home, a place that says ‘you’re worthy.’ ”Previous transitional housing options for women were largely limited to those treating addiction. Home Free, on Treasure Island, a former Naval base in San Francisco Bay, was forged during the pandemic last year on a tight start-up budget of $750,000, including staff. The formerly grimy apartments were renovated with the help of nearly 100 volunteers — architects and landscape architects, flooring and cabinetry installers, plumbers, haulers, electricians and city construction apprentices. They all gathered on this somewhat bizarre island originally built for the 1939 Golden Gate International Exhibition.The landscaping is largely in the form of container gardens of flowers and trees because the land is tainted by chemicals. Mithun, a design firm, help get the trees donated.Talia Herman for The New York TimesInterior design students from the Academy of Art University in San Francisco devoted a semester to the project, joining mini-charettes on Zoom with Irving A. Gonzales of G7 Architects. They also brainstormed with the women, whose desires included full-length mirrors (they had been deprived in prison of eyeballing their shape for years).“We wanted color!” said Dyer, who visited the construction site while she was still in temporary housing. She and others had a particular aversion to gray, a shade associated with metal prison bunks and lockers.A 69-year-old cancer survivor with congestive heart failure, Dyer has used a wheelchair since she injured her hip in prison. A huge pirate flag — a nod to the Treasure Island theme — greets visitors upon arrival. Her accessible apartment adjoins a patio where she grows pots of tomatoes and radishes.The landscape itself was designed by Hyunch Sung, of the firm Mithun, who chose 10 different tree species. (Because Treasure Island’s soil is tainted by industrial chemicals, the trees are planted in brightly-painted containers.) Sung said she approached her work there as if she were designing for high-end clients. “The idea of beauty is underplayed for disadvantaged communities,” she said.Nilda Palacios, 38, who lives upstairs, said it was “emotionally moving” to join the complex. She grew up with a history of abuse: She was molested as a child by an uncle and stepfather and then raped as a 15-year-old by a high school teacher. The stressful trial of the teacher led her to rely on drugs and alcohol (“I was trying to sleep my life away,” she said). Palacios became distraught and suicidal. When a panhandler cornered her one day, she said, she thought he intended to attack her and “lashed out,” strangling him. She was convicted of second-degree murder. Incarcerated for 17 years, she benefited from therapists in prison who helped her understand “how the depth of my crime was related to my history,” she said. “I confused someone who wasn’t a threat with someone who was.”Nilda Palacios, 38, with her dog, Milo, in their Home Free apartment. Therapists helped her understand the relationship between her own traumas and the violent act that led to her imprisonment for 17 years.Talia Herman for The New York TimesPalacios was released on parole. She has benefited from a more expansive vision for Home Free, which now welcome women like her, whose crimes were linked directly to their abuse.Moving in, she was “shocked” at the prospect of a private bedroom after years of sharing an 8-x-10-foot cell and cramming all her belongings into a six-cubic-foot box, with, as a current inmate puts it, “your panties right against the noodles and peanut butter.”“No way, this is my room?” Palacios recalled. “It felt to me like a real home.”A Path to Humane HousingThe idea for Home Free was born during a conversation between Schwartz, its founder, and the California State Treasurer Fiona Ma, then a state assemblywoman. Ma’s legislation, signed by Gov. Jerry Brown in 2012, allowed women who had suffered domestic abuse and been convicted of violent felonies related to their abuse the opportunity to have their cases reheard using Battered Women’s Syndrome (as it was then called) as a defense. The legislation also gave them the right to present evidence of abuse by intimate partners during the parole process. It applied to those convicted before August 1996.From left, Tammy Cooper Garvin, residential coordinator of Home Free, and Sunny Schwartz, the founder of Five Keys Home Free, the group behind the project.Talia Herman for The New York TimesThe number of Rosemary Dyers still behind bars is unknown. About 12,000 women are currently incarcerated for homicide offenses nationally, said Debbie Mukamal, the executive director of the Stanford Criminal Justice Center at Stanford Law School and the director of the Regilla Project, a three-year effort to study the frequency with which women in the United States are imprisoned for killing their abusers. Small studies, including one in Canada, suggest that 65% of women serving a life sentence for murdering their intimate partners had been abused by them before the offense. The link between abuse and violent crime was underscored by grim statistics in a 1999 U.S. Department of Justice report showing that a quarter to a third of incarcerated women had been abused as juveniles and a quarter to almost half as adults.Despite increased public awareness, “there are still a vast number of criminal attorneys who don’t understand how intimate-partner violence creates the context for a crime,” said Leigh Goodmark, director of the gender violence clinic at the University of Maryland School of Law.In New York State, the Domestic Violence Survivors Justice Act, enacted in 2019, was put to the test in the much-publicized case of Nicole Addimando, a young mother of two in Poughkeepsie who fatally her live-in boyfriend and father of her children in 2017 after years of harrowing abuse (the case is dramatically captured in the documentary film “And So I Stayed.”)Cooper Garvin (left) and Schwartz (right), outside the apartment building on Treasure Island, renovated naval housing.Talia Herman for The New York TimesSentenced to 19 years to life for second-degree murder, Addimando was entitled to a subsequent hearing under the Act, where her claims of abuse might be factored into a reduced sentence. The county court judge rejected those claims, believing she “had the opportunity to safely leave her abuser.” In July, the state Supreme Court’s Appellate Division reversed that decision, reducing Ms. Addimando’s time behind bars to 7 ½ years.To Kate Mogulescu, an associate professor at Brooklyn Law School and director of its Survivors Justice Project, the case illustrates “the impossible burdens we put on survivors to prove their victimization.” Women are scrutinized in court in ways that are very different from men, she added. “With women, they’re a bad mother, or promiscuous. Tropes get trotted out on women and the punishments reflect that.” Nevertheless, so far, 16 women have been resentenced in New York.By far the most common reason women who have been abused by intimate partners wind up in prison is the so-called accomplice laws, in which a victim is coerced into being at the scene of an abuser’s violence, such as driving the getaway car, said Colby Lenz, a co-founder of Survived and Punished, a national advocacy organization.That was the case with Tammy Cooper Garvin, who was sex trafficked at age 14 and was imprisoned for 28 years for being in the car while her pimp murdered a client. Her sentence was commuted and she was hired by Home Free as its residential coordinator.Rosemary Dryer, 69, outside her  apartment in the garden she calls “Freedom Forest” provided by Five Keys Home Free.Talia Herman for The New York TimesAnother advocate — and a guiding force behind the founding of Home Free — is a fellow survivor named Brenda Clubine, who started a weekly support group at the California Institution for Women. Some 72 women soon joined. Dyer was one of the original members, though until Clubine encouraged her, she was so terrified of life that she could hardly speak.Clubine herself had sustained years of abuse, including fractures and stab wounds, by her husband, a former police detective She hit his head with a wine bottle and he died of blunt force trauma. She served 26 years of a 16-to-life sentence. Her fierce retelling of the stories of the women in the prison group — which she sent to state legislators and governors — led to public hearings and the 2009 documentary “Sin by Silence,” which in turn inspired the California laws.Clubine’s close friendship with Dyer has continued and is pivotal to Dyer’s rebounding confidence. At Home Free, Dyer now revels in making homemade noodles with chicken from her grandmother’s recipe. Clubine, her BFF, observed that a safe and fortifying place for her “sisters” has been a long time coming. “I can’t say how full my heart feels that it’s available to them now,” she said.

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Sequencing the unknown made easy: Metaplatanus improves metagenome assembly

Metagenomics often involves sequencing DNA samples that can only be described as “tricky.” Such DNA shows high heterogeneity, which can cause interspecies misassemblies. These misassemblies threaten the very purpose of metagenome sequencing, which is to comprehensively study the gene pool, by generating multiple draft genomes in a given sample. This issue is further complicated by the presence of certain organisms in these samples that cannot be cultured using standard microbiology techniques. How can this cascade of issues be resolved?
Scientists from Tokyo Tech now have the answer. They have developed a novel metagenome assembler called MetaPlatanus, which can generate accurate DNA sequences, including those of uncultured organisms. Their breakthrough findings have been published as a research article in Nucleic Acids Research.
MetaPlatanus uses accurate short DNA sequence reads to assemble contigs. Contigs are slightly longer stretches of DNA sequence that are analogous to jigsaw puzzle pieces in the larger genome. The contigs are assembled into larger chromosome-scale scaffolds by repeatedly using inputs like long-range sequence links, species-specific sequence compositions, coverage depth, and binning information.
Explaining the choice of inputs for MetaPlatanus-based scaffold generation, Dr. Rei Kajitani, Assistant Professor at the School of Life Science and Technology, Tokyo Tech, and the lead scientist of the study, says, “We employ a hybrid metagenome assembly method that not only utilizes the advantages of both short-range and long-range sequence reads, but also compensates for the shortcomings posed by either read lengths, and the sample itself.”
He further adds, “We have applied binning to link sequences divided by regions that are hard to assemble, such as repetitive ones. Our approach is novel since the combination of binning and assembly processes have not been implemented as a public tool, so far!”
Dr. Kajitani and his team left no stone unturned in checking the accuracy of results churned out by MetaPlatanus. In this regard, they performed a process called benchmarking using mock datasets of known bacteria. Not surprisingly, MetaPlatanus gave outputs that were highly contiguous, with very few interspecies misassemblies.
Notably, while testing MetaPlatanus’ accuracy with already published human gut data, it additionally assembled many biologically important elements, including coding genes, gene clusters, viral sequences, and over-half bacterial genomes.
Also, compared to other existing tools, only MetaPlatanus was able to perform near-complete assembly of some high-abundance bacterial genomes, while benchmarking using already published human saliva data.
Indeed, Dr. Kajitani and his team appear to have struck metagenomic gold with MetaPlatanus. Excited about the potential applications of MetaPlatanus, he exclaims, “We believe that the metagenome assembler that we have developed at Tokyo Tech could help examine the contexts of sequence elements spreading over the genome, which could have innumerable real-world applications.”
Undoubtedly, this study could prove to be a milestone in the field of metagenomics.
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Excess deaths in people with mental health conditions increased during the COVID-19 pandemic

The greater number of deaths amongst those with mental health conditions and intellectual disabilities has been amplified during the COVID-19 pandemic, a study based on more than 160,000 patients has revealed.
Before the pandemic the rates of mortality in those with severe mental health conditions were already higher than the general population. New research published in The Lancet Regional Health — Europe shows that between March and June 2020, during the first wave of COVID-19, mortality further increased in people with mental health conditions and intellectual disabilities compared with the general population.
The study was published in the run up to World Mental Health Day on 10 October 2021 which this year has the theme ‘Mental Health in an Unequal World’.
Deaths from COVID-19 among those with learning disabilities were nine times higher than the general population during the first lockdown period, according to the study, and for those with eating disorders almost five times higher. For those with personality disorders and those with dementia, deaths from COVID-19 were about four times higher than the general population and more than three times higher in people with schizophrenia.
The research was part-funded by the National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre (BRC) and used the Clinical Record Interactive Search (CRIS) system to analyse anonymised data from clinical e-records of patients from South London.
Lead author Dr Jayati Das-Munshi, Reader in Social and Psychiatric Epidemiology at King’s College London and Honorary Consultant Psychiatrist with South London and Maudsley NHS Foundation Trust, said: “The results from our study paint a stark picture of how the existing vulnerability of those with mental health conditions and intellectual disabilities have worsened during the COVID-19 pandemic. The higher death rates compared to the general population were associated with more deaths from COVID-19 infection itself, as well as deaths from other causes.

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Using indoor air sampling surveillance to sniff out COVID-19

A team of scientists and doctors from the Singapore Centre for Environmental Life Sciences Engineering (SCELSE) at Nanyang Technological University, Singapore (NTU Singapore) and the NUS Yong Loo Lin School of Medicine has developed a capability to detect airborne SARS-CoV-2 RNA — the nucleic acid coding for the virus that causes COVID-19 — indoors through air sampling.
When trialled in two inpatient wards of a major Singaporean hospital caring for active COVID-19 patients the air surveillance approach produced a higher detection rate of environmental SARS-CoV-2 RNA compared to surface swab samples collected in the same area.
The COVID-19 Delta variant’s rapid spread in Singapore and globally underlines the need for rapid identification of the presence of SARS-CoV-2 in the environment. While wastewater testing is a reliable indicator of the presence of virus in sewage discharge, the retrospective nature of this approach means pre-emptive action is not possible.
The findings, described in a study published in Indoor Air on 14 Sept, indicate the potential for an airborne surveillance system that monitors for the presence of the virus and provides early warning of infection risks, which would be especially valuable in hospitals and nursing homes, and in enclosed places where large numbers of people congregate, said the research team.
Professor Paul Tambyah, deputy director of NUS Medicine’s Infectious Diseases Translational Research Programme and President of Asia Pacific Society of Clinical Microbiology and Infection, said “The results of this air sampling study are encouraging, with the potential for the simple monitoring for the presence of COVID-19 in possible hotspots. This will allow for timely intervention where necessary to prevent the emergence of clusters. Hopefully this will prove useful as the country gradually transitions into recognising that the disease has become endemic and everyone learns to live as normally as possible with the virus.”
Dr Irvan Luhung, SCELSE senior research fellow and study co-lead author, said “This study demonstrated the versatility and sensitivity of air sampling for monitoring SARS-CoV-2 in hospital settings, something that was previously not thought possible due to the high ventilation rate of hospital wards. Such an air surveillance capability could make a valuable contribution towards keeping frontline medical staff safe in this pandemic. In hospitals with a high daily number of COVID-19 patients, employing a routine air surveillance programme with high sensitivity could be beneficial in detecting the virus early and help to keep frontline medical staff safe.”
Associate Professor David Allen from NUS Medicine’s Infectious Diseases Translational Research Programme and an infectious diseases clinician at the National University Health System (NUHS), said “The paper’s findings expand our knowledge of the extent to which the virus may potentially be transmitted in different types of wards — this impacts safety and needed precautions for health care workers. The findings also advance the potential use of different methods of detecting virus in the environment to provide additional tools for mass screening (other methods are screening each person, sampling sewage, etc) — in our case a device which samples the air for the presence of virus.”

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Stem cell population identified that is key for bone regeneration

Mesenchymal stem cells (MSCs) are thought to have great potential in the field of regenerative medicine, which has the aim of restoring damaged tissues. However, not much was known about in vivo plasticity of them — until now. Researchers have identified a subpopulation of MSCs that promote the healing of bone fractures and show an enhanced ability to differentiate into various cell types.
MSCs are found in bone marrow, and are “multipotent,” meaning that they can both renew themselves and develop into a variety of specialized cell types, such as bone, fat, and cartilage cells. The researchers had previously developed a mouse line that uses green fluorescent protein to highlight cells expressing a particular molecule known as CD73. Studies of the bone marrow in this mouse revealed that a subpopulation of MSCs expressed CD73, as well as the sinusoidal endothelial cells (sECs) that are part of the vascular system of the bone marrow.
The CD73-positive MSCs could be seen to proliferate more than the CD73- negative MSCs, and to have a higher potential to differentiate into different cell types, indicating that this group of MSCs may be particularly effective for bone repair. The researchers therefore went on to study the functions of these CD73-positive MSCs in fracture healing.
As a fracture heals, it progresses through various stages. These include clotted blood forming at the fracture, which becomes replaced by a callus of fibrous tissues and cartilage, followed by formation of a hard bony callus. The bone is then remodeled, as regular bone replaces the hard callus and the bone returns to its usual shape.
“The generation of the callus is critically dependent on the recruitment of MSCs from the surrounding tissue and the bone marrow,” explains lead author Assistant Professor Kenichi Kimura. “Therefore, fracture healing models are helpful for exploring the cellular dynamics of MSC migration and differentiation during tissue regeneration.”
The team was able to observe the CD73-positive MSCs moving towards the site of the fracture and forming new cartilage and bone cells to heal the fracture. The CD73-positive sECs were also involved in the healing of the fracture, as they contributed to the process of “neovascularization,” the formation of new blood vessels to support the healed bone.
Finally, they went on to graft CD73-positive MSCs into the area of a fracture, which markedly enhanced the healing process compared with when they grafted into CD73-negative MSCs.
Says Assistant Professor Kimura, “The identification of this subpopulation of MSCs could be of great benefit for regenerative medicine and the treatment of fractures.”
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Personalized medicine: Platform enables comparative research on cancerous tumors

Researchers at the Technion’s Rappaport Faculty of Medicine have developed an innovative algorithm that detects an uninterrupted common denominator in multidimensional data gathered from tumors of different patients. The study, which was published in Cell Systems, was led by Professor Shai Shen-Orr, Dr. Yishai Ofran, and Dr. Ayelet Alpert, and conducted in collaboration between researchers at the Technion, the Rambam Health Care Campus, the Shaare Zedek Medical Center and the University of Texas.
In recent years, cancer research has undergone a series of significant revolutions, including the introduction of single-cell high-resolution characterization capabilities, or, more specifically, simultaneous high-throughput profiling of cancer samples using single-cell RNA sequencing and proteomics analysis. This has led to the generation of vast quantities of multidimensional data on a huge number of cells, allowing for the characterization of both the healthy tissue and malignant tissues. This high amount of data has revealed the great variability between tumors of different patients, where cellular characterization that is derived from the patient’s genetic background is unique to each patient.
Despite the substantial advantage that is derived from such an accurate characterization of the specific patient, this development hinders comparison of different patients: in the absence of a common denominator, the comparison, which is essential for identifying prognostic markers (e.g. mortality or severity of illness), becomes impossible.
The tuMap algorithm developed by the Technion researchers provides a solution to this complex challenge by means of a “variance-based comparison.” The innovative algorithm delivers the possibility to place numerous different tumors on a uniform scale that provides a benchmark for comparison. In this way, the tumors of different patients can be meaningfully compared, as well as tumors of the same patient over the disease course (for example, on diagnosis and after treatment). The resolution provided by the algorithm can be leveraged for clinical applications such as prediction of various clinical indices with a very high accuracy, outperforming traditional tools. Although the researchers tested the algorithm on leukemia tumors, they believe that it will also be relevant for other cancer types.
The research was sponsored by the Israel Science Foundation, the Rappaport Family Institute for Research in the Medical Sciences, and the National Institutes of Health (NIH).
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What makes us human? The answer may be found in overlooked DNA

Our DNA is very similar to that of the chimpanzee, which in evolutionary terms is our closest living relative. Stem cell researchers at Lund University in Sweden have now found a previously overlooked part of our DNA, so-called non-coded DNA, that appears to contribute to a difference which, despite all our similarities, may explain why our brains work differently. The study is published in the journal Cell Stem Cell.
The chimpanzee is our closest living relative in evolutionary terms and research suggests our kinship derives from a common ancestor. About five to six million years ago, our evolutionary paths separated, leading to the chimpanzee of today, and Homo Sapiens, humankind in the 21st century.
In a new study, stem cell researchers at Lund examined what it is in our DNA that makes human and chimpanzee brains different — and they have found answers.
“Instead of studying living humans and chimpanzees, we used stem cells grown in a lab. The stem cells were reprogrammed from skin cells by our partners in Germany, the USA and Japan. Then we examined the stem cells that we had developed into brain cells,” explains Johan Jakobsson, professor of neuroscience at Lund University, who led the study.
Using the stem cells, the researchers specifically grew brain cells from humans and chimpanzees and compared the two cell types. The researchers then found that humans and chimpanzees use a part of their DNA in different ways, which appears to play a considerable role in the development of our brains.
“The part of our DNA identified as different was unexpected. It was a so-called structural variant of DNA that were previously called “junk DNA,” a long repetitive DNA string which has long been deemed to have no function. Previously, researchers have looked for answers in the part of the DNA where the protein-producing genes are — which only makes up about two per cent of our entire DNA — and examined the proteins themselves to find examples of differences.”
The new findings thus indicate that the differences appear to lie outside the protein-coding genes in what has been labelled as “junk DNA,” which was thought to have no function and which constitutes the majority of our DNA.

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Psychiatric disorders in teenage years associated with social exclusion in later life

Adolescents who had received a mental health disorder diagnosis were often excluded from the labour market and education as young adults. This particularly applied to adolescents who had been diagnosed with an autism spectrum disorder or psychosis. The results were found out in a birth cohort study of people born in Finland in 1987. The study was published on 6 October in British Journal of Psychiatry.
Almost eleven percent of adolescents who had received a psychiatric diagnosis were excluded from education and labour market for at least five years in their early adulthood. For other adolescents, this number was slightly under three percent. The results highlight the importance of the treatment and rehabilitation of people with mental health disorders in the prevention of adolescents’ social exclusion. ”
“To help prevent the social exclusion of adolescents, their treatment and rehabilitation require more resources than are currently being used as well as development of evidence-based treatment and rehabilitation,” says Adolescent Psychiatrist and Doctoral Candidate Ida Ringbom from the Research Centre for Child Psychiatry at the University of Turku.
The results are concerning because they highlight the link between mental health disorders and long-term exclusion from education and labour market. In the study, long-term exclusion was defined as a period spent outside education or paid employment lasting a minimum of five years. The link was particularly strong with those teenagers who had not completed their upper secondary education and who had been diagnosed with a mental health disorder. Almost half of these teenagers who had experienced psychosis and almost three quarters of teenagers who had been diagnosed with an autism spectrum disorder experienced long-term exclusion from education and labour market in their early adulthood.
“Vocational rehabilitation and tight collaboration between psychiatry and social services are important for enabling adolescents suffering from mental health problems to access the labour market,” says Assistant Professor David Gyllenberg who led the study.
“Adolescents who have not completed their upper secondary education require more targeted support because their risk of becoming socially excluded is particularly high.”
The research was conducted at the Research Centre for Child Psychiatry as a part of the INVEST flagship programme for the study of inequality, interventions, and the welfare state. A joint project of the University of Turku and Finnish Institute for Health and Welfare and funded by the Academy of Finland, INVEST focuses on reducing social inequality and reforming the welfare state. Finnish Institute for Health and Welfare is responsible for the national birth cohort of 1987. The research group included researchers from e.g. the University of Turku, Finnish Institute for Health and Welfare, Helsinki University Hospital, and Itla Children’s Foundation.
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Researcher investigates ways to enhance neurolysin activity in the brain

Ischemic stroke, the second leading cause of death worldwide, occurs when a vessel to the brain is blocked, reducing blood flow to the brain and depriving it of critical supplies of oxygen and nutrients. This process leads to the death of brain cells and leaves the patient with a sudden loss of certain body functions.
Tissue plasminogen activator, also known as tPA, is the lone pharmacological treatment for stroke, and while it is considered to be highly effective, it comes with one important, and often hard-to-meet caveat: it must be administered to the patient within 3-5 hours of stroke onset. Though many other significant efforts have been undertaken to discover and develop new drugs, there have been no new therapeutics approved to treat stroke since tPA was approved in 1996.
However, some recent advances in understanding signaling pathways that are relevant to the brain’s self-protective mechanisms have allowed investigators to identify novel targets for further study. One of those investigators, Vardan Karamyan, Ph.D., from the Texas Tech University Health Sciences Center (TTUHSC) Jerry H. Hodge School of Pharmacy, has researched and collaborated with others to develop an effective treatment for stroke that focuses on the use of a peptidase known as neurolysin (Nln). Peptidases are enzymes that have the ability to cleave, or split peptides, which often leads to their inactivation.
Karamyan’s most recent collaborative study is a continuation of his previous work and evaluates the potential of Nln as a therapeutic target for stroke by seeking to identify small molecules capable of enhancing the activity and catalytic efficiency of Nln.
That study, “Discovery of First-in-Class Peptidomimetic Neurolysin Activators Possessing Enhanced Brain Penetration and Stability,” was published Aug. 26 in the Journal of Medicinal Chemistry. Members of the Karamyan collaborative research team included Thomas J. Abbruscato, Ph.D., Andrew Baez, Shiva Hadi Esfahani, Pharm.D., Delaney Farris, Srinidhi Jayaraman, Ph.D., Nihar Kinarivala, Ph.D., Joanna Kocot, Ph.D., and Saeideh Nozohouri, Pharm.D., from TTUHSC; and Shikha Kumari, Ph.D., Md. Shafikur Rahman and Paul C. Trippier, Ph.D., from the University of Nebraska Medical Center. The project was supported by a grant from the National Institutes of Health.
In previous research, Karamyan’s lab first identified Nln as a key internal peptidase that helps protect the brain during acute neurodegenerative disorders such as stroke. His research showed that when Nln was inhibited after a stroke, there was more damage to the brain. However, when the amounts of Nln in the brain were increased prior to stroke, the damage was significantly reduced.

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Nerve repair, with help from stem cells

A new approach to repairing peripheral nerves marries the regenerating power of gingiva-derived mesenchymal stem cells with a biological scaffold to enable the functional recovery of nerves following a facial injury, according to a study by a cross-disciplinary team from the University of Pennsylvania School of Dental Medicine and Perelman School of Medicine.
Faced with repairing a major nerve injury to the face or mouth, skilled surgeons can take a nerve from an arm or leg and use to it restore movement or sensation to the original site of trauma. This approach, known as a nerve autograft, is the standard of care for nerve repair, but has its shortcomings. Besides taking a toll on a previously uninjured body part, the procedure doesn’t always result in complete and functional nerve regrowth, especially for larger injuries.
Scientists and clinicians have recently been employing a different strategy for regrowing functional nerves involving commercially-available scaffolds to guide nerve growth. In experimental approaches, these scaffolds are infused with growth factors and cells to support regeneration. But to date, these efforts have not been completely successful. Recovery can fall short due to a failure to coax large numbers of regenerating axons to cross the graft and then adequately mature and regrow myelin, the insulating material around peripheral nerves that allows them to fire quickly and efficiently.
In an innovative approach to guided nerve repair, shared in the journal npj Regenerative Medicine, the Penn team coaxed human gingiva-derived mesenchymal stem cells (GMSCs) to grow Schwann-like cells, the pro-regenerative cells of the peripheral nervous system that make myelin and neural growth factors. The current work demonstrated that infusing a scaffold with these cells and using them to guide the repair of facial nerve injuries in an animal model had the same effectiveness as an autograft procedure.
“Instead of an autograft, which causes unnecessary morbidity, we wanted to create a biological approach and use the regenerating ability of stem cells,” says Anh Le, senior author on the study and chair and a professor in the Department of Oral and Maxillofacial Surgery/Pharmacology in Penn’s School of Dental Medicine. “To be able to recreate nerve cells in this way is really a new paradigm.”
For more than a decade, Le’s lab has pioneered the use of GMSCs to treat several inflammatory diseases and to regrow a variety of types of craniofacial tissue. Gingival tissue is easily extracted and heals rapidly, offering an accessible source of GMSCs. In fact, gingival tissue is often discarded from routine dental procedures. Le says the potential of GMSCs to help in nerve regrowth also owes in part to the cells’ common lineage. “Embryologically, we know that craniofacial tissue is derived from the same neural crest progenitor cells as nerves,” Le says. “That’s part of the beauty of this system.”
Le and colleagues led by Qunzhou Zhang, now a faculty member at Penn Dental Medicine, were able to apply their previous understanding of GMSCs to grow them in a collagen matrix using specific conditions that encouraged the cells to grow more like Schwann cells, the cells’ identity confirmed with a variety of genetic markers.

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