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Touched by light: Photoexcited stannyl anions are great for producing organotin compounds

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Scientists at Tokyo Institute of Technology developed a new strategy for producing a wide range of organotin compounds, which are the building blocks of many organic synthesis methods. Their approach is based on the photoexcitation of stannyl anions, which alters their electronic state and increases their selectivity and reactivity to form useful compounds. This protocol will be helpful for the efficient synthesis of many bioactive products, novel drugs, and functional materials.

Organotin compounds, also known as stannanes, are made of tin (Sn), hydrocarbons, and sometimes other elements like nitrogen and oxygen. During the 1970s, stannanes rapidly took the spotlight as building blocks in the field of organic synthesis mainly because of their use as reagents in the Stille reaction, which remains essential for chemists to combine various organic molecules.

Equally important to the organotin reagents are the techniques and molecules that we rely on to make them. Stannyl anions have gained their place as the most widely used precursor for organotin reagents. However, their chemical properties make them prone to partake in unwanted reactions that compete with the synthesis of the target organotin reagent. This decreases yield and puts constraints on the main reaction, restricting the possible organotin reagents that can be produced in practice.

Surprisingly, in a recent collaborative study by Tokyo Institute of Technology and The University of Tokyo, Japan, scientists discovered a new type of stannyl species useful for producing organotin reagents. In their paper, published in the Journal of the American Chemical Society, they explain that this new stannyl species was first theorized to exist based on small anomalies observed in previous works. “During our studies involving stannyl anions, we occasionally detected small amounts of compounds called distannanes that were probably generated by the irradiation of stannyl anions with light. Inspired by these observations, we became interested in exploring the synthesis applications of these theoretical photoexcited stannyl anion species,” explains Assistant Professor Yuki Nagashima, lead researcher from Tokyo Tech.

Through density functional theory calculations, the team determined that trimethyltin anion (Me3Sn), a model stannyl anion, has a special affinity for blue light, which energizes the molecule to an excited ‘single’ state. From this state, the system naturally progresses to another state known as excited ‘triplet,’ where two electrons are unpaired. This easy-to-induce progression from a stannyl anion to a stannyl radical in an excited ‘triplet’ state gives the stannyl species vastly different chemical properties, including enhanced reactivity and selectivity towards certain compounds.

The scientists explored reactions between photoexcited stannyl anions and several compounds, including alkynes, aryl fluorides, and aryl halides. They found that the photoexcited stannyl species had unprecedented selectivity for the synthesis of various useful reagents that conventional stannyl anions could not easily produce. Moreover, these photoexcited anions had a remarkable ability for the defluorostannylation and dehalostannylation of aryl molecules. In simpler terms, this means that if you have an aryl fluoride or halide (an organic molecule with a fluorine or halide group, respectively), it is easy to set up a reaction that substitutes the fluorine or halide group with a stannyl group. This allowed the researchers to create a wide variety of organotin reagents useful for Stille reactions.

Excited about the results, Prof. Nagashima remarks: “Although many stannylation methods and reagents have been established over almost two centuries, our protocol using photoexcited anion species provides a new and complementary tool for preparing a wide range of organotin compounds.”

This new method will certainly be helpful for synthesizing many bioactive products, novel drugs, and functional materials, and further studies are already underway to see how far it will take us.

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About Tokyo Institute of Technology

Tokyo Tech stands at the forefront of research and higher education as the leading university for science and technology in Japan. Tokyo Tech researchers excel in fields ranging from materials science to biology, computer science, and physics. Founded in 1881, Tokyo Tech hosts over 10,000 undergraduate and graduate students per year, who develop into scientific leaders and some of the most sought-after engineers in industry. Embodying the Japanese philosophy of “monotsukuri,” meaning “technical ingenuity and innovation,” the Tokyo Tech community strives to contribute to society through high-impact research.
https://www.titech.ac.jp/english/

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Source: https://bioengineer.org/touched-by-light-photoexcited-stannyl-anions-are-great-for-producing-organotin-compounds/

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Alzheimer Europe calls for people with dementia and carers to be prioritized for vaccine

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Alzheimer Europe calls for prioritisation of people with dementia and carers in COVID-19 vaccination programs across Europe

Luxembourg, 7 May 2021 – In a new position statement, Alzheimer Europe has issued a call for prioritisation of people with dementia and their carers in national COVID-19 vaccination strategies, urging governments to recognise the disproportionate effect of the pandemic on these groups.

Alzheimer Europe has today issued a call for people with dementia and their carers to be given priority in the ongoing COVID-19 vaccination campaigns across Europe.

In its position statement, Alzheimer Europe notes that people with dementia have almost twice the risk for developing COVID-19 compared to their peers without dementia, with high rates of hospitalisation and a risk of mortality within six months of approximately 20% in certain populations. Those who become infected are also more prone to developing delirium, which can complicate the management of their current and future cognitive health.

Currently, countries vary significantly in their prioritisation of different groups for COVID-19 vaccination. The vast majority of European countries have prioritised frontline healthcare workers, long-term care facility residents and the oldest old in the first phases of vaccination, with a smaller number also prioritising social care personnel and professional carers. A small number of European countries, recognising dementia per se as a risk category for severe COVID-19, have prioritised people with dementia for COVID-19 vaccination. However, in the majority of countries, neither people with dementia, nor informal carers have been specifically identified as priority groups for the COVID-19 vaccination, despite their increased risk.

Alzheimer Europe notes the disproportionate impact of the pandemic already experienced by people with dementia and their carers, as a result of service cancellations, care home restrictions etc., and accordingly, makes the following three demands of European governments:

  • Include dementia as a risk category for severe COVID-19, prioritising people with dementia for the COVID-19 vaccine, independent of age, place of residence or other risk factors for severe COVID-19.
  • Prioritise informal carers for the COVID-19 vaccine, acknowledging their important contribution during the pandemic to the care, support and even survival of people with dementia, as well as the indirect protection vaccination can confer for the people for whom they care.
  • Ensure that reasonable accommodations are made and that support mechanisms are in place when organising and rolling out the vaccine to people with dementia, such as the possibility to be vaccinated at home and to have decision-making support, if required.

Commenting further, Alzheimer Europe’s Executive Director, Jean Georges, stated:

“People with dementia and their carers have often been overlooked and forgotten during this pandemic. Particularly during the early stages of the outbreak, public health measures designed to control the spread of the virus have had profound and often tragic consequences for people with dementia, their families and carers.

Governments must recognise that people with dementia, their families and carers have already been disproportionately affected by the pandemic and ensure that people with dementia and their carers will not be overlooked again in the development and implementation of vaccination strategies.

We urge governments across Europe to revise their approaches to vaccination campaigns and prioritise people with dementia and their carers, allowing a return to some semblance of normality for this vulnerable group.”

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To download the position paper and the briefing document visit:
http://bit.ly/AEPositionCOVIDVaccine

For further information, contact: Jean Georges, Executive Director, Alzheimer Europe, 14, rue Dicks, L-1417 Luxembourg, Tel.: +352-29 79 70, Fax: +352-29 79 72, [email protected], http://www.alzheimer-europe.org

Notes to editors:

To support people with dementia, carers and Alzheimer’s associations during the COVID-19 pandemic, the organisation has dedicated a special section of its website to useful resources and links: https://www.alzheimer-europe.org/Living-with-dementia/COVID-19

A detailed briefing document has been included alongside the position statement, providing further details and references demonstrating the disproportionate impact of the pandemic on people with dementia. This paper also explores the ethical, legal and human rights issues associated with public health interventions and the current vaccination campaigns. This is also available to download at: https://www.alzheimer-europe.org/Policy/Our-opinion-on/COVID-19-Vaccinations-and-People-with-Dementia

The position and briefing document received funding under an operating grant from the European Union’s Health Programme (2014-2020). The contents represent the views of the author only and is his/her sole responsibility; it cannot be considered to reflect the views of the European Commission and/or the Consumers, Health, Agriculture and Food Executive Agency or any other body of the European Union. The European Commission and the Agency do not accept any responsibility for use that may be made of the information it contains.

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Source: https://bioengineer.org/alzheimer-europe-calls-for-people-with-dementia-and-carers-to-be-prioritized-for-vaccine/

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Rare genetic disease caused by mutations in protein that controls RNA metabolism

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PITTSBURGH, May 7, 2021 – In a paper published today in Nature Communications, an international group of collaborators led by researchers at UPMC Children’s Hospital of Pittsburgh have identified a genetic cause of a rare neurological disorder marked by developmental delay and loss of coordination, or ataxia.

The disorder, scientists found, is caused by mutations in a protein called GEMIN5–one of the key building blocks of a protein complex that controls RNA metabolism in neurons. No mutations in GEMIN5 were previously linked to any genetic disease.

“It’s just like building a house,” said senior author Udai Pandey, Ph.D., associate professor of pediatrics, human genetics and neurology at the University of Pittsburgh School of Medicine. “You take out the most important brick at the base and the whole building falls apart.”

GEMIN5 is part of a protein complex that regulates a slew of important cellular processes, including development of specialized outgrowths from nerve cells called dendrites and axons. Interestingly, mutations in another key protein of the complex, named survival motor neuron protein, cause a different devastating disorder–spinal muscular atrophy.

To gather material for the study, Pittsburgh researchers contacted pediatricians, geneticists and neurologists from all over the globe, eventually collecting data from 30 patient families in 12 different countries.

Because isolating live neurons from people isn’t possible, researchers had to come up with another way of getting samples for future testing. They collected blood samples from pediatric patients who were referred to neurogenetic clinics with undiagnosed neurological symptoms. Blood samples were then processed to isolate cells that, with careful tinkering in the lab, were reprogrammed into neurons.

After comparing genetic material of reprogrammed neurons from sick children with that of unaffected relatives, scientists linked neurologic manifestations of the disease to 26 mutations in the GEMIN5 gene that cause damage to the structure of the protein.

“Children came into the clinic with non-specific symptoms, such as developmental delay and abnormal gait. Their doctors ran all the possible tests, including assessing a child’s metabolic function, to no avail–their conditions had no easy explanation,” said Deepa Rajan, M.D., assistant professor of pediatrics, Pitt School of Medicine, neurologist at UPMC Children’s Hospital and a co-first author of the study. “It was not until we did an extensive genome analysis that we found that these patients had mutations in the GEMIN5 gene.”

“Many genetic disorders seem individually rare, but collectively they are relatively common,” added Rajan, who also is director of the Neurogenetics Clinic at UPMC Children’s Hospital. “We now are able to harness next-generation technology to help diagnose previously undiagnosed children, and each new gene discovery is the start of the journey to understanding each of these diseases better.”

Additional experiments linked damage to GEMIN5 protein to disease manifestations more definitively. Scientists found that depleting an analog of human neuronal GEMIN5 protein in fruit flies was deadly if it happened in early stages of the fly’s life cycle, or drastically delayed its development if such disruption happened later.

“The most exciting part of being a researcher is working on a project that directly helps families,” said Pandey. “We are hopeful that because of our study, neurologists will now consider testing for GEMIN5 mutations and that labs will include GEMIN5 in their testing for ataxic disorders. Genetic diseases are challenging to identify and treat, but if we find a cure, it will make a massive difference in someone’s life.”

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Other authors on the manuscript include Sukhleen Kour, Ph.D., Tyler Fortuna, Ph.D., Eric Anderson, Ph.D., Dhivyaa Rajasundaram, Ph.D., and Caroline Ward, all of Pitt, among 70 total authors.

This work was supported by a University of Pittsburgh Children’s Neuroscience Institute research grant.

To read this release online or share it, visit https://www.upmc.com/media/news/050721-Pandey-GEMIN5 [when embargo lifts].

About UPMC Children’s Hospital of Pittsburgh

Regionally, nationally, and globally, UPMC Children’s Hospital of Pittsburgh is a leader in the treatment of childhood conditions and diseases, a pioneer in the development of new and improved therapies, and a top educator of the next generation of pediatricians and pediatric subspecialists. With generous community support, UPMC Children’s Hospital has fulfilled this mission since its founding in 1890. UPMC Children’s is recognized consistently for its clinical, research, educational, and advocacy-related accomplishments, including ranking in the top 10 on the 2020-2021 U.S. News & World Report Honor Roll of America’s Best Children’s Hospitals. UPMC Children’s also ranks 15th among children’s hospitals and schools of medicine in funding for pediatric research provided by the National Institutes of Health (FY2019).

About the University of Pittsburgh Schools of the Health Sciences

The University of Pittsburgh Schools of the Health Sciences include the schools of Medicine, Nursing, Dental Medicine, Pharmacy, Health and Rehabilitation Sciences and the Graduate School of Public Health. The schools serve as the academic partner to the UPMC (University of Pittsburgh Medical Center). Together, their combined mission is to train tomorrow’s health care specialists and biomedical scientists, engage in groundbreaking research that will advance understanding of the causes and treatments of disease and participate in the delivery of outstanding patient care. Since 1998, Pitt and its affiliated university faculty have ranked among the top 10 educational institutions in grant support from the National Institutes of Health. For additional information about the Schools of the Health Sciences, please visit http://www.health.pitt.edu.

http://www.upmc.com/media

Contact: Anastasia Gorelova

Mobile: 412-491-9411

E-mail: [email protected]

Contact: Andrea Kunicky

Mobile: 412-552-7448

E-mail: [email protected]

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Source: https://bioengineer.org/rare-genetic-disease-caused-by-mutations-in-protein-that-controls-rna-metabolism/

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Learning on the fly

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Computational model demonstrates similarity in how humans and insects learn about their surroundings

Even the humble fruit fly craves a dose of the happy hormone, according to a new study from the University of Sussex which shows how they may use dopamine to learn in a similar manner to humans.

Informatics experts at the University of Sussex have developed a new computational model that demonstrates a long sought after link between insect and mammalian learning, as detailed in a new paper published today in Nature Communications.

Incorporating anatomical and functional data from recent experiments, Dr James Bennett and colleagues modelled how the anatomy and physiology of the fruit fly’s brain can support learning according to the reward prediction error (RPE) hypothesis.

The computational model indicates how dopamine neurons in an area of a fruit fly’s brain, known as the mushroom body, can produce similar signals to dopamine neurons in mammals, and how these dopamine signals can reliably instruct learning.

The academics believe that establishing whether flies also use prediction errors to learn could lead to more humane animal research allowing researchers to replace animals with more simple insect species for future studies into the mechanisms of learning.

By opening up new opportunities to study neural mechanisms of learning, the researchers hope the model could also be helpful in illuminating greater understanding of mental health issues such as depression or addiction which are underpinned by the RPE hypothesis.

Dr Bennett, research fellow in the University of Sussex’s School of Engineering and Informatics, said: “Using our computational model, we were able to show that data from insect experiments did not necessarily conflict with predictions from the RPE hypothesis, as had been thought previously.

“Establishing a bridge between insect and mammal studies on learning may open up the possibility to exploit the powerful genetic tools available for performing experiments in insects, and the smaller scale of their brains, to make sense of brain function and disease in mammals, including humans.”

Understanding of how mammals learn has come a long way thanks to the RPE hypothesis, which suggests that associative memories are learned in proportion to how inaccurate they are.

The hypothesis has had considerable success explaining experimental data about learning in mammals, and has been extensively applied to decision-making and mental health illnesses such as addiction and depression. But scientists have encountered difficulties when applying the hypothesis to learning in insects due to conflicting results from different experiments.

The University of Sussex research team created a computational model to show how the major features of mushroom body anatomy and physiology can implement learning according to the RPE hypothesis.

The model simulates a simplification of the mushroom body, including different neuron types and the connections between them, and how the activity of those neurons promote learning and influence the decisions a fly makes when certain choices are rewarded.

To further understanding of learning in fly brains, the research team used their model to make five novel predictions about the influence different neurons in the mushroom body have on learning and decision-making, in the hope that they promote future experimental work.

Dr Bennett said: “While other models of the mushroom body have been created, to the best of our knowledge no other model until now has included connections between dopamine neurons and another set of neurons that predict and drive behaviour towards rewards. For example, when the reward is the sugar content of food, these connections would allow the predicted sugar availability to be compared with the actual sugar ingested, allowing more accurate predictions and appropriate sugar-seeking behaviours to be learned.

“The model can explain a large array of behaviours exhibited by fruit flies when the activity of particular neurons in their brains are either silenced or activated artificially in experiments. We also propose connections between dopamine neurons and other neurons in the mushroom body, which have not yet been reported in experiments, but would help to explain even more experimental data.”

Thomas Nowotny, Professor of Informatics at the University of Sussex, said: “The model brings together learning theory and experimental knowledge in a way that allows us to think systematically how fly brains actually work. The results show how learning in simple flies might be more similar to how we learn than previously thought.”

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Source: https://bioengineer.org/learning-on-the-fly/

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A bridge from classroom to providing actual patient care: A study of the Regenstrief tEMR

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Anonymized real-world platform gives learners realistic experience with health IT

INDIANAPOLIS – As electronic medical records (EMRs) are increasingly used across the United States, the next generation of physicians, nurses, social workers, pharmacists and other clinicians need to acquire new knowledge and competencies related to use of EMRs early in their clinical education. But training is not routinely provided.

A new study presents the functions and application of the novel, scalable Regenstrief teaching electronic medical record (tEMR) platform which contains a unique, large, anonymized patient database enabling health professions students to learn how to use health information technology (HIT) to best manage the complex issues presented by real-world patients.

“HIPAA [Health Insurance Portability and Accountability Act of 1996] has restricted access to EMRs so, ironically, the more EMRs are used, the less access students have to patient data, but the more they need to know,” said Regenstrief Institute Research Scientist Debra Litzelman, M.D., M.A., corresponding author of the new study and a professor of medicine at Indiana University School of Medicine. “Regenstrief tEMR offers detailed, anonymized data on complex patients as well as unique real-world functionality including patient sharing among care team members.”

“Medical, nursing, social work and other clinical trainees who have early exposure to EMRs will think differently about patient care and about future EMR development because of that early exposure. It creates a different mindset.”

Regenstrief tEMR offers a realistic virtual patient care experience, which the study noted was especially helpful during the early months of the COVID pandemic when students’ access to patients in health care settings was limited. The tEMR platform also enables and encourages interprofessional collaboration between learners pursuing different careers at diverse locations working at the same or different times.

Professional schools often have simulation centers teaching various skills such as CPR, intubation or robotic surgery procedures which trainees need to learn before they are on the job. Similarly, Regenstrief tEMR provides real-life simulation which prepares individuals for the real-world health IT environments they will enter.

The Regenstrief tEMR was created by the Regenstrief Institute along with IU School of Medicine, Eskenazi Health and the American Medical Association (AMA). Since 2013, the Regenstrief tEMR has been used at 12 health profession educational institutions. More than 11,800 students have accessed the system.

“Regenstrief teaching electronic medical record (tEMR) platform: a novel tool for teaching and evaluating applied health information technology” is published in JAMIA Open. Co-authors in addition to Dr. Litzelman are Blaine Y. Takesue, M.D., of IU School of Medicine and Regenstrief Institute; William M. Tierney, M.D., of IU Fairbanks School of Public Health at IUPUI and IU School of Medicine; Peter J. Embí, M.D., and Burke W. Mamlin, M.D., of Regenstrief Institute and IU School of Medicine and Jeff Warvel of Regenstrief Institute.

“With the exponential growth of health-related data and the impact of health information technology (HIT) on work-life balance, it is critical for students to get early EHR skills practice and understand how EHRs work. The ultimate tEMR project aim is to create tools through which our students — future educators, administrators, practice leaders, and front-line physicians — can develop enough HIT savvy to influence how HIT should be used in health care rather than HIT dictating how health care is delivered,” the study authors concluded.

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This project was supported by funding from the American Medical Association Accelerating Change in Medical Education initiative, a program that has provided more than $14 million to innovative projects at 37 medical schools since 2013, and the Regenstrief Institute.

About Regenstrief Institute

Founded in 1969 in Indianapolis, the Regenstrief Institute is a local, national and global leader dedicated to a world where better information empowers people to end disease and realize true health. A key research partner to Indiana University, Regenstrief and its research scientists are responsible for a growing number of major healthcare innovations and studies. Examples range from the development of global health information technology standards that enable the use and interoperability of electronic health records to improving patient-physician communications, to creating models of care that inform practice and improve the lives of patients around the globe.

About IU School of Medicine

IU School of Medicine is the largest medical school in the U.S. and is annually ranked among the top medical schools in the nation by U.S. News & World Report. The school offers high-quality medical education, access to leading medical research and rich campus life in nine Indiana cities, including rural and urban locations consistently recognized for livability.

About Debra Litzelman, M.D., M.A.

Debra Litzelman, M.D., M.A., is the associate director of the Regenstrief Institute William M. Tierney Center for Health Services Research and Indiana University Center for Health Services and Outcomes Research. She is also the D. Craig Brater Professor of Global Health Education at Indiana University School of Medicine.

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Source: https://bioengineer.org/a-bridge-from-classroom-to-providing-actual-patient-care-a-study-of-the-regenstrief-temr/

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