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The hypothesis that raising the brain levels of the natural antioxidant urate could slow the progression of Parkinson’s disease (PD) has been disproven by researchers at Massachusetts General Hospital (MGH). Still, the rigor of the clinical study and some of its novel investigative approaches are seen as improving the prospects for future clinical trials to demonstrate the benefits of disease-modifying therapies for people with Parkinson’s disease. The results were published in Journal of the American Medical Association.
“The convergence of epidemiological, biological, and clinical data from past research made a compelling argument that elevating urate, the main antioxidant circulating in the blood, could protect against the oxidative damage thought to play a role in Parkinson’s disease,” says senior author Michael Schwarzschild, MD, PhD, a neurologist at MGH and co-leader of the MGH-based Parkinson Study Group, a network of North American researchers dedicated to improving therapy for people with PD. “While our study did not rule out a protective effect of urate in Parkinson’s, it clearly showed that increasing urate did not slow disease progression based on clinical assessments and serial bran scan biomarkers of neurodegeneration.”
No treatment to date has been shown to prevent or forestall progression of Parkinson’s disease, which affects the body’s motor system. For its Phase III trial, known as SURE-PD3, the MGH-led team enrolled 298 individuals recently diagnosed with early Parkinson’s disease based on scans that indicated substantial loss of the dopamine-producing brain cells characteristic of PD. The results showed that of participants who received over the course of two years the metabolite inosine — which raises levels of urate in the brain and blood and has shown neuroprotective properties in preclinical models — there was no significant difference in the rate of disease progression compared to those in the placebo group. The study did reveal, however, an increased rate of kidney stones among those randomized to inosine treatment.
Despite the lack of evidence to support urate elevation, Schwarzschild found the study successful in other ways. “The findings were very helpful in providing a reality check that now allows the field to move on to other therapeutic approaches,” he explains. “We also learned a lot in terms of clinical trials science for Parkinson’s, and ways to conduct future studies that will increase their chance of success.” One of those ways is to tailor treatment to subsets of patients who are most likely to benefit — a hallmark of the move to precision medicine in Parkinson’s research. In SURE-PD3, for example, only patients who had lower levels of urate were enrolled to increase the chance of benefit and reduce the chance of side effects.
Another innovative feature of the trial is that many participants gave blood samples for genotyping — a valuable source of genetic information that could figure in the hunt for clinical solutions in smaller subpopulations of PD patients. A significant number also volunteered for an extension of the study to help determine how monitoring at home could provide more efficient ways to conduct future clinical trials. “There were many positive results from SURE-PD3 which we believe will improve the prospects of researchers discovering a disease-modifying therapy which people with Parkinson’s have been desperately seeking,” concludes Schwarzschild.
Schwarzschild is professor of Neurology at Harvard Medical School. Co-authors include Alberto Ascherio, DPH, MD, professor of Medicine, Harvard T.H. Chan School of Public Health, Eric Macklin, PhD, biostatistician, MGH, and David Oakes, PhD, University of Rochester.
The study was supported by the National Institutes of Health/National Institute of Neurological Disorders and Stroke, and the Michael J. Fox Foundation for Parkinson’s Research.
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As we age, our bones become thinner, we suffer fractures more often, and bone-diseases such as osteoporosis are more likely to occur. One responsible mechanism involves the impaired function of the bone-marrow stem cells, which are required for the maintenance of bone integrity. Researchers from the Max Planck Institute for Biology of Ageing and CECAD Cluster of Excellence for Ageing Research at the University of Cologne have now shown that the reduced stem cell function upon ageing is due to changes in their epigenome. They were able to reverse these changes in isolated stem cells by adding acetate. This fountain of youth for the epigenome could become important for the treatment of diseases such as osteoporosis.
Ageing Researchers have been looking at epigenetics as a cause of ageing processes for some time. Epigenetics looks at changes in genetic information and chromosomes that do not alter the sequence of the genes themselves, but do affect their activity. One possibility is changes in proteins called histones, which package the DNA in our cells and thus control access to DNA. The Cologne research group of Peter Tessarz has now studied the epigenome of mesenchymal stem cells. These stem cells are found in bone marrow and can give rise to different types of cells such as cartilage, bone and fat cells.
“We wanted to know why these stem cells produce less material for the development and maintenance of bones as we age, causing more and more fat to accumulate in the bone marrow. To do this, we compared the epigenome of stem cells from young and old mice,” explains Andromachi Pouikli, first author of the study. “We could see that the epigenome changes significantly with age. Genes that are important for bone production are particularly affected.”
Rejuvenation of the epigenome
The researchers then investigated whether the epigenome of stem cells could be rejuvenated. To do this, they treated isolated stem cells from mouse bone marrow with a nutrient solution which contained sodium acetate. The cell converts the acetate into a building block that enzymes can attach to histones to increase access to genes, thereby boosting their activity. “This treatment impressively caused the epigenome to rejuvenate, improving stem cell activity and leading to higher production of bone cells,” Pouikli said.
To clarify whether this change in the epigenome could also be the cause of the increased risk in old age for bone fractures or osteoporosis in humans, the researchers studied human mesenchymal stem cells from patients after hip surgery. The cells from elderly patients who also suffered from osteoporosis showed the same epigenetic changes as previously observed in the mice.
A new therapeutic approach against osteoporosis?
“Sodium acetate is also available as a food additive, however, it is not advisable to use it in this form against osteoporosis, as our observed effect is very specific to certain cells. However, there are already first experiences with stem cell therapies for osteoporosis. Such a treatment with acetate could also work in such a case. However, we still need to investigate in more detail the effects on the whole organism in order to exclude possible risks and side effects,” explains Peter Tessarz, who led the study.
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The neurotransmitter dopamine influences the activity of a wide variety of brain areas. A deficiency of this substance can have drastic consequences: The death of dopamine-producing nerve cells in the substantia nigra — a particularly sensitive part of the brain — is what causes the core symptoms of Parkinson’s disease. An international team from the University of Bonn has now investigated the role played by the transcription factor BCL11A in mice and human cells. If this important factor is missing, the neurons are even more sensitive and more likely to die. The researchers suspect that BCL11A plays a protective role for neurons. The study is now published in Cell Reports.
The human midbrain contains nerve cells that produce dopamine (dopaminergic neurons). “This neurotransmitter influences other neurons by amplifying or dampening their activity,” explains Prof. Dr. Sandra Blaess from the Institute for Reconstructive Neurobiology at the University Hospital Bonn. Like the treble and bass controls on a radio, these special neurons do not change the song or the tune, but they can drastically alter the effect. Dopamine-producing neurons also play a major role in Parkinson’s disease: the dopamine cells located in the substantia nigra, a dark-appearing structure in the midbrain, die off. The resulting lack of dopamine causes the movement dysfunctions associated with the disease.
The dopamine-producing neurons form extensive connections in a large number of brain areas, for example in the cerebral cortex or the striatum. “This raises the question of whether there are specialized groups within these dopaminergic neurons that affect only certain areas of the brain,” Dr. Emmanouil Metzakopian of the UK Dementia Research Institute at The University of Cambridge explains, who contributed data on human cells to the study. The transcription factor BCL11A is known to be important for determining cell properties, for example in the cerebral cortex and also in the immune system. Prof. Blaess’ team now investigated for the first time what role BCL11A plays in the different properties of dopaminergic neurons.
Labeling with fluorescent molecules
The researchers analyzed both developing and mature mouse brains and human cells to determine in which of the dopamine neurons the transcription factor BCL11A is switched on. They then labeled BCL11A-producing neurons in mice with fluorescent molecules, which then lit up under the microscope.
“This allowed us to see which neighboring brain regions the extensions of these dopaminergic neurons grew into,” explains Blaess, who is also a member of the Collaborative Research Center 1089 “Synaptic Micronetworks in Health and Disease” and the Transdisciplinary Research Area “Life and Health” at the University of Bonn. The areas in the brain with which the BCL11A-positive dopamine-producing neurons made contact were not arbitrary. For example, the target region was not the entire striatum, which is part of the complex motor control circuits of the cerebrum, but only a small part of this brain area.
Substantia nigra particularly susceptible to neurodegeneration
The researchers investigated neurodegenerative processes in the substantia nigra using mice from the German Center for Neurodegenerative Diseases (DZNE), which had a loss of dopamine-producing neurons, similar to Parkinson’s disease. “It is known that in Parkinson’s patients, dopaminergic neurons in the substantia nigra die off to a greater extent than neurons in other brain regions,” says Prof. Dr. Donato Di Monte of the DZNE, who was involved in this part of the study. “This area is therefore considered particularly sensitive to neurodegeneration.”
The team compared dopamine neurons with and without BCL11A in the “Parkinson’s mice.” In the substantia nigra, this transcription factor marked dopaminergic neurons that were particularly susceptible to neurodegeneration. If the researchers switched off the production of BCL11A in these cells, even more of the dopamine cells perished. “This suggests that BCL11A may have a neuroprotective function,” says Prof. Blaess, summarizing the main finding. The molecular mechanism behind this still needs to be investigated in more detail in further studies. Whether the findings can be transferred from mice to humans will also be investigated.
In addition to the Institute of Reconstructive Neurobiology, the Institute of Anatomy and the Department of Neuropathology of the University of Bonn, the German Center for Neurodegenerative Diseases (DZNE), the University of Ulm, the University of Cambridge, the UK Dementia Research Institute (UK DRI) at Cambridge and the University of Hong Kong are involved. The study was mainly funded by the German Research Foundation (DFG).
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Our bodies can fine-tune the immune response to an infection and make it proportional to the threat at hand. New research from Karolinska Institutet in Sweden describes how B lymphocytes, the immune cells that make antibodies, choose between different cell fates to balance the magnitude of the acute immune response and the memory response that protects against future threats. The study, published in Immunity, may contribute to the optimisation of vaccines to fight viruses or other pathogens.
An efficient immune response to infections and vaccines requires antibodies, which are produced by specialised effector B cells of the immune system. Effector B cells produce large amounts of antibodies that fight off the acute threat, while memory B cells protect us from future threats by quickly generating new effector B cells producing antibodies if the intruder returns. To date, our understanding of how the immune system controls the balance between effector and memory B cells has been limited.
An early wave of memory cells
In a new study, researchers at Karolinska Institutet have studied the generation of B cells early after infection and vaccination in animal models. They found that B cells early on make cell fate decisions that have consequences for the balance between the effector and memory response.
“We show that there is an extensive early wave of memory cells that seems to be a ‘default’ fate for many activated B cells, and that these early memory cells seem to be equally long-lived as the traditional late wave of memory cells,” says Taras Kreslavsky, assistant professor at the Department of Medicine, Solna, Karolinska Institutet, who led the study. “The early memory cells are kept as a reserve and can rapidly be re-activated and transformed into effector B cells if the threat increases. This way, our bodies can fine-tune the antibody response proportionally to the threat level.”
Could improve vaccine design
The research team also shows that the early memory response is evolutionarily conserved, which opens the possibility of influencing the B cell response in humans through vaccination.
“We believe that rational vaccine design may enable manipulation of the type of B cells that are formed and thus make the body’s defence more effective,” says the study’s first author, Vassilis Glaros, a doctoral student in Taras Kreslavsky’s research team.
The researchers plan to further study how the early B cell response can be modulated and the consequences of skewing the response between effector and memory cell fates.
Crucial to our body’s defence
“The memory B cells are crucial to our body’s defence against evolving pathogens, such as SARS-CoV-2 virus variants which cause COVID-19,” says co-author Sebastian Ols, a doctoral student in Karin Loré’s research group at the Department of Medicine, Solna, Karolinska Institutet. “Our memory cells are better equipped at adapting and parrying new variants than our effector cells are, and it is therefore critical for vaccines to elicit diverse memory B cell responses.”
The study was done in collaboration with the Research Institute of Molecular Pathology (IMP) in Vienna and Medical University of Vienna, among others. The research was supported by the Swedish Research Council, the Swedish Cancer Society, SciLifeLab, the Åke Wiberg Foundation, the Wenner-Gren Foundations, the German Research Foundation DFG, Boehringer Ingelheim, the European Research Council (ERC), the Bill & Melinda Gates Foundation, and the Ministry of Science and Higher Education of the Russian Federation. Co-author Neil P. King is a co-founder, shareholder, and chair of the scientific advisory board of Icosavax, Inc. and the King laboratory has an unrelated sponsored research agreement with Pfizer.
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Scientists at the Massachusetts Institute of Technology (MIT) and the Institut Pasteur in France have developed a technique for reconstructing whole genomes, including the human genome, on a personal computer. This technique is about a hundred times faster than current state-of-the-art approaches and uses one-fifth the resources. The study, published September 14 in the journal Cell Systems, allows for a more compact representation of genome data inspired by the way in which words, rather than letters, offer condensed building blocks for language models.
“We can quickly assemble entire genomes and metagenomes, including microbial genomes, on a modest laptop computer,” says Bonnie Berger (@lab_berger), the Simons Professor of Mathematics at the Computer Science and AI Lab at MIT and an author of the study. “This ability is essential in assessing changes in the gut microbiome linked to disease and bacterial infections, such as sepsis, so that we can more rapidly treat them and save lives.”
Genome assembly projects have come a long way since the Human Genome Project, which finished assembling the first complete human genome in 2003 for the cost of about $2.7 billion and more than a decade of international collaboration. But while human genome assembly projects no longer take years, they still require several days and massive computer power. Third-generation sequencing technologies offer terabytes of high-quality genomic sequences with tens of thousands of base pairs, yet genome assembly using such an immense quantity of data has proved challenging.
To approach genome assembly more efficiently than current techniques, which involve making pairwise comparisons between all possible pairs of reads, Berger and colleagues turned to language models. Building from the concept of a de Bruijn graph, a simple, efficient data structure used for genome assembly, the researchers developed a minimizer-space de Bruin graph (mdBG), which uses short sequences of nucleotides called minimizers instead of single nucleotides.
“Our minimizer-space de Bruijn graphs store only a small fraction of the total nucleotides, while preserving the overall genome structure, enabling them to be orders of magnitude more efficient than classical de Bruijn graphs,” says Berger.
The researchers applied their method to assemble real HiFi data (which has almost perfect single-molecule read accuracy) for Drosophila melanogaster fruit flies, as well as human genome data provided by Pacific Biosciences (PacBio). When they evaluated the resulting genomes, Berger and colleagues found that their mdBG-based software required about 33 times less time and 8 times less random-access memory (RAM) computing hardware than other genome assemblers. Their software performed genome assembly for the HiFi human data 81 times faster with 18 times less memory usage than the Peregrine assembler and 338 times faster with 19 times less memory usage than the hifiasm assembler.

Reducing naturally occurring errors in protein synthesis (production) improves both health and lifespan, finds a new study in simple model organisms led by researchers at UCL and MRC London Institute of Medical Sciences.
The novel findings, published in Cell Metabolism, are the first to demonstrate a direct link between fewer protein mistakes and longevity.
Explaining the study, lead author Dr Ivana Bjedov (UCL Cancer Institute), said: “We commonly hear about DNA mutations, which can cause cancer, and are considered one of the underlying causes of ageing.
“However, mistakes in proteins which affect organismal health are largely neglected, despite the fact that errors introduced during synthesis of new proteins are much more frequent than mutations made during DNA replication.
“For this study we therefore focused on protein errors, and we questioned if fewer mistakes in proteins improve health.”
For the study, scientists investigated an evolutionary ‘hyper-accuracy’ mutation, known as RPS23 K60R, found in the ribosomes (cell’s protein producing factories) of hyperthermophilic Archaea, a single-celled organism that can live at extremely high temperatures.
Using genome editing, scientists engineered a metazoan (meaning, of the animal kingdom) ribosome to carry the identical mutation (a single amino acid change) as the hyperthermophilic Archaea, and thereby replicated its effect on protein synthesis in simple model organisms, namely yeast, worms and fruit flies.
The team observed that the organisms’ proteins had fewer errors and, as a result, the organisms became heat resistant and lived longer.
First author, Dr Victoria Eugenia Martinez-Miguel (UCL Cancer Institute) said: “The process of making proteins is not error free — ribosomes make mistakes.
“We have shown, for the first time, that changing a single amino acid in the ribosome decoding centre reduces protein synthesis mistakes and improves an organism’s stress resilience and longevity.”
In addition to the reengineered ribosomes, researchers found some drugs approved for human use can also reduce mistakes in proteins. Interestingly, these drugs, rapamycin, torin and trametinib, are also known to be anti-ageing drugs. They affect the cell’s ability to sense nutrients and therefore when applied in small quantities can have a similar effect as calorie restriction, a known pro-longevity treatment. This novel study suggests that reduction of protein errors is a unifying mechanism of anti-ageing drugs that could contribute to healthy ageing.
Co-corresponding author Professor Filipe Cabreiro (MRC London Institute of Medical Sciences) said: “This is the first study in a metazoan organism, to reveal that fewer mistakes in proteins can prolong health and longevity; we expect our results on yeast, worms and flies to be extended to mammals, which could potentially lead to treatments for improved health in the elderly.”
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A common eye test could expel tear droplets up to a meter away from the patient, potentially spreading viruses that cause COVID-19 and other pathogens.
In Physics of Fluids, by AIP Publishing, scientists from the Indian Institute of Science and the Narayana Nethralaya Foundation explain how tears ejected from the eye during a procedure that tests for glaucoma can theoretically transmit disease.
Ophthalmologists use a tonometer to measure the pressure in an eye. A high-pressure reading can indicate a risk for developing glaucoma. The instrument emits an air puff that hits the surface of the eye.
The researchers modeled the eye’s response to this puff and took high speed images of eyes undergoing the procedure. They were specifically looking at the liquid in the eye and how it responded.
As the eye was hit with the air puff, the film of tears on the surface expanded into a sheet that spilled out over the eyelids. The cornea also deflected away from the incoming air.
“The cornea is like an elastic surface. So, as it deforms and as it recovers its shape, it gives the eye an additional kick,” said author Saptarshi Basu. “It’s a capillary wave merged with this corneal deflection, which gives rise to a consolidated wave, and that is what makes the tear fluid expand and go out.”
The waves moving within the eye and tear liquid eventually become unstable, and the tears break up into droplets. The team tracked the speed of those droplets as they left the eye and  predicted they could travel up to a meter away from the patient. The distance depends on the air flow within the room.
Eyes with more tears created more droplets than dry eyes. The scientists recommend not using eye drops before the glaucoma test unless medically necessary.
“It is not just limited to SARS-CoV-2. It can be extrapolated to other types of pathogens as well,” said Basu. “What you think is a very safe, noncontact procedure, even then, one needs to be a little careful.”
This work can help eye care practitioners to develop and follow health and safety protocols, like improved room ventilation and cleaning nearby instruments and surfaces, that may not have been considered necessary in the past.
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WASHINGTON, September 14, 2021 — Since the spread of virus causing COVID-19 continues, experts recommended wearing homemade facemasks when surgical or N95 masks are not available to prevent the spread of the pandemic. While such makeshift masks are more economical and accessible in low-capita countries, the effectiveness of cloth masks has not been studied in depth.
In Physics of Fluids, by AIP Publishing, researchers from the Indian Institute of Science studied the fate of a large-sized surrogate cough droplets at different velocities, corresponding from mild to severe, while using various locally procured fabrics as masks.
“Our results show cotton, towel-based fabrics were most effective among the considered fabrics and must be stitched together as multiple layers for making homemade facemasks,” said author Saptarshi Basu. “A three or more-layered homemade mask is recommended, since it can suppress aerosolization significantly.”
The researchers analysed the effect of washing on mask effectiveness, and results showed a negligible influence of washing on mask efficacy for up to 70 wash cycles.
Using a piezoelectric-based droplet dispenser, the researchers created surrogate cough droplets that impacted a single layer of different fabric samples at different velocities. The fabrics used in the research included single layers of summer stole, handkerchief, cotton towel, and surgical masks.
The specific cotton-fabric materials were selected based on their daily usage and the propensity of people to cover their face using these cloth materials. The researchers used high-speed imaging to quantify the threshold for penetration and amount of droplet penetration at different velocities.
The researchers looked at how fabric properties, like pore size and porosity, influences droplet penetration through the mask.
The results are relevant for many groups including policy makers investigating how to counter aerosol generation through secondary atomization of cough droplets as they penetrate the mask fabric. For mask fabricators and the general population, it is helpful to know that N95 and surgical masks are most effective, but when those aren’t available, some specific cotton materials or homemade fabrics are suitable for effective makeshift face masks.
The findings also could be applicable in applications ranging from agriculture to medical practices, where placing a wire mesh or perhaps an engineered cellulose mesh of variable porosity can reduce the momentum of incoming spray from a nozzle, thereby ensuring optimal spread of nutrients or pesticides to crops or better disinfection in hospital  
The article, “Efficacy of homemade face masks against human coughs: Insights on penetration, atomization and aerosolization of cough droplets,” is authored by Bal Krishan, Dipendra Gupta, Gautham Vadlamudi, Shubham Sharma, Dipshikha Chakravortty, and Saptarshi Basu. The article will appear in Physics of Fluids on Sept. 14, 2021 (DOI: 10.1063/5.0061007). After that date, it can be accessed at https://aip.scitation.org/doi/full/10.1063/5.0061007.
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Scientists have discovered an important cause of stroke occurring in the womb or just after birth, paving the way for new treatments.
The research identified that a low number of platelets (small blood cells known for enabling clotting) in babies, either in the womb or in newborns, could cause bleeding in the brain. These types of bleeds can lead to fatal strokes or permanent neurological conditions, such as cerebral palsy.
Published in Blood, the research led by Dr Alison Farley and Dr Samir Taoudi identified that platelets played a crucial role in the fetal and newborn brain in preclinical models.
Platelet loss linked to stroke in newborns
Platelets are tiny blood cells that help blood clot. Normally, platelets prevent bleeding by clumping and forming plugs to stem blood vessel injuries, such as cuts or abrasions, restricting blood loss.
‘Thrombocytopenia’ is a reduction of platelets, which can allow excessive bleeding to occur if blood vessels are already damaged.

Travel within your own country in response to the government announcing a national lockdown is directly linked to a sharp rise in Covid-19 infections, according to an international study led by Bangladesh and involving a researcher from the University of Bath in the UK.
The study — the first of its kind to combine genome sequencing and mobile phone data — has found a direct link between mass migration from Dhaka, the capital of Bangladesh (an area of high infection), and the spread of coronavirus to the rest of the country after a stay-at-home order was announced during the nation’s first wave of infection in March 2020.
It is hoped that insights from this project will be used by other countries to track the virus and to inform the way governments respond when fresh outbreaks occur.
For the Bangladesh study, a consortium of scientists that included Dr Lauren Cowley from the Department of Biology and Biochemistry at the UK’s University of Bath investigated the spatial spread of the coronavirus during Bangladesh’s first wave by analysing the genome sequences of 391 viral samples collected from different parts of the country. This information was integrated with anonymised population-mobility data collected from Facebook and three mobile phone operators. This analysis gave the researchers insight into the evolution of the virus, and allowed them to track the different times and locations where new lineages of the virus appeared. It also enabled the authors to work directly with the government on the detection of variants of concern (Alpha and Beta) in Bangladesh.
The researchers established that much of the virus’ spread from the capital to all other areas of the country occurred during a three-day window between the government announcing a stay-at-home order and this order coming into effect (March 23-26, 2020). The population mobility data showed that a large proportion of Dhaka’s usual residents left the city for regional towns and villages in response to workplaces being closed.
As a result of the researchers’ findings, the government of Bangladesh restricted intercity travel during subsequent waves of infection, thereby making it harder for the virus to spread using the same channels as it did during the first wave.