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5 Questions About Booster Shots, AnsweredEmily AnthesReporting on the coronavirusWhen would I need to get it?Eight months after your second Pfizer or Moderna shot. If the F.D.A. authorizes a third dose, the first booster doses will be available on Sept. 20. Health care workers, nursing home residents and other older Americans — the first to receive the vaccines — will be the first in line for boosters.Officials are likely to recommend that people get a third dose of the same vaccine they initially received.

When it comes to building a kidney, only nature possesses the complete set of blueprints. But a USC-led team of scientists has managed to borrow some of nature’s pages through a comprehensive analysis of how kidneys form their filtering units, known as nephrons.
Published in the journal Developmental Cell, the study from Andy McMahon’s lab in the Department of Stem Cell Biology and Regenerative Medicine at USC was led by Nils Lindström, who started the research as a postdoctoral fellow and is now an assistant professor in the same department. The study also brought in the expertise of collaborators from Princeton University and the University of Edinburgh in the UK.
The team traced the blueprints for how cells interact to lay the foundations of the human kidney, and how abnormal developmental processes could contribute to disease. Their findings are publicly available as part of the Human Nephrogenesis Atlas, which is a searchable database showing when and where genes are active in the developing human kidney, and predicting regulatory interactions going on in developing cell types.
“There’s only one way to build a kidney, and that’s nature’s way,” said McMahon, who is the director of the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC. “Only by understanding the logical framework of normal embryonic development can we improve our ability to synthesize cell types, model disease and ultimately build functional systems to replace defective kidneys.”
To reconstruct nature’s molecular and cellular blueprints, the team studied hundreds of human and mouse nephrons at various points along their typical developmental trajectories. This allowed the researchers to compare important processes that have been conserved during the nearly 200 million years of evolution since humans and mice diverged from their common mammalian ancestor.
The study details the similar genetic machinery that underpins nephron formation in humans and mice, enabling other groups of scientists to follow the logic of these developmental programs to make new types of kidney cells. All told, there are at least 20 specialized cell types that form the kidney’s intricate tubular network, which helps maintain the body’s fluid and pH balance, filter the blood, and concentrate toxins into the urine for excretion.
“By generating detailed views of the beautifully complex process by which human nephrons form, we aim to enhance our understanding of development and disease, while guiding efforts to build synthetic kidney structures,” said Lindström.
The scientists were also able to determine the precise positions of expressed genes with known roles in Congenital Abnormalities of the Kidney and Urinary Tract (CAKUT). In specific types of cells, the researchers identified networks of interacting genes. Based on these associations, the team predicted new candidate genes to explore in CAKUT and other kidney diseases.
“Our approach of inferring spatial coordinates for genes expressed in individual cells could be widely used to create similar atlases of other developing organ systems — something that is an important focus of many research groups around the world,” said Lindström. “The study exemplifies the impact of collaborative science bringing together expertise across the US and Europe to connect developmental anatomy with cutting-edge molecular, computational and microscopy tools.”
Additional co-authors are: Riana K. Parvez, Andrew Ransick, Guilherme De Sena Brandine, Jinjin Guo, Tracy Tran, Albert D. Kim, Brendan H. Grubbs, Matthew E. Thornton, Jill A. McMahon, Seth W. Ruffins, and Andrew D. Smith from USC; Rachel Sealfon, Xi Chen, and Jian Zhou from the Flatiron Institute and Princeton University; Alicja Tadych from Princeton University; Aaron Watters, Aaron Wong, and Elizabeth Lovero from the Flatiron Institute; Bill Hill from the University of Edinburgh; and Chris Armit the University of Edinburgh and BGI Hong Kong.
Fifty percent of the research was supported by federal funds from the National Institutes of Health (DK054364, DK110792, U24DK100845, UGDK114907, U2CDK114886, and UH3TR002158). Additional support came from the California Institute for Regenerative Medicine (LA1-06536), and the Genetic Networks program of the Canadian Institute for Advanced Research (CIFAR).

The highest-ever resolution imaging of an infectious prion provides the first atomic-level data of how these abnormal proteins are assembled to cause fatal neurodegenerative diseases in people and animals — and how they can be potentially targeted by new therapies.
Conducted by Case Western Reserve University and the National Institutes of Health (NIH), the research is available at Molecular Cell.
“These detailed prion structures provide a new premise for understanding and targeting these currently untreatable diseases,” said Allison Kraus, lead and co-corresponding author of the research and an assistant professor in the Department of Pathology at the Case Western Reserve School of Medicine. “It will now be much easier to develop and test hypotheses about how prions are assembled as highly infectious and deadly protein structures.
Seeing the basic building blocks of these lethal proteins, she said, provides a foundation for therapeutic strategies to block the spread, buildup and toxicity of prions.
Prions are proteins in brain tissue that transmit their irregular “misfolded” shapes onto the regular version of the same protein — and are the source of mammalian diseases, including human conditions like Creutzfeldt-Jakob disease (CJD) and its variant, known as vCJD, as well as Gerstmann-Sträussler-Scheinker syndrome, and others.
Similar prion-like mechanisms occur in the characteristic proteins suspected in the development of other neurodegenerative conditions, including Parkinson’s disease, Lou Gehrig’s disease (also known as ALS, or amyotrophic lateral sclerosis), chronic traumatic encephalopathy (CTE) and Alzheimer’s disease.

Amyloid plaques are protein deposits that collect between brain cells, hindering function and eventually leading to neuronal death. They are considered a hallmark of Alzheimer’s disease (AD), and the focus of multiple investigations designed to reduce or prevent their formation, including the nationwide A4 study.
But amyloid deposits may also occur in the retina of the eye, often in patients clinically diagnosed with AD, suggesting similar pathologies in both organs. In a small, cross-sectional study, a team of researchers, led by scientists at University of California San Diego School of Medicine, compared tests of retinal and brain amyloids in patients from the A4 study and another study (Longitudinal Evaluation of Amyloid Risk and Neurodegeneration) assessing neurodegeneration risk in persons with low levels of amyloid.
Like the proverbial “windows to the soul,” the researchers observed that the presence of retinal spots in the eyes correlated with brain scans showing higher levels of cerebral amyloid. The finding suggests that non-invasive retinal imaging may be useful as a biomarker for detecting early-stage AD risk.
The findings published in the August 17, 2021 issue of Alzheimer’s & Dementia.
“This was a small initial dataset from the screening visit. It involved eight patients,” said senior author Robert Rissman, PhD, professor of neurosciences at UC San Diego School of Medicine and director of the Biomarker Core for the Alzheimer’s Disease Cooperative Study and Alzheimer’s Disease Research Center at UC San Diego. “But these findings are encouraging because they suggest it may be possible to determine the onset, spread and morphology of AD — a preclinical diagnosis — using retinal imaging, rather than more difficult and costly brain scans. We look forward to seeing the results of additional timepoint retinal scans and the impact of solanezumab (a monoclonal antibody) on retinal imaging. Unfortunately we will need to wait to see and analyze these data when the A4 trial is completed.”
The next step, said Rissman, will be to conduct a larger study to more fully document and ascertain the relationship between retinal amyloid and cerebral amyloid, both cross-sectionally and over time.
Co-authors include: Jennifer Ngolab and Shaina Korouri, UC San Diego; Michael Donohue, Alison Belsha, Jennifer Salazar, Paula Cohen, Sandhya Jaiswal, Veasna Tan, Devon Gessert, Paul S. Aisen and Michael S. Rafii, all at University of Southern California; Neelum T. Aggarwal, Rush University Medical Center; Jessica Alber, University of Rhode Island; Ken Johnson, NeuroVision Imaging Inc; Gregory Jicha, University of Kentucky; Christopher van Dyck, Yale University; James Lah, Emory University; Stephen Salloway, Butler Hospital, R.I.; Reisa A. Sperling, Brigham and Women’s Hospital/Massachusetts General Hospital, Boston.
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Materials provided by University of California – San Diego. Original written by Scott La Fee. Note: Content may be edited for style and length.

Researchers have developed a mathematical model that can predict the optimum exercise regime for building muscle.
The researchers, from the University of Cambridge, used methods of theoretical biophysics to construct the model, which can tell how much a specific amount of exertion will cause a muscle to grow and how long it will take. The model could form the basis of a software product, where users could optimise their exercise regimes by entering a few details of their individual physiology.
The model is based on earlier work by the same team, which found that a component of muscle called titin is responsible for generating the chemical signals which affect muscle growth.
The results, reported in the Biophysical Journal, suggest that there is an optimal weight at which to do resistance training for each person and each muscle growth target. Muscles can only be near their maximal load for a very short time, and it is the load integrated over time which activates the cell signalling pathway that leads to synthesis of new muscle proteins. But below a certain value, the load is insufficient to cause much signalling, and exercise time would have to increase exponentially to compensate. The value of this critical load is likely to depend on the particular physiology of the individual.
We all know that exercise builds muscle. Or do we? “Surprisingly, not very much is known about why or how exercise builds muscles: there’s a lot of anecdotal knowledge and acquired wisdom, but very little in the way of hard or proven data,” said Professor Eugene Terentjev from Cambridge’s Cavendish Laboratory, one of the paper’s authors.
When exercising, the higher the load, the more repetitions or the greater the frequency, then the greater the increase in muscle size. However, even when looking at the whole muscle, why or how much this happens isn’t known. The answers to both questions get even trickier as the focus goes down to a single muscle or its individual fibres.

Sjögren’s syndrome is an autoimmune disease that attacks the tear system in the eyes and salivary glands, leading to patients experiencing extremely dry eyes and mouth. Current treatment options for Sjögren’s syndrome are lacking. But a new animal model may help elucidate the pathogenic mechanisms behind the disease, leading to better therapeutic methods.
Professor Tetsuya Kodama, from the Laboratory of Biomedical Engineering for Cancer, at Tohoku University’s Graduate School of Biomedical Engineering, led a research group that reported on how McH-lpr/lpr-RA1 (McH/lpr-RA1) mice can act as a Sjögren’s syndrome animal model.
McH/lpr-RA1 mice are inbred strains of mice. Dr. Shiro Mori, a lecturer at Tohoku University Hospital, and his colleagues have been cultivating them for many years as disease models for the spontaneous development of severe autoimmune arthritis, sialadenitis, and vasculitis.
Kodama, Mori, and Dr. Keiichi Saito, an assistant professor at the Liaison Centre for Innovative Dentistry at Tohoku University’s Graduate School of Dentistry, collaborated to analyze the pathogenesis of this mouse model. Their research revealed that the McH/lpr-RA1 mice spontaneously developed autoimmune inflammation in the salivary gland tissue and blood vessels.
Further observations of the McH/lpr-RA1 mice unveiled extensive infiltration of inflammatory cells (mainly lymphocytes) in the salivary gland tissue and destruction of the existing salivary gland structure. In addition, inflammation occurred at the foot and knee joint and blood vessels in the kidneys.
Aquaporin 5, a protein that is critical for saliva production and its secretion, was absent or weakly expressed, indicating an inhibited salivary secretomotor system in the mouse model. The study also suggests that the significant inflammation of salivary glands, along with tissue destruction, contributes to Aquaporin 5 expression being suppressed.
The research group is hopeful the relationship between Sjögren’s syndrome and malignant lymphoma could be investigated in the model mice since vasculitis has been associated with malignant lymphoma development in patients with this disease.
Kodama believes that McH/lpr-RA1 mice are a superior disease model for autoimmune sialadenitis when compared to other model mice since they do not develop nephritis and have a longer life span.
With the McH/lpr-RA1 mouse now registered at the RIKEN BioResource Center in Tsukuba, Japan (BRC No. RBRC11160), Kodama and his team are ready to provide this mouse model to researchers who need it for their research. “We believe the McH/lpr-RA1 mouse will reveal more about inflammation in the salivary glands and blood vessels, leading to new treatment methods for Sjögren’s syndrome,” said Kodama.
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Materials provided by Tohoku University. Note: Content may be edited for style and length.

Diclofenac and other non-steroidal anti-inflammatory drugs (NSAIDs) may limit the passage of gamma hydroxybutyric acid (a narcolepsy medication and illicit party drug commonly known as GHB) to the brain, decreasing the potential for fatal overdose, according to a University at Buffalo study.
The research found that treatment with diclofenac after taking GHB led to decreased concentrations of GHB in the brain and an improved respiration. The study, completed in animal models, was published in Biopharmaceutics & Drug Disposition. Previous studies completed by the UB researchers found that the NSAIDs ibuprofen and ketoprofen also affected the movement of GHB in the body.
GHB is approved for a number of clinical uses, including the treatment of narcolepsy, a chronic sleep disorder, and alcoholism. However, GHB prescriptions are limited due to its high potential for abuse as a club and date-rape drug. At high doses, the drug can cause amnesia, drowsiness and depressed breathing. There are currently no approved antidotes for GHB overdose.
“The therapeutic utility of GHB in the treatment of narcolepsy [as Xyrem] has been overshadowed by its high prevalence of abuse. The abuse of GHB — known as Fantasy, Liquid Ecstasy and G — carries the risk of severe adverse effects including sedation, respiratory depression, hypothermia, coma and death,” says Marilyn Morris, PhD, SUNY Distinguished Professor and chair of the Department of Pharmaceutical Sciences in the UB School of Pharmacy and Pharmaceutical Sciences.
“Current treatment of GHB overdose is limited to supportive care. My laboratory has identified MCT1 inhibitors as a treatment strategy to prevent death after GHB overdoses. In this research, we identified the NSAID diclofenac as a MCT1 inhibitor and demonstrated its effectiveness as a potential antidote for GHB overdose. Also, our findings significantly suggest that diclofenac and other NSAIDs may decrease the effectiveness of Xyrem used in the treatment of narcolepsy.”
Additional investigators include first author, UB alumna and former graduate student in Morris’ lab Vivian Rodriguez-Cruz, PhD, research scientist at Eli Lilly and Company; and Tianjing Ren, PhD, postdoctoral researcher in the UB School of Pharmacy and Pharmaceutical Sciences.
Commonly sold under the brand name Voltaren, diclofenac is prescribed to treat pain and inflammation. Morris’ lab has found that some NSAIDs can block tissue uptake of drugs by monocarboxylate transporters (MCTs), a family of proteins that transport molecules across biological membranes, including the blood-brain barrier, which protects the brain from toxins and pathogens circulating in the blood while allowing for the passage of nutrients.
GHB relies on MCTs for transport throughout the body, making the study of the inhibition of MCTs as an antidote a focus of Morris’ lab.
The recent study sought to understand the impact diclofenac has on GHB toxicity by measuring the effect of their interaction on respiratory depression — the main cause of death following GHB overdose.
Diclofenac was found to inhibit the brain uptake of GHB by MCT1, the only monocarboxylate transporter present at the blood-brain barrier, resulting in a reversal of respiratory depression after GHB overdose.
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Materials provided by University at Buffalo. Original written by Marcene Robinson. Note: Content may be edited for style and length.

Each year nearly 5,000 patients die while waiting for kidney transplants, and yet an estimated 3,500 procured kidneys are discarded.
In a recent study published online July 9 in the INFORMS journal Management Science, a researcher from The University of Texas at Dallas investigated how introducing new airline routes impacts the sharing of cadaveric kidneys.
“This mismatch between supply and demand of donor organs and the time-sensitive nature of kidney transplantation made us wonder whether better airline logistics infrastructure could help match that supply and demand,” said Dr. Guihua Wang, assistant professor of operations management in the Naveen Jindal School of Management and the study’s lead author.
Wang and co-authors Dr. Ronghuo Zheng of UT Austin and Dr. Tinglong Dai of Johns Hopkins University created a unique sample that tracked both the evolution of airline routes connecting all U.S. airports, and kidney transplants between donors and recipients connected by these airports.
To do this, the researchers merged monthly air-carrier traffic information from the U.S. Bureau of Transportation Statistics and individual-level data for all U.S. kidney transplant candidates, donors and recipients from the United Network for Organ Sharing.
The study estimates that each new airline route led to a 7.3% increase in the number of kidneys sent to transplant centers across the U.S. The findings also suggest that introducing a new airline route reduces the discard rate of kidneys by facilitating kidney sharing.

Females and males differ in many ways and yet they share the same genome. The only exception is the male Y chromosome. Using beetles as a study system, new research from Uppsala University, now published in Nature Ecology & Evolution, shows that despite of the Y chromosome containing very few genes, it can dramatically change male body size and thus facilitate the evolution of sex differences.
Females and males typically differ in many ways in their morphology, physiology and behaviour. How such sex differences, known as sexual dimorphism, evolve is a puzzle because females and males share the same set of genes and an evolutionary change in one sex should cause a correlated change even in the other sex, thereby preventing sex differences from evolving. The new study shows that even small amounts of genetic differences between the sexes can facilitate the evolution of sexual dimorphism such that it can evolve in just a few generations.
“Our experiments show that the autosomes as well as both sex chromosomes, the X and Y, can harbor genetic variation important for sexual dimorphism, but the Y chromosome alone can alter the sex difference in size by as much as 30 percent. This is remarkable because in these beetles the Y chromosome contains just a handful of genes and represents a very small fraction of the genome, just like in humans. Many have thought that the Y only affects the most important reproductive processes in males, namely sperm production. Our findings suggest that the Y chromosome may have a broader role than previously appreciated,” says Philipp Kaufmann, a PhD student at the Uppsala University’s Department of Ecology and Genetics and the first author of the study.
The evolution of sexual dimorphism is however not only dependent on where in the genome genetic variation resides, but also on how natural and sexual selection can act on it. With the help of lab evolution, the research team showed that sexual size dimorphism could evolve when selecting on male size, but that when selection acted only on females, the shared part of the genome caused a correlated evolutionary response in males preventing dimorphism from evolving.
“The most drastic change in sexual dimorphism, an increase by 50 percent in only ten generations, occurred when we applied selection sexually antagonistically — favoring the opposite body size in the two sexes. This shows that under right kind of selection sex differences can clearly evolve rapidly, perhaps more easily than was previously thought,” says Elina Immonen, Assistant Professor at the Department of Ecology and Genetics, Uppsala University, and the principle investigator of the study.
“Combining information of what kind of genetic variation is available to selection with different forms of selection is a powerful way to test the determinants of evolution of sex differences. By isolating the effect of Y chromosome variation from the rest of the genome, we could directly demonstrate how large the effect of the Y chromosome is, something we didn’t expect to see when we started the work and this has helped understand how sexual dimorphism has evolved in this species. Future work will tell us more regarding how the Y chromosome can have such a large effect on males and how general its role is in the evolution of sex differences across taxa,” Immonen concludes.
More about the experiments
In their study, the researchers characterized the genetic architecture of body size in males and females by creating a large pedigree of over 8,000 beetles (the seed beetle Callosobruchus maculatus). This multi-generational family tree was used to quantify autosomal and sex chromosome linked genetic variation in body size. The use of artificial selection allowed testing how different forms of selection affect the evolution of size dimorphism and included selection acting only on males, only on females, or acting sexually antagonistically (in the opposite directions) in the two sexes. After ten generations of selection, the sexual size dimorphism was compared between the selection lines and the ancestral pedigree population. These two experiments clearly indicated that the Y chromosome play an important role in determining male response to selection. In order to test further the effect of the Y linked variation in isolation from variation in the rest of the genome, the research team carried out a third experiment. They isolated the effect of the Y chromosome on sexual size dimorphism in these beetles by introducing the different Y chromosomes into a genetically identical background. In other words, creating beetles that are identical twins to each other except for the Y chromosome.
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Materials provided by Uppsala University. Note: Content may be edited for style and length.

While the proper pronunciation of pecan remains a subject of debate, University of Georgia researchers have shown the tree nut can dramatically improve a person’s cholesterol levels.
Participants at risk for cardiovascular disease who ate pecans during an eight-week intervention showed significant improvements in total cholesterol, triglycerides and low-density lipoprotein (LDL), or “bad” cholesterol, in a study conducted by researchers in the UGA College of Family and Consumer Sciences.
“This dietary intervention, when put in the context of different intervention studies, was extremely successful,” said Jamie Cooper, a professor in the FACS department of nutritional sciences and one of the study’s authors. “We had some people who actually went from having high cholesterol at the start of the study to no longer being in that category after the intervention.”
Researchers saw an average drop of 5% in total cholesterol and between 6% and 9% in LDL among participants who consumed pecans.
For context, researchers referred to a previous meta-analysis of 51 exercise interventions designed to lower cholesterol that reported an average reduction of 1% in total cholesterol and 5% in LDL cholesterol.
“The addition of pecans to the diet not only produced a greater and more consistent reduction in total cholesterol and LDL compared to many other lifestyle interventions, but may also be a more sustainable approach for long-term health,” Cooper said. “Some research shows that even a 1% reduction in LDL is associated with a small reduction of coronary artery disease risk, so these reductions are definitely clinically meaningful.”
Researchers assigned 52 adults between the ages of 30 and 75 who were at higher risk for cardiovascular disease to one of three groups.