Worms don’t wiggle when they have Alzheimer’s disease. Yet something helped worms with the disease hold onto their wiggle in Professor Jessica Tanis’s lab at the University of Delaware.
In solving the mystery, Tanis and her team have yielded new clues into the potential impact of diet on Alzheimer’s, the dreaded degenerative brain disease afflicting more than 6 million Americans.
A few years ago, Tanis and her team began investigating factors affecting the onset and progression of Alzheimer’s disease. They were doing genetic research with C. elegans, a tiny soil-dwelling worm that is the subject of numerous studies.
Expression of amyloid beta, a toxic protein implicated in Alzheimer’s disease, paralyzes worms within 36 hours after they reach adulthood. While the worms in one petri dish in Tanis’s lab were rendered completely immobile, the worms of the same age in the adjacent petri dish still had their wiggle, documented as “body bends,” by the scientists.
“It was an observation my master’s student Kirsten Kervin made,” said Tanis, an assistant professor in UD’s Department of Biological Sciences. “She repeated the experiment again and again, with the same results.”
After years of research, the team finally turned up an important difference, Tanis said. While all the worms were grown on a diet of E. coli, it turns out that one strain of E. coli had higher levels of vitamin B12 than the other. Although Tanis’s work was focused on genetic factors at the time, she redirected her research to examine this vitamin and its protective role.

Sepsis, the body’s life-threatening response to infection affecting about 1.7 million adults in the United States each year, can lead to multisystem organ failure with a high mortality rate.
No targeted therapeutics against this condition have been developed in the last decades. Now, however, a team led by biomedical scientists at the University of California, Riverside, offers some hope for future treatment during sepsis awareness month.
The researchers, led by Meera Nair and Adam Godzik in the School of Medicine, identified molecular biomarkers, pathways and immune cell dynamics associated with sepsis that could be therapeutically targeted to prevent the condition from leading to death. These blood cell biomarkers — the protein CD52 in lymphocytes; and the protein S100A9 involved in inflammatory processes — are present in all blood cells but highly expressed in people with sepsis. How these biomarkers change early in sepsis — specifically, within the first six hours — could determine whether the patient survives or dies.
“These biomarkers were found to uniquely change within six hours in the blood of patients with sepsis and affected specific cellular pathways in specific immune cells,” said Nair, an associate professor of biomedical sciences, who co-led the study published in the Journal of Leukocyte Biology. “Changes in CD52 expression were associated with good outcomes, which means promoting the activation of protective immune cells. S100A9, on the other hand, acted as a molecular driver of fatal sepsis. We appear to have found a molecular driver and a molecular protector of sepsis.”
According to Nair, the team also found the molecular pathways for fatal sepsis and COVID-19 converge.
“Severe COVID appears to trigger molecular pathways identical to sepsis,” she said. “Further analysis of these pathways can help us diagnose and treat both diseases.”
In particular, the research team also found that in people with sepsis, blood platelets — cell types involved in normal blood flow and coagulation — lost their function, as they do in COVID patients. The researchers argue that if the platelets’ function could be restored by targeting the main regulators of this process, it could promote survival in both sepsis and COVID.

As SARS-CoV-2 continues to evolve, new variants are expected to arise that may have an increased ability to infect their hosts and evade the hosts’ immune systems. The first key step in infection is when the virus’ spike protein binds to the ACE2 receptor on human cells. Researchers at Penn State have created a novel framework that can predict with reasonable accuracy the amino-acid changes in the virus’ spike protein that may improve its binding to human cells and confer increased infectivity to the virus.
The tool could enable the computational surveillance of SARS-CoV-2 and provide advance warning of potentially dangerous variants with an even higher binding affinity potential. This can aid in the early implementation of public health measures to prevent the virus’s spread and perhaps even may inform vaccine booster formulations.
“Emerging variants could potentially be highly contagious in humans and other animals,” said Suresh Kuchipudi, clinical professor of veterinary and biomedical sciences and associate director of the Animal Diagnostic Lab, Penn State. “Therefore, it is critical to proactively assess what amino acid changes may likely increase the infectiousness of the virus. Our framework is a powerful tool for determining the impact of amino acid changes in the SARS-CoV-2 spike protein that affect the ability of the virus to bind to ACE2 receptors in humans and multiple animal species.”
The team used a novel, two-step computational procedure to create a model for predicting which changes in amino acids — molecules linked together to form proteins — may occur in the receptor binding domain (RBD) of SARS-CoV-2’s spike protein that could affect its ability to bind to the ACE2 receptors of human and other animal cells.
According to Kuchipudi, the currently circulating variants include one or more mutations that have led to amino-acid changes in the RBD of the spike protein.
“These amino-acid changes may have conferred fitness advantages and increased infectivity through a variety of mechanisms,” he said. “Increased binding affinity of the RBD of the spike protein with the human ACE2 receptor is one such mechanism.”
Kuchipudi explained that the spike protein binding to the ACE2 receptor is the first and crucial step in viral entry to the cell.

One of modern biologists’ most ambitious goals is to learn how to expand or otherwise modify the genetic code of life on Earth, in order to make new, artificial life forms. Part of the motivation for this “synthetic biology” research is to understand more about the evolution and the logic of the natural biology we’ve inherited. But there’s also a very practical motivation: Cells can be used as efficient factories for making a broad array of useful molecules — especially protein-based therapeutics, which account for an increasing share of new medicines. Cells working with an expanded genetic code could make a much more diverse set of such medicines and could do so in a way that greatly simplifies the overall process of developing and manufacturing them.
The realization of the grand goal of a working, useful synthetic biology is still some years off. But in a study published this week in Nature Communications, scientists have taken a significant step closer to it, by developing and demonstrating key components of an expanded genetic code system.
“We’ve supplemented the synthetic biology toolkit to streamline investigations into genetic code expansion,” says study senior author Ahmed Badran, PhD, an assistant professor in the Department of Chemistry at Scripps Research.
The natural genetic code underlying life on Earth is used by cells to translate information contained in DNA and RNA into the amino-acid building blocks of proteins. DNA and RNA molecules are chain-like molecules that encode information using an “alphabet” of four nucleotide building blocks, or “letters.” Molecules called transfer RNAs (tRNAs) decode this information by recognizing three letters at a time, translating each three-letter “codon” into a single amino-acid building block of a protein. This triplet codon system in principle can encode 64 different amino acids (43) — yet typically only 20 amino acids are used in most organisms.
By contrast, the envisioned quadruplet system, based on four-letter codons, could encode 256 (44) distinct amino acids. Obviously, most of those would not exist in natural proteins, although some could be slight variations on natural amino acids, enabling proteins to be made with much more finely tuned characteristics, for example to optimize their effectiveness and safety as medicines.
The enormous challenge here comes from the fact that the system of gene-to-protein translation is a complex one in which multiple components must work together smoothly. The system that exists in living organisms on Earth presumably took many millions of years to evolve to its present levels of accuracy and efficiency. Prior efforts to engineer whole new systems, including quadruplet-codon systems, have shown some promise in recent years.
In the new study, Badran and his team used an evolutionary, survival-of-the-fittest, technique called directed evolution to evolve a small set of tRNAs that in principle could work in a quadruplet system. The scientists showed that these quadruplet tRNAs could be used to translate segments of a protein within bacterial cells. They were able to translate six identical quadruplet codons after one another, and even translate four very different quadruplet codons in the same protein — and could do so at efficiencies that are for the first time within striking distance of what would be needed for a functional quadruplet system.
Badran emphasizes that although a quadruplet code system is still very much in the early, methods-development stage, it should be very useful if it can be made to work — especially in enabling the straightforward synthesis of proteins with “non-canonical” amino acids that aren’t found naturally in proteins. Such ncAAs, as they are called, could be used to give proteins novel biological properties, including the provision of convenient, safe “handles” on a protein — for the placing of chemical modifications to improve the protein’s therapeutic properties, for example, or for the attachment of a toxic “warhead” on a tumor-homing cancer drug.
“One could theoretically program a sequence of DNA that would be translated, in a living cell, into a protein that contains a complex set of modifications — modifications that otherwise would be difficult or impossible to add,” Badran says.
Badran, who joined Scripps Research earlier this year, worked at the Broad Institute of MIT and Harvard during the study.
In addition to Badran, the study, “Multiplex suppression of four quadruplet codons via tRNA directed evolution,” was co-authored by Erika DeBenedictis and Gavriela Carver, of the Broad Institute, and Christina Chung and Dieter Söll of Yale University.
Story Source:
Materials provided by Scripps Research Institute. Note: Content may be edited for style and length.

Blood sugar control has always been important for people with diabetes when it comes to preventing a stroke. But a new study finds for people with diabetes who have a stroke, there may be an ideal target blood sugar range to lower the risk of different types of vascular diseases like a stroke or heart attack later on. The research is published in the September 29, 2021, online issue of Neurology®, the medical journal of the American Academy of Neurology.
“We know that having diabetes may be associated with an increased risk of having a first stroke,” said study author Moon-Ku Han, MD, PhD, of Seoul National University College of Medicine in Korea. “But our results indicate that there is an optimal blood sugar level that may start to minimize the risk of having another stroke, a heart attack or other vascular problems, and it’s right in the 6.8% to 7.0% range.”
The study involved 18,567 people with diabetes with an average age of 70. All participants were admitted to the hospital for an ischemic stroke, which is caused by a blood clot. Upon admission, researchers used a test called the hemoglobin A1C to determine people’s average blood sugar level over the past two to three months. This test measures a percentage of hemoglobin proteins in the blood coated with sugar. A level below 5.7% is considered normal; 6.5% or higher generally indicates diabetes. The participants had an average A1C of 7.5%.
Researchers then followed up one year later to find out if there was an association between A1C levels with the risk of having another stroke, a heart attack, or dying from these or other vascular causes.
Of all participants, 1,437, or about 8%, had a heart attack or died from vascular disease within a year of starting the study, and 954, or 5%, had another stroke.
The study found that people admitted to the hospital with A1C levels above the 6.8% to 7.0% range had an increased risk of having a vascular event like a heart attack, as well as having another stroke.
After adjusting for factors like age and sex, researchers found that people’s risk for a heart attack or similar vascular diseases was 27% greater when they were admitted to the hospital with A1C levels above 7.0%, compared to those admitted with A1C levels below 6.5%. People’s risk for having another stroke was 28% greater when admitted to the hospital with A1C levels above 7.0%, compared to those below 6.5%.
“Our findings highlight the importance of keeping a close eye on your blood sugar if you’re diabetic and have had a stroke,” Han said.
A limitation of the study is that people’s blood sugar levels were measured only at the start of the study; no follow-up levels were available.
Story Source:
Materials provided by American Academy of Neurology. Note: Content may be edited for style and length.

Women and people who menstruate experienced irregularities in their menstrual cycle because of increased stress during the COVID-19 pandemic, a new Northwestern Medicine study has found.
This is the first U.S. study to evaluate the impact of stress on peoples’ periods.
The study surveyed more than 200 women and people who menstruate in the United States between July and August 2020 in order to better understand how stress during the COVID-19 pandemic influenced their menstrual cycles. More than half (54%) of the individuals in the study experienced changes in their menstrual cycle following the start of the COVID-19 pandemic in March 2020.
Individuals who experienced higher levels of stress during the COVID-19 pandemic were more likely to experience heavier menstrual bleeding and a longer duration of their period, compared to individuals with moderate stress levels, the study found.
The study, “Impact of Stress on Menstrual Cyclicity During the COVID-19 Pandemic: A Survey Study,” was published September 28 in the Journal of Women’s Health. It provides a better understanding of how the COVID-19 pandemic has impacted women’s mental and reproductive health, the study authors said.
“We know added stress can negatively impact our overall health and well-being, but for women and people who menstruate, stress can also disrupt normal menstrual cycle patterns and overall reproductive health,” said lead and corresponding author Nicole Woitowich, research assistant professor of medical social sciences at Northwestern University Feinberg School of Medicine.
Prior research has found that menstrual cycle irregularities are often reported by women who experience mood disorders such as anxiety and depression, or by those who are facing acute life stressors such as natural disasters, displacement, famine or defection.
“Given the unprecedented nature of the pandemic and its significant impact on mental health, this data is unsurprising and confirms many anecdotal reports in the popular press and on social media,” Woitowich said.
Since the onset of the pandemic, social media has been one of the major platforms where women and people who menstruate could share questions or concerns about their menstrual cycles. Only recently have these concerns been addressed by the biomedical research community.
“Reproductive health should not be ignored in the context of COVID-19,” Woitowich said. “We are already seeing the ripple effects of what happens when we fail to consider this important facet of women’s health as many are now experiencing menstrual cycle irregularities as a result of the COVID-19 vaccines or COVID-19 infection.”
Other Northwestern co-authors include Dr. Kara Goldman, associate professor of obstetrics and gynecology (reproductive endocrinology and infertility) at Feinberg, and former Feinberg students Noelle Ozimek, Karen Velez, Hannah Anvari and Lauren Butler.
Story Source:
Materials provided by Northwestern University. Original written by Kristin Samuelson. Note: Content may be edited for style and length.

A common mutation in gliomas sensitizes them to immunotherapy, a finding which researchers believe could have broader therapeutic implications for all glioma patients.
A single common genetic mutation, or error, may hold the key to making immunotherapy more effective against gliomas, according to new mouse model findings from the University of Michigan Health Rogel Cancer Center.
The flip of a single amino acid from arginine to histidine in a subset of these brain and nervous system tumors sets off a series of changes that, it turns out, sensitizes them to treatment with immune-stimulating therapy, to which they would otherwise be largely resistant.
Having discovered this sensitivity and mapped the underlying mechanisms, the research team identified a blood growth factor secreted by tumors harboring the mutation — one already used by doctors to stimulate the production of white blood cells and reduce the risk of infection in patients receiving chemotherapy — that holds promise for making treatments against gliomas more effective. The findings appear in Science Advances.
“It’s been known for about a decade that patients with low-grade gliomas that have this IDH1 mutation have a much longer median survival,” said the study’s co-senior author Maria Castro, Ph.D., a professor of neurosurgery and cell and developmental biology at U-M. “We set out to try to understand why, and to see if there were any differences that could be harnessed to improve outcomes more broadly.”
In a mouse model of glioma without the IDH1 mutation, administering G-CSF, the blood growth factor produced by their mutant cousins, more than doubled median survival times. When immunotherapy was also added in, the effect was even more profound, the study found.

Mount Sinai researchers have developed a therapy that shows promise against a deadly pediatric leukemia. The small-molecule therapy was highly effective in fighting a type of acute myeloid leukemia in both in vitro and in vivo experiments, according to research published in Science Translational Medicine in September.
The therapy, named MS67, causes the degradation of the WDR5 protein, which drives the proliferation of acute myeloid leukemia with a specific genetic makeup called mixed lineage leukemia rearrangement. This type of leukemia is more common in children, has very poor response to standard treatments and a dismal prognosis, and until now has confounded researchers.
WDR5 also plays an important role in driving the proliferation of other cancers such as pancreatic cancer, so researchers believe that it is likely that WDR5 small-molecule degraders such as MS67 could also be effective in treating those cancers.
“This study is the first to demonstrate that pharmacological degradation of WDR5, which selectively eliminates the proten, is an effective and superior therapeutic strategy than pharmacological inhibition, or blocking, of WDR5 for the treatment of WDR5-dependent cancers including acute myeloid leukemia with mixed lineage leukemia rearrangement,” said Jian Jin, PhD, the Mount Sinai Professor in Therapeutics Discovery and Director of the Mount Sinai Center for Therapeutics Discovery at the Icahn School of Medicine at Mount Sinai. “In addition, MS67 is the first WDR5 small-molecule degrader that exhibits robust anti-tumor activities in vivo.”
The research team led by Dr. Jin; Greg Wang, PhD, of the University of North Carolina at Chapel Hill; and Aneel Aggarwal, PhD, Professor of Pharmacological Sciences, and Oncological Sciences, at The Tisch Cancer Institute at Mount Sinai, discovered MS67, a novel, highly potent and selective small-molecule degrader of WDR5, which effectively suppressed the growth of this type of acute myeloid leukemia cells derived from patients both in vitro and in vivo, using patient cancer cells in mouse models. Using a battery of biochemical, biophysical, structural, cellular, genomic, and in vivo studies, the research team demonstrated that MS67 is a much superior therapeutic agent than other therapies that inhibit instead of degrade WDR5.
This research was supported in part by the grants R01GM122749, P30CA196521, R01CA211336, R01CA215284, and R35GM131780 from the U.S. National Institutes of Health.

UT Southwestern stem cell scientists find that stringent lineage tracing is crucial for studies of nerve cell regeneration. Their results, which are published in Cell, show that this tracing is far from routine in the field and suggest that earlier studies reporting “striking” regeneration results must be reexamined.
Lineage tracing, which is a fundamental approach in developmental biology, refers to tests used to map out the progeny — or descendants — of a given cell in an organism.
Lineage tracing is also central to the field of stem cell biology, so it was surprising to learn how often such testing had been omitted, the authors write in the newly published study in Cell. The two corresponding authors are Chun-Li Zhang, Ph.D., a Professor of Molecular Biology and a W.W. Caruth, Jr. Scholar in Biomedical Research; and Lei-Lei Wang, Ph.D., an Instructor of Molecular Biology and member of the Zhang lab, which studies nerve cell regeneration in the brain and spinal cord.
“We have from the start employed the most stringent methods to analyze nerve cell regeneration. It was therefore astonishing to read a number of other papers — including some that make phenomenal claims — that failed to do careful analyses,” said Dr. Zhang, a member of the Hamon Center for Regenerative Science and Medicine at UT Southwestern.
After running dozens of experiments using a range of protocols, the researchers identified which specific lineage tracing assays appeared most robust and reliable — the so-called gold standard tests. “We employed the currently available lineage tracing assays. No new ones were developed,” Dr. Zhang said. The scientists also identified tests that were less likely to provide precise results.
The study concludes by listing reliable lineage tracing tests and strongly recommending these assays be used in all laboratories doing nerve cell regeneration research. “The methods we list are straightforward to establish in a laboratory, and we believe they should always be used,” he said.
Dr. Zhang received his Ph.D. in genetics and development from UT Southwestern Medical Center, where he worked on muscle development and heart disease. He conducted postdoctoral research on neural stem cells as a Howard Hughes Medical Institute Fellow of the Life Sciences Research Foundation at the Salk Institute in La Jolla, California.
At UT Southwestern, Dr. Zhang’s laboratory has reported several advances in neural stem cell biology, such as regeneration of the brain and spinal cord in mice following injury. The Scientist recognized his lab’s work on cell fate reprogramming in live animals as one of 2014’s Big Advances in Science. He won a National Institutes of Health Director’s New Innovator Award in 2009.
Using rigorous lineage tracing, the team of Drs. Wang and Zhang reported in 2018 that while attempting to transform a type of brain cell known as a glial cell into a neuron, they instead reprogrammed mature inhibitory neurons into a different type of neuron that produces the neurotransmitter lost in Parkinson’s disease. Their study indicated that the brain’s neurons were more malleable in adulthood than previously thought.
Earlier this year, they reported in Cell Stem Cell that the latent neurogenic potential of glial cells can be leveraged to produce new neurons and lead to functional recovery after spinal cord injury in mice.
UTSW co-authors include: Carolina Serrano Garcia, Xiaoling Zhong, Shuaipeng Ma, and Yuhua Zou.
The Welch Foundation supported the study (I-1724), as did the Decherd Foundation, the Kent Waldrep Foundation Center for Basic Research on Nerve Growth and Regeneration, the Texas Alzheimer’s Research and Care Consortium (TARCC2020), and the NIH (NS099073, NS092616, NS111776, NS117065, and NS088095).

According to 2021 research in the Orthopaedic Journal of Sports Medicine, 35 percent of athletes who have recovered from anterior cruciate ligament (ACL) injuries will re-injure it after returning to their sport.
For Jenna Mesisca, that number is too high.
The fourth-year biomedical engineering undergraduate student has conducted research to better understand the biomechanics of returning to sport after an ACL injury, including better ways to measure landing mechanics to improve clinical recommendations for injured athletes.
Mesisca looks forward to working alongside Queen for two more years, as a senior and in her final year as a master’s student. She is participating in the department’s accelerated undergraduate/graduate degree program, which will enable her to graduate with a master’s degree in biomedical engineering after a fifth year of study.
Mesisca is also part of the first cohort of students in Virginia Tech’s new and unique biomedical engineering degree program. “I have always had an interest in sports rehab and injury prevention, particularly as a club lacrosse player at Virginia Tech and an athlete myself,” Mesisca said. “I was so excited to be part of this first cohort of biomedical engineers – a major that combines my passion for helping injured athletes, my interest in mechanics and medicine, and my knowledge and skills as a science and math student. It couldn’t have worked out better.”
After graduation, Mesisca wants to work in sports rehabilitation. Her dream is to conduct research and apply that to clinical settings to help athletes improve. Whether it is work with devices like knee braces or understanding the biomechanics of movement, like landing from hops, she said she just wants to help others heal and improve.