Publisher Health

A new study from the University of Missouri School of Medicine is the first evidence in humans that short-term lifestyle changes can disrupt the response to insulin of blood vessels. It’s also the first study to show men and women react differently to these changes.
Vascular insulin resistance is a feature of obesity and type 2 diabetes that contributes to vascular disease. Researchers examined vascular insulin resistance in 36 young and healthy men and women by exposing them to 10 days of reduced physical activity, cutting their step count from 10,000 to 5,000 steps per day. The participants also increased their sugary beverage intake to six cans of soda per day.
“We know that incidence of insulin resistance and cardiovascular disease is lower in premenopausal women compared to men, but we wanted to see how men and women reacted to reduced physical activity and increased sugar in their diet over a short period of time,” said Camila Manrique-Acevedo, MD, associate professor of medicine.
The results showed that only in men did the sedentary lifestyle and high sugar intake cause decreased insulin-stimulated leg blood flow and a drop in a protein called adropin, which regulates insulin sensitivity and is an important biomarker for cardiovascular disease.
“These findings underscore a sex-related difference in the development of vascular insulin resistance induced by adopting a lifestyle high in sugar and low on exercise,” said Manrique-Acevedo. “To our knowledge, this is the first evidence in humans that vascular insulin resistance can be provoked by short-term adverse lifestyle changes, and it’s the first documentation of sex-related differences in the development of vascular insulin resistance in association with changes in adropin levels.”
Manrique-Acevedo said she would next like to examine how long it takes to reverse these vascular and metabolic changes and more fully assess the impact of the role of sex in the development of vascular insulin resistance.
The entire MU research team consisted of Jaume Padilla, PhD, associate professor of nutrition and exercise physiology and co-corresponding author of this work; Luis Martinez-Lemus, DVM, PhD, professor of medical pharmacology and physiology, and R. Scott Rector, PhD, associate professor of nutrition. It also included postdoctoral fellows Rogerio Soares, PhD; and graduate students James A. Smith and Thomas Jurrissen.
Their study, “Young women are protected against vascular insulin resistance induced by adoption of an obesogenic lifestyle,” was recently published in the journal Endocrinology. Part of the support for this study was provided by the National Institutes of Health and a VA Merit Grant. The content does not necessarily represent the official views of the funding agency. The authors declare no potential conflicts of interest.
Manrique-Acevedo and her collaborators work from the Roy Blunt NextGen Precision Health building at MU, which anchors the statewide initiative to unite government and industry leaders with innovators from across the system’s four research universities in pursuit of life-changing precision health advancements. The University of Missouri System’s bold NextGen initiative highlights the promise of personalized health care and the impact of large-scale interdisciplinary collaboration.
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It’s impossible to hide from a female mosquito — she will hunt down any member of the human species by tracking our CO2 exhalations, body heat, and body odor. But some of us are distinct “mosquito magnets” who get more than our fair share of bites. Blood type, blood sugar level, consuming garlic or bananas, being a woman, and being a child are all popular theories for why someone might be a preferred snack. Yet for most of them, there is little credible data, says Leslie Vosshall, head of Rockefeller’s Laboratory of Neurogenetics and Behavior.
This is why Vosshall and Maria Elena De Obaldia, a former postdoc in her lab, set out to explore the leading theory to explain varying mosquito appeal: individual odor variations connected to skin microbiota. They recently demonstrated through a study that fatty acids emanating from the skin may create a heady perfume that mosquitoes can’t resist. They published their results in Cell.
“There’s a very, very strong association between having large quantities of these fatty acids on your skin and being a mosquito magnet,” says Vosshall, the Robin Chemers Neustein Professor at The Rockefeller University and Chief Scientific Officer of the Howard Hughes Medical Institute.
A tournament no one wants to win
In the three-year study, eight participants were asked to wear nylon stockings over their forearms for six hours a day. They repeated this process on multiple days. Over the next few years, the researchers tested the nylons against each other in all possible pairings through a round-robin style “tournament.” They used a two-choice olfactometer assay that De Obaldia built, consisting of a plexiglass chamber divided into two tubes, each ending in a box that held a stocking. They placed Aedes Aegypti mosquitoes — the primary vector species for Zika, dengue, yellow fever, and chikungunya — in the main chamber and observed as the insects flew down the tubes towards one nylon or the other.
By far the most compelling target for Aedes aegypti was Subject 33, who was four times more attractive to the mosquitoes than the next most-attractive study participant, and an astonishing 100 times more appealing than the least attractive, Subject 19.

America was unprepared for the magnitude of the pandemic, which overwhelmed many counties and filled some hospitals to capacity. A new paper in PNAS suggests there may have been a mathematical method, of sorts, to the madness of those early COVID days.
The study tests a model that closely matches the patterns of case counts and deaths reported, county by county, across the United States between April 2020 and June 2021. The model suggests that unprecedented COVID spikes could, even now, overwhelm local jurisdictions.
“Our best estimate, based on the data, is that the numbers of cases and deaths per county have infinite variance, which means that a county could get hit with a tremendous number of cases or deaths,” says Rockefeller’s Joel Cohen. “We cannot reasonably anticipate that any county will have the resources to cope with extremely large, rare events, so it is crucial that counties — as well as states and even countries — develop plans, ahead of time, to share resources.”
Predicting 99 percent of a pandemic
Ecologists might have guessed that the spread of COVID cases and deaths would at least roughly conform to Taylor’s Law, a formula that relates a population’s mean to its variance (a measure of the scatter around the average). From how crop yields fluctuate, to the frequency of tornado outbreaks, to how cancer cells multiply, Taylor’s Law forms the backbone of many statistical models that experts use to describe thousands of species, including humans.
But when Cohen began looking into whether Taylor’s Law could also describe the grim COVID statistics provided by The New York Times, he ran into a surprise.

Inside the leading edge of a crawling cell, intricate networks of rod-like actin filaments extend toward the cell membrane at various angles, lengthening protein by protein. Upon impact, the crisscrossing rods glance off the membrane and bend as the collective force of myriad filaments pushes the cell forward.
How flexible these filaments are, and how effectively they recruit essential regulatory proteins to their cause, depends on the properties of the individual actin proteins composing them. Now, a new study in Nature provides high-resolution structures showing how two key biochemical states of actin work jointly with bending forces to determine how actin can interact with other proteins.
“When you add force to the mix, you see substantial changes,” says Rockefeller’s Gregory Alushin. “We provide clear evidence that these biochemical changes in actin are only readable through the mechanical properties of the filaments.”
Revisiting protein control
Actin filaments are long polymers of actin proteins, linked end to end. Actin proteins within a filament can exist in one of two important biochemical states. Actin newly added to the polymer contains a phosphate molecule and aged actin does not; otherwise, the two states are more or less identical. But actin-binding proteins can tell them apart, and they will bind or ignore a filament based on the state of its actin.
How actin-binding proteins distinguish between these states is a long-standing mystery. Some have proposed that phosphate somehow changes the shape of actin, allowing actin-binding proteins to pick it out of the crowd in vivo. Indeed, many enzymes can switch between shapes when other molecules latch onto them, in a process known as allosteric regulation. It made some sense to assume that actin would be no different.

Researchers at the University of Amsterdam have developed a novel approach to infrared spectroscopy that enables simultaneous characterization of molecular structure and size. Called Infrared Diffusion-Ordered Spectroscopy (IR-DOSY), the method nicely separates molecules with different sizes into distinct sets of IR peaks. Reporting on IR-DOSY in a paper that has just been accepted by Angewandte Chemie, the researchers foresee analytical applications in fields as diverse as proteins, polymers, pharmaceuticals and biomedicine. They are currently developing a first version of a practical chemical probe implementing the IR-DOSY concept.
Infrared (IR) spectroscopy is an important workhorse in the analysis of chemical compounds. It helps to identify molecules based on their functional groups and spatial conformation. In general, IR spectroscopy is not sensitive to the size of the molecules. Inspired by an already existing approach in NMR spectroscopy, the Amsterdam researchers now applied the principle of diffusion ordered spectroscopy to IR. Here, the molecules present in a sample are separated based on their diffusion behaviour prior to spectral analysis. IR-DOSY relies on the fact that the diffusion of a molecule is determined completely by its size — a concept that was first established by Albert Einstein in his 1905 classic paper on the brownian motion of microscopic particles.
The IR-DOSY spectrometer creates a spatially inhomogeneous distribution of solute molecules using a simple yet effective flow method that transports both the mixture and pure solvent into a sample chamber. After the stopping the flow, the solute molecules start to diffuse into the pure solvent region, at a rate that depends on their diffusion coefficient. The infrared absorption is measured at a position in the chamber where there was initially only solvent. As time progresses, the diffusing solute molecules start appearing in the IR beam. In this way, for all type of molecules the individual IR spectra are recorded at different moments in time, depending on their sizes. IR-DOSY thus produces a two-dimensional spectrum with the IR frequency along one axis and the diffusion constant (or equivalently, the size) along the other axis.
Proteins, polymers and nanoparticles
In their Angewandte paper, the researchers argue that although the separating power of IR-DOSY is less than that of typical chromatographic methods, it has the advantage that no prior knowledge is required of the chemical structure of the compounds present in the sample. The separating power might even be increased by adding an electrophoresis device to actively separate the species in the sample solution.
Among the applications presented in the paper is the analysis of protein aggregates and fibrils. Here, IR-DOSY makes it possible to simultaneously investigate monomers, oligomers, and fibrils, which typically coexist in a sample. Polymers and plastic nanoparticles constitute another interesting field of research since samples usually contain many different molecules of many sizes. The size-selectivity and structure-sensitivity could also render IR-DOSY useful in the pharmaceutical and biomedical domains. For instance it has potential to detect trace amounts of small molecules present in pharmaceutical products.
In the biomedical context, it could for instance be used to detect and structurally characterize low-molecular weight species in human blood serum. In all cases, the IR-DOSY analysis provides valuable information about the size or size distribution of the molecules or molecular aggregates in a sample.
A practical probe
The IR-DOSY method was developed in a joint effort of the university’s Institute of Physics and the Van ‘t Hoff Institute for Molecular Sciences. At the latter, Prof. Sander Woutersen and Dr Giulia Giubertoni, in collaboration with Dr Saer Samanipour, are now further developing the method into a cost-effective device that can be used by researchers from different disciplines in any laboratory as an analytical or diagnostic tool. For this they were recently awarded a € 160,000 euro ‘Demonstrator Grant’ by the Dutch Research Council NWO. Development of the probe is a joint effort in cooperation with the university’s Technology Centre, the technology transfer office IXA, and Demonstrator Lab Science Park.
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On average, students experience an estimated total of 102 alcohol-related consequences, such as blacking out, being hung over, or missing work or school, due to drinking across their four years in college, according to a new study led by Penn State. The research also revealed that students who think their parents disapprove of the consequences of drinking are likely to experience fewer negative consequences from drinking during college.
“We often think of peers as having an influence on drinking behaviors, but we found that parents can make a difference, even after their child has left home,” said Kimberly Mallett, research professor at the Edna Bennett Pierce Prevention Center and a clinical psychologist.
The research team surveyed students at a large, public northeastern U.S. university about how many alcohol-related consequences they experienced and which predictors resulted in higher rates of consequences. Although the work was conducted at a single university, the researchers said the findings likely apply to students at all colleges and universities. The findings are published in the journal Addictive Behaviors.
The team followed 1,700 students for four years, surveying them twice a year. The surveys included questions to determine the amount of alcohol students were drinking, as well as the total number of alcohol-related consequences students experienced across all four years of college, as well as questions about why people experience consequences and how they view them.
Specifically, the surveys assessed the prevalence of 21 possible consequences from drinking and focused on whether they thought their parents would disapprove of 12 of those consequences, including blacking out, being hung over, or missing work or school due to drinking, said Shannon Glenn, Penn State doctoral candidate in biobehavioral health and the paper’s lead author.
The team found that the average number of alcohol-related consequences per student over the four-year period was 102. The amount of alcohol students drank impacted the total number of consequences they experienced. As drinking increased, so did consequences, Glenn said.

Patient-derived parathyroid organoids (PTOs) could pave the way for future physiology studies and drug-screening applications, as shown in a study published on October 27 in the journal Stem Cell Reports.
“We are the first group in the world that was able to isolate parathyroid stem cells and maintain these cells in our lab as organoids for an extended period of time,” says co-senior study author Schelto Kruijff of the University Medical Center Groningen. “Our research introduces the PTO as a new model for research on parathyroid diseases.”
Parathyroid diseases are characterized by alterations in the excretion of parathyroid hormone, leading to abnormal blood calcium concentrations. The development of parathyroid-targeted treatments and imaging tracers could benefit from in vitro models. Organoids are 3D structures that closely recapitulate tissue architecture and cellular composition and are developed from stem cells. These models have proven very useful for studying tumor behavior and assessing drug responses and have provided a platform for long-term in vitro experimentation.
“We have shown that the parathyroid gland contains stem cells that are able to produce organoids. These organoids mimic the patient condition, are able to produce hormone, express specific markers, and show comparable reactions to drugs,” says Kruijff.
In this study, Kruijff and co-senior study author Rob Coppes of the University Medical Center Groningen set out to establish a patient-derived PTO model representing human parathyroid tissue. The researchers obtained human benign hyperplastic parathyroid tissue from patients undergoing parathyroid surgery. They isolated parathyroid stem cells from the tissue and examined their potential to expand and form PTOs.
The PTOs resembled the original tissue on both gene and protein expression levels and functionality. Additional results demonstrated increased and decreased hormone secretion in response to changes in calcium concentration and parathyroid hormone-lowering drugs. Moreover, the researchers found specific parathyroid-targeted tracer uptake in the PTOs. Taken together, the results demonstrate that these organoids could model human parathyroid functionality.
One study limitation was the absence of the original microenvironment, including blood vessels and fluctuating concentrations of extracellular signals. Nonetheless, the functional testing and tracer experiment showed that the PTOs are a highly suitable model that resembles functional parathyroid tissue.
In future studies, the researchers are planning to transplant these organoids in rats with hypoparathyroidism to study their function in a living animal model. “These organoids can be used to test future parathyroid-targeted drugs and imaging tracers. When using organoids, less animal testing needs to be performed,” Kruijff says. “Also, this technique could be used to try to culture healthy parathyroid gland organoids in order to treat patients with hypoparathyroidism.”
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Researchers at the Broad Institute of MIT and Harvard and the McGovern Institute for Brain Research at MIT have developed a system that can detect a particular RNA sequence in live cells and produce a protein of interest in response. Using the technology, the team showed how they could identify specific cell types, detect and measure changes in the expression of individual genes, track transcriptional states, and control the production of proteins encoded by synthetic mRNA.
The platform, called Reprogrammable ADAR Sensors, or RADARS, even allowed the team to target and kill a specific cell type. The team said RADARS could one day help researchers detect and selectively kill tumor cells, or edit the genome in specific cells. The study appears today in Nature Biotechnology and was led by co-first authors Kaiyi Jiang (MIT), Jeremy Koob (Broad), Xi Chen (Broad), Rohan Krajeski (MIT), and Yifan Zhang (Broad).
“One of the revolutions in genomics has been the ability to sequence the transcriptomes of cells,” said Fei Chen, a core institute member at the Broad, Merkin Fellow, assistant professor at Harvard University, and co-corresponding author on the study. “That has really allowed us to learn about cell types and states. But, often, we haven’t been able to manipulate those cells specifically. RADARS is a big step in that direction.”
“Right now, the tools that we have to leverage cell markers are hard to develop and engineer,” added Omar Abudayyeh, a McGovern Institute Fellow and co-corresponding author on the study. “We really wanted to make a programmable way of sensing and responding to a cell state.”
Jonathan Gootenberg, who is also a McGovern Institute Fellow and co-corresponding author, says that their team was eager to build a tool to take advantage of all the data provided by single-cell RNA sequencing, which has revealed a vast array of cell types and cell states in the body.
“We wanted to ask how we could manipulate cellular identities in a way that was as easy as editing the genome with CRISPR,” he said. “And we’re excited to see what the field does with it.”
Repurposing RNA editing

Nanoparticles, or tiny molecules that can deliver a payload of drug treatments and other agents, show great promise for treating cancers. Scientists can build them in various shapes with different materials, often as porous, crystal-like structures formed by a lattice of metal and organic compounds, or as capsules that enclose their contents inside a shell. When injected into a tumor, these particles can release treatments that attack cancer cells directly or complement other treatments like immunotherapy and radiation.
In a collaborative effort by cancer specialists and chemists, researchers at the University of Chicago have formulated an advanced type of nanoparticle that carries a compound derived from bacteria to target a potent immune system pathway called STING. The particles disrupt the tumor’s blood vessel structure and stimulate an immune response. This approach also helps overcome resistance to immunotherapy treatments in certain pancreatic tumors and boosts response to radiation therapy in glioma as well.
“This was an unusual collaboration between medicine and inorganic chemistry to solve this unmet need of treating tumors that are intractable to conventional therapy,” said Ralph Weichselbaum, MD, the Daniel K. Ludwig Distinguished Service Professor and Chair of Radiation and Cellular Oncology at UChicago. “We were able to deliver an immune stimulant that has anti-tumor activity on its own, and enabled radiation and immunotherapy to cure these tumors.”
The study, “Zinc cyclic di-AMP nanoparticles target and suppress tumours via endothelial STING activation and tumour-associated macrophage reinvigoration,” was published in Nature Nanotechnology on October 26, 2022.
Cold, hot, and hotter tumors
As always with cancer, some tumors prove resistant to even the most high-tech of treatments. Immunotherapy unleashes the body’s immune system to find and destroy cancer cells, but the tumors must be “hot” or inflamed for these treatments to be effective. So called “cold” tumors that aren’t inflamed can hide from the immune system but continue to grow and metastasize.

A global study, co-led by University of Galway, into causes of stroke has found that high and moderate alcohol consumption was associated with increased odds of stroke.
The study also found that there was no link between low level drinking and stroke.
The INTERSTROKE research looked at the alcohol consumption of almost 26,000 people worldwide, of which one quarter were current drinkers, and two-thirds were teetotal.
The study involved people from a range of ethnic backgrounds in 27 countries, including Ireland and the UK.
The findings have been published in Neurology, the most read and highly-cited neurology journal.
Professor Martin O’Donnell, Professor of Neurovascular Medicine at University of Galway and Consultant Stroke Physician at Galway University Hospitals, co-led the international INTERSTROKE study in partnership with Professor Salim Yusuf from the Population Health Research Institute at McMaster University, Canada.