Cell size regulates molecular separation

New research shows that cell size and membranes may play a key role in regulating the distribution of molecules inside cells. This discovery offers a new unconventional method for manipulating artificial cells via their size and interfacial properties, or their boundaries, instead of through molecular modification of their chemical structure. This could aid multiple industries, from cosmetics to pharmaceuticals, which want to avoid unexpected changes to the properties of artificial cells in their products, such as when creating new medicines like vaccines.
Artificial cells can be little lifesavers, such as the COVID-19 mRNA vaccine. These engineered wonders can be made to mimic the functions of biological cells and perform all sorts of tasks, from “teaching” our own cells how to respond to a virus, growing artificial skin for testing cosmetics, or making food preservatives.
However, creating and manipulating these cells comes with many challenges. “In recent years, artificial cells containing solutions (or mixtures) of multicomponent molecules have been used in cosmetic and pharmaceutical products. Although such solutions did not separate in test tubes, they sometimes separated in artificial cells, which was problematic for applications,” explained Associate Professor Miho Yanagisawa from the Graduate School of Arts and Sciences at the University of Tokyo.
This separation, called liquid-liquid phase separation (LLPS), has emerged as a fundamental mechanism for regulating biological activity in living organisms. However, the type of biomolecules that separate and the conditions under which this occurs is yet to be fully understood. This latest research published in ACS Materials Letters provides some much-needed insight.
“Conventionally, separation conditions and the degree of separation were considered to be size-independent, as long as the size of the container was about 1 micrometer, or micron (one-thousandth of a millimeter), or larger,” said Yanagisawa. However, a surprising finding of this research was that the smaller the artificial cell, the greater the degree to which separation occurred.
The idea of cell size-dependent behavior was suggested in 2012, but the details of this phenomenon remained unclear. The team at the University of Tokyo performed multiscale experiments using different-sized droplets of two polymers — short, polyethylene glycol (PEG) and long, dextran — in blends contained within a lipid membrane to create different-sized artificial cells.
“From such experiments, we realized that the membrane senses slight differences between molecules and selects the preferred molecule, which is the origin of the cell size-dependent behavior. This was the major climax of the study,” explained Yanagisawa. “We believe that this discovery offers a new method of manipulating materials via the space size and interfacial properties of the containers of artificial cells. This idea is quite different from the conventional ones through manipulation of molecular structures.”
So what next? According to Yanagisawa, “There are mainly two directions for the next step: one is toward a physical understanding and formulation of the cell-size space effects on the molecular behaviors; another is toward pharmaceuticals and cosmetics applications, using the artificial cells considering the cell-size effect.”
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Materials provided by University of Tokyo. Note: Content may be edited for style and length.

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Scientists develop new technique to reveal the hidden genome

Using an innovative new technique, scientists at Duke-NUS Medical School and their collaborators have identified thousands of previously unknown DNA sequences in the human genome that code for microproteins and peptides potentially critical to human health and disease.
“Much of what we understand about the known two per cent of the genome that codes for proteins comes from looking for long strands of protein-coding nucleotide sequences, or long open reading frames,” explained computational biologist Dr Sonia Chothani, a research fellow with Duke-NUS’ Cardiovascular and Metabolic Disorders (CVMD) Programme and first author of the study. “Recently, however, scientists have discovered small open reading frames (smORFs) that can also be translated from RNA into small peptides, which have roles in DNA repair, muscle formation and genetic regulation.”
Scientists have been trying to identify smORFs and the small peptides they code for, since disruption in these smORFs can cause disease. However, currently available approaches are very limited.
“Much of the current datasets do not provide information that is detailed enough to identify smORFs in RNA,” added Dr Chothani. “The majority also comes from analyses of immortalised human cells that are propagated — sometimes for decades — to study cell physiology, function and disease. However, these cell lines aren’t always accurate representations of human physiology.”
Publishing in Molecular Cell, Chothani and her colleagues in Singapore, Germany, the UK and Australia describe a methodology they developed to address these issues. They screened currently available ribosome profiling datasets for short strands of RNA with periodic three-base sections, covering more than 60 per cent of the RNA’s length. They then conducted their own RNA sequencing and Ribosome profiling to generate a combined data resource of six types of cells and five types of tissue, such as from the heart and the brain, derived from hundreds of patients.
Analyses of these data identified nearly 8,000 smORFs. Interestingly, they were highly specific to the tissues that they were found in, meaning that these smORFs may perform a function specific to their environment. The team also identified 603 microproteins coded by some of these smORFs.
“The genome is littered with smORFs,” said Assistant Professor Owen Rackham, senior author of the study from the CVMD Programme. “Our comprehensive and spatially resolved map of human smORFs highlights overlooked functional components of the genome, pinpoints new players in health and disease and provides a resource for the scientific community as a platform to accelerate discoveries.”
Professor Patrick Casey, Senior Vice-Dean of Research at Duke-NUS, said, “With the healthcare system evolving to not only treat diseases but also prevent them, identifying potential new targets for disease research and drug development could open avenues to new solutions. This research by Dr Chothani and her team, published as a resource for the scientific community, brings important insights to the field.”
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Health care spending may help explain link between MS and latitude

Researchers have known people who live farther from the equator are more likely to develop multiple sclerosis (MS) and have often attributed that to vitamin D exposure. But countries farther from the equator are also more likely to be wealthier than countries nearer to the equator. A new analysis shows that the amount a country spends on health care may help explain the link between MS and latitude. This new research is published in the August 24, 2022, online issue of Neurology®, the medical journal of the American Academy of Neurology.
According to study author Deanna Saylor, MD, MHS, of Johns Hopkins University School of Medicine in Baltimore and a member of the American Academy of Neurology, the results suggest that MS rates may be greatly underestimated in low-income countries with lower health care spending, which means that people have less access to neurologists who have the expertise to diagnose MS and MRI scanners that are needed to make the diagnosis.
For the analysis, researchers analyzed data from scientific studies and databases to determine current rates of MS in 203 countries and territories. They then grouped these countries into world regions and by income levels.
Rates of MS varied by region and income level. For example, in high-income countries an average of 46 of every 100,000 people had MS, compared to 10 people per 100,000 in low-income countries. Health care spending per capita was $2,805 for high-income countries, compared to $45 in low-income countries.
For each location, researchers examined gross domestic product per capita, current health expenditure per capita, income levels, the availability of brain scans to diagnose MS, the number of neurologists per capita and universal health care. They also reviewed lifestyle factors such as obesity and tobacco use.
Once the researchers adjusted the data for other factors that could affect the risk of MS, such as age and sex, they found that health care spending and latitude were strongly associated with MS rates. The research showed that, with every increase of one standard deviation in health expenditure per capita, a country’s MS prevalence increased by 0.49. Alternatively, with every increase of one standard deviation in latitude, a country’s MS prevalence increased by 0.65.

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NIH experts review monkeypox challenges

Lessons learned from the public health responses to the HIV and COVID-19 pandemics should help guide the response to the current outbreak of monkeypox, National Institutes of Health experts write in an editorial published today in the New England Journal of Medicine.
Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), and H. Clifford Lane, M.D., NIAID deputy director for clinical research and special projects, discuss a published case series (JP Thornhill et al.) detailing the symptoms and outcomes of 528 people with monkeypox from 16 countries in five continents.
The authors note that the epidemiologic pattern of the multi-continent outbreak of monkeypox resembles that of the early cases of AIDS in that most cases are among men who have sex with men. They caution, however, that it should not be assumed that cases of monkeypox will remain confined to this population. Monkeypox virus has been known to spread from direct lesion-to-skin contact — in prior outbreaks, such spread was often from an infected child to a caregiver. Data suggest that sexual transmission likely plays a role in the current outbreak, the authors note. They call for detailed observational studies, serosurveys and ongoing surveillance to learn more about the epidemiology of the current outbreak.
Drs. Fauci and Lane also compare monkeypox, HIV/AIDS and COVID-19 regarding the causes of each disease and the countermeasures available to fight them. Fortunately, diagnostics, vaccines and treatments for monkeypox already exist. A challenge for the public health and research communities is ensuring equitable, efficient distribution of these existing countermeasures while simultaneously conducting rigorous clinical research to gather more data on their safety and optimal use, they conclude.
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A new kind of chemo

Chemotherapy sucks. The treatments generally have awful side effects, and it’s no secret that the drugs involved are often toxic to the patient as well as their cancer. The idea is that, since cancers grow so quickly, chemotherapy will kill off the disease before its side effects kill the patient. That’s why scientists and doctors are constantly searching for more effective therapies.
A team led by researchers at UC Santa Barbara, and including collaborators from UC San Francisco and Baylor College of Medicine, has identified two compounds that are more potent and less toxic than current leukemia therapies. The molecules work in a different way than standard cancer treatments and could form the basis of an entirely new class of drugs. What’s more, the compounds are already used for treating other diseases, which drastically cuts the amount of red tape involved in tailoring them toward leukemia or even prescribing them off-label. The findings appear in the Journal of Medicinal Chemistry.
“Our work on an enzyme that is mutated in leukemia patients has led to the discovery of an entirely new way of regulating this enzyme, as well as new molecules that are more effective and less toxic to human cells,” said UC Santa Barbara Distinguished Professor Norbert Reich, the study’s corresponding author.
The epigenome
All cells in your body contain the same DNA, or genome, but each one uses a different part of this blueprint based on what type of cell it is. This enables different cells to carry out their specialized functions while still using the same instruction manual; essentially, they just use different parts of the manual. The epigenome tells cells how to use these instructions. For instance, chemical markers determine which parts get read, dictating a cell’s actual fate.
A cell’s epigenome is copied and preserved by an enzyme (a type of protein) called DNMT1. This enzyme ensures, for example, that a dividing liver cell turns into two liver cells and not a brain cell.

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Physical activity may have a stronger role than genes in longevity

Previous research has shown that low physical activity and greater time spent sitting are associated with a higher risk of death. Does risk change if a person is genetically predisposed to live a long life?
That is the question researchers at the Herbert Wertheim School of Public Health and Human Longevity Science at University of California San Diego set out to answer in a study published in the August 24, 2022 online edition of the Journal of Aging and Physical Activity.
“The goal of this research was to understand whether associations between physical activity and sedentary time with death varied based on different levels of genetic predisposition for longevity,” said lead author Alexander Posis, M.P.H., a fourth-year doctoral student in the San Diego State University/UC San Diego Joint Doctoral Program in Public Health.
In 2012, as part of the Women’s Health Initiative Objective Physical Activity and Cardiovascular Health study (OPACH), researchers began measuring the physical activity of 5,446 women in the United States who were 63 and older, following them through 2020 to determine mortality. Participants wore a research-grade accelerometer for up to seven days to measure how much time they spent moving, the intensity of physical activity, and sedentary time.
The prospective study found that higher levels of light physical activity and moderate-to-vigorous physical activity were associated with lower risk of death. Higher sedentary time was associated with higher risk of mortality. These associations were consistent among women who had different levels of genetic predisposition for longevity.
“Our study showed that, even if you aren’t likely to live long based on your genes, you can still extend your lifespan by engaging in positive lifestyle behaviors such as regular exercise and sitting less,” said senior author Aladdin H. Shadyab, Ph.D., assistant professor at the Herbert Wertheim School of Public Health and Human Longevity Science at UC San Diego. “Conversely, even if your genes predispose you to a long life, remaining physically active is still important to achieve longevity.”
Given the aging adult population in the United States, and longer time spent engaging in lower intensity activities, the study findings support recommendations that older women should participate in physical activity of any intensity to reduce the risk of disease and premature death, wrote the authors.
The OPACH Study is funded by the National Heart, Lung, and Blood Institute (RO1 HL105065). Funding also came from the National Institute on Aging (P01 AG052352) and a T32 Predoctoral Training Fellowship (T32 AG058529). The Women’s Health Initiative was funded by the National Heart, Lung, and Blood Institute (75N92021-D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004, 75N92021D00005).
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Materials provided by University of California – San Diego. Original written by Yadira Galindo. Note: Content may be edited for style and length.

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Socioeconomic and health risk profiles among mothers of young children predicts risk of food insecurity, study finds

A new study identified multiple risk factors, including high utility bills, employment hardship, and medical hardship, that may lead to food insecurity among mothers of young children, according to researchers at UTHealth Houston.
Food security is the measure of the availability of food to an individual, or family, and their ability to access it. The study was published today in PLOS ONE.
Using what is known as the latent class analysis method, which created profiles of families to help predict who would be at risk for food insecurity, investigators determined five class profiles: high utility and medical hardship (Class 1); high housing and employment hardship, high substance use, and incarceration (Class 2); high housing and medical hardship, poor health, and health care (Class 3); high employment hardship and low income (Class 4); and low-risk (Class 5).
“What these profiles show is it’s not a one-and-done deal,” said Daphne Hernandez, PhD, associate professor at Cizik School of Nursing and corresponding author on the study.
“We were seeing that some people were having food insecurity concerns because they had medical hardships and housing hardships,” said Hernandez, the Lee and Joseph Jamail Distinguished Professor in the School of Nursing. “Sometimes people think if you’re unemployed, you’re at risk. Well, there’s other forms of hardship that result from the unemployment, such as not being able to pay your medical bills, not able to pay your electricity and gas bills, that put you at risk for food insecurity.”
While pediatrician offices do a two-item screener to see if families are at risk or experiencing food insecurity or food hardships, identifying these additional risks can help clinicians identify food insecurity, according to the researchers.
“Not every family looks the same,” Hernandez said. “So, these risk profiles could help pediatricians identify families that are at risk for food insecurity that may have been more reluctant to answer those questions for fear that their child will be taken away because they’re admitting that they’re not able to feed their child.”
Additional researchers include first author Sajeevika Saumali Daundasekara, PhD, former researcher at Cizik School of Nursing; and Brittany R. Schuler, PhD, with Temple University’s School of Social Work.
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Materials provided by University of Texas Health Science Center at Houston. Original written by Halle Jones. Note: Content may be edited for style and length.

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Nanoelectronic sensor simultaneously measures electrical and mechanical activity in heart cells

Using a suspended nanowire, a University of Massachusetts research team has, for the first time, created a tiny sensor that can simultaneously measure electrical and mechanical cellular responses in cardiac tissue, work promising for cardiac disease studies, drug testing and regenerative medicine.
Electrical and computer engineering (ECE) Ph.D. student Hongyan Gao, first author of the paper published online by the journal Science Advances, describes the invention as “a new tool for improved cardiac studies that has the potential for leading-edge applications in cardiac-disease experiments.”
Because the cell is a basic functional element in biology, its mechanical and electrical behaviors are two key properties that indicate cell state and consequently are important for health monitoring, disease diagnosis and tissue repair.
“A comprehensive assessment of cellular status requires knowledge of both mechanical and electrical properties at the same time,” says research team leader Jun Yao, ECE assistant professor and a biomedical engineering adjunct. These two properties are usually measured by different sensors, and the degree to which the cell’s function is disturbed increases with the number of sensors used.
The sensor is constructed from a 3D suspended semiconducting silicon nanowire. With its size much smaller than a single cell, the nanowire can tightly patch onto the cell membrane and “listen to” cellular activities very closely. It also has unique properties to convert “heard” bioelectrical and biomechanical activities into electrical sensing signals for detection.
The research accomplishes goals proposed in a five-year, $500,000 grant from the National Science Foundation’s Faculty Early Career Development (CAREER) program that Yao received in 2019.
“Other than developing integrated biochips, our next step is to integrate the nanosensors on free-standing scaffolds to innervate in vitro tissue for deep-tissue studies,” Yao says. “In the long run, we hope the nanosensors can be safely delivered to living cardiac systems for improved health monitoring and early disease diagnosis.”
The concept of merging multiple sensing functions in one device will also broaden the capabilities of general bio-interface engineering, Yao says.
Yubing Sun and Xian Du, assistant professors of mechanical and industrial engineering, also contributed to the work. Yao, Sun and Du are all affiliated with the Institute for Applied Life Sciences at UMass Amherst, which combines deep and interdisciplinary expertise from 29 departments on campus to translate fundamental research into innovations that benefit humankind.
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Twitter shows lower-to-middle income countries have higher unemployment post pandemic

Lower-to-middle-income countries still struggle with high unemployment rates after COVID-19 lockdowns and economic restrictions, unlike higher-income countries such as Canada, finds a new study led by York University with the University of Witwatersrand in Johannesburg.
This is opposite from the 2008-2009 global economic crisis when higher-income countries suffered more from the recession than lower-income countries.
The study used Twitter sentiments to help compare macroeconomic factors including unemployment and inflation across Nigeria, South Africa and Canada representing lower-middle, upper-middle and high-income countries respectively.
They found the unemployment rate increased for all three countries at the beginning of the pandemic, however, Canada was able to control the rate after the first couple of months unlike Nigeria and South Africa, where they continue to struggle with high unemployment.
“This indicates how vulnerable lower-middle income countries are to lockdowns and economic limitations, bearing a greater loss during the COVID-19 pandemic than higher income countries,” says York University Assistant Professor Jude Kong, the study’s corresponding author and director of the Africa-Canada AI & Data Innovation Consortium (ACADIC).
Before COVID-19, lockdowns and economic restrictions, Nigeria’s unemployment rate was lower than South Africa’s, while the inflation rate of South Africa was lower than Nigeria. During the pandemic, however, unemployment and inflation rates in Nigeria have increased more than Canada and South Africa.

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Psychedelics may lessen fear of death and dying, similar to feelings reported by those who've had near death experiences

In a survey study of more than 3,000 adults, Johns Hopkins Medicine researchers compared psychedelic experiences with near-death experiences that were not drug related and found notable similarities in people’s attitudes toward death. Survey participants in both groups reported having less fear of death and dying after the experience. They also reported that the experience had a lasting positive effect, providing personal meaning, spiritual significance and psychological insight.
The study was published Aug. 24, 2022 in the journal PLOS ONE.
The results are consistent with several recent clinical trials showing that a single treatment with the psychedelic psilocybin produced sustained decreases in anxiety and depression among patients with a life-threatening cancer diagnosis. The largest of these trials (Griffiths et al., 2016) was conducted at Johns Hopkins Medicine by the authors of this survey. That study, a randomized trial of 51 patients with cancer who had clinically significant anxiety or depressive symptoms, demonstrated that receiving a controlled, high dose of psilocybin given with supportive psychotherapy resulted in significant increases in ratings of death acceptance, as well as decreases in anxiety about death.
For the present study, the researchers analyzed data gathered from 3,192 people who answered an online survey between December 2015 and April 2018. Participants were divided into groups: 933 individuals had non-drug-related near-death experiences, and the rest of the participants had psychedelic experiences, which were prompted by either lysergic acid diethylamide (LSD) (904), psilocybin (766), ayahuasca (282) or N,N-dimethyltryptamine (DMT) (307). Participants were predominantly white (85%) and mostly from the United States. Compared with the non-drug group, there were more men in the psychedelic group (78% versus 32%), and they tended to be younger (32 versus 55 years of age) at the time of the experience.
Similarities between the groups include: About 90% of participants in both groups reported a decrease in fear of death when considering changes in their views from before to after the experience. Most participants in both groups (non-drug group, 85%; psychedelics group, 75%) rated the experience to be among the top five most personally meaningful and spiritually significant of their life. Participants in both groups reported moderate to strong persisting positive changes in personal well-being and life purpose and meaning.Differences between the groups include: The non-drug group was more likely to report that their life was in danger (47% versus the psychedelics group, 3%), being medically unconscious (36% versus the psychedelics group, 10%), or being clinically dead (21% versus the psychedelics group, less than 1%). The non-drug group was more likely to report that their experience was very brief, lasting five minutes or less (40% versus the psychedelics group, 7%).The researchers say that future studies are needed to better understand the potential clinical use of psychedelics in ameliorating suffering related to fear of death.
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