Publisher Health

Researchers at the RIKEN Center for Sustainable Research Science (CSRS) and the University of Toronto have discovered a new way to attack fungal infections. The key is to block fungi from being able to make fatty acids, the major component of fats. Resistance to anti-fungal drugs is increasing and this new approach will be particularly useful because it works in a new way and affects a broad range of fungal species. The study was published in the scientific journal Cell Chemical Biology.
Most of us are familiar with athlete’s foot, a relatively harmless health issue that can be solved by a trip to the drug store. But other fungal infections are more serious, and the Candida, Cryptococcus, and Aspergillus types of fungus are responsible for millions of deaths every year. Like bacterial resistance to antibiotics, fungal resistance to medications is also growing worldwide, and the death toll will likely rise in the near future unless something is done now.
Currently there are only three major classes of anti-fungal medications, and all of them work by destroying the barrier that surrounds fungal cells. Paradoxically, even though they all attack the barrier, current treatments are actually very specific, meaning that what kills one species of fungus might not kill another.
The group of researchers wanted to find another way to combat harmful fungi, one that would be useful against numerous species. Their approach was to first screen the structurally-diverse RIKEN natural product depository (NPDepo) against four pathogenic yeasts — three Candida and one Cryptococcus species — which have been identified as critical human pathogens by the World Health Organization. They were looking for something that would affect all four species, which would indicate that it might be effective against a broad range of fungi.
The screening identified several compounds that reduced fungal growth by at least 50% in each of the four species, and after eliminating ones which were already known, the researchers were left with three new possibilities. Among these three, the one least toxic to human cells also reduced growth of Aspergillus fumigatus, an extremely common fungal mold that is deadly to immuno-compromised individuals. The name given to this compound in the RIKEN NPDepo is NPD6433. The next step was to find out what it does.
For almost 1000 different genes, the researchers looked at how much NPD6433 suppressed growth in yeast when the yeast was missing one copy of the gene. They found that reduction in only one gene, fatty acid synthase, made yeast more susceptible to NPD6433. This result meant that NPD6433 likely works by inhibiting fatty acid synthase and thus prevents fatty acids from being made inside fungal cells. Further experiments showed that NPD6433 and cerulenin, another fatty acid synthase inhibitor, were able to kill numerous yeast species in culture.
The final experiment tested how well NPD6433 treatment worked in a live laboratory model organism — the worm Caenorhabditis elegans — which was infected with a pathogenic yeast that can cause systemic infection in humans after invading through the intestines. C. elegans was chosen because it has an intestinal tract that works like ours. Tests showed that treating infected worms with NPD6433 reduced fatalities by about 50%. Importantly, this was true in worms infected with yeast that were resistant to a standard anti-fungal medication.
“Drug-resistant fungi are a growing problem, and leads for the development of new drugs offer hope against these evolving pathogens,” says Yoko Yashiroda, lead RIKEN CSRS author of the study. “Our research indicates that targeting fatty acid synthesis is a promising alternative therapeutic strategy for fungal infections, and one which might not require tailor-made solutions for individual species.”

People with type-II diabetes who drank the fermented tea drink kombucha for four weeks had lower fasting blood glucose levels compared to when they consumed a similar-tasting placebo beverage, according to results from a clinical trial conducted by researchers at Georgetown University’s School of Health, the University of Nebraska-Lincoln and MedStar Health. This finding, from a pilot 12-person feasibility trial, points to the potential for a dietary intervention that could help lower blood sugar levels in people with diabetes and also establishes the basis for a larger trial to confirm and expand upon these results.
This finding was reported in Frontiers in Nutrition on August 1, 2023.
Kombucha is a tea fermented with bacteria and yeasts and was consumed as early as 200 B.C. in China, but it did not become popular in the U.S. until the 1990s. Its popularity has been bolstered by anecdotal claims of improved immunity and energy and reductions in food cravings and inflammation, but proof of these benefits has been limited.
“Some laboratory and rodent studies of kombucha have shown promise and one small study in people without diabetes showed kombucha lowered blood sugar, but to our knowledge this is the first clinical trial examining effects of kombucha in people with diabetes,” says study author Dan Merenstein, M.D., professor of Human Sciences in Georgetown’s School of Health and professor of family medicine at Georgetown University School of Medicine. “A lot more research needs to be done but this is very promising.”
Merenstein continued, “A strength of our trial was that we didn’t tell people what to eat because we used a crossover design that limited the effects of any variability in a person’s diet.”
The crossover design had one group of people drinking about eight ounces of kombucha or placebo beverage daily for four weeks and then after a two-month period to ‘wash out’ the biological effects of the beverages, the kombucha and placebo were swapped between groups with another four weeks of drinking the beverages. Neither group was told which drink they were receiving at the time.
Kombucha appeared to lower average fasting blood glucose levels after four weeks from 164 to 116 milligrams per deciliter while the difference after four weeks with the placebo was not statistically significant. Guidelines from the American Diabetes Association recommended blood sugar levels before meals should be between 70 to 130 milligrams per deciliter.

Researchers at the University of Eastern Finland have identified plasma protein-based biomarkers capable of identifying adolescents at risk of developing mental health issues. The results were published in Nature Mental Health.
An estimated 10-20% of adolescents struggle with mental health conditions, with the majority remaining undiagnosed and untreated. New, early indicators of mental health problems are urgently needed, as they could revolutionize early detection and, in the future, the prevention of mental health problems in young individuals.
In the study carried out in the research group of Professor Katja Kanninen, the researchers used self-reported Strengths and Difficulties Questionnaire (SDQ) scores to evaluate mental health risk in participants aged between 11 and 16 years. Blood sample analyses showed that 58 proteins were significantly associated with the SDQ score. Bioinformatic analyses were used to identify the biological processes and pathways linked with the identified plasma protein biomarker candidates. Key enriched pathways related to these proteins included immune responses, blood coagulation, neurogenesis, and neuronal degeneration. The study employed a novel symbolic regression algorithm to create predictive models that best separate low and high SDQ score groups.
According to Professor Kanninen, plasma biomarker studies in mental disorders are an emerging field.
“Alterations in plasma proteins have been previously associated with various mental health disorders, such as depression, schizophrenia, psychotic disorders, and bipolar disorders. Our study supports these earlier findings and further revealed that specific plasma protein alterations could indicate a high risk for mental dysfunction in adolescents,” Professor Kanninen notes.
According to the researchers, this pilot study will be followed by more specific investigations of the potential biomarkers for identification of individuals at risk of mental health problems, opening a new avenue for advancements in adolescent mental health care.

Ion channels play a crucial role in many cellular processes, including neuronal communication, muscle contraction or cell proliferation. Most multi subunit ion channels exist in two functional states, either closed or open. During gating, one should expect that all subunits undergo conformational changes. The absence of intermediate conduction levels is surprising and asks for an explanation. A team of researchers from the University of Vienna and the Washington University in St. Louis created a smart model system to answer this important question. The study is currently published in Nature Communications.
Ion channels are membrane proteins that regulate the electrical activity of cells. In this study the scientific team investigated the inwardly rectifying potassium channel Kir2. This channel is crucial for maintaining a negative membrane potential in many cells. These channels are promising drug targets for treatment of cardiovascular diseases. To foster drug development, a detailed understanding of the gating mechanism is important.
Intelligent model system & innovative methods
“We designed a model system that allowed us to visualize the gating of individual subunits and track conductance changes,” explains Grigory Maksaev from the Washington University in St. Louis. As a model system, the inwardly rectifying potassium channel Kir2 was used. This channel is crucial for maintaining a negative membrane potential in many cells. “We introduced an acidic residue near the channel gate. This led to novel states, so-called sub-conductance states” explains Eva Plessl from the Department of Pharmaceutical Sciences, University of Vienna. The life times of these sub-states were long enough to resolve them experimentally. Each of the observed sub-states represents a distinct subunit conformation. Interestingly, the sub-state occupancy is titratable by pH. “This suggests that protonation or deprotonation of individual acidic residues causes this phenomenon,” explains Sun-Joo Lee from the Washington University in St. Louis.
Sour is…less conductive
“Molecular dynamics simulations with different protonation states of the acidic residue support this finding,” explains Anna Weinzinger from the Department of Pharmaceutical Sciences, University of Vienna. The study reveals that each subunit gating transition leads to conductance level changes. This suggests that for a fully open channel, all subunits must move together. “By designing a smart model system, wehave answered a long-standing question about ion channel gating,” explains Colin Nichols from the Washington University in St. Louis.

When you need accurate information about a serious illness, should you go to Google or ChatGPT?
An interdisciplinary study led by University of California, Riverside, computer scientists found that both internet information gathering services have strengths and weaknesses for people seeking information about Alzheimer’s disease and other forms of dementia. The team included clinical scientists from the University of Alabama and Florida International University.
Google provides the most current information, but query results are skewed by service and product providers seeking customers, the researchers found. ChatGPT, meanwhile, provides more objective information, but it can be outdated and lacks the sources of its information in its narrative responses.
“If you pick the best features of both, you can build a better system, and I think that this is what will happen in the next couple of years,” said Vagelis Hristidis, a professor of computer science and engineering in UCR’s Bourns College of Engineering.
In their study, Hristidis and his co-authors submitted 60 queries to both Google and ChatGPT that would be typical submissions from people living with dementia and their families.
The researchers focused on dementia because more than 6 million Americans are impacted by Alzheimer’s disease or a related condition, said study co-author Nicole Ruggiano, a professor of social work at the University of Alabama.
“Research also shows that caregivers of people living with dementia are among the most engaged stakeholders in pursuing health information, since they often are tasked with making decisions for their loved one’s care,” Ruggiano said.

It’s an elegant solution: Remove the habitat of a parasite-carrying aquatic snail and reduce the level of infection in the local community; all while generating more feed and compost for local farmers.
A collaboration of scientists from the United States and Senegal focused on doing just that by removing overgrown aquatic vegetation from areas upstream of the Diama Dam in northeastern Senegal. In doing so, they generated positive impacts to the local communities’ health and economies.
“It is rare and gratifying when we can find a potential win-win solution to both human health and livelihoods,” said UC Santa Barbara geography professor David López-Carr, a co-author of a paper that appears in the journal Nature. In it, the researchers provide proof for a hypothesis that agricultural activities, including the use of fertilizers, contribute to parasitic infections by fueling the growth of aquatic vegetation. “The results suggest a simple solution to positively impact society at the intersections of health, society and economy of northern Senegal, with implications for the over 700 million people globally in schistosomiasis endemic areas.”
Since the construction of the Diama Dam in 1986, local farmers have had better access to fresh water to irrigate their fields. However, the presence of the new infrastructure also has increased the prevalence of the schistosoma parasite, a tiny freshwater flatworm commonly found in Africa, South America and Southeast Asia. Nearly 250 million people around the world are estimated to be infected with this parasite.
As far as tropical diseases go, schistosomiasis (also known as bilharzia or snail fever) isn’t immediately fatal or even transmissible between people. But in the long term, the condition is debilitating.
“The disease is most prevalent in poor communities lacking potable water and adequate sanitation,” said López-Carr, an anthropogeographer who specializes in human-environment dynamics in the developing world. Adult worms take up residence in blood vessels and lay eggs in tissue, causing reactions and generally wreaking havoc on organs. Long-term effects include increased risk for cancer and infertility, and those infected are less able to work and go to school, keeping them in the cycle of poverty. “Poor farmers can lose up to half of their yields due to infection,” he said.
Health agencies and organizations have been fighting these infections with drugs that work well, however, the medicine does not prevent reinfection, which can happen as soon as the individual encounters contaminated water. Previous research has also focused on using the snails’ natural predators — prawns — which were cut off by the dam.

Whether they’re made from soybeans, almonds, oats, or just sourced straight from the cow, milk products must go through heat treatment to prevent harmful bacterial growth and keep them safe. But understanding how these processes affect new, plant-based milk formulations could make the beverages more pleasant to drink as well. Researchers reporting in ACS Omega have discovered how pasteurization and sterilization affects the look and feel of one such drink made from coconut and rice.
Despite the ubiquity of dairy-based foods, many people have some form of lactose intolerance — up to 36% of Americans, according to the National Institutes of Health. As a result, many turn to lactose-free, plant-based alternatives, some of which have added health benefits. For example, one drink under development combines rice flour and coconut water: Rice is hypoallergenic and high in fiber, and coconut water is hydrating and low in calories. To understand how heat treatment might alter this beverage, Jorge Yán?ez-Fernández, Diana Castro-Rodríguez and colleagues wanted to test the formulation against two different high-temperature processing steps.
The team used three versions of the beverage, containing either 2%, 5% or 8% rice flour, with coconut water comprising the rest. These were heated either by pasteurization in a water bath at 140 degrees Fahrenheit or by sterilization in an autoclave at almost 250 degrees Fahrenheit. After these treatments, the team found that the starches in the rice flour gelatinized and underwent the Maillard reaction, producing a slightly darkened color and stickier fluid for all three versions. Additionally, the drinks’ acidities increased, and there were fewer sugars, which may alter the way they taste. The team plans to use these results to inform future research into similar, dairy-free, “functional beverages,” including those that could one day contain probiotic, lactic-acid bacteria.

Sperm play a critical role in the creation of new life, delivering essentially half of the genetic material required.
The success of this process relies on the generation of a developmentally competent sperm cell, which is often determined by shape. Indeed, during in vitro fertilization, the “best-looking” sperm is selected to fertilize an egg.
However, how this optimal shape translates to proper sperm function is difficult to assess because of many confounding factors.
Researchers at the University of Michigan are now delving into the molecular-level details of sperm formation, with a particular focus on how abnormalities in this process might lead to male-factor infertility.
Unlike other cells in the body, sperm possess a unique characteristic — their genetic material is packed with proteins called protamines.
Protamines have been found in various living organisms such as plants, fish, and mammals, spanning hundreds of millions of years of evolution.
The significance of this protamine-based packaging system of sperm cells raises an intriguing question: why do sperm use protamines to package DNA instead of histones, which are employed by all other cell types?

Cases of human papillomavirus (HPV)-associated cancers of the head and neck, known as head and neck squamous cell carcinoma (HNSCC), are rapidly increasing throughout the United States. Unfortunately, relatively little is known about the factors that contribute to these tumors and what makes some tumors more aggressive and treatment-resistant than others.
To determine why some patients respond better to radiation therapy than others, researchers in UNC School of Medicine’s Department of Otolaryngology/Head and Neck Surgery and the Lineberger Comprehensive Cancer Center formed a robust collaboration with researchers at Yale Cancer Center, the Yale Head and Neck Cancer Specialized Program of Research Excellence (SPORE), and the ECOG-ACRIN Cancer Research Group (ECOG-ACRIN).
Together, they published a new study in Proceedings of the National Academy of Sciences, which reveals that HPV+ head and neck cancers can be divided into two distinct subtypes that determine how well patients will respond to therapy, with one subtype being more responsive to radiation therapy. Researchers also discovered a new mechanism of HPV carcinogenesis through the study which enhances growing efforts to personalize treatment for patients with HPV+ HNSCC.
“We’re the first ones to describe these two subtypes,” said Wendell Yarbrough, MD, MMHC, FACS, the Thomas J. Dark Distinguished Professor of Otolaryngology/Head and Neck Surgery, “Using this research, we can firmly identify two groups of patients and are able to associate their tumor subtype with treatment outcomes.”
Currently, many patients with HPV+ HNSCC are treated with high doses of radiation combined with chemotherapy. But the side effects — which include muscle fibrosis, swallowing difficulties, and artery hardening — can last a lifetime. Personalized therapy may allow oncologists to make better treatment choices for their patients; however, it can be difficult for doctors to determine the type and intensity of treatment without knowing how the patient’s tumor will respond to therapy.
To address this need, members of Yarbrough’s team, including Travis Schrank, MD, PhD, Natalia Isaeva, PhD, and Wesley Stepp, MD, PhD, who were also co-authors ion the paper, began coordinating a research cohort at UNC, grabbing publicly available data from the University of Chicago, and some validation data from E1308, a large national cooperative group clinical trial that was done through ECOG-ACRIN.
They then analyzed the tumor samples and identified several groups of co-expressed genes. Only one of these co-expressed gene sets separated tumors with high and low expression, and analysis of genes in this set found that they represented targets of a master transcription factor called NF-kB. NF-kB plays important roles in inflammation and cell death and has been associated with carcinogenesis of HNSCC.

For years, we’ve known that a special kind of molecular assembly known as a “polyelectrolyte complex” helps your cells keep themselves organized. These complexes are very good at forming interfaces to keep two liquids separated: your cells use them to create compartments. These abilities have led scientists to consider them for technological applications, including filtering water, better batteries, and even underwater glue, as well as for better pharmaceutical drugs.
But for decades, no one knew exactly how the regions looked inside a polyelectrolyte complex. There are positively charged and negatively charged chains, but how do they line up? Were they arranged in neat alternating lines, or more like what a Russian scientist termed “scrambled eggs”?
A new study from the University of Chicago’s Pritzker School of Molecular Engineering has laid out the internal structure of polyelectrolyte complexes for the first time.
“Knowing the molecular structure means you can synthesize them and prepare them more precisely, which creates opportunities for applications,” said study co-author Juan de Pablo, the Liew Family Professor of Molecular Engineering and senior scientist at Argonne National Laboratory.
Simulations and scattering
A team of scientists led by de Pablo and Matt Tirrell, dean of the Pritzker School of Molecular Engineering and also a senior scientist at Argonne, undertook a years-long exploration to pin down the mystery. First, postdoctoral researchers Artem Rumyantsev (now on the faculty of North Carolina State University) and Heyi Liang developed molecular models and carried out thousands of simulations, as well as theoretical calculations based on statistical mechanics, to understand the most likely way these molecules would assemble.
Next, a group led by graduate student Yan Fang and postdoctoral researcher Angelika Neitzel (now at the University of Florida) worked to create precise versions of these molecules in the laboratory and use an advanced technique to determine their structure.