Researchers identify previously unknown step in cholesterol absorption in the gut

Illustration Credit: Scientific Frontline

UCLA researchers have described a previously unknown step in the complex process by which dietary cholesterol is processed in the intestines before being released into the bloodstream – potentially revealing a new pathway to target in cholesterol treatment.

Although an existing drug and statins impact part of the process, an experimental drug being studied in UCLA research labs appears to specifically target the newfound pathway, possibly adding a new approach to the cholesterol management toolbox.

“Our results show that certain proteins in the Aster family play a critical role in moving cholesterol through the absorption and uptake process,” said Dr. Peter Tontonoz, a UCLA professor and researcher in Pathology and Laboratory Medicine and Biological Chemistry, senior author of an article in Science. “The Aster pathway appears to be a potentially attractive target for limiting intestinal cholesterol absorption and reducing levels of plasma cholesterol.”

Cholesterol from food is absorbed by cells that line the inner surface of the intestines – enterocytes – where it is processed into droplets that eventually reach the bloodstream. But this journey involves a multistep process.

New antifungal molecule kills fungi without toxicity in human cells, mice

The mechanism for a critical but highly toxic antifungal is revealed in high resolution. Self-assembled Amphotericin B sponges (depicted in light blue) rapidly extract sterols (depicted in orange and white) from cells. This atomic level understanding yielded a novel kidney-sparing antifungal agent. 
Illustration Credit: Jose Vazquez

A new antifungal molecule, devised by tweaking the structure of prominent antifungal drug Amphotericin B, has the potential to harness the drug’s power against fungal infections while doing away with its toxicity, researchers at the University of Illinois Urbana-Champaign and collaborators at the University of Wisconsin-Madison report in the journal Nature.

Amphotericin B, a naturally occurring small molecule produced by bacteria, is a drug used as a last resort to treat fungal infections. While AmB excels at killing fungi, it is reserved as a last line of defense because it also is toxic to the human patient – particularly the kidneys. 

Ural Scientists Have Synthesized a New Substance for the Treatment of Alzheimer’s Disease

Scientists from the Ural Federal University, the Institute of Organic Synthesis of the Ural Branch of the Russian Academy of Sciences, together with colleagues from India have developed a method for creating safe and non-toxic substances that could become the basis for drugs for Alzheimer's disease. Using the new technology, they synthesized and tested several compounds of tacrine analogues, which toxicity is estimated to be from two to five times lower than that of the known drug. The description of the new method and the compounds obtained was published in the Journal of Heterocyclic Chemistry. 

"We believe that our technology will help to create safe substances that will become the basis for future drugs for Alzheimer's disease. Our studies have shown that the toxicity of the resulting substances is two to five times lower than that of tacrine. At the same time, they are effective as they help to increase the level of acetylcholine in the cerebral cortex, which slows down the destruction of neuronal connections. This allows patients to maintain their cognitive functions and lead an active and fulfilling life for as long as possible," explains Nibin Joy Muthipeedika, Senior Researcher at the UrFU Organic Synthesis Laboratory.

Phytoplankton uptake of methylmercury is controlled by thiols

In the sea, phytoplankton are the first step when methylmercury is absorbed into the food web. The image was taken under a microscope and shows a spring bloom of phytoplankton in the Bothnian Sea.
 Image Credit: Marlene Johansson

Methylmercury is one of the chemicals that poses the greatest threat to global public health. People ingest methylmercury by eating fish, but how does the mercury end up in the fish? A new study shows that the concentrations of so-called thiols in the water control how available methylmercury is to living organisms.

For methylmercury to enter the food web, it must be absorbed from the water by organisms and the uptake takes place primarily by phytoplankton. This results in a dramatic enrichment, where the levels of methylmercury can increase by a factor of 10,000 to 100,000. However, there is a great deal of variation between different aquatic environments, and it has so far been unclear what controls the process and why the variation is so large.

One Punch Isn’t Enough to Overcome a Common Cancer Mutation

Acute myeloid leukemia as seen under a microscope.
Image Credit: Animalculist
(CC BY-SA 4.0)

Cancer cells are often a mess of mutations. About 20 to 25 percent of cancers involve mutations in a complex of molecules called SWI/SNF. Yet drugs designed to block SWI/SNF activity haven’t always worked as expected.

Researchers at Harvard Medical School have now figured out why.

As reported Nov. 2 in Cell, the team found that when drugs block SWI/SNF, a second molecule steps up to compensate.

Blocking this second molecule alongside SWI/SNF suppressed cancer cell growth in lab dishes, suggesting that a two-drug approach could make treatments more effective in people.

“I am excited about this work because it shows an alternative path forward for treating cancers in which the SWI/SNF complex is mutated,” said senior author Karen Adelman, the Edward S. Harkness Professor of Biological Chemistry and Molecular Pharmacology in the Blavatnik Institute at HMS, whose lab conducted the work.

“What’s interesting and meaningful about this study is it shows that a one-two punch, a double-agent therapy, could be really useful for keeping these cancer cells at bay,” she said.

FSU researchers capture high-resolution images of magnesium ions interacting with CRISPR gene-editing enzyme

Hong Li, professor in the Department of Chemistry and Biochemistry and director of the Institute of Molecular Biophysics.
Photo Credit: Devin Bittner/FSU College of Arts and Sciences

The gene-editing technology known as CRISPR has led to revolutionary changes in agriculture, health research and more.

In research published in Nature Catalysis, scientists at Florida State University produced the first high-resolution, time-lapsed images showing magnesium ions interacting with the CRISPR-Cas9 enzyme while it cut strands of DNA, providing clear evidence that magnesium plays a role in both chemical bond breakage and near-simultaneous DNA cutting.

“If you are cutting genes, you don’t want to have only one strand of DNA broken, because the cell can repair it easily without editing. You want both strands to be broken,” said Hong Li, professor in the Department of Chemistry and Biochemistry and director of the Institute of Molecular Biophysics. “You need two cuts firing close together. Magnesium plays a role in that, and we saw exactly how that works.”

Mechanics of breast cancer metastasis discovered, offering target for treatment

A human breast cancer cell, adenocarcinoma MDA-MB-231, demonstrates metastatic-like adhesion, spreading and migrating in a collagen matrix designed to mimic soft tissue. New research led by Penn State reveals for the first time the mechanics behind how breast cancer cells may invade healthy tissues. The discovery, showing that a motor protein called dynein powers the movement of cancer cells in soft tissue models, offers new clinical targets against metastasis and has the potential to fundamentally change how cancer is treated. 
Image Credit: Erdem Tabdanov / Pennsylvania State University
(CC BY-NC-ND 4.0 DEED)

The most lethal feature of any cancer is metastasis, the spread of cancer cells throughout the body. New research led by Penn State reveals for the first time the mechanics behind how breast cancer cells may invade healthy tissues. The discovery, showing that a motor protein called dynein powers the movement of cancer cells in soft tissue models, offers new clinical targets against metastasis and has the potential to fundamentally change how cancer is treated.

“This discovery marks a paradigm shift in many ways,” said Erdem Tabdanov, assistant professor of pharmacology at Penn State and a lead co-corresponding author on the study, recently published in the journal Advanced Science. “Until now, dynein has never been caught in the business of providing the mechanical force for cancer cell motility, which is their ability to move themselves. Now we can see that if you target dynein, you could effectively stop motility of those cells and, therefore, stop metastatic dissemination.”

The project began as a collaboration between Penn State’s Department of Chemical Engineering and Penn State’s College of Medicine, before growing into a multi-institution partnership with researchers at the University of Rochester Medical Center, Georgia Institute of Technology, Emory University, and the U.S. Food and Drug Administration.

Breakthrough synthesis method improves solar cell stability

Jin Hou is a Rice University graduate student and lead author on a study published in Nature Synthesis. Photo Credit: Courtesy of Jin Hou

Solar cell efficiency has soared in recent years due to light-harvesting materials like halide perovskites, but the ability to produce them reliably at scale continues to be a challenge.

A process developed by Rice University chemical and biomolecular engineer Aditya Mohite and collaborators at Northwestern University, the University of Pennsylvania and the University of Rennes yields 2D perovskite-based semiconductor layers of ideal thickness and purity by controlling the temperature and duration of the crystallization process.

Known as kinetically controlled space confinement, the process could help improve the stability and reduce the cost of halide perovskite-based emerging technologies like optoelectronics and photovoltaics.

Machine can quickly produce needed cells for cancer treatment

WSU researchers have developed a minifridge-sized bioreactor that is able to manufacture the cells, called T cells, at 95% of the maximum growth rate – about 30% faster than current technologies.
Photo Credit: Courtesy of Washington State University

A new tool to rapidly grow cancer-killing white blood cells could advance the availability of immunotherapy, a promising therapy which harnesses the power of the body’s immune response to target cancer cells.

Washington State University researchers have developed a minifridge-sized bioreactor that is able to manufacture the cells, called T cells, at 95% of the maximum growth rate – about 30% faster than current technologies. The researchers report on their work in the journal Biotechnology Progress. They developed it using T cells from cattle, developed by co-author Bill Davis of WSU’s Veterinary College, and anticipate it will perform similarly on human cells.

In 2022, there were over 1,400 different types of therapies using T cells in development, with seven approved by the FDA for a variety of cancer treatments. Use of the therapy, called chimeric antigen receptor T cell (CAR-T), is limited, however, because of the cost and time needed to grow T cells. Each infusion treatment for a cancer patient requires up to 250 million cells.

Better batteries for electric cars

Eric Ricardo Carreon Ruiz (left) and Pierre Boillat in front of part of PSI's Swiss spallation neutron source SINQ. There, at the BOA experimental station, they conducted their investigations.
Photo Credit: Paul Scherrer Institute/Mahir Dzambegovic

PSI researchers are using neutrons to make changes in battery electrolytes visible. The analysis enables better understanding of the physical and chemical processes and could aid in the development of batteries with better characteristics. The results have now been published in Science Advances.

The range is too limited, charging is too slow when it’s cold . . . the list of prejudices against electric cars is long. Even though progress is rapid, batteries remain the critical component for electromobility – as well as for many other applications, from smartphones to large storage devices designed to stabilize the power grid. The problem: Battery developers still lack a full understanding of what is happening, chemically and physically, during charging and discharging, especially in liquid electrolytes between the two electrodes through which charge carriers are exchanged.

Now Eric Ricardo Carreon Ruiz of PSI is bringing light into this darkness. A doctoral researcher in Pierre Boillat’s group at PSI, he is using neutrons from the Swiss spallation neutron source SINQ to investigate different electrolytes, studying for example their behavior at fluctuating temperatures. His results provide important insights that could help in the development of new electrolytes and higher-performance batteries.

SLAC scientists shed light on potential breakthrough biomedical molecule

Researchers employed advanced X-ray spectroscopic techniques at SLAC’s Stanford Synchrotron Radiation Lightsource (SSRL), which allowed them to peer deeper into the chemical properties of nitroxide.
Illustration Credit: Greg Stewart/SLAC National Accelerator Laboratory

Scientists from the Department of Energy’s SLAC National Accelerator Laboratory have gained valuable insights into producing nitroxide, a molecule with potential applications in the biomedical field. While nitric oxide (NO) has long been on researchers' radar for its significant physiological effects, its lesser-known cousin, nitroxide (HNO), has remained largely unexplored.

The study, published recently in the Journal of the American Chemical Society, was born out of a joint endeavor between teams at SLAC’s Linac Coherent Light Source (LCLS) X-ray laser and Stanford Synchrotron Radiation Lightsource (SSRL).

Nitroxide has many of the same physiological effects of nitric oxide – such as its ability to fight germs, prevent blood clots, and relax and dilate blood vessels – with additional therapeutic properties, such as efficacy in treating heart failure, as well as more potent antioxidant activity and wound healing. However, it is not a chemically long-lived species so methods that enable its targeted delivery are key to future biomedical applications.

Cathode active materials for lithium-ion batteries could be produced at low temperatures

Reaction pathway of the hydroflux process to form layered lithium cobalt oxide (LiCoO2) at 300 °C.
Full Size Image
 Illustration Credit: Masaki Matsui

Lithium-ion batteries (LIB) are the most commonly used type of battery in consumer electronics and electric vehicles. Lithium cobalt oxide (LiCoO2) is the compound used for the cathode in LIB for handheld electronics. Traditionally, the synthesis of this compound requires temperatures over 800°C and takes 10 to 20 hours to complete.

A team of researchers at Hokkaido University and Kobe University, led by Professor Masaki Matsui at Hokkaido University’s Faculty of Science, have developed a new method to synthesize lithium cobalt oxide at temperatures as low as 300°C and durations as short as 30 minutes. Their findings were published in the journal Inorganic Chemistry.

“Lithium cobalt oxide can typically be synthesized in two forms,” Matsui explains. “One form is layered rocksalt structure, called the high-temperature phase, and the other form is spinel-framework structure, called the low-temperature phase. The layered LiCoO2 is used in Li-ion batteries.”

Treating the inflamed intestinal wall locally

For their self-forming gel, the researchers chose a lipid that is well tolerated and safe for use in humans. It is a fluid material at room temperature and can be administered as an enema into the inflamed area of the colon. There, at body temperature, it forms a viscous and sticky gel and remains adherent for at least six hours, gradually releasing the active ingredient.
Illustration Credit: © University of Bern, Marianna Carone

Treatment of the chronic inflammatory bowel disease ulcerative colitis often produces unsatisfactory results. Researchers at the University of Bern have now developed a lipid gel that is administered directly to the inflamed part of the intestine, where it remains and releases its active substance evenly. This could result in a new, targeted therapy approach with fewer side effects.

For diseases that affect a specific organ or tissue, a drug is usually most effective and well-tolerated if it is administered exactly where it is supposed to work in the body. If it is swallowed or injected, it distributes throughout the body, thus increasing the risk of side effects.

Researchers from the Department of Chemistry, Biochemistry and Pharmaceutical Sciences and the Institute of Tissue Medicine and Pathology at the University of Bern, together with colleagues from the University Hospital Zurich, have developed a self-forming, viscous lipid gel to deliver anti-inflammatory drugs directly to the wall of the colon or rectum. Thanks to this innovation, patients with ulcerative colitis, a chronic inflammation of the terminal part of the intestine, could be helped in a more targeted way and with fewer side effects.

Antibiotic resistance can impair subsequent adaptations in bacteria, new Concordia research suggests

Farhan Chowdhury (left) and Brandon Findlay; “Instead of relying on antibiotic cocktails, we can have an alternative where sequential antibiotic therapies are applied. This can lead to better therapies and give patients more time to recover before resistance evolves.”
Photo Credit: Courtesy of Concordia University

Researchers at Concordia’s Department of Biology and Department of Chemistry and Biochemistry have discovered a possible new avenue of treatment that can help slow antibiotic resistance in bacteria.

PhD candidate Farhan Chowdhury and associate professor Brandon Findlay recently shared the results of their research in a recent paper published in the journal ACS Infectious Diseases. The researchers describe how a strain of the bacteria E. coli is left severely weakened after it has developed resistance to the antibiotic chloramphenicol (CHL). This weakness leaves the bacteria unable to adapt to other types of antibiotics.

Understanding the ways in which resistance impairments evolve can help clinicians better target pathogens in patients.

“Instead of relying on antibiotic cocktails, we can have an alternative where sequential antibiotic therapies are applied,” Chowdhury explains.

“Clinicians can select the sequence of medication by seeing if a first antibiotic imposes deficits on the bacteria, which would slow down the evolution of resistance in the subsequent ones. This can lead to better therapies and give patients more time to recover before resistance evolves.”

Electrons are quick-change artists in molten salts, chemists show

When exposed to radiation, electrons produced within molten zinc chloride, or ZnCl2, can be observed in three distinct singly occupied molecular orbital states, plus a more diffuse, delocalized state.
Illustration Credit: Hung H. Nguyen/University of Iowa

In a finding that helps elucidate how molten salts in advanced nuclear reactors might behave, scientists have shown how electrons interacting with the ions of the molten salt can form three states with different properties. Understanding these states can help predict the impact of radiation on the performance of salt-fueled reactors.

The researchers, from the Department of Energy’s Oak Ridge National Laboratory and the University of Iowa, computationally simulated the introduction of an excess electron into molten zinc chloride salt to see what would happen.

They found three possible scenarios. In one, the electron becomes part of a molecular radical that includes two zinc ions. In another, the electron localizes on a single zinc ion. In the third, the electron is delocalized, or spread out diffusely over multiple salt ions.

Because molten salt reactors are one of the reactor designs under consideration for future nuclear power plants, “the big question is what happens to molten salts when they’re exposed to high radiation,” said Vyacheslav Bryantsev, leader of the Chemical Separations group at ORNL and one of the scientists on the study and an author of the paper. “What happens to the salt that is used to carry the fuel in one of those advanced reactor concepts?”

Physical theory improves protein folding prediction

Protein folding models. Four iterations of WSME, from the original to the new, and two specialized versions for more specific circumstances.
Illustration Credit: ©2023 Ooka & Arai CC-BY

Proteins are important molecules that perform a variety of functions essential to life. To function properly, many proteins must fold into specific structures. However, the way proteins fold into specific structures is still largely unknown. Researchers from the University of Tokyo developed a novel physical theory that can accurately predict how proteins fold. Their model can predict things previous models cannot. Improved knowledge of protein folding could offer huge benefits to medical research, as well as to various industrial processes.

You are literally made of proteins. These chainlike molecules, made from tens to thousands of smaller molecules called amino acids, form things like hair, bones, muscles, enzymes for digestion, antibodies to fight diseases, and more. Proteins make these things by folding into various structures that in turn build up these larger tissues and biological components. And by knowing more about this folding process, researchers can better understand more about the processes that constitute life itself. Such knowledge is also essential to medicine, not only for the development of new treatments and industrial processes to produce medicines, but also for knowledge of how certain diseases work, as some are examples of protein folding gone wrong. So, to say proteins are important is putting it mildly. Proteins are the stuff of life.

Revealing structural secrets of a key cancer protein

Left (a): Three-dimensional structure of active K-Ras protein previously determined by X-ray crystallography with the functionally critical switch regions (red and blue) mostly invisible (dashed lines). Right (b): Two-dimensional NMR spectrum of the same system in solution, with its features annotated to the corresponding amino-acid residues of K-Ras. Tiny features belonging to the switch regions that were previously undetectable are now observable, allowing the detailed characterization of their structure and functional dynamics by solution NMR.
Image Credit: Alexander Hansen et al. (2023)

Scientists have breathed new life into the study of a protein with an outsized link to human cancers because of its dangerous mutations, using advanced research techniques to detect its hidden regions.

The Ras family of proteins are enzymes that set-in motion the growth, division and differentiation of many types of cells, and their genes have been identified as the most frequently mutated cancer-related genes in humans. The subject of this study, the K-Ras protein, is linked to 75% of all Ras-associated cancers.

Researchers at The Ohio State University are the first to detect a section of this protein’s structure that had previously been unobservable by standard lab tools, revealing features and interactions related to the protein’s mutations that put cells into a state of perpetual division – a classic cancer characteristic.  

“We know these mutations are a significant problem: They cause deaths,” said senior study author Rafael Brüschweiler, Ohio Research Scholar and professor of chemistry and biochemistry at Ohio State. “We know that structural biology can provide unique insights into the mechanisms of those mutations and can stimulate the search for potential cures.

Decontamination method zaps pollutants from soil

Yi Cheng (from left), James Tour and Bing Deng
Photo Credit: Gustavo Raskosky/Rice University

Filtration systems are designed to capture multiple harmful substances from water or air simultaneously, but pollutants in soil can only be tackled individually or a few at a time ⎯ at least for now.

A method developed by Rice University scientists and collaborators at the United States Army Engineer Research and Development Center (ERDC) could help turn soil remediation processes from piecemeal to wholesale.

A team of Rice scientists led by chemist James Tour and researchers from the geotechnical structures and environmental engineering branches of the ERDC showed that mixing polluted soil with nontoxic, carbon-rich compounds that propel electrical current, such as biochar, then zapping the mix with short bursts of electricity flushes out both organic pollutants and heavy metals without using water or generating waste.

New Polymer Membranes, AI Predictions Could Dramatically Reduce Energy, Water Use in Oil Refining

A sample of a DUCKY polymer membrane researchers created to perform the initial separation of crude oils using significantly less energy.
Photo Credit: Candler Hobbs

A new kind of polymer membrane created by researchers at Georgia Tech could reshape how refineries process crude oil, dramatically reducing the energy and water required while extracting even more useful materials.

The so-called DUCKY polymers — more on the unusual name in a minute — are reported in Nature Materials. And they’re just the beginning for the team of Georgia Tech chemists, chemical engineers, and materials scientists. They also have created artificial intelligence tools to predict the performance of these kinds of polymer membranes, which could accelerate development of new ones.

The implications are stark: the initial separation of crude oil components is responsible for roughly 1% of energy used across the globe. What’s more, the membrane separation technology the researchers are developing could have several uses, from biofuels and biodegradable plastics to pulp and paper products.

“We’re establishing concepts here that we can then use with different molecules or polymers, but we apply them to crude oil because that’s the most challenging target right now,” said M.G. Finn, professor and James A. Carlos Family Chair in the School of Chemistry and Biochemistry.

Single cell genomics reveal key cell factor for dangerous identity loss in tumor cells

Maxim Frolov, professor of biochemistry and molecular genetics.
Photo: Jenny Fontaine/University of Illinois Chicago

When proliferating cells reach their mature form as part of the eye, kidney or blood, they typically differentiate and stop dividing. But in some cases, genetic errors cause these cells to turn back the clock and dedifferentiate — losing their final identity and regaining the ability to proliferate. This phenomenon can result in tumors, and pathologists often use the extent of dedifferentiation to assess the aggressiveness of a cancer. 

In a new paper published by Developmental Cell, UIC researchers used single-cell genomics to identify a key factor in this process. By carefully examining how two tumor suppressor pathways interact in the eye of the fruit fly, a team led by Maxim Frolov pinpointed the cellular elements responsible for dedifferentiation. 

Single-cell genomics is a laboratory method that allows researchers to measure the DNA and RNA from just one cell, instead of collectively across many cells in a sample. In 2018, Frolov’s group was the first at UIC to publish a study that used single-cell genomics to systematically identify cell types in a heterogeneous tissue based on gene expression.