How hepatitis E viruses penetrate cells

It was only around three years ago that a cell culture model was developed that can be used to examine hepatitis E exactly in the laboratory.
Photo Credit: RUB, Marquar

A certain surface protein is important for the cell entry of the hepatitis E virus. Medicines can suppress it.

Although hepatitis E is a common disease, little is known about the life cycle of the virus. A team from Molecular and Medical Virology at the Ruhr University Bochum and Carl von Ossietzky University Oldenburg reports on initial findings on how he manages to infect cells in the journal Hepatology from 7. February 2023. A protein called EGFR, short for Epidermal Growth Factor Receptor, plays a decisive role in the penetration of virus particles into cells. This finding could open up new treatment routes for hepatitis E. Because there are already approved drugs against EGFR that inhibit the activity of this receptor.

Cell culture model makes investigations possible

One of the reasons why hepatitis E has been researched comparatively little is that it was only around three years ago in Bochum and Hanover a robust cell culture model has been developed for its investigation is. Using this model, the researchers were now able to investigate how the virus manages to infect cells.

"With medication, we suppressed the activity of the EGFR protein at the time the virus entered some cell lines," explains first author Jil Alexandra Schrader. “With these cultures, we could see that there were significantly fewer infected cells." The researchers used cell cultures as a cross-check, in which the co-receptor was produced in excess. In this case, there were more infections than untreated cells.

Complications in pregnancy linked to increased risk of heart disease

Photo Credit: freestocks

Certain complications during pregnancy bring an increased risk of heart disease later on. However, there is still much to learn about how arteriosclerosis develops between pregnancy and heart disease later in life. A large new study led by researchers from Lund University in Sweden shows that narrowing and calcification of the blood vessels of the heart are more common in women previously affected by pregnancy complications.

Despite complications in pregnancy having increasingly been acknowledged as a new type of risk factor for heart disease, it is yet to be determined how this information can best be used within healthcare.

“Our results suggest that the correlation exists even among women with a low expected risk of cardiovascular disease. The study is an important piece of the puzzle in understanding how women with pregnancy complications should be followed-up by their healthcare provider after pregnancy,” says Simon Timpka, associate professor of clinical epidemiology who leads the research team Perinatal and Cardiovascular Epidemiology at Lund University and is a resident in obstetrics and gynecology at Skåne University Hospital.

Making molecules faster

Replica of the complex molecule, stemoamide, built in mere three steps in Tim Cernak’s Lab.
Photo Credit: Austin Thomason, Michigan Photography

With a big assist from artificial intelligence and a heavy dose of human touch, Tim Cernak’s lab at the University of Michigan made a discovery that dramatically speeds up the time-consuming chemical process of building molecules that will be tomorrow’s medicines, agrichemicals or materials.

The discovery, published in the journal of Science, is the culmination of years of chemical synthesis and data science research by the Cernak Lab in the College of Pharmacy and Department of Chemistry.

The goal of the research was to identify key reactions in the synthesis of a molecule, ultimately reducing the process to as few steps as possible. In the end, Cernak and his team achieved the synthesis of a complex alkaloid found in nature in just three steps. Previous syntheses took between seven and 26 steps.

Researchers successfully prevent peanut allergic reactions in mice, blocking onset in its tracks

Basar Bilgicer, Associate Professor of Chemical and Biomolecular Engineering
Photo Credit: Courtesy of University of Notre Dame

An allergen-specific inhibitor devised by researchers at the University of Notre Dame and the Indiana University School of Medicine has successfully prevented potentially life-threatening allergic responses to peanuts.

The results of the new study were just published in Science Translational Medicine.

Peanuts cause severe, sometimes fatal, reactions in an estimated 1.1 percent of the global population. Strict dietary avoidance is the most common therapy for peanut allergies, but the risk of accidental exposure is high. There currently are no therapies to prevent allergic events from happening in the first place.

"Our approach is unique because our inhibitor starts working before the allergen has a chance to trigger an allergic reaction," said Başar Bilgiçer, professor of chemical and biomolecular engineering at the University of Notre Dame. “Our collaboration with Dr. Mark Kaplan at Indiana University School of Medicine and Dr. Scott Smith at Vanderbilt University Medical Center made the development of these inhibitors possible. With their help, we were able to demonstrate the potency of our approach in animal studies.”

Pharmacy Researchers Develop Treatment for Glioblastoma

Dr. Shipra Malik, left, and associate professor of pharmaceutics Dr. Raman Bahal pose for a photo in a lab inside the Pharmacy/Biology Building on Jan. 20, 2023.
Photo Credit: Sydney Herdle/UConn Photo

A team of researchers, including those at the University of Connecticut, has developed a nanoparticle-based treatment that targets multiple culprits in glioblastoma, a particularly aggressive and deadly form of brain cancer.

The results, a collaboration between UConn and Yale University, were published today in Science Advances.

The new treatment uses bioadhesive nanoparticles that adhere to the site of the tumor and then slowly release the synthesized peptide nucleic acids that they’re carrying. These peptide nucleic acids target certain microRNAs – that is, short strands of RNA that play a role in gene expression. Specifically, they’re directed at a type of overexpressed microRNA known as “oncomiRs” that lead to the proliferation of cancer cells and growth of the tumor.  When the peptide nucleic acids attach to the oncomiRs, they stop their tumor-promoting activity.

‘Game-changing’ findings for sustainable hydrogen production

Illustration Credit: Courtesy of University of Surrey

Hydrogen fuel could be a more viable alternative to traditional fossil fuels, according to University of Surrey researchers who have found that a type of metal-free catalysts could contribute to the development of cost-effective and sustainable hydrogen production technologies. 

The study has shown promising results for the use of edge-decorated nano carbons as metal-free catalysts for the direct conversion of methane, which is also a powerful greenhouse gas, into hydrogen. Among the nano carbons investigated, nitrogen-doped nano carbons presented the highest level of performance for hydrogen production at high temperatures. 

Crucially, the researchers also found that the nitrogen-doped and phosphorous-doped nano carbons had strong resistance to carbon poisoning, which is a common issue with catalysts in this process. 

Study finds much still not known about cognitive decline

Why do some elderly people keep their cognitive ability much longer than others? Scientists still have much to learn.
Photo Credit: Alexandra Lowenthal

The risk factors linked to cognitive decline in older adults explain a surprisingly modest amount about the large variation in mental abilities between older people, according to a new national study.

Researchers found that the factors most commonly associated with cognitive functioning – including socioeconomic status, education and race – explained only 38% of the variation in functioning among Americans at age 54.

Health behaviors such as avoiding obesity and smoking and participating in vigorous exercise had only very small effects on functioning by the time people reached their mid-50s.

In addition, the factors studied explained only 5.6% of the variation in how quickly cognitive functioning declined in people between age 54 and 85.

Protein droplets may cause many types of genetic disease

Close-ups of cell nuclei in a human cell culture: HMGB1 protein (green) is usually found throughout the nucleus (dotted line). Mutant HMGB1, shown on the right, preferentially localizes at the nucleolus (marked in magenta) and forms a solidified layer over it, which causes disease.
Image Credit: MPIMG/ Henri Niskanen

Malfunction of cellular condensates is a disease mechanism relevant for congenital malformations, common diseases, and cancer

Most proteins localize to distinct protein-rich droplets in cells, also known as “cellular condensates”. Such proteins contain sequence features that function as address labels, telling the protein which condensate to move into. When the labels get screwed up, proteins may end up in the wrong condensate. According to an international team of researchers from clinical medicine and basic biology, this could be the cause of many unresolved diseases.

Patients with BPTA syndrome have characteristically malformed limbs featuring short fingers and additional toes, missing tibia bones in their legs and reduced brain size. As the researchers found out, BPTAS is caused by a special genetic change that causes an essential protein to migrate to the nucleolus, a large proteinaceous droplet in the cell nucleus. As a result, the function of the nucleolar condensate is inhibited and developmental disease develops.

Scientists discover toughest known material at ultra-cold temperatures

Microstructure and fractography of the CrCoNi-based alloys
Image Credit: Dr Dong Liu

Researchers at the University of Bristol have discovered an alloy that shows increased strength at over -250°C, making it the toughest material on record.

The findings, published in Science, show that chromium-cobalt-nickel alloy displays a high fracture toughness in cryogenic temperatures paving the way for its use in extreme environments on Earth and in space.

The behavior of this particular combination of metals is caused by a phase transformation that, when combined with other nano-scale mechanisms, prevents crack formation and propagation.

Lead author Dr Dong Liu of Bristol’s School of Physics, explained: “This is very interesting because most alloys become more brittle with a decrease in temperature. I reference the sinking of liberty ships in WWII and Titanic which were due to the metals losing its ductility at low temperatures.”

“People often mix the concept of strength and toughness. If you Google, ‘what is the toughest materials on earth?’ ‘Diamond’ will jump out on the top line. Diamond is the hardest known material to date, but hardness is usually related to strength of a material - diamond is indeed very hard and strong but it is not tough.”

Mapping How Singlet Oxygen Molecules Travel Along DNA Strands

A recent study has unveiled with unprecedented detail how singlet oxygen molecules diffuse along double strand DNAs, paving the way to more effective nucleic acid-targeting photodynamic therapy (PDT). A research team at Tokyo Tech used a novel photosensitizer and custom-made DNA sequences to shed light on the optimal position to anchor the photosensitizer to achieve the best oxidizing effect. This could help make this type of PDT more lethal to cancer cells.

Nucleic acid-targeting photodynamic therapy (PDT) is a promising type of targeted therapy that is being actively researched. This treatment relies on special photosensitizers, a type of drug that binds at specific locations in a cell's DNA. Once bound, the cells are irradiated at a precise frequency, which in turn causes the photosensitizer to produce reactive oxygen species (ROS) or singlet oxygen (1O2) molecules. These molecules tend to oxidize nearby nucleic acids, damaging the genetic material and ultimately killing the irradiated cell.

Although the overall process may sound straightforward, there are still many hurdles to overcome before this type of PDT is good enough for clinical practice. One of them is that even though type II oxidation (the one caused by 1O2) has certain advantages over type I oxidation (the one caused by ROS), there is very little information on how far 1O2 molecules can reach once generated. Because of this knowledge gap, it is difficult to decide which location in the DNA should be targeted to achieve the best effect.