Biology & Medicine News and Discussions

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A new class of functional elements in the human genome?
June 29, 2021

Some regions of the human genome where the DNA can fold into unusual three-dimensional structures called G-quadruplexes (G4s) show signs that they are preserved by natural selection. When G4s are located in the regulatory sequences that control how genes are expressed or in other functional, but non-protein coding, regions of the genome, they are maintained by selection, are more common, and their unusual structures are more stable, according to a new study. Conversely, the structures are less common, less stable, and evolve neutrally outside of these regions, including within the protein-coding regions of genes themselves.

Together, these lines of evidence suggest that G4 elements should be added to the list of functional elements of the genome along with genes, regulatory sequences, and non-protein coding RNAs, among others. A paper describing the study, by a team of researchers led by Penn State scientists, appears June 29, 2021 in the journal Genome Research.

"There have been only a handful of studies that provided experimental evidence for individual G4 elements playing functional roles," said Wilfried Guiblet, first author of the paper, a graduate student at Penn State at the time of research, and now a postdoctoral scholar at the National Cancer Institute. "Our study is the first to look at G4s across the genome to see if they show the characteristics of functional elements as a general rule."

As much as 1% of the genome can fold into G4s, rather than the typical double helix (in comparison, protein-coding genes occupy approximately 1.5% of the genome). G4s are one of several non-canonical shapes into which DNA can fold, collectively known as "non-B DNA." The G4 structure forms in DNA sequences rich in the nucleotide guanine, the "G" in the ACGT alphabet of the genome. G4s have been implicated in several key cellular processes and have been suggested to play a role in several human diseases, including neurological disorders and cancer.

To better understand the function of G4s at a genome-wide scale, the research team looked at their distribution across the genome, their thermostability, and whether or not they showed signs of being under the influence of natural selection, all in relation to other functional elements of the genome. They confirmed that, as a rule, G4s are more common in regions of the genome known to have important cellular functions and that the G4s in these regions are more stable than elsewhere in the genome.
https://www.sciencedaily.com/releases/2 ... 134330.htm
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Researchers identify muscle proteins whose quantity is reduced in type 2 diabetes
June 29, 2021

Globally, more than 400 million people have diabetes, most of them suffering from type 2 diabetes.

Before the onset of actual type 2 diabetes, people are often diagnosed with abnormalities in glucose metabolism that are milder than those associated with diabetes. The term used to indicate such cases is prediabetes. Roughly 5-10% of people with prediabetes develop type 2 diabetes within a year-long follow-up.

Insulin resistance in muscle tissue is one of the earliest metabolic abnormalities detected in individuals who are developing type 2 diabetes, and the phenomenon is already seen in prediabetes.

In a collaborative study, researchers from the University of Helsinki, the Helsinki University Hospital and the Minerva Foundation Institute for Medical Research investigated the link between skeletal muscle proteome and type 2 diabetes.

In the study, the protein composition of the thigh muscle was surveyed in men whose glucose tolerance varied from normal to that associated with prediabetes and type 2 diabetes. A total of 148 muscle samples were analysed.
https://www.sciencedaily.com/releases/2 ... 134307.htm
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Newly discovered proteins protect against progression of diabetic kidney disease

by Joslin Diabetes Center
https://medicalxpress.com/news/2021-06- ... sease.html
Elevated levels of three specific circulating proteins are associated with protection against kidney failure in diabetes, according to research from the Joslin Diabetes Center that will be published 30th June in Science Translational Medicine.

"As well as acting as biomarkers for advancing kidney disease risk in diabetes, the proteins may also serve as the basis for future therapies against progression to the most serious types of kidney disease," said Andrzej S. Krolewski MD, Ph.D., senior author on the publication, senior investigator at Joslin Diabetes Center and professor of medicine at Harvard Medical School. This would likely include the delay and prevention of end stage renal disease (ESRD), which is the most serious and advanced stage of diabetic kidney disease.
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Aspirin could cut risk of death in cancer patients by 20%, study suggests
Friday 2 July 2021

Cancer patients who take aspirin as part of their treatment could cut their risk of death by 20%, according to a major review of studies.

Researchers at Cardiff University said the medication - commonly used as pain relief - not only has "biological mechanisms" that help reduce mortality risk, but they also found it to reduce the spread of cancer within the body.

They said "serious consideration" could be given to using aspirin alongside other therapies to treat cancer, based on a body of evidence on its efficacy and safety.

As part of the study, the team reviewed 118 earlier published studies, which included 250,000 patients with 18 different cancers.

They also considered the risks of aspirin-taking and wrote to the authors of the papers, asking about any stomach or other bleeding episodes.
https://news.sky.com/story/aspirin-coul ... s-12347232
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Building a better biosensor polymer

by King Abdullah University of Science and Technology
https://phys.org/news/2021-07-biosensor-polymer.html
A new organic (carbon-based) semiconducting material has been developed that outperforms existing options for building the next generation of biosensors. An international research team led by KAUST is the first to overcome some critical challenges in developing this polymer.

Much research effort is currently expended into novel types of biosensors that interact directly with the body to detect key biochemicals and serve as indicators of health and disease.

"For a sensor to be compatible with the body, we need to use soft organic materials with mechanical properties that match those of biological tissues," says Rawad Hallani, a former research scientist in the KAUST team, who developed the polymer along with researchers at several universities in the U.S. and the U.K.
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Student designs device to save stabbing victims' lives
By Ben Coxworth
July 05, 2021
https://newatlas.com/good-thinking/reac ... ms-device/
When someone is suffering from a deep stab wound, it's important to apply pressure within that wound, not just down onto it. A new student-designed device is intended to let first responders do just that, potentially saving lives that might otherwise be lost.

Police officers are often the first people to arrive at the scene of a stabbing. If the knife or other implement is still inside the wound, it's typically left in place until an ambulance arrives. This is because it acts somewhat like a cork, with the pressure that it's applying actually helping to limit internal bleeding.

In many cases, however, police arrive to find an open stab wound that urgently needs to be "plugged." It was with such scenarios in mind that Joseph Bentley – a final-year Product Design and Technology student at Britain's Loughborough University – created the REACT tool.
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Our genes shape our gut bacteria, new research shows

by University of Notre Dame
https://medicalxpress.com/news/2021-07- ... teria.html
Our gut microbiome—the ever-changing "rainforest" of bacteria living in our intestines—is primarily affected by our lifestyle, including what we eat or the medications we take, most studies show.

But a University of Notre Dame study has found a much greater genetic component at play than was once known.

In the study, published recently in Science, researchers discovered that most bacteria in the gut microbiome are heritable after looking at more than 16,000 gut microbiome profiles collected over 14 years from a long-studied population of baboons in Kenya's Amboseli National Park. However, this heritability changes over time, across seasons and with age. The team also found that several of the microbiome traits heritable in baboons are also heritable in humans.
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Biomaterial vaccines ward off broad range of bacterial infections and septic shock
https://medicalxpress.com/news/2021-07- ... range.html
by Harvard University
This illustration shows how a ciVax infection vaccine against a pathogenic E. coli strain is produced and applied. First, carbohydrate-containing surface molecules (PAMPs) of killed bacteria are captured with magnetic beads coated with FcMBL. The beads are then combined with mesoporous silica (MPS) rods, immune cell-recruiting GMCSF, and immune cell-activating CpG adjuvant to form the complete ciVax vaccine. Upon injection under the skin of mice, the ciVAX vaccine forms a permeable scaffold that recruits immature dendritic cells (DCs), educates them to present PAMP-derived antigens, and additionally activates and releases them again. The reprogrammed DCs then migrate to draining lymph nodes where they orchestrate a complex immune response, including reactive T cells and antibody-producing B cells reacting against the E. coli pathogen. Credit: Wyss Institute at Harvard University.

Current clinical interventions for infectious diseases are facing increasing challenges due to the ever-rising number of drug-resistant microbial infections, epidemic outbreaks of pathogenic bacteria, and the continued possibility of new biothreats that might emerge in the future. Effective vaccines could act as a bulwark to prevent many bacterial infections and some of their most severe consequences, including sepsis. According to the Centers of Disease Control and Prevention (CDC), "Each year, at least 1.7 million adults in America develop sepsis. Nearly 270,000 Americans die as a result of sepsis [and] 1 in 3 patients who dies in a hospital has sepsis." However, for the most common bacterial pathogens that cause sepsis and many other diseases, still no vaccines are available.
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Selective, toxin-bearing antibodies could help treat liver fibrosis
https://medicalxpress.com/news/2021-07- ... rosis.html
by Heather Buschman, University of California - San Diego
Chronic alcohol abuse and hepatitis can injure the liver and lead to fibrosis, the buildup of collagen and scar tissue. As a potential approach to treating liver fibrosis, University of California San Diego School of Medicine researchers and their collaborators are looking for ways to stop liver cells from producing collagen.

"So we thought... what if we take immunotoxins and try to get them to kill collagen-producing cells in the liver?" said team lead Tatiana Kisseleva, MD, Ph.D., associate professor of surgery at UC San Diego School of Medicine. "If these antibodies carrying toxic molecules can find and bind the cells, the cells will eat up the 'gift' and die."
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Progress towards new treatments for tuberculosis
https://medicalxpress.com/news/2021-07- ... losis.html
by Walter and Eliza Hall Institute
Boosting the body's own disease-fighting immune pathway could provide answers in the desperate search for new treatments for tuberculosis.

Tuberculosis still represents an enormous global disease burden and is one of the top 10 causes of death worldwide.

Led by WEHI's Dr. Michael Stutz and Professor Marc Pellegrini and published in Immunity, the study uncovered how cells infected with tuberculosis bacteria can die, and that using new medicines to enhance particular forms of cell death decreased the severity of the disease in a preclinical model.
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