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Category: biotech/medical – Page 938

Failed NGS or qPCR? Spectrophotometry can tell why

Genomic analyses, such as next-generation sequencing (NGS) and quantitative polymerase chain reaction (qPCR), require pure nucleic acids and accurate analyte concentrations to perform successful reactions. The purification process to access this genetic material uses methods that rely on detergents, mechanical disruption, and heat to disrupt the cellular structures of nuclei, ribosomes, bacteria, and viruses. Nucleic acid is then purified by performing a solvent extraction, alcohol precipitation, and salting-out.

Contaminants can copurify with nucleic acids

Isolation of nucleic acids (including various forms of DNA and RNA) may be needed from cell harvest, PCR, restriction enzyme digest, agarose gel, and other sources. Several avenues in nucleic acid extraction protocols inadvertently allow the co-precipitation of contaminants owing to the type of starting material or the chosen extraction method (Table 1). In some cases, changing the method or adding another purification step can mitigate or eliminate the copurification issue. However, when contamination remains an issue, it is important to learn as much as possible about the impurities that can denature enzymes, block templates, or otherwise lead to failed chemical reactions necessary for downstream applications.

New insights into glucose metabolism: targeting ATP synthase with chromium (III) nutritional supplement for improved blood sugar control

Recently, a research team led by Professor Hongzhe SUN from the Department of Chemistry, Faculty of Science, The University of Hong Kong, has published a paper in Nature Communications.

The researchers found that, chromium(III) (Cr(III)), a nutritional supplement, can enhance cells’ ability to metabolise glucose by regulating ATP synthase activity. This process improves mitochondrial deformation caused by high glucose levels and significantly boosts glucose metabolism in type 2 diabetic mice. To uncover the protein targets of Cr(III) and elucidate the molecular mechanism, the team has developed a fluorescent probe for detecting transient metal-protein interactions, achieving a high spatiotemporal resolution tracking of the Cr(III) proteome in HepG2 cells. This led to the identification of Cr(III)-binding proteins within cells. The team then revealed that Cr(III) replaces magnesium ions (Mg2+) in ATP synthase, reduces ATP synthase activity, and activates the downstream AMPK pathway, resulting in improved glucose metabolism. This study provides a novel concept for hypoglycaemic research.

“Although Cr(III) compounds have long been used as a nutritional supplement for diabetes treatment, weight loss and muscle development, its protein target and mechanism of action remain concealed for over half a century. We used a novel fluorescent probe, along with other chemical biology approaches, to uncover the long-standing scientific problem of the biological chemistry of Cr(III) and discovered that Cr(III) targets ATP synthase to regulate glucose,” commented Professor Sun.

Scientists track nanoscale processes of CRISPR-Cas complexes

Scientists at Leipzig University, in collaboration with colleagues at Vilnius University in Lithuania, have developed a new method to measure the smallest twists and torques of molecules within milliseconds. The method makes it possible to track the gene recognition of CRISPR-Cas protein complexes, also known as “genetic scissors”, in real time and with the highest resolution. With the data obtained, the recognition process can be accurately characterised and modelled to improve the precision of the genetic scissors. The results obtained by the team led by Professor Ralf Seidel and Dominik Kauert from the Faculty of Physics and Earth Sciences have now been published in the prestigious journal Nature Structural and Molecular Biology.

When bacteria are attacked by a virus, they can defend themselves with a mechanism that fends off the genetic material introduced by the intruder. The key is CRISPR-Cas protein complexes. It is only in the last decade that their function for adaptive immunity in microorganisms has been discovered and elucidated. With the help of an embedded RNA, the CRISPR complexes recognize a short sequence in the attacker’s DNA. The mechanism of sequence recognition by RNA has since been used to selectively switch off and modify genes in any organism. This discovery revolutionized genetic engineering and was already honored in 2020 with the Nobel Prize in Chemistry awarded to Emmanuelle Charpentier and Jennifer A. Doudna.

Occasionally, however, CRISPR complexes also react to gene segments that differ slightly from the sequence specified by the RNA. This leads to undesirable side effects in medical applications. “The causes of this are not yet well understood, as the process could not be observed directly until now,” says Dominik Kauert, who worked on the project as a PhD student.

3D bioprinting reveals a new approach for killing solid cancer tumors

CIPhotos/iStock.

Standard immunotherapy procedures also employ intravenous injections loaded with NK cells to treat cancer but several limitations with this approach prevent it from delivering satisfying results. For instance, many NK cells lose their viability during the therapy and often fail to target the tumors, according to the researchers.

Altered gut bacteria could be early warning sign of Alzheimer’s

A new study conducted by researchers at Washington University School of Medicine in St Louis has explored the composition of gut bacteria in individuals in the earliest stage of Alzheimer’s disease. The research, which is published in Science Translational Medicine, not only identifies potential indicators of heightened dementia risk, but also offers prospects for developing microbiome-altering preventive treatments to combat cognitive decline.

Longevity. Technology: Previously, science has noted differences in the gut microbiomes of individuals with symptomatic Alzheimer’s compared with their healthy counterparts. However, the current study delves deeper, focusing on the gut microbiomes of individuals in the crucial pre-symptomatic phase. During this phase, individuals accumulate amyloid beta and tau proteins in their brains without exhibiting neurodegeneration or cognitive decline, which can persist for over two decades. Earlier diagnosis would enable people to access support and resources, plan for the future and well as onboarding treatments that could slow the progression of the disease. An idea of future numbers of patients would also allow health care infrastructure to be better prepared.

The researchers evaluated participants who volunteered at the Charles F and Joanne Knight Alzheimer Disease Research Center at Washington University, specifically selecting cognitively normal individuals. These participants provided samples of stool, blood, and cerebrospinal fluid, recorded their dietary habits, and underwent PET and MRI brain scans.

Opdivo Could Boost Outcomes for People Battling Hodgkin Lymphoma

TUESDAY, July 6, 2023 (HealthDay News) — The widely used immunotherapy drug nivolumab (Opdivo) is safer and more effective in treating adults and children with advanced Hodgkin lymphoma than the targeted therapy now used as standard care is, new clinical trial results show.

Nivolumab outperformed the drug brentuximab vedotin (Adcetris), extending progression-free survival by 94% at one year compared to 86%, said lead researcher Dr. Alex Herrera, a hematologist-oncologist at City of Hope in Duarte, Calif.

Nivolumab also produced significantly fewer side effects than brentuximab vedotin, which was the first novel therapy developed for Hodgkin lymphoma, Herrera said in a presentation Sunday at the American Society for Clinical Oncology (ASCO) annual meeting in Chicago.

Researchers develop compound that prevents free radical production in mitochondria

Back in 1956, Denham Harman proposed that the aging is caused by the build up of oxidative damage to cells, and that this damage is caused by free radicals which have been produced during aerobic respiration [1]. Free radicals are u nstable atoms that have an unpaired electron, meaning a free radical is constantly on the look-out for an atom that has an electron it can pinch to fill the space. This makes them highly reactive, and when they steal atoms from your body’s cells, it is very damaging.

Longevity. Technology: As well as being generated in normal cell metabolism, free radicals can be acquired from external sources (pollution, cigarette smoke, radiation, medication, &c) and while the free radical theory of aging has been the subject of much debate [2], the understanding of the danger free radicals pose led to an increase in the public’s interest in superfoods, vitamins and minerals that were antioxidants – substances that have a spare electron which they are happy to give away to passing free radicals, thus removing them from the danger equation.

But before you reach for the blueberries, it is important to know that, as so often in biology, the story is not black and white. Like a misunderstood cartoon villain, free radicals have a beneficial side, too – albeit in moderation. Free radicals generated by the cell’s mitochondria are beneficial in wound-healing, and others elsewhere act as important signal substances. Used as weapons by the body’s defense system, free radicals destroy invading pathogenic microbes to prevent disease.

Restoring the blood-brain barrier?

There’s a bouncer in everyone: The blood-brain barrier, a layer of cells between blood vessels and the rest of the brain, kicks out toxins, pathogens and other undesirables that can sabotage the brain’s precious gray matter.

When the bouncer is off its guard and a rowdy element gains entry, a variety of conditions can crop up. Barrier-invading cancer cells can develop into tumors, and multiple sclerosis can occur when too many white blood cells slip pass the barrier, leading to an autoimmune attack on the protective layer of brain nerves, hindering their communication with the rest of the body.

“A leaky blood-brain barrier is a common pathway for a lot of brain diseases, so to be able to seal off the barrier has been a long sought-after goal in medicine,” said Calvin Kuo, MD, PhD, the Maureen Lyles D’Ambrogio Professor and a professor of hematology.

Researchers uncover a cellular process that leads to inflammation

Cedars-Sinai investigators have identified several steps in a cellular process responsible for triggering one of the body’s important inflammatory responses. Their findings, published in the journal Science Immunology, open up possibilities for modulating the type of inflammation associated with several infections and inflammatory diseases.

Specifically, the investigators have improved understanding of the steps that lead to the production of IL-1 beta, a potent inflammatory protein signal released during many inflammatory responses.

“We now have a clearer understanding of the stepwise process that leads to the production of IL-1 beta,” said Andrea Wolf, Ph.D., assistant professor of Biomedical Sciences and Medicine at Cedars-Sinai, and a senior and corresponding author on the new study. “By understanding the process, we hope to one day find a treatment for diseases associated with this inflammatory response.”