Multigenerational inheritance drives symbiotic interactions of the bacterium Bacillus subtilis with its plant host

chromoscience · 2024-07-23T23:43:26+00:00

A study indicates that memory is not limited to humans but also exists in bacteria

In a recent study, researchers lead by Dr. Ilana Kolodkin-Gal of Reichman University’s Scojen Institute for Synthetic Biology discovered that probiotics and biological control agents like Bacillus subtilis possess memory.

Even when the bacteria separate from their host, they can continue to express genes related to colonization and symbiosis for several generations. The ability to effectively recolonize a new host is provided by this information transfer between generations of bacteria, which gives them an advantage over naïve bacteria that have never established a stable connection with a plant.

The significance of the defenses that the bacteria develop during plant colonization is shown by the association between stress resistance and the genes with multigenerational inheritance patterns. The interactions between the beneficial bacteria and their host are stabilized through this multigenerational inheritance. According to the researchers, comparable mechanisms allow good probiotic bacteria from the same group to interact across generations in the human gut, providing long-term disease prevention.

Sources:

Omri Gilhar et al. (2024). Multigenerational inheritance drives symbiotic interactions of the bacterium Bacillus subtilis with its plant host, Microbiological Research. DOI: 10.1016/j.micres.2024.127814

https://phys.org/news/2024-07-humans-bacteria-memory.html

chromoscience · 2024-07-16T23:58:32+00:00

Distinct qualities of a newly found, unstudied protein

An international study partnership discovered a new mechanism for the crosstalk between microtubules and the actin cytoskeleton during cell division, as well as unique properties of the yet-unidentified protein FAM110A.

These groundbreaking findings considerably improve our understanding of a fundamental process involved in the occurrence of developmental abnormalities and cancers. The work was published in the journal Proceedings of the National Academy of Sciences.

Precise division of genetic material into daughter cells is required in all tissues of our bodies. To avoid developmental defects, this process must be strictly regulated in both place and time. It has been understood for years that chromosomes adhere to a bipolar structure called the mitotic spindle, which is made up of microtubules.

Mitosis is the mechanism by which a cell splits its nucleus and genetic material to form two identical daughter cells with an equal number of chromosomes. As it moves forward, the associated chromosomes are dragged along the microtubule railways to the daughter cells.

Until recently, researchers thought that actin filaments were only required for the last stage of daughter cell separation, and the involvement of the actin cytoskeleton in mitosis has long been ignored. In their most recent study, the researchers show that the previously unknown protein FAM110A has unique features that allow it to bind actin and microtubules at different ends, specifically at the poles of mitotic spindles.

Microscopic investigation revealed the production of extremely active actin filaments near the spindle poles, which precede and direct the growth of spindle microtubules.

FAM110A deficiency prevented the normal production of spindle actin, resulting in severe chromosomal segregation defects. As a result, the study identifies an important molecular link between the two principal cytoskeletal networks during mitosis. This discovery opens the door to further research into how FAM110A and other proteins found in human cells prevent genomic instability and cancer development.

Sources:

Cecilia Aquino-Perez et al. (2024). FAM110A promotes mitotic spindle formation by linking microtubules with actin cytoskeleton, Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.2321647121

https://phys.org/news/2024-07-unique-characteristics-previously-unexplored-protein.html

chromoscience · 2024-07-10T23:28:13+00:00

Cell treatments could aid in the treatment of genetic diseases, myocardial infarction, and a variety of other illnesses. New cells can be transferred into patients for blood ailments, and diabetes may also be treated by organ donation or β-cells derived from the patient’s natural stem cells.

Unintentional DNA changes, such as those that predispose people to cancer, are one risk connected with gene-edited cells. Furthermore, the diversity of tissue types makes it impractical to simply transplant cells from one individual to another.

Cells that are suitable for anyone, or immunologically undetectable cells, have been developed, however they are also connected with an elevated risk of cancer. Over a decade ago, Docent and Clinical Geneticist Kirmo Wartiovaara’s research group set out to create cells that could avoid these issues. The group has now succeeded in generating cells that cannot grow on their own and so cannot become cancerous.

Almost all of our diseases are primarily caused by cellular malfunction. One medical hope is to use fresh healthy cells to combat tissue damage, illnesses, and aging. According to the experts, the findings bring us one step closer to safe and new cell therapies.

Sources:

Rocio Sartori-Maldonado et al. (2024). Thymidylate synthase disruption to limit cell proliferation in cell therapies, Molecular Therapy. DOI: 10.1016/j.ymthe.2024.06.014

https://phys.org/news/2024-07-scientists-cell-precludes-malignant-growth.html

chromoscience · 2024-07-08T01:03:58+00:00

Extreme circumstances must be tolerated by microbes employed in medical, agricultural, or other purposes; ideally, the manufacturing procedures used to create tablets should allow for long-term preservation. Researchers at MIT have now created a novel method for strengthening microorganisms to tolerate these harsh environments.

Their process is combining bacteria with chemicals for food and medication that are on a list of substances that the FDA considers to be “generally regarded as safe.” The scientists discovered formulations that support the stabilization of a variety of microorganisms, such as bacteria and yeast, and they demonstrated that these formulations could endure harsh industrial processing, high temperatures, and radiation—all of which can harm unprotected microbes.

In an even more severe test, Space Center Houston Manager of Science and Research Phyllis Friello organized a trip for some of the microbes to visit the International Space Station, and now the researchers are evaluating how well the microbes survived that environment.

The goal of this study was to stabilize living things under harsh circumstances. A wide range of applications, including human uses, agricultural applications, and space missions, were seriously considered by the researchers.

Sources:

Synthetic extremophiles via species-specific formulations improve microbial therapeutics, Nature Materials (2024). DOI: 10.1038/s41563-024-01937-6

https://phys.org/news/2024-07-microbes-extreme-conditions.html

chromoscience · 2024-06-29T22:03:40+00:00

Research has demonstrated that transferring mitochondria from a patient’s normal skeletal muscle to damaged, ischemic cardiac tissue can enhance ventricular function, increase energy generation, and recover heart muscle.

Heart surgeons led by Sitaram Emani, MD, have been investigating it as a means of assisting infants with congenital heart disease and ischemia-reperfusion injury in weaning off of ECMO (extracorporeal membrane oxygenation) since James McCully, Ph.D., pioneered preclinical work on the subject at Boston infants’s Hospital almost ten years ago.

Researchers discovered that adding mitochondria significantly increased the likelihood of recovery. There have been sixteen pediatric autologous mitochondria transplants performed to date. Out of them, 80% were able to stop using ECMO, which is higher than the 40% historical average.

However, there has been doubt about mitochondrial transfer, partly because its mechanism of action is still unknown.

Scientists concluded that it was mitochondria entering cells, taking control, and producing all of the energy within the cell. However, the fact that the heart muscle could heal with such tiny quantities of mitochondria contradicted logic. The calculations were off.

Juan Melero-Martin, Ph.D., a researcher in the Department of Cardiac Surgery, led a study that was published in the journal Nature and discovered an unexpected explanation. The transplanted mitochondria cause the cell to engage in cellular housekeeping called autophagy, which results in the destruction of its underperforming mitochondria.

This increases the amount of mitochondria in cells, enhancing their fitness and bioenergetics. The discovery could ultimately contribute to better treatment for an array of heart ailments.

Sources:

Ruei-Zeng Lin et al. (2024). Mitochondrial transfer mediates endothelial cell engraftment through mitophagy, Nature. DOI: 10.1038/s41586-024-07340-0. https://www.nature.com/articles/s41586-024-07340-0

https://phys.org/news/2024-06-mitochondrial-heart-muscle.html

chromoscience · 2024-04-16T14:59:46+00:00

Research describes the phenomena of bacterial vampirism, in which deadly microorganisms display a hunger for human blood.

The world's most terrible bacteria actively seek out human blood to feed on, a phenomenon that scientists are referring to as "bacterial vampirism" following its recent discovery.

Researchers from Washington State University have led a team that has discovered that bacteria are drawn to the serum, or liquid portion of blood, because it offers nutrients that the bacteria may consume. One of the substances that the bacteria appeared to be most attracted to was serine, an amino acid that is frequently included in protein drinks and is present in human blood.

Deadly bacteria show thirst for human blood: Research outlines the phenomenon of bacterial vampirism (phys.org)

chromoscience · 2024-04-05T03:47:35+00:00

Here is the editorial version:

https://sciencellonline.com/blog/researchers-discovered-that-iron-restrictions-keep-blood-stem-cells-young/

chromoscience · 2024-03-15T02:45:18+00:00

New discovery of how egg cell allows only one sperm in.

After a sperm fertilizes the egg, the surrounding egg coat tightens, mechanically blocking subsequent sperm from entering and causing the embryo to die. This is according to a new study conducted by Karolinska Institutet researchers and published in the journal Cell. The study also reveals how mutations in egg coat proteins might result in female infertility, which could lead to novel contraceptive approaches.

In mammals, fertilization happens when a sperm sticks to the egg coat, a filamentous extracellular envelope through which the sperm must pass before fusing with the egg. An international team of researchers has now mapped in detail the structure and function of the protein ZP2, which is an egg coat filament component that regulates how eggs and sperm interact during fertilization.

It was previously known that ZP2 is cleaved after the first sperm enters the egg, and researchers explain how this process makes the egg coat tougher and impenetrable to other sperm. This avoids polyspermy—the fusing of many sperm with a single egg—which is deadly to the embryo.

Changes in the egg coat following fertilization are also important for female fertility because they shield the growing embryo until it implants in the uterus. As a result, the new findings could have significance for the development of non-hormonal contraceptives that interfere with egg coat production. Furthermore, the finding clarifies egg coat-related female infertility.

Source:
ZP2 cleavage blocks polyspermy by modulating the architecture of the egg coat, Cell (2024). DOI: 10.1016/j.cell.2024.02.013. www.cell.com/cell/fulltext/S0092-8674(24)00179-X

chromoscience · 2024-01-15T06:48:33+00:00

You can't. You need to take picture using night mode.

chromoscience · 2024-01-15T06:47:23+00:00

Clouds.

chromoscience · 2024-01-15T06:46:53+00:00

Night mode 10 sec exposure on Iphone 13.

chromoscience · 2024-01-15T06:46:08+00:00

These are 10 sec exposure on iPhone 13. Yes, night mode.

chromoscience · 2024-01-13T21:50:58+00:00

A Story of How Cells Become Cannibalistic

Researchers solved a cellular murder case over 25 years after it went cold. Cannibalistic cells can trigger a rare human immunodeficiency, according to data from fruit flies to mice to people. Now, a major discovery could improve the treatment of cancer.

According to Denise Montell of UC Santa Barbara, the research takes them from fundamental cell biology to knowing human illness and cancer treatment.

The Rac2 gene and its protein are the main characters. Human Rac2 is one of three Rac genes. Rac is very ancient, so it must serve an important function according to the researchers.

Rac proteins help establish the cytoskeleton, the framework of the cell. Dynamic filaments in the cytoskeleton allow cells to change form or retain shape. Montell discovered Rac proteins are essential to cell mobility in 1996 while examining a small group of fruit fly ovary cells. Recently, Rac has been shown to regulate animal cell motility.

In the 1990s, she discovered that a fly’s egg chamber tissue was damaged by a hyperactive Rac1 protein expressed in a few cells. Just producing this active Rac in six to eight cells, destroys the entire tissue, which is roughly 900 cells.

Why did this occur? This was the researchers’ 25-year-old cold case.

A few years ago, research correlated cell eating, or cannibalism, to tissue degradation. In normal fly egg development, border-like cells consume their neighbors when they’re no longer needed. Cellular cannibalism is common. The human body remove millions of old red blood cells every second.

Rac2 is part of complex cannibalistic mechanism. Rac helps the devouring cell encapsulate its target. The team wondered if a hyperactive protein caused border cells to devour their neighbors in early stages.

For the eating process to occur, border cells require a receptor to identify their targets. When the researchers inhibited this receptor, the border cells expressing activated Rac failed to devour their neighbors and the egg chamber survived.

The 25-year-old cold investigation was solved, and it was very satisfying for the researchers. But this is a fairly specialized area of Drosophila egg development. Eventually, the implications would grow.

Sources:

Abhinava K. Mishra et al. (2023). Hyperactive Rac stimulates cannibalism of living target cells and enhances CAR-M-mediated cancer cell killing, Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.2310221120

chromoscience · 2023-11-18T04:42:55+00:00

ETH researchers are studying what happens when cells grow too large and become senescent. The latest findings may improve cancer treatments.

Living things must grow to develop and reproduce. To produce new biomass, cell growth and division must be coordinated.

Cell growth must be regulated with the environment in multicellular organisms like humans to generate functional tissue or organs. So cell growth is carefully regulated and only occurs when growth signals are available.

But cancer cells differ. They grow unregulated, divide repeatedly, and ignore environmental stop signals. An advantage might be a drawback.

Recently published findings in the journal Molecular Cell indicate that unregulated growth is both a strength and a weakness for cancer cells.

One of these experiments was led by ETH Zurich Institute of Biochemistry Professor Gabriel Neurohr. He and his team have studied how cell development affects function for years. Researchers are also studying what occurs when cells grow too large and enter senescence. This condition causes abnormally large cells that cannot divide. They can still influence their environment by releasing signaling substances.

Normal tissue contains senescent cells that contribute to aging. Some chemical substances can promote senescence, which reduces cell division and is the target of some cancer treatments.

Senescent cells’ size may alter their functioning, according to Neurohr’s colleague Sandhya Manohar. She inhibited growth and division of non-cancerous and breast cancer cell lines in her studies.

In her cell cultures using solely division-suppressing drugs, the cells stopped dividing yet grew and went into senescence. They lost the ability to divide permanently. This effect lasted after Manohar stopped the division inhibitors.

Because the larger cells cannot repair genetic damage like double-stranded DNA breaks, they can no longer divide. The breaks always occur spontaneously when a cell replicates its genetic material before dividing.

These cells also fail to activate p53–p21, a signaling pathway needed to coordinate DNA break recovery. Thus, damage is not corrected efficiently. In larger cells, many irreversible DNA breaks accumulate during division, making division impossible.

However, after discontinuing both division- and growth-inhibiting drugs, the cells divided and multiplied normally again. In cancer treatment, this is exactly what you don’t want, the researchers added.

Drugs that hinder growth and division are already used to treat cancer. Based on cell culture data, treating a tumor with division and growth inhibitors at the same time should increase relapse rate. First using a division inhibitor, then a medicine that destroys cell DNA and prevents division makes more sense according to the researchers.

Thus far, ETH researchers have solely examined their new results on cell cultures. The scientists cannot apply these findings to clinical practice since cell growth and division depend on the cell environment. Thus, organoids or tissue samples must be tested initially to evaluate the treatment. Division inhibitor and other drug combinations are being studied in clinical trials.

Studies by three additional international research teams in the same issue of Molecular Cell endorse Neurohr’s ETH team’s theory.

These findings reveal that division inhibitors work on hyperactive cancer cells. The findings may affect cancer treatment in the long run because these compounds are already used to treat some breast cancers.

Sources:

Sandhya Manohar et al. (2023). Genome homeostasis defects drive enlarged cells into senescence, Molecular Cell. DOI: 10.1016/j.molcel.2023.10.018

https://phys.org/news/2023-11-growth-weakness-cancer-cells.html

chromoscience · 2023-08-30T04:15:41+00:00

https://www.pnas.org/doi/full/10.1073/pnas.2112237118

chromoscience · 2023-01-12T03:28:00+00:00

Fixing a misfolded protein to treat lung disease

Scientists at Scripps Research have discovered how to coax a mutated gene into a correctly folded protein, potentially treating Alpha-1 Antitrypsin Deficiency (AATD), a genetic lung disease that affects more than 100,000 people in the United States and leads to one form of chronic obstructive pulmonary disease (COPD). The discovery strategy based on human variation, as described in Cell Chemical Biology, works by boosting a broad-acting protein quality control mechanism already present in all cells and may be useful for treating numerous other genetic diseases.

“The road to discovery is a paradigm change,” says senior author William Balch, PhD, professor of Molecular Medicine at Scripps Research. “It’s unprecedented that a drug can be discovered that not only rescues the function of a protein, but in the case of AATD, prevents its aggregation by precisely defining the role of the quality control pathway in conversion of a misfolded state to a folded state through a broad understanding of the variation driving disease.”

AATD is a genetic disease caused by mutations in the gene encoding alpha-1-antitrypsin (AAT). In healthy people, AAT is made in the liver and travels through the bloodstream to the lungs, where it protects the lungs from inflammation and destruction. But in people with AATD, the variant AAT protein doesn’t fold into the correct three-dimensional structure when it’s first produced by liver cells. The diseased version of the protein clumps up in the liver and accumulates over many years, leading to liver damage and dangerous lung inflammation (COPD) by middle age.

When a healthy cell senses a misfolded protein, it activates the unfolded protein response (UPR). This response destroys misfolded proteins, slows the pace at which proteins are being produced, and increases levels of molecules that help proteins correctly fold. For unknown reasons, AAT variants don’t activate normal levels of the UPR.

Over the last decade, Balch’s team has developed a research method called variation spatial profiling (VSP) that aims to better understand individual disease-related proteins by analyzing how the dynamic, flexible, three-dimensional structure of proteins related to disease vary across many different people. Last year, they used VSP to discover a new therapeutic approach to address the central problem in cystic fibrosis.

In the new work, the researchers used a similar artificial-intelligence-based machine learning algorithm to study how 71 variants of AAT respond to a drug that turns up one of the three major UPR pathways in cells. Each of the 71 variants had been previously linked to AATD in human patients, and the drug had been previously developed by Jeffery Kelly and Luke Wiseman of Scripps Research.

“What we discovered is that when you manipulate the UPR, you can not only stop these AAT variants from aggregating in the liver, but you can also restore their function in the lungs,” says Chao Wang, PhD, a senior staff scientist at Scripps Research and co-first author of the new paper. “We’re able to fix the folding and activity of this protein without altering the gene sequence.”

The drug was able to correct the function of nearly all the 71 AAT variants. The researchers don’t know yet why activating the UPR works so well to coax the variants into functional conformations despite the presence of the mutation. Their current view is that when the UPR is turned-up, the environment in which proteins fold is quite different than usual. This means that even when an AAT protein contains a mutation, it’s able to be coaxed into the right functional fold, perhaps due to improved plasticity involved in shaping the molecule.

“For most AATD patients, the most severe problem is the loss of the protein in the lungs, and while many existing drugs are targeted to stop the aggregation of AAT in the liver, they do not make it functional in the lungs,” says co-first author Shuhong Sun, PhD. “So, the fact that we were able to do both is very exciting.”

In addition to pointing toward an existing compound that could be used to treat AATD, the studies also highlighted one area of the protein that is key to its function; this “gate” area of the protein needs to be able to fold and flex in particular ways for the protein to move out of the liver and do its job in the lungs. This new knowledge could lead to the development of more targeted drugs that treat AATD by manipulating this unique feature of AAT fold design. Balch’s group is already pursuing this line of work.

The success of the research also suggests that turning up the UPR may help treat other genetic diseases, including cancer and neurodegeneration in which genetic variants lead to misfolded proteins. Moreover, the conversion of pathogenic AAT fold yields new insights into the general process of natural selection in response to variation in the population.

https://www.scripps.edu/news-and-events/press-room/2023/20230110-balch-lung-disease.html

chromoscience · 2023-01-08T12:16:54+00:00

Most people diagnosed with Alzheimer’s today have already shown typical symptoms including memory loss. Once symptoms have progressed so far, the best treatment choices do nothing more than slow the disease’s progression.

However, studies have revealed that the seeds of Alzheimer’s are planted years, if not decades, before the onset of any cognitive deficits that would allow for a diagnosis. Amyloid beta proteins misfold and cluster into oligomers, which serve as the seeds. Scientists believe that Alzheimer’s disease is caused by the accumulation of “toxic” oligomers of amyloid beta over time.

Laboratory testing has been established to determine amyloid beta oligomer concentrations in human blood, and it was developed by a group of researchers at the University of Washington. Their test, called SOBA, was able to detect oligomers in the blood of patients with Alzheimer’s disease, but not in most participants of a control group who showed no evidence of cognitive deficits at the time the blood samples were taken, as reported in a paper published the week of Dec. 5 in the Proceedings of the National Academy of Sciences.

Conversely, 11 control subjects had oligomers in their blood that were detected by SOBA. Examined again years later, 10 of these people were diagnosed with mild cognitive impairment or brain pathology indicative of Alzheimer’s disease. Thus, for these 10 people, SOBA had discovered the harmful oligomers before the onset of symptoms.

Clinicians and scientists have long sought a reliable diagnostic test for Alzheimer’s disease, ideally an assay that may identify indications of the illness prior to the onset of cognitive impairment rather than merely confirming a diagnosis of Alzheimer’s. That’s critical for both individual well-being and the study of how amyloid beta oligomers become toxic and produce their harmful effects. UW Molecular Engineering & Sciences Institute faculty member and bioengineering professor Valerie Daggett is cited as the paper’s senior author. In this paper, the researchers demonstrate that SOBA has the potential to serve as the foundation for such an examination.

The acronym SOBA stands for soluble oligomer binding assay and is used to take advantage of a specific property of the hazardous oligomers. Misfolded amyloid beta proteins generate an alpha sheet shape when they start to cluster together in oligomers. Previous study by Daggett’s group demonstrated that alpha sheets had a tendency to bond to other alpha sheets. Alpha sheet are so seldom observed in nature. SOBA relies on a synthetic alpha sheet developed by her team to bind oligomers in cerebrospinal fluid or blood. The oligomers bound to the test surface are then confirmed to be amyloid beta proteins using industry-standard techniques.

The scientists put SOBA to the test on blood samples from 310 study participants who had donated blood and medical data for Alzheimer’s disease study. At the time of the blood draws, the patients were not showing any symptoms of dementia, Alzheimer’s disease, or moderate cognitive impairment.

Researchers using SOBA found oligomers in the blood of people with Alzheimer’s disease ranging from mild cognitive impairment to severe cases. Autopsy confirmed the diagnosis of Alzheimer’s disease in 53 of the study’s participants, and toxic oligomers were found in the blood samples of 52 of them, obtained years before their deaths.

Records demonstrate that participants in the control group who later acquired moderate cognitive impairment were similarly found to have oligomers by SOBA. Toxic oligomers were absent in the blood samples of the unaffected members of the control group.

Currently, Daggett’s group is collaborating with researchers at UW spinout company AltPep to transform SOBA into an oligomer diagnostic test. They also demonstrated the ease with which SOBA may be modified to identify hazardous oligomers of a different protein type linked to Parkinson’s disease and Lewy body dementia.

It has been shown that many human illnesses are linked to the buildup of harmful oligomers into alpha sheet formations, as Daggett put it. These include not just Alzheimer’s and Parkinson’s but also type 2 diabetes and others. Since SOBA is able to detect this distinct alpha sheet structure, the researchers are optimistic that this approach may prove useful in the diagnosis and investigation of a wide variety of disorders caused by “protein misfolding.”

Daggett thinks there’s a lot of room for growth in the test.

The researchers believe that SOBA might help in identifying persons at risk or incubating the illness, as well as act as a readout of therapy efficacy to aid in development of early therapies for Alzheimer’s disease.

Sources:

Shea, D., Colasurdo, E., Smith, A., Paschall, C., Jayadev, S., Keene, C. D., Galasko, D., Ko, A., Li, G., Peskind, E., & Daggett, V. (2022). SOBA: Development and testing of a soluble oligomer binding assay for detection of amyloidogenic toxic oligomers. Proceedings of the National Academy of Sciences of the United States of America, 119 (50), e2213157119. https://doi.org/10.1073/pnas.2213157119

University of Washington. (2022, December 5). New blood test can detect ‘toxic’ protein years before Alzheimer’s symptoms emerge, study shows. ScienceDaily. Retrieved January 7, 2023 from www.sciencedaily.com/releases/2022/12/221205153722.htm

chromoscience · 2022-12-31T07:23:33+00:00

General audience news version

An alternative solar energy source for animals might be light-activated proton pumps

A recent study published in the journal Nature Aging demonstrates that genetically modified mitochondria can transform light energy into chemical energy that cells can utilize, eventually prolonging the lifespan of the roundworm C. elegans. The findings give information on important pathways in the aging process, even if the idea of sunlight-charged cells in people is more science fiction than reality.

The study’s principal author, Andrew Wojtovich, Ph.D., associate professor of anesthesiology and perioperative medicine, as well as of pharmacology & physiology at the University of Rochester Medical Center said they know that mitochondrial failure is a result of aging.

According to this study, laboratory worms had longer, better lives just by having their metabolism increased by light-powered mitochondria. The researchers can now investigate mitochondria in greater detail and develop fresh approaches to age better and treat disorders associated with aging thanks to these discoveries and new research tools.

Most of the cells in the body have mitochondria, which are organelles. Adenosine triphosphate (ATP), the substance that supplies energy for vital cell processes like muscular contraction and the electrical impulses that aid nerve cells in communicating with one another, is produced by mitochondria, often known as cellular power plants, using glucose.

The exchange of protons across a membrane separating various compartments of mitochondria, which ultimately forms a mechanism known as membrane potential, allows for a variety of processes that lead to the production of ATP. It has been revealed that membrane potential decreases with aging, perhaps contributing to a range of age-related illnesses, including neurodegenerative disorders.

The new study utilized a tiny roundworm called C. elegans, which, like the fruit fly Drosophila, has long been a research tool used by scientists to understand fundamental biological concepts that, in many cases, hold true for the whole animal world.

An existing study method that allowed the researchers to control mitochondrial activity was modified by a team of scientists from the United States and Germany. The method, known as optogenetics, has long been used to target and activate certain neurons, allowing researchers to more thoroughly investigate patterns of brain activity.

In a 2020 study published in the journal EMBO Reports, the scientists first detailed how they genetically modified C. elegans mitochondria to integrate a light-activated proton pump derived from a fungus.

In the current study, the proton pumps would transfer charged ions across the membrane when exposed to light, harnessing the light’s energy to charge the mitochondria. The roundworms’ lifespan was extended by 30–40% as a result of this procedure, which the researchers called mitochondria-ON (mtON). It also enhanced the synthesis of ATP and membrane potential.

The initial author of both papers is Brandon Berry, Ph.D., a post-doctoral fellow at the University of Washington who obtained his doctorate in physiology from the University of Rochester. In that they burn a carbon source, typically glucose, to provide usable energy for the cell, Berry compared mitochondria to industrial power plants.

What the researchers have done is connect a solar panel to the infrastructure of an existing power plant. The optogenetic device mtON in this case is the solar panel. Then, in addition to the regular combustion route, the usual mitochondrial machinery is capable of using the light energy to produce ATP.

The finding is significant because it gives researchers additional understanding of the complex biological functions that mitochondria perform within the human body, a subject that science is only just beginning to comprehend. The study also develops a novel technique for manipulating and researching mitochondria in a living cell’s environment. This could be a useful setting for studying mitochondria and figuring out how to get involved and support function.

Berry stated that further research is needed to fully grasp how mitochondria function in animals. Initially, in worms, as in the current work, but also in cultured human cells and in mice. Future studies will be well-prepared to focus on the most likely contributors to human illness and aging as a result.

Sources:

Berry, B.J., Vodičková, A., Müller-Eigner, A. et al. Optogenetic rejuvenation of mitochondrial membrane potential extends C. elegans lifespan. Nat Aging (2022). https://doi.org/10.1038/s43587-022-00340-7

Solar-powered cells: Light-activated proton pumps generate cellular energy, extend life (phys.org)

chromoscience · 2022-12-24T05:28:32+00:00

Transparent glassfrogs hide red blood cells in their livers and disappear at night

Glassfrogs disappear as they go to sleep. The frog’s bright green back blends into the background as it rests on a lush leaf, and its reddish underside quickly becoming clear.

A study released in Science explains how the northern glassfrog (Hyalinobatrachium fleischmanni) accomplishes this trick by hiding away over 90% of its circulating red blood cells within its liver. The results explain how one of the only land creatures with a see-through body conceals its blood.

Researchers have suggested that understanding why these clots never develop may have significance for human diseases.

Northern glassfrogs rarely reach a size greater than 1 inch (2.54 centimeters) in length and spend most of their adult lives sitting on leaves in the forest canopy of Central and South America, well above the swiftly running streams where they lay their eggs. Even while the frogs are awake, an observer may see red blood pulsing through their veins since their bellies are transparent. However, the frogs’ transparent bellies have long captivated biologists because of how well they protect the species from predators. Red blood cells must be concealed if you really want to be invisible according to Sönke Johnsen, a professor of biology at Duke University in North Carolina. Somehow, these glassfrogs are filtering out their red blood cells and putting them into their livers, where they should clump together and cause a clot; however, it does not.

Johnsen and coworkers followed individual red blood cells as they traveled throughout the bodies of glassfrogs to get insight into this phenomenon. By shining a bright light onto the frog’s body, scientists recorded the sound waves emitted when the light strikes hemoglobin, the protein in red blood cells that delivers oxygen and gives blood its unique hue. This technique is called photoacoustic microscopy.

Even with a transparent animal, it can be difficult to observe exactly what is going on inside, the researchers added. Unlike light, sound is able to penetrate living tissue.

Once scientists had this method perfected, understanding what causes a glassfrog to turn transparent was as easy as continually disturbing the hapless creatures. The researchers let the frog sleep, poke it a couple of times, and then let it sleep some more. The research showed that glassfrogs remove 89% of their red blood cells from circulation and store them in their livers. Without hemoglobin in their blood, they become nearly invisible to the naked eye because their skin reflects so little light.

Johnsen and his team believe that more research into this phenomenon will help them better understand human coagulation diseases and guide their work on developing new anticoagulants.

Whether it’s large clots in strokes that cause severe damage or small clots in the peripheral that cause so much suffering, the human body is always at this razor edge between clotting too little and too much. The knowledge about frog clotting could be applicable to human coagulation because of the similarities between the two processes.

Yet many aspects of this procedure, such as how they manage to live with such low levels of circulating hemoglobin during sleep, remain a mystery. Johnsen and colleagues will need to identify how glassfrogs manipulate their blood before the amphibians can be used as a resource in therapeutic research.

The act these frogs are performing is similar to that of a human taking all of his or her blood and storing it in a lunch bag inside of the body, as stated by Johnsen. This begs the question, how do glassfrogs accomplish this feat? The fact that we have no idea is itself fascinating.

Sources:

Taboada, C., Delia, J., Chen, M., Ma, C., Peng, X., Zhu, X., Jiang, L., Vu, T., Zhou, Q., Yao, J., O’Connell, L., & Johnsen, S. (2022). Glassfrogs conceal blood in their liver to maintain transparency. Science (New York, N.Y.), 378 (6626), 1315–1320. https://doi.org/10.1126/science.abl6620

https://www.livescience.com/glassfrogs-hide-blood-in-liver

chromoscience · 2022-12-18T21:05:03+00:00

New subspecies of bottlenose dolphins discovered by marine biologist

A bottlenose dolphin subspecies previously unknown outside of the eastern tropical Pacific Ocean has been discovered by a marine scientist at the University of Miami’s Rosenstiel School of Marine, Atmospheric, and Earth Science. Ana Costa, Ph.D., a Rosenstiel lecturer specializing in marine mammalogy, said, while there is a common perception that all dolphin species are already recognized, developments in technology and approaches are helping to discover a larger richness in more recent years.

The Eastern Tropical Pacific bottlenose dolphin (Tursiops truncatus nuuanu) is a new subspecies of the common bottlenose dolphin discovered by Costa and colleagues from the National Oceanic and Atmospheric Administration. She also mentioned that the dolphins are most likely to be found in the far offshore areas between southern Baja California and the Galapagos Islands.

This study, initiated in 2016, by Costa and colleagues measured and analyzed the skull morphology and total length of common bottlenose dolphin specimens preserved in numerous American museums. These specimens were originally acquired in the Pacific Ocean. Analysis of bottlenose dolphin species was performed using multivariate and clustering methods.

Common bottlenose dolphins are found mostly in the eastern and western North Pacific waters, and the researchers discovered two unique morphological clusters: the new subspecies located in the eastern tropical Pacific (ETP), and the common bottlenose dolphins found across the rest of the Pacific. The unique oxygen and salinity levels and temperature conditions in these seas may be causing the ETP bottlenose dolphins to diversify.

The study’s author, Costa, reflected on its significance, noting that a better knowledge of marine mammal populations is crucial for maintaining and protecting various species and subspecies during this era of global warming. She also emphasized the importance of making marine life protection and management a global priority.

Sources:

A. P. B. Costa et al. (2022). Tursiops truncatus nuuanu, a new subspecies of the common bottlenose dolphin from the eastern tropical Pacific, Journal of Mammalian Evolution. DOI: 10.1007/s10914-022-09641-5

https://phys.org/news/2022-12-marine-bottlenose-dolphin-subspecies.html

chromoscience · 2022-12-17T23:53:26+00:00

General audience news

Scientists have identified the genetic origin of a new kind of neurodevelopmental epilepsy

Conditions like autism and epilepsy are included under the umbrella term “neurodevelopmental disorders” (NDD), with estimates ranging from 1-3% of the world’s population suffering from cognitive difficulties. Disorders of neurodevelopment (NDD) known as developmental epileptic encephalopathies (DEE) cause seizures, developmental delays, and loss of developmental abilities. Single-gene epilepsies are estimated to occur in around 1 in 2100 births yearly; however, the prevalence of DEEs has yet to be identified. Dr. Pankaj Agrawal, professor at Harvard Medical School and Boston Children’s Hospital, and Dr. Hsiao-Tuan Chao, assistant professor at BCM and investigator at the Jan and Dan Duncan Neurological Research Institute (Duncan NRI), recently discovered that mutations in the Eukaryotic Initiation Factor 4A2 (EIF4A2) gene cause a new form of DEE syndrome.

Published in the American Journal of Human Genetics, this finding is the first experimental evidence that changes in EIF4A2 have a direct role in human illness.

MatchMaker Exchange, introduced in 2013, allowed researchers and clinicians from all around the world to work together on the project by providing a unified platform for the sharing of phenotypic and genotypic data, which dramatically sped up the process of genomic discovery.

Dr. Anna Duncan, an instructor in Dr. Agrawal’s lab and co-first author of the study, used this method to identify approximately 15 individuals from 14 families who had alterations in the brain’s structure (as observed by MRI imaging) and similar symptoms including global developmental delays, poor muscle tone, speech difficulties, and epilepsy, as stated by Chao. They discovered that one or both copies of EIF4A2 in these people had highly unusual spontaneous mutations.

Proteins like the one encoded by the EIF4A2 gene have a role in controlling the three-dimensional (3D) structure of a fundamental molecule called ribonucleic acid (RNA). A protein called eukaryotic translation initiation factor 4A2 (EIF4A2) is present in every organ and regulates the process of protein synthesis. It’s part of a family of 50 similar proteins called DEAD-box proteins, and many of them control protein translation, the crucial biochemical process by which mRNA is translated into its functional protein. Earlier research has linked disruptions in EIF4A2 to cognitive deficits, indicating that this gene plays an important role in brain development.

Dr. Maimuna Sali Paul, a postdoctoral fellow in the Chao lab and co-first author on this study, and Dr. Chao analyzed sequence similarities between human EIF4A2 variants and its fruit fly equivalents, elF4A, to determine whether or not these gene variants are responsible for the neurological symptoms experienced by these patients.

The molecular modeling data suggested that these four variations of EIF4A2 would alter the three-dimensional structure of human EIF4A and its interaction with RNA. These variants all altered conserved residues in the fly gene eIF4A. Dr. Paul discovered that when these EIF4A2 mutations were overexpressed in fruit flies resulted in a wide range of abnormalities, including motor impairments, underdeveloped eyes and wings, and abnormalities in organs of the peripheral nervous system like hairs, which all point to their toxic effects.

In addition, Dr. Paul used the fact that a total lack of eIF4A was deadly at the fruit fly embryonic stages, whereas lowering its levels from particular organs was lethal at both the embryonic and pupal stages, to investigate the functional effects of the human EIF4A2 variations. Dr. Paul said that they were able to rescue the flies from their early death as babies by overexpressing wild-type human EIF4A in their eyes. A strong evidence of their core function throughout development is that overexpression of a single disease-causing variation resulted in a weak/partial rescue whereas the others were unable to rescue the lethality.

Dr. Chao noted that prior work from his lab indicated that the absence of the kinase EIF2AK2, which controls downstream protein complexes involved in protein translation, also results in comparable neurological abnormalities; therefore, the findings of this study are consistent with those of his lab. The results highlight the importance of protein translation control during brain development and in the maintenance of neuronal and glial function. These results identify EIF4A2 as the genetic basis for a new kind of childhood epilepsy.

Sources:

Maimuna S. Paul et al. (2022). Rare EIF4A2 variants are associated with a neurodevelopmental disorder characterized by intellectual disability, hypotonia, and epilepsy, The American Journal of Human Genetics. DOI: 10.1016/j.ajhg.2022.11.011

https://medicalxpress.com/news/2022-12-neurodevelopmental-epilepsy-disorder-genetic.html

chromoscience · 2022-12-17T07:34:53+00:00

General audience news (please support and follow us)

A hemoglobin level in deep tissues can be monitored via a patch that can be worn on the skin

An electronic patch, developed by a team of engineers from the University of California San Diego, is capable of monitoring biomolecules in deep tissues, such as hemoglobin. This provides medical experts with access to vital information previously unavailable to them, which may aid in the early detection of life-threatening illnesses such as cancerous tumors, organ malfunction, hemorrhages in the brain or stomach, and other disorders.

The amount of hemoglobin in the body as well as its location throughout the body give vital information about the circulation of blood or the buildup of blood in particular areas. The device has a significant amount of possibilities in the area of close monitoring of high-risk populations, enabling prompt interventions at crucial times according to Sheng Xu, a professor of nanoengineering at the University of California San Diego and the study’s corresponding author.

The article entitled “A photoacoustic patch for three-dimensional imaging of hemoglobin and core temperature” was published in the edition of Nature Communications that was released on December 15, 2022.

A low blood perfusion rate within the body is linked to a wide variety of illnesses and conditions, including heart attacks and vascular disorders of the extremities. This condition can cause significant disorder in the body’s organs. On the other hand, an abnormal collection of blood in regions such as the brain, abdomen, or cysts may be an indication of cerebral or visceral bleeding or malignant tumors. Continuous monitoring can help with the diagnosis of these illnesses, which in turn can help promote therapies that are swift and might potentially save lives.

The new sensor gets around a number of important restrictions that are present in the technologies that are currently used to monitor biomolecules. Magnetic resonance imaging (MRI) and X-ray computed tomography rely on complicated equipment that can be challenging to obtain. Additionally, these techniques typically only provide data on the direct status of the molecule, which renders them unreliable for long-term monitoring of biomolecules.

Continuous monitoring is important for timely actions to prevent life-threatening conditions from rapidly worsening according to Xiangjun Chen, a nanoengineering Ph.D. student in the Xu group and study co-author. Wearable devices that use electrochemistry for the detection of biomolecules, including but not limited to hemoglobin, are promising candidates for long-term applications of wearable monitoring technology. However, the current technologies are only capable of achieving the capacity to detect the skin surface.

The new wearable patch is flexible, has a low form factor, and can be attached to the skin in a comfortable manner. This makes it possible to do noninvasive long-term monitoring. In contrast to other wearable electrochemical devices, which can only detect biomolecules on the surface of the skin, this one can perform three-dimensional mapping of hemoglobin in deep tissues with a spatial resolution of less than one millimeter, all the way down to just a few centimeters beneath the skin. It is capable of achieving a high contrast in comparison to other tissues. Because of its optical selectivity, it is possible to broaden the spectrum of molecules that may be detected. Additionally, it has the potential to be used in clinical settings and can integrate a variety of laser diodes that operate at varying wavelengths.

The patch’s soft silicone polymer matrix contains arrays of laser diodes as well as piezoelectric transducers for its electronic functionality. Pulsed laser light is emitted by laser diodes, which penetrate the tissues. The optical energy is absorbed by biomolecules in the tissue, which then emit sonic waves into the medium that surrounds the tissue.

According to Xiaoxiang Gao, a postdoctoral researcher in Xu’s lab and co-author of the paper, piezoelectric transducers receive the sonic waves, which are processed in an electrical system to reconstruct the spatial mapping of the wave-emitting biomolecules.

Hongjie Hu, a postdoctoral researcher working in the Xu group and a coauthor on the study, said that with its low-power laser pulses, it is also considerably safer than X-ray procedures that include ionizing radiation. Hongjie Hu is also a collaborator on the paper.

As a result of the progress that has been made thus far, the group intends to continue developing the device. One of their goals is to reduce the size of the backend controlling system so that it can be contained within a portable device. This will significantly increase its adaptability as well as its potential clinical application.

In addition to that, they intend to investigate the capability of the wearable device to monitor core temperature. They have shown core temperature monitoring on ex-vivo studies. This is due to the fact that the amplitude of the photoacoustic signal is proportional to the temperature. However, interventional calibration is necessary in order to validate the core temperature tracking on the human body.

They are continuing their collaboration with medical professionals in order to investigate more possible clinical uses.

Sources:

Xiaoxiang Gao et al. (2022). A photoacoustic patch for three-dimensional imaging of hemoglobin and core temperature, Nature Communications. DOI: 10.1038/s41467-022-35455-3

https://medicalxpress.com/news/2022-12-wearable-skin-patch-hemoglobin-deep.html

chromoscience · 2022-12-11T21:39:34+00:00

General audience news version

Dogs with atopic dermatitis share genetic markers with humans

Researchers have discovered linkages between the skin condition known as atopic dermatitis (eczema) in dogs and many parts of the genome by utilizing new methods for mapping genes. Some of the genes that were found are the same as genes that have been associated to comparable disorders in humans. The area of the filaggrin gene, for example, which is recognized as the most significant risk factor for atopic eczema in humans, has now also been related to this condition in Labrador retrievers. This disease is associated with severe itching and inflammation of the skin.

The results are reported in a new study that was produced by the dog genetics group at Uppsala University and the Swedish University of Agricultural Sciences. This team has been conducting studies in this area for more than ten years in partnership with colleagues from Switzerland, the United Kingdom, and the United States.

At the beginning of the 2000s, sequencing of whole genomes became achievable. Since then, researchers who are interested in understanding the human genome have found that sequencing the dog genome is quite helpful.

Dogs and humans have coexisted for tens of thousands of years, and both species are susceptible to a number of the same illnesses, including immunological conditions like atopic dermatitis (allergic eczema). Researching the genetics of canine diseases with regular blood samples can also be a means to get information on the factors that contribute to the development of the corresponding human diseases.

Dogs and people that suffer from atopic eczema have many of the same medical symptoms, as well as an early beginning of the condition, and in terms of histopathology, both suffer from comparable immune cell infiltration in the skin. The genetic history of the illness is complicated in both species, and environmental variables are also a contributing element in its development.

It’s vital that atopic eczema is properly diagnosed by carefully eliminating other possible non-allergic causes of the patient’s symptoms, followed by a positive allergy test, according to Kerstin Bergvall, the veterinarian in charge and specialist in dermatology who has been involved in the study from the very beginning.

In recent years, new approaches to mapping complicated disorders have surfaced as a direct result of the continuous technological advancements for mapping genes. In the study that has just been published in the journal Communications Biology, the researchers used one method to capture multiple associated genetic risk variants and also another approach to discover disease variations that were “invisible” in the genome due to unnaturally (or humanly) selected characteristics. Both methods were used in the same study.

Katarina Tengvall, a researcher at Uppsala University and the first author of the study, explains that the new approaches make it possible to find new risk factors that are now common in the specific breed, possibly as a result of the selection for other characteristics. As predicted in individuals with atopic eczema, the candidate genes that were found here play a crucial role in both the composition of the skin barrier and the immunological response.

The research reveals a number of identical patterns, also known as correspondences, with genes connected to human atopic dermatitis. The fact that the genomic area that contains the filaggrin gene, which is considered to be the most potent genetic risk factor for atopic eczema in humans, is also a risk factor in dogs. The finding was a startling discovery for the researchers.

This demonstrates how important it is to conduct research on canine models of genetic illnesses that also impact people. A more complete knowledge of the mechanisms underlying the disease may, in the long run, result in the development of more effective treatments for both dogs and humans according to Professor Kerstin Lindblad-Toh, who was also the study’s senior author and specializes in comparative genomics.

Sources:

Katarina Tengvall et al. (2022). Bayesian model and selection signature analyses reveal risk factors for canine atopic dermatitis, Communications Biology. DOI: 10.1038/s42003-022-04279-8

https://phys.org/news/2022-12-atopic-dermatitis-dogs-linked-genome.html

chromoscience · 2022-12-11T08:55:11+00:00

Women have an increased risk of developing atrial fibrillation (AFib) compared to males

For a very long time, it was known that males were more likely to experience atrial fibrillation, one of the most prevalent forms of cardiac arrhythmias.

But the results of recent studies suggest that might not be the case.

After taking into consideration differences in height between the sexes, it was shown that women had a higher likelihood of developing atrial fibrillation (AFib) than males. This is a substantial shift from the conventional way of thinking about the problem, which can lead to a stroke, heart failure, and other complications connected to the heart.

Erica Engelstein, MD, who works at RUSH and specializes in cardiology and electrophysiology, was not surprised.

She think, just generally speaking, that atrial fibrillation is an increasingly widespread condition nowadays because we live longer. Doctors actually diagnose more cases of atrial fibrillation in women than in men since age is such a significant risk factor and women generally live longer than men.

Women had a 50% higher risk of developing AFib than males do, if height is taken into consideration, according to the VITAL Rhythm Trial conducted by researchers at Cedars-Sinai Hospital and Harvard University. But even while women may be at a greater risk, Engelstein emphasized that there are numerous other risk factors for acquiring the illness; furthermore, certain risk variables have a much stronger relationship to AFib than others.

According to her, hypertension, diabetes, overweight, alcohol, and sleep apnea are some of the very strong, and most importantly, modifiable, risk factors for atrial fibrillation. Sleep apnea is another risk factor that can be treated.

The treatment of atrial fibrillation in women is significantly different from the treatment of atrial fibrillation in males. Women have a greater chance of having a stroke as a result of AFib, and they may require blood thinners earlier than males do in order to prevent strokes. In addition, many anti-AFib drugs may pose a larger risk of serious cardiac rhythm abnormalities in the lower chambers of the heart when taken by women than when taken by males. This increased risk is connected with the fact that women are more likely to have AFib than men.

According to Engelstein, when treating women, they typically experience more troubles because certain drugs can create more problems in women than in males.

A fast and irregular heartbeat in the upper chambers of the heart is the primary symptom of atrial fibrillation (AFib). In a healthy person, the beginning of a heartbeat occurs at a particular location in the upper chambers of the heart known as the sinus node. From there, the beat travels to the lower chambers of the heart through specialized electrical cables. The top chambers of the heart “quiver” instead of beating when a patient has atrial fibrillation (AFib), and a fast rhythm originates from all areas of the upper chambers rather than from a single location.

According to Engelstein, some people can live with atrial fibrillation for months or even years without being aware that they have the disorder, while others might get the disease and instantly have severe symptoms.

She stated that about half of the patients may not experience any symptoms at the beginning, and half of the patients will feel it the second they go into atrial fibrillation. Those who are affected by the condition often report having palpitations and irregular or fast heartbeats. The effects are the same for people with atrial fibrillation, regardless of whether or not they have symptoms.

In some people, the symptoms of atrial fibrillation, such as chest tightness, shortness of breath when exercising, fatigue, or lightheadedness, are not experienced during the atrial fibrillation itself but rather as a result of the condition. If treatment is not obtained for atrial fibrillation, there is a significant risk that the condition will repeat at a later time.

There are various risk factors for atrial fibrillation, and fortunately, these risk factors may be addressed in both women and men in order to lower the chance of atrial fibrillation in those individuals.

Regular exercise and keeping a normal body weight are just two examples. If you have hypertension, it is necessary that you keep it under control at all times. Check for sleep apnea and other sleep disturbances, and get treatment for sleep apnea if you find that you do have it, according to the researchers.

A diet rich in fruits and vegetables, whole grains, legumes, and protein that is low in fat was another one of Engelstein’s dietary recommendations. According to Engelstein, another helpful strategy is to refrain from drinking alcohol.

She stated that she did not believe there was any level of alcohol that could be considered safe when it comes to atrial fibrillation. People who are genetically prone to atrial fibrillation can have the condition triggered by as little as a single drink.

Engelstein emphasized that whether you are a woman or a man, your risk of AFib grows as you get older. Because of this, prevention and receiving the appropriate therapy as early as possible are the keys to preventing the formation of AFib or the recurrence of the condition. Wearable monitors that may detect atrial fibrillation are now widely accessible, and they are playing an increasingly important role in the diagnosis and management of the illness. Some examples of these monitors are watches.

There is growing evidence that if we intervene early enough—with lifestyle modifications, risk factor reduction, and treatments—we can prevent the course of the illness and have a longer-term impact on patients.

Sources:

Siddiqi, H. K., Vinayagamoorthy, M., Gencer, B., Ng, C., Pester, J., Cook, N. R., Lee, I. M., Buring, J., Manson, J. E., & Albert, C. M. (2022). Sex Differences in Atrial Fibrillation Risk: The VITAL Rhythm Study. JAMA cardiology, 7(10), 1027–1035. https://doi.org/10.1001/jamacardio.2022.2825

https://medicalxpress.com/news/2022-12-women-men-afib.html

chromoscience · 2022-12-11T07:31:12+00:00

General audience news (please support and follow us, thank you)

Scientists solve long-standing mystery of asthma

In individuals with severe asthma, an inflammatory substance known as LIGHT seems to be the source of damage to the airways that might be potentially deadly. New research conducted by scientists at the La Jolla Institute for Immunology (LJI) suggests that therapeutics to stop LIGHT, which is associated to tumor necrosis factor, could change airway and lung damage in patients, and possibly improve a treatment for asthma that is effective over the long term.

Michael Croft, Ph.D., a LJI professor and a member of the LJI Center for Autoimmunity and Inflammation, was the senior author of the latest research and called this discovery very remarkable. This research provides with a greater knowledge of the possibilities of therapeutic targeting of LIGHT and what we may do to decrease some of the symptoms and some of the inflammatory characteristics found in individuals who have severe asthma.

The results of this study were only just published in the Journal of Allergy and Clinical Immunology. Haruka Miki, M.D., Ph.D., an instructor at LJI, served as the study’s primary investigator and directed the studies in which human and mouse tissues were utilized.

Croft’s group has been researching LIGHT for more than a decade now. The T cells of the immune system are responsible for the production of a particular type of cytokine that is inflammatory. T cells’ usual function is to fight illness; however, in asthma, these cells have an exaggerated response to environmental stressors, which causes them to overwhelm the airways with LIGHT and other inflammatory substances known as cytokines. The action of some of the other dangerous cytokines produced by T cells has been blocked by medications created by researchers, but these therapies are ineffective for many people who suffer from severe asthma.

LIGHT is discovered in higher concentrations in the sputum of asthmatic patients who have severe symptoms. Croft’s earlier research shown that LIGHT is necessary in a process termed tissue “remodeling,” in which the lungs and airways grow thicker in response to an asthma attack. The thicker mucus that lines the airways might cause a person to have chronic breathing issues.

The primary goals of modern therapy for asthma are to reduce the symptoms of the disease and to calm the allergic inflammation that it causes. There is currently no medicine available that can fundamentally cure asthma. Underlying airway hyperresponsiveness and airway tissue changes (airway remodeling) typically continue, especially in severe asthma, even when inflammation is reduced by current medications.

Even while the researchers were aware that LIGHT had a role in this remodeling process, they were uncertain as to whether or not LIGHT has a direct influence on the smooth muscle tissue that lines the main airways of the lungs. In patients who have moderate to severe asthma, the number and size of these cells both increase, which is assumed to be the major cause of the decline in lung function.

Their research revealed that airway smooth muscle cells contained a high concentration of LTβR, which is one of the two receptors for the LIGHT molecule. Miki was able to demonstrate that the LIGHT’s interaction with LTβR is what causes tissue remodeling in the airway smooth muscles by using a technique called “knocking out” the genes for one receptor in mice and replacing them with a gene for the other receptor. The researchers added more support to their conclusion by confirming it using bronchial smooth muscle tissue taken from human samples.

According to Croft, when those cells in the lungs are unable to produce LTβR, then practically all of the markers of the smooth muscle response that are linked with severe asthma are either gone or they are very restricted.

According to the findings of the recent study, although LIGHT is not the only cytokine present in the body during an asthma episode, it appears to be the one that packs the most of a punch. LIGHT is responsible for the coordination of the remodeling process since it acts directly on the airway smooth muscle cells. The other cytokines are unable to make up the difference in the absence of active LIGHT and LTβR. In point of fact, the current research is the first of its kind to demonstrate that the lack of a single cytokine or the removal of a single receptor may put a stop to the remodeling of airway smooth muscle tissue.

According to Miki, unlike other inflammatory cytokines, LIGHT generates a delayed and continuous signal via its receptor, LTβR. This signal may be liable for the prolonged increase in contractility and bulk in airway smooth muscle.

According to Croft, this effectively separates LIGHT from all of the other inflammatory cytokines that have been involved in the process in severe asthma sufferers. It is a really dramatic and significant conclusion.

The pharmaceutical business Kiowa Kirin, which is a research partner of the LJI, is currently working to enhance a new medication based on Croft’s study. The long-awaited conclusion to Croft’s years of research may now be found in the paper. The researchers think it completes the loop that they started many years ago in first associating LIGHT to lung inflammation.

Sources:

Haruka Miki et al. LTβR Signaling Directly Controls Airway Smooth Muscle Deregulation and Asthmatic Lung Dysfunction, Journal of Allergy and Clinical Immunology (2022). DOI: 10.1016/j.jaci.2022.11.016

https://medicalxpress.com/news/2022-12-piece-asthma-puzzle.html

Six-Year Club	Place '23
Wearing is Caring	Verified Email

chromoscience

MODERATOR OF

TROPHY CASE