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Fri, 29 Oct 2021
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How Does Body Temperature Reset the Biological Clock?

Numerous processes in our body fluctuate in a regular pattern during the day. These circadian (or daily) variations can be driven by local oscillators present within our cells or by systemic signals controlled by the master pacemaker, located in the brain. Ueli Schibler, professor at the University of Geneva (UNIGE), Switzerland, unveils a molecular mechanism by which body temperature rhythms influence the expression of 'clock genes' and synchronize local oscillators. This study, made in collaboration with a team at the Ecole polytechnique fédérale of Lausanne (EPFL), also demonstrates how the production of DBP, a protein involved in detoxification and drug metabolism, is modulated by daily variations of temperature.

This research has been published in Science.

Many of our physiological functions, such as heart beat frequency, hormone secretion or body temperature, are regulated by internal clocks. Most of our body's cells possess one of them, formed by a group of 'clock genes' displaying a cyclic activity that peaks every twenty-four hours. These local oscillators are synchronized by a central pacemaker, located in the brain which adapts to geophysical time by light-dark cycles.
The master clock also controls coordination signals that are sent to subsidiary oscillators. 'Body temperature variations constitute one of these daily resetting cues, but we did not know how it functioned', explains Ueli Schibler, professor at the Department of Molecular Biology of the UNIGE. To address this issue, the researcher's team has developed a system allowing to expose cells to simulated body temperatures cycles.

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Human Melanoma Stem Cells Identified

Cancer stem cells are defined by three abilities: differentiation, self-renewal and their ability to seed a tumor. These stem cells resist chemotherapy and many researchers posit their role in relapse. A University of Colorado Cancer Center study recently published in the journal Stem Cells, shows that melanoma cells with these abilities are marked by the enzyme ALDH, and imagines new therapies to target high-ALDH cells, potentially weeding the body of these most dangerous cancer creators.

''We've seen ALDH as a stem cell marker in other cancer types, but not in melanoma, and until now its function has been largely unknown," says the paper's senior author, Mayumi Fujita, MD, PhD, investigator at the CU Cancer Center and associate professor in the Department of Dermatology at the CU School of Medicine.

Fujita's group transplanted ALDH+ and ALDH- melanoma cells into animal models, showing the ALDH+ cells were much more powerfully tumorigenic. In the same ALDH+ cells, the group then silenced the gene that creates this protein, finding that with ALDH knocked down, melanoma cells died in cultures and lost their ability to form tumors in animal models. In cell cultures, silencing this ALDH gene also sensitized melanoma cells to existing chemotherapies. When the group explored human tumor samples, they found distinct subpopulations of these ALDH+ cells, which made up about 0.1-0.2 percent of patients' primary tumors. In samples of metastatic melanoma -- the most aggressive form of the disease -- the percentage of ALDH+ cells was greater, even over 10 percent in some tumors, further implying the powerful danger of these cells.

Health

Astrocytes Control the Generation of New Neurons from Neural Stem Cells

Researchers from the Laboratory of astrocyte biology and CNS regeneration headed by Prof. Milos Pekny just published a research article in a journal Stem Cells on the molecular mechanism that controls generation of new neurons in the brain.

Astrocytes are cells that have many functions in the central nervous system, such as the control of neuronal synapses, blood flow, or the brain's response to neurotrauma or stroke.

Reduces brain tissue damage

Prof. Pekny's laboratory together with collaborators have earlier demonstrated that astrocytes reduce the brain tissue damage after stroke and that the integration of transplanted neural stem cells can be largely improved by modulating the activity of astrocytes.

Health

Cup of Herbal Tea Could Help Fight Breast Cancer

Scientists at Aston University and Russells Hall Hospital have discovered that an extract from a common plant in Pakistan may help treat breast cancer.

The plant, Fagonia cretica, and known as Virgon's Mantlem, is commonly used in herbal tea. It has been traditionally used to treat women in rural Pakistan who have breast cancer, but up until now this treatment has been regarded as something of a folklore remedy. However, patients in Pakistan who have taken the plant extract have reported that it does not appear to generate any of the serious common side effects associated with other cancer treatments, such as loss of hair, drop in blood count or diarrhea.

Now, scientists at Aston University in Birmingham and Russells Hall Hospital in Dudley have undertaken tests of the plant extract and demonstrated that it kills cancer cells without damage to normal breast cells in laboratory conditions.

Professor Helen Griffith and Professor Amutul R Carmichael who lead the study are now aiming to identify which element or elements of the plant are responsible for killing the cancer cells with a view to eventually begin trails with human cancer patients.

Health

Women With Alzheimer's Deteriorate Faster Than Men, Study

Women with Alzheimer's show worse mental deterioration than men with the disease, even when at the same stage of the condition, according to researchers from the University of Hertfordshire.

In the paper published in the Journal of Clinical and Experimental Neuropsychology, the researchers discovered that men with Alzheimer's consistently and significantly performed better than women with the disease across the five cognitive areas they examined. Most remarkably, the verbal skills of women with Alzheimer's are worse when compared to men with the disease, which is a striking difference to the profile for the healthy population where females have a distinct advantage.

The researchers led by Professor Keith Laws completed a meta-analysis of neurocognitive data from fifteen published studies, which revealed a consistent male advantage on verbal and visuospatial tasks, and tests of both episodic1 and semantic2 memory.

Keith Laws, Professor of psychology, said: "Unlike mental decline associated with normal aging, something about Alzheimer's specifically disadvantages women.

Health

Newly Discovered Genetic Markers Could Signal Colon Cancer Development

University of Minnesota Medical School and Masonic Cancer Center researchers have partnered with geneticists from Genentech, Inc., to discover how some proteins may cause the development of some forms of colon cancers.

The proteins -- part of R-spondin family -- normally help activate cell proliferation during embryonic development. Now, University of Minnesota researchers have discovered that when two types of R-spondins -- RSPO2 and RSPO 3 -- are reactivated in adults through certain gene mutations, they can signal cells to restart the cell proliferation process, which can lead to tumor growth in the colon.

The discovery, which involved multiple researchers from the University's Masonic Cancer Center, could lead the way to more personalized colon cancer therapy designed around the genetics of a patient's specific cancer. The results are available online now, in the journal Nature.

"These results suggest there is a potential for personalized therapies based on knowing a tumor's specific genetics," said David Largaespada, Ph.D., associate director of Basic Sciences and professor in the Department of Genetics, Cell Biology and Development. "And because these R-spondins are related to embryonic growth, and seem to not have major roles in the adult, targeting them would likely be low in side effects."

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New insights into salt transport in the kidney

Image
© Tilman Breiderhoff/ Copyright: MDC
The photo shows sections of a kidney from a claudin-10-deficient mouse and from a control mouse. Black staining (right) shows calcium deposits in the renal medulla, which are characteristic for nephrocalcinosis, a serious disease characterized by calcium deposits in the kidney.
Sodium chloride, better known as salt, is vital for the organism, and the kidneys play a crucial role in the regulation of sodium balance. However, the underlying mechanisms of sodium balance are not yet completely understood. Researchers of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Charité - Universitätsmedizin Berlin and the University of Kiel have now deciphered the function of a gene in the kidney and have thus gained new insights into this complex regulation process (PNAS Early Edition, doi/10.1073/pnas.1203834109)*.

In humans, the kidneys filter around 1700 liters of blood every day, of which 180 liters are collected as primary urine and ultimately one to two liters of urine are excreted. The kidneys thus wash toxic waste products out of the body, but retain some useful substances and reintroduce them into the body, thus simultaneously regulating the salt and water balance.

Molecular velcro

In the study just published by Dr. Tilman Breiderhoff, Prof. Thomas Willnow (both MDC), as well as Dr. Nina Himmerkus and Prof. Markus Bleich (both of the University of Kiel) and Dr. Dominik Müller (Charité) the focus is on the claudin-10 gene, which is expressed in a specific segment of the kidney, in Henle's loop. In the thick ascending limb of this loop, , a large part of the filtered sodium chloride, as well as calcium and magnesium are reabsorbed. The gene product under investigation, the claudin 10 protein, belongs to a family of proteins that connect the epithelial cells which cover the inner and outer surfaces of the body and stick them together like velcro. Claudins, however, also form pores, through which ions and substances are transported between the cells.

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For mitochondria, bigger may not be better

Image
© Unknown
Researchers find that optimal length of mitochondria in neurons is essential to preventing onset of Alzheimer's and other tau-related diseases.

Goldilocks was on to something when she preferred everything "just right." Harvard Medical School researchers have found that when it comes to the length of mitochondria, the power-producing organelles, applying the fairy tale's mantra is crucial to the health of a cell. More specifically, abnormalities in mitochondrial length promote the development of neurodegenerative diseases such as Alzheimer's.

"There had been a fair amount of interest in mitochondria in Alzheimer's and tau-related diseases, but causality was unknown," said Brian DuBoff, first author of the study and a post-doctoral research fellow at Massachusetts General Hospital.

"Ultimately, a deeper understanding of the relationship between mitochondrial function and Alzheimer's may guide us to develop more targeted therapies in the future," said Mel Feany, HMS professor of pathology at Brigham and Women's Hospital and senior author of the paper.

The findings will be published online in the August 23 issue of Neuron.

Tau-related diseases are caused when tau, a protein most commonly found in neurons, malfunctions. Tau binds to microtubules in cells, a process known as stabilization. This binding is necessary so the microtubules can help maintain cell structure and aid in intracellular processes such as transporting molecules. When tau is defective, most often due to changes introduced during protein synthesis, it can accumulate in neurofibrillary tangles, one of the primary markers of Alzheimer's.

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Scientists Promote Featherless Cross Bred Chickens For Mass Poultry Farming

Featherless Chicken
© PreventDisease.com
Chickens have feathers for a reason, or at least that's how nature intended it. Nine years after the first information on featherless chickens became known, the attention of the public and world media has once again focused on this experiment designed for one purpose--to create a commercial chicken under the assumption of economic and environmental advantages.

The Israeli scientist, Professor Avigdor Cahaner of the Hebrew University of Jerusalem's Faculty of Agriculture, Rehovot, listed expected benefits of the featherless broilers, especially recognised for hot climate countries.

Now, after genetic modifications and many trials, Cahaner says that all the expected benefits had been proved. He is convinced that there is a clear economic advantage of growing featherless birds in hot and humid regions.

Cahaner claims the chickens are more efficient, faster growing, heat resistant which will ultimately benefit the poultry industry. It's necessary to understand how scientists such Cahaner think to better understand their motives in genetic experimentation.

Cahaner explains that in hot conditions the feathers of standard chickens prevent efficient dissipation of excess or internally-produced heat. Consequently reducing their actual growth rate, meat yield and meat quality. Also, many die before marketing. "Currently, these negative consequences can be countered only by expensive energy-dependent cooling and ventilation systems that increase costs and reduce competitiveness of broiler production in hot climates."

Indeed, featherless chickens do not need any artificial cooling or ventilation, and may improved marketability, however when did scientists stop questioning whether they should instead of persisting with whether they could.

Health

The Hidden Risks of Getting a Tattoo

Tattoo Artist
© Tatiana Morozova | Dreamstime
Even in otherwise hygienic tattoo parlors, the ink could harbor infectious bacteria.
When a cluster of skin infections in upstate New York last fall led back to one tattoo artist, local public health officials took the usual step of investigating the artist's hygiene practices. They found that all of his equipment and methods were sanitary, but the nationally distributed ink he had been using, even in unopened bottles, wasn't.

Soon, similar investigations in Colorado, Washington and Iowa turned up harmful strains of bacteria in three other brands of ink. At least 22 skin infections across the four states were linked to contaminated ink, according to research reported Wednesday (Aug. 22) in the New England Journal of Medicine.

The offending pathogen in the New York outbreak was identified as Mycobacterium chelonae, a relative of the bacteria behind tuberculosis and leprosy that is commonly found in tap water. Though M. chelonae is usually harmless to people with normal immune systems, when it's escorted beneath the skin by a tattoo needle, it can cause a painful rash that can last for months, requiring strong antibiotic regimens and sometimes surgery to eradicate.