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September 27th, 2020

Two Marine Protists (Choanozoans and Picozoans) Are Probably Virus-Eaters, New Study Suggests; No Other Virus-Eating Organisms Are Known

Viruses occur in astronomic numbers everywhere on Earth, from the atmosphere to the deepest ocean. Surprisingly, considering the abundance and nutrient-richness of viruses, no organisms are known to use them as food. On September 24, 2020, in Frontiers in Microbiology (https://www.frontiersin.org/articles/10.3389/fmicb.2020.524828/full), researchers published the first compelling evidence that two groups of ecologically important marine protists, choanozoans (image) and picozoans, are virus eaters, catching their "prey" through phagocytosis (i.e., engulfing). The open-access article is titled “Single Cell Genomics Reveals Viruses Consumed by Marine Protists.” "Our data show that many protist cells contain DNA of a wide variety of non-infectious viruses but not bacteria, strong evidence that they are feeding on viruses rather than on bacteria. That came as a big surprise, as these findings go against the currently predominant views of the role of viruses and protists in the marine food webs," says corresponding author Ramunas Stepanauskas, PhD, Director of the Single Cell Genomics Center at Bigelow Laboratory for Ocean Sciences in East Boothbay, Maine, USA. Dr. Stepanauskas and colleagues sampled surface seawater from two sites: the Northwestern Atlantic in the Gulf of Maine, USA, in July 2009, and the Mediterranean off Catalonia, Spain, in January and July 2016. They used modern single-cell genomics tools to sequence the total DNA from 1,698 individual protists in the water. Each of the resulting “single amplified genomes” (SAGs) consists of the genome of a single protist, with or without associated DNA: for example, from symbionts, ingested prey, or viruses or bacteria sticking to its exterior.

Last-Resort Life Support Option (ECMO) Helped Majority of Critically Ill COVID-19 Patients Survive In Large Study; Results Support Recommendations for ECMO-Experienced Hospitals to Consider ECMO in COVID-19 If Ventilator Treatment Is Failing

It saved lives in past epidemics of lung-damaging viruses. Now, the life-support option known as ECMO (extracorporeal membrane oxygenation) appears to be doing the same for many of the critically ill COVID-19 patients who receive it, according to a new international study. The 1,035 patients in the study faced a staggeringly high risk of death, as ventilators and other care had failed to support their lungs. But after they were placed on ECMO, their actual death rate was less than 40%. That's similar to the rate for patients treated with ECMO in past outbreaks of lung-damaging viruses, and other severe forms of viral pneumonia. The new study was published online on September 25, 2020 in The Lancet (https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32008-0/fulltext) and provides strong support for the use of ECMO in appropriate patients as the pandemic rages on worldwide. The Lancet article is titled “Extracorporeal Membrane Oxygenation Support In COVID-19: An International Cohort Study of the Extracorporeal Life Support Organization Registry.” The research team also presented its findings at the ELSO Annual Meeting on September 26. The ELSO is the “Extracorporeal Life Support Organization.”The study results may help more hospitals that have ECMO capability understand which of their COVID-19 patients might benefit from the technique, which channels blood out of the body and into a circuit of equipment that adds oxygen directly to the blood before pumping it back into regular circulation. Small studies published early in the pandemic had cast doubt on the technique's usefulness.

September 26th

Male & Female Birds Have Much the Same Genes; But Achieve Many Distinct Differences Via Alternative Splicing

Scientists from the University of Sheffield in the UK have found that although male and female birds have an almost identical set of genes, they function differently in each sex through a mechanism called alternative splicing. Males and females of the same bird species can be strikingly different. For example, in addition to fundamental differences in reproduction, the sexes can show profound variation in behavior, coloration, metabolism, disease incidence, and life history. The research team wanted to understand how these remarkable differences develop despite males and females sharing mostly the same DNA. Thea Rogers, a PhD student at the University of Sheffield and lead author of the study, said: "One notable example of differences between male and female birds is in the peafowl; peacocks have magnificent plumage, whereas the female peahen is relatively dull. The peacock's long tail and bright colors evolved to help them attract mates, but having such eye-catching looks can come with negatives such as making them more noticeable to predators. Features like this are beneficial to the males, but may not be beneficial for females, so birds must find a way to evolve different characteristics. We predicted that the secret to these differences must lie in understanding how the same genes are expressed and function differently in males and females." The team studied the genomes of multiple bird species to understand how they expressed these different qualities in males and females. Genes encode proteins, large complex molecules which drive processes in the body and are responsible for the function and structure of the body's tissues. Before genes can be used to make proteins, their DNA sequence is transcribed into RNA, an intermediary molecule that contains the instructions for making proteins.

Researchers Discover Non-Sex-Organ Functions Controlled by Human Y Chromosome Genes; Findings May Ultimately Lead to Understanding Why Certain Diseases Affect Men & Women Differently

New light is being shed on a little-known role of Y chromosome genes, specific to males, that could explain why men suffer differently than women from various diseases, including COVID-19. The findings were published Septmber 10, 2020 in Scientific Reports by Université de Montréal Professor Christian Deschepper, MD, PhD, Director of the Experimental Cardiovascular Biology Research Unit of the Montreal Clinical Research Institute. The open-access article is titled “Regulatory Effects of the Uty/Ddx3y Locus on Neighboring Chromosome Y Genes and Autosomal mRNA Transcripts in Adult Mouse Non-Reproductive Cells." "Our discovery provides a better understanding of how male genes on the Y chromosome allow male cells to function differently from female cells," said Dr. Deschepper, the study's sole author, who is also an Associate Professor at McGill University. "In the future, these results could help to shed some light on why some diseases occur differently in men and women." Humans each have 23 pairs of chromosomes, including one pair of sex chromosomes. While females carry two X sex chromosomes, males carry one X and one Y chromosome. This male Y chromosome carries genes that females lack. Although these male genes are expressed in all cells of the body, their only confirmed role to date has been essentially limited to the functions of the sex organs.

Carriers of Either of Two Genetic Mutations Causing Alpha-1 Antitrypsin Deficiency at Greater Risk for Illness & Death from COVID-19; Mutations Found Less Frequently in East and Southeast Asia and Sub-Saharan Africa, Which Have Suffered Less from COVID-19

Tel Aviv University (TAU) researchers suggest that carriers of the genetic mutations PiZ or PiS are at high risk for severe illness and even death from COVID-19. These mutations lead to deficiency in the alpha1-antitrypsin protein, which protects lung tissues from damage in case of severe infections. Other studies have already associated deficiency in this protein with inflammatory damage to lung function in other diseases. The study was led by Professor David Gurwitz, Professor Noam Shomron, and MSc candidate Guy Shapira of TAU's Sackler Faculty of Medicine, and was published online in The FASEB Journal on September 22, 2020 (https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202002097). The open-access article is titled “Ethnic Differences in Alpha‐1 Antitrypsin Deficiency Allele Frequencies May Partially Explain National Differences In COVID‐19 Fatality Rates.” The researchers analyzed data from 67 countries on all continents. Comparisons revealed a highly significant positive correlation between the prevalence of the two mutations in the population and COVID-19 mortality rates (adjusted to size of the population) in many countries, such as the USA, the UK, Belgium, Spain, Italy, and more. Consequently, the researchers suggest that these mutations may be additional risk factors for severe COVID-19. They now propose that their findings should be corroborated by clinical trials, and, if validated, should lead to population-wide screening for identifying carriers of the PiS and/or PiZ mutations. Such individuals should then be advised to take extra measures of social distancing and later be prioritized for vaccination once vaccines are available. According to the researchers, these steps can be effective in reducing COVID-19 morbidity and fatality rates.

Scientists Explore Why Supposedly Color-Blind Tarantulas Are Often Colored in Vivid Blues and Greens; Blues May Be Related to Mating and Greens to Environmental Camouflage

Why are some tarantulas so vividly colored? Scientists have puzzled over why these large, hairy spiders, active primarily during the evening and at night-time, would sport such vibrant blue and green coloration - especially as they were long thought to be unable to differentiate between colors, let alone possess true color vision. In a recent study, researchers from Yale-NUS College (Singapore) and Carnegie Mellon University (CMU) (USA) find support for new hypotheses: that these vibrant blue colors may be used to communicate between potential mates, while green coloration confers the ability to conceal among foliage. The scientists’ research also suggests that tarantulas are not as color-blind as previously believed, and that these arachnids may be able to perceive the bright blue tones on their bodies. The open-access study was published online in Proceedings of the Royal Society B (https://royalsocietypublishing.org/doi/10.1098/rspb.2020.1688) on 23 September 23, 2020, and is featured on the front cover of the current issue (30 September 2020). The research was jointly led by Dr. Saoirse Foley from CMU, and Dr. Vinod Kumar Saranathan, in collaboration with Dr. William Piel, both from the Division of Science at Yale-NUS College. To understand the evolutionary basis of tarantula coloration, they surveyed the bodily expression of various opsins (light-sensitive proteins usually found in animal eyes) in tarantulas. They found, contrary to current assumptions, that most tarantulas have nearly an entire complement of opsins that are normally expressed in day-active spiders with good color vision, such as the Peacock Spider. These findings suggest that tarantulas, long thought to be color-blind, can perceive the bright blue colors of other tarantulas.

September 17th

Yale Researchers ID Target Region in Key Molecule in Duchenne Muscular Dystrophy (DMD); Tyrosine Phosphatase Molecule (MKP5) Previously Thought “Undruggable”—Finding Suggests Possible Treatment Strategy for DMD & Possibly Broader Applications in Fibrosis

Researchers at Yale University have identified a possible treatment for Duchenne muscular dystrophy (DMD), a rare genetic disease for which there is currently no cure or treatment, by targeting an enzyme that had been considered "undruggable." The finding appears in the August 25, 2020 issue of Science Signaling. The article is titled “An Allosteric Site on MKP5 Reveals a Strategy for Small-Molecule Inhibition.” DMD is the most common form of muscular dystrophy, a disease that leads to progressive weakness and eventual loss of the skeletal and heart muscles. It occurs in 16 of 100,000 male births in the U.S. People with the disease exhibit clumsiness and weakness in early childhood and typically need wheelchairs by the time they reach their teens. The average life expectancy is 26. While earlier research had revealed the crucial role played by an enzyme called MKP5 in the development of DMD, making it a promising target for possible treatment, scientists for decades had been unable to disrupt this family of enzymes, known as protein tyrosine phosphatases, at the enzymes' "active" site where chemical reactions occur. In the new study, Anton Bennett, PhD, the Dorys McConnell Duberg Professor of Pharmacology and Professor of Comparative Medicine at the Yale School of Medicine, and his team screened over 162,000 compounds. They identified one molecular compound that blocked the enzyme's activity by binding to a previously undiscovered allosteric site--a spot near the enzyme's active site. "There have been many attempts to design inhibitors for this family of enzymes, but those compounds have failed to produce the right properties," Dr. Bennett said.

Princeton Research Team ID’s Recycling Enzymes That Can Control SNA12 Levels; SNA12 Can Drive Breast Cancer Metastasis

By isolating the enzymes responsible for recycling a dangerous protein, Princeton's Yibin Kang (photo), PhD, has identified a promising new target for cancer treatments. "Do not erase." "Recycle me." "Free to a good home." Humans post these signs to indicate whether something has value or not, whether it should be disposed of or not. Inside our cells, a sophisticated recycling system uses its own enzymatic signs to flag certain cells for destruction -- and a different set of enzymes can remove those flags. Changing the balance between those two groups might provide a way to control a dangerous protein called SNAI2 that helps cancers metastasize, said Dr. Kang, Princeton University's Warner-Lambert/Parke-Davis Professor of Molecular Biology, who has spent his career studying the cells and molecules behind metastatic cancers. His team has a pair of papers coming out in next month's issue of Genes & Development, released online on Septemer 17, 2020. The key is the cell's recycling system. In 2004, the Nobel Prize (https://www.nobelprize.org/prizes/chemistry/2004/summary/) was awarded to the three scientists who discovered that the body will shred proteins into tiny pieces after they are tagged with a "recycle me" sign (https://www.nobelprize.org/prizes/chemistry/2004/popular-information/) by a molecule called "ubiquitin." Some scientists refer to ubiquitin as the "kiss of death," because once a protein has enough ubiquitin tags, that protein is headed on a one-way trip to the shredder -- unless another enzyme comes along to remove its "recycle me" sign.

September 16th

Gilead Acquires Immunomedics for $21 Billion; Gilead Thus Adds Trodelvy, First-in-Class Antibody-Drug Conjugate Approved to Treat Triple-Negative Breast Cancer, with Promise in Other Forms of Breast Cancer and Additional Solid Tumors

On September 13, 2020, Gilead Sciences, Inc. (Nasdaq: GILD) and Immunomedics (Nasdaq: IMMU) announced that the companies have entered into a definitive agreement pursuant to which Gilead will acquire Immunomedics for $88.00 per share in cash. The transaction, which values Immunomedics at approximately $21 billion, was unanimously approved by both the Gilead and Immunomedics Boards of Directors and is anticipated to close during the fourth quarter of 2020. The agreement will provide Gilead with TrodelvyTM (sacituzumab govitecan-hziy), a first-in-class Trop-2 directed antibody-drug conjugate (ADC) that was granted accelerated approval by the U.S. FDA in April for the treatment of adult patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies for metastatic disease. Immunomedics plans to submit a supplemental Biologics License Application (BLA) to support full approval of Trodelvy in the United States in the fourth quarter of 2020. Immunomedics is also on track to file for regulatory approval in Europe in the first half of 2021.

September 15th

Dyslexia Problems Reduced by Non-Invasive Electrical Stimulation of Brain’s Left Auditory Cortex

Dyslexia is a frequent disorder of reading acquisition that affects up to 10% of the population, and is characterized by lifelong difficulties with written material. Although several possible causes have been proposed for dyslexia, the predominant one is a phonological deficit, a difficulty in processing language sounds. The phonological deficit in dyslexia is associated with changes in rhythmic or repetitive patterns of neural activity in a sound-processing region of the brain, the left auditory cortex. Neuroscientists from the University of Geneva (UNIGE) have demonstrated, in a study published on line on September 8, 2020 in Plos Biology, a causal relationship between brain oscillations at a specific frequency (30 Hz) and the ability to process phonemes that is essential for reading. Using a non-invasive electrical stimulation technique capable of synchronizing neural activity at the stimulation frequency, phonological deficits and reading accuracy could be improved in adults with dyslexia. Silvia Marchesotti, PhD, and Anne-Lise Giraud, PhD, respectively researcher and professor in the Department of Basic Neurosciences of the Faculty of Medicine at UNIGE, together with their colleagues, investigated the main possible cause of dyslexia: the phonological deficit. The article is titled “Selective Enhancement of Low-Gamma Activity by tACS Improves Phonemic Processing and Reading Accuracy in Dyslexia.” "We know that during brain development, when children start to read, some experience tremendous difficulties matching speech sounds with letters," explains Dr. Marchesotti. These specific difficulties are associated with anomalies of neural activity synchronization in the left auditory cortex at the frequency of 30 Hz.