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Archive - 2019

October 25th

Lupus Study Illustrates Importance of Considering Diversity In Genetic Research

Scientists at the HudsonAlpha Institute for Biotechnology in Huntsville, Alabama, have pinpointed epigenetic differences in the way lupus affects black women compared to other lupus patients, revealing important mechanics of the puzzling disease. Epidemiologists have identified that lupus impacts black women with greater frequency and severity than other populations. Scientists in Dr. Devin Absher's Lab (https://hudsonalpha.org/faculty/devin-absher/) at HudsonAlpha published findings on August 20, 2019, in an open-access article in Arthritis & Rheumatology, showing that increased risk and harm to lupus patients can be linked to epigenetic differences--essentially, the degree to which certain genes are functioning. The finding helps create a more complete understanding of an often misunderstood disease, revealing some of the mechanisms that contribute to it. The article is titled “Epigenetic Defects in the B cell lineage of Systemic Lupus Erythematosus Patients Display Population‐Specific Patterns.” The study also reveals a gap in genetic research, highlighting the lack of information scientists have regarding racial differences on the genetic level. Lupus is an autoimmune disorder, meaning that the immune system attacks healthy cells in the body. It causes symptoms that are often difficult to quantify, including fatigue and extreme joint pain. Lupus is one of the most historically chronicled diseases, having first been documented by Socrates in 400 BC. The disease gets its name from a common rash that forms on the face which is said to resemble the markings of wolves, hence the latin name "lupus" meaning wolf. There are more than 200,000 cases of lupus in the US every year, yet there is no universally accepted cause or cure. The disease is chronic, meaning it can last for years or even an entire lifetime.

October 25th

Mutation Discovery in Monkeys Could Lead to Treatment for Blindness-Causing Syndrome (Bardet-Biedl Syndrome or BBS), and Other Forms of Retinitis Pigmentosa in Humans; OHSU Scientists Report First-Ever Non-Human Primate Model for BBS

A genetic mutation that leads to a rare, but devastating blindness-causing syndrome has been discovered in monkeys for the first time. The finding offers a promising way to develop gene and cell therapies that could treat the condition in people. Three rhesus macaques with a mutated gene that's associated with Bardet-Biedl syndrome (BBS) have been discovered, according to a study published in the December 2019 issue of Experimental Eye Research. The article is titled “Bardet-Biedel Syndrome in Rhesus Macaques: A Nonhuman Primate Model of Retinitis Pigmentosa.” It is the first known naturally occurring non-human primate model of the syndrome. BBS leads to vision loss, kidney disfunction, extra fingers or toes, and other symptoms. It occurs in 1 of 140,000 to 160,000 North American births. "There is no cure for Bardet-Biedel Syndrome today, but having a naturally occurring animal model for the condition could help us find one in the future," said the paper's corresponding author, Martha Neuringer, PhD, a Professor of Neuroscience at the Oregon National Primate Research Center at Oregon Health & Science University (OHSU), and a research associate Professor of Ophthalmology in the OHSU School of Medicine and OHSU Casey Eye Institute. Rhesus macaques with this disease could help more than just BBS patients. BBS is part of a larger family of diseases called retinitis pigmentosa, in which all of the diseases affect the retina, or the back part of the eye. A naturally occurring animal model for BBS might help researchers find treatments for a variety of retinitis pigmentosa diseases.

October 23rd

New Alpha-Gel; An Environment-Friendly and Easily Producible Surfactant Used to Prepare Effective Water-Retaining Mixture That Can Be Used in Skincare

A layer of lipids covers our skin, and with its help our skin retains moisture and remains healthy. In the lipid layer, a compound called ceramide forms a "lamellar gel" with cholesterol, fatty acids, and water. Lamellar gels are mixtures that are thick, do not flow easily, and can hold large amounts of water. Natural ceramide is therefore an important factor for water retention in our skin. A type of lamellar gel, called the "α-gel," can be formulated by mixing compounds called surfactants with a fatty alcohol and water. As you may have guessed by this explanation, α-gels are widely used in skincare products such as skin creams. In a new study published in Colloids and Surfaces A (https://www.sciencedirect.com/journal/colloids-and-surfaces), scientists from Tokyo University of Science and Miyoshi Oil and Fat Co. Ltd., Japan, led by Dr Kenichi Sakai, synthesized an α-gel using an oleic acid-based surfactant, which can potentially be used in skincare products. This is a surfactant they had previously developed and is structurally similar to natural ceramide (both are amphiphiles with two tails). "I was interested in whether α-gels could be prepared using gemini surfactants (two-tailed and two-headed surfactants), and in what their structural and physical properties would be," Dr Sakai says. Once the α-gel was ready, Dr Sakai and his team used a technique called small- and wide-angle X-ray scattering (SWAXS), another technique called nuclear magnetic resonance (NMR) spectroscopy, and an optical microscope to confirm its characteristics. For this, they prepared several mixtures containing different molar ratios of the oleic acid-based surfactant, water, and 1-tetradecanol (a fatty alcohol). The findings were, indeed, satisfactory.

Breakthrough in Genetic Skin Disease; Epigenetic Modifers DNMT3A and BCOR Are Recurrently Mutated in CYLD Cutaneous Syndrome (CCS)

A breakthrough has been made in understanding a rare genetic skin disease that causes progressively enlarging skin tumors over the scalp, face, and body. For the first time, scientists at Newcastle University, UK, have identified changes in the DNA of the tumor cells in those with CYLD (CYLD lysine 63 deubiquitinase) (image) cutaneous syndrome (CCS) that may help them grow. A study published online on October 17, 2019 in Nature Communications suggest that the tumor cells gain a “survival advantage” when the changes occur - an important step in understanding ways to develop treatments. The open-access article is titled “Epigenetic Modifiers DNMT3A and BCOR Are Recurrently Mutated in CYLD Cutaneous Syndrome.” CCS is a hereditary condition that affects areas of the body where there are hair follicles and leads to skin tumors called "cylindromas" forming and continually growing. The alterations discovered by the experts were in two genes (DNMT3A and BCOR) that are found in the skin tumors. One of the changes highlights a mechanism that the skin tumor cells use to survive and it is hoped that these could be targeted with a new class of drug to inhibit their growth. The change to the second gene is novel for skin tumors and warrants further investigation to establish the significance it has on the growth of the tumors. Dr. Neil Rajan, Senior Lecturer and Honorary Consultant Dermatologist at Newcastle University's Faculty of Medical Sciences, led the research, which was done in collaboration with Dr Serena Nik-Zainal's team at the University of Cambridge.Dr. Rajan said: "This research is an important step in the ongoing work to develop treatments for patients with CCS, which is a central goal of my research group.

Scientists Reveal Novel Oncogenic Driver Gene (DEPDC5) on Chromosome 22q in Human Gastrointestinal Stromal Tumors (GISTs); Intriguing Connection with Focal Epilepsy; DEPCD5 Agonists May Serve As Anti-Cancer Drugs

Sarcomas - cancers that arise from transformed mesenchymal cells (a type of connective tissue) - are quite deadly. Gastrointestinal stromal tumors (GISTs) are the most common human sarcoma and are initiated by activating mutations in the KIT receptor tyrosine kinase. Micro-GISTs are a smaller variation of clinical GISTs and are found in one-third of the general population without clinical symptoms. Although the micro-GISTs and clinical GISTs share the same KIT mutations, micro-GISTs have limited growth potential and do not exceed a centimeter. This size limitation suggests that additional genetic alterations contribute to the progression of clinical GISTs. Chromosome 22q deletions are frequent chromosomal abnormalities in human GISTs, occurring in ~50% of GISTs, and are thought to contribute to the pathogenesis of this disease. However, the crucial gene in 22q was unknown for decades. In a study published online on October 21, 2019 in PNAS, a team led by Professor Yuexiang Wang of the Shanghai Institute of Nutrition and Health (SINH) of the Chinese Academy of Sciences, together with Professor Jonathan Fletcher from Brigham and Women's Hospital and Harvard Medical School, described a novel druggable driver gene in GISTs. The PNAS article is titled “Mutational Inactivation of mTORC1 Repressor Gene DEPDC5 in Human Gastrointestinal Stromal Tumors.” The researchers performed whole exome sequencing and reported recurrent genomic inactivated DEPDC5 gene mutations in GISTs. DEPDC5 was shown to be a chromosome 22q-targeting tumor suppressor, silenced by mutations in GIST specifically. The scientists further provided evidence that inactivation of DEPDC5 promotes GIST cell proliferation by activating the mTORC1 signaling pathway and subsequently inhibiting cell cycle arrest.

October 23rd

In Nine-Year Effort, Scientists Sequence Transcriptomes of Over 1,100 Plants, Illuminating 1 Billion Years of Evolution

Plants are evolutionary champions, dominating Earth's ecosystems for more than a billion years and making the planet habitable for countless other life forms, including us. Now, scientists have completed a nine-year genetic quest to shine a light on the long, complex history of land plants and green algae, revealing the plot twists and furious pace of the rise of this super group of organisms. The project, known as the “One Thousand Plant Transcriptomes Initiative” (1KP), brought together nearly 200 plant biologists to sequence and analyze genes from more than 1,100 plant species spanning the green tree of life. A summary of the team’s findings was published online on October 23, 2019 in Nature. The open-access article is tited “One Thousand Plant Transcriptomes and the Phylogenomics of Green Plants.” "In the tree of life, everything is interrelated," said Gane Ka-Shu Wong, PhD, lead investigator of 1KP and Professor in the University of Alberta's Department of Biological Sciences. "And if we want to understand how the tree of life works, we need to examine the relationships between species. That's where genetic sequencing comes in." Much of plant research has focused on crops and a few model species, obscuring the evolutionary backstory of a clade that is nearly half a million species strong. To get a bird's-eye view of plant evolution, the 1KP team sequenced transcriptomes - the set of genes that is actively expressed to produce proteins - to illuminate the genetic underpinnings of green algae, mosses, ferns, conifers, flowering plants, and all other lineages of green plants.

MIT Scientists Build Proteins That Avoid Crosstalk with Existing Molecules; Engineered Signaling Pathways Could Offer New Strategy for Building Synthetic Biology Circuits; Approach Could Improve CAR-T Cell Therapy for Cancer, Among Other Applications

Inside a living cell, many important messages are communicated via interactions between proteins. For these signals to be accurately relayed, each protein must interact only with its specific partner, avoiding unwanted crosstalk with any similar proteins. A new MIT study sheds light on how cells are able to prevent crosstalk between these proteins, and also shows that there remains a huge number of possible protein interactions that cells have not used for signaling. This means that synthetic biologists could generate new pairs of proteins that can act as artificial circuits for applications such as diagnosing disease, without interfering with cells’ existing signaling pathways. “Using our high-throughput approach, you can generate many orthogonal versions of a particular interaction, allowing you to see how many different insulated versions of that protein complex can be built,” says Conor McClune, an MIT graduate student and the lead author of the study. In the new paper, which was published online on October 23, 2019 in Nature (https://www.nature.com/articles/s41586-019-1639-8), the researchers produced novel pairs of signaling proteins and demonstrated how they can be used to link new signals to new outputs by engineering E. coli cells that produce yellow fluorescence after encountering a specific plant hormone. The Nature article is titled “Engineering Orthogonal Signalling Pathways Reveals the Sparse Occupancy Of Sequence Space.” Michael Laub (photo), PhD, an MIT Professor of Biology, is the senior author of the study. Other authors are recent MIT graduate Aurora Alvarez-Buylla and Christopher Voigt, PhD, the Daniel I.C. Wang Professor of Advanced Biotechnology.

October 22nd

Haptoglobin Binds Free Hemoglobin and Can Prevent Neuron Damage After Brain Hemorrhage; Haptoglobin Not Normally Present at Effective Concentration in Brain, But Direct Administration in Cerebrospinal Fluid Is Protective in Animal Model

Patients who survive a cerebral hemorrhage may suffer delayed severe brain damage caused by free hemoglobin, which comes from red blood cells and damages neurons. Researchers at the University of Zurich and the University Hospital Zurich have now discovered a protective protein in the body called haptoglobin, which prevents this effect. Bleeding in the narrow space between the inner and middle meninges is life-threatening. This type of cerebral hemorrhage is normally caused by small protrusions in the major arteries at the base of the brain (aneurysms) that can burst without warning. A third of patients suffering such a hemorrhage, who are often still young, die as a result of the massive increase of pressure inside the skull. "Even if we manage to stop the bleeding and to stabilize the patients, in the first two weeks after bleeding there can be delayed brain damage. This often leads to severe impairments or can even be fatal," explains Luca Regli, MD, Director of the Department of Neurosurgery at the University Hospital Zurich (USZ). Despite great research efforts, until now, it has not been possible to prevent these serious consequences of bleeding in the subarachnoid space. An interdisciplinary team of researchers from the University of Zurich (UZH), USZ, and the Veterinary Teaching Hospital Zurich have now discovered a promising strategy: haptoglobin, a protective protein found in the blood, binds the hemoglobin that has been released in the cerebrospinal fluid before it can cause damage. The results of their work were published online on August 27, 2019 in the Journal of Clinical Investigation. The open-access article is titled “Haptoglobin Administration into the Subarachnoid Space Prevents Hemoglobin-Induced Cerebral Vasospasm.”

Blood Factor (GDF11) Stimulates Secretion of Adiponectin and Induces Calorie-Restriction-Like Phenotype in Aged Mice; Injection of GDF11 Stimulates Neurogenesis and Blood Vessel Remodeling

Aging is a process that affects all functions of the human body, particularly brain function. However, aging can be delayed through lifestyle changes (physical exercise, restricting calorie intake, etc.). Researchers at the Institut Pasteur and CNRS (Centre National de la Recherche Scientifique) have elucidated the properties of a molecule in the blood - GDF11 (image) - whose mechanisms were previously unknown. In a mouse model, they showed that this molecule could mimic the benefits of certain calorie restrictions - dietary regimens that have proven their efficacy in reducing cardiovascular disease, preventing cancer, and increasing neurogenesis in the brain. The results of this research were published in the journal Aging Cell on October 22, 2019. The open-access article is titled “Systemic GDF11 Stimulates the Secretion of Adiponectin and Induces a Calorie Restriction-Like Phenotype in Aged Mice.” Today it is possible to maintain a healthy brain in the long term. For the past 30 years, it has been generally acknowledged that certain diet restrictions such as intermittent fasting can improve cognitive performance and extend life expectancy in several species. It has also been proven that calorie restriction (a reduction in calorie intake of 20% to 30% while preserving nutritional quality) reduces the risk of cardiovascular disease and cancer, while increasing production of new neurons in the brain. In a previous study using mouse models, scientists observed that injecting aged mice with blood from young mice rejuvenated blood vessels in the brain, and consequently improved cerebral blood flow, while increasing neurogenesis and cognition .

White Bellbirds in Amazon Shatter Record for Loudest Bird Call Ever Measured

Researchers reporting in the journal Current Biology, on October 21, 2019, have captured the loudest bird calls yet documented. The calls are the mating songs of male white bellbirds, which live atop mountains in the Amazon region of northern Brazil. The open-access Current Biology article is titled “"Extremely Loud Mating Songs At Close Range In White Bellbirds.” The calls have a sound pressure about three times that of screaming pihas, now the second loudest bird singer that's been documented. In fact, the calls are so loud that the researchers are left to wonder how white bellbird females listen to them at close range without doing permanent damage to their hearing. "While watching white bellbirds, we were lucky enough to see females join males on their display perches," said Jeff Podos, PhD, of the University of Massachusetts, Amherst. "In these cases, we saw that the males sing only their loudest songs. Not only that, they swivel dramatically during these songs, so as to blast the song's final note directly at the females." "We would love to know why females willingly stay so close to males as they sing so loudly," he says. "Maybe they are trying to assess males up close, though at the risk of some damage to their hearing systems." The researchers say it's hard to describe just how loud the call really is because it's tough to make comparisons between sounds heard at different distances. Dr. Podos says that the howls of howler monkeys and bellows of bison are well studied and are both pretty loud. But they are not nearly as loud as the songs of bellbirds. That's especially impressive because of the bellbird's tiny size in comparison to those mammals. Bellbirds weigh only about a quarter of a kilogram.