To better understand which species are most vulnerable and identify the most cost-effective actions, researchers combined expert assessments with scientific data to evaluate threats and conservation strategies for Antarctica. They asked 29 experts to define possible management strategies, estimate their cost and feasibility, and assess the potential benefit to different species between now and 2100.

Climate change was identified as the most serious threat to Antarctic biodiversity and influencing global policy to limit warming was the most beneficial conservation strategy. Under current management strategies and more than 2 degrees Celsius of warming, 65% of land plants and animals will decline by 2100. Emperor penguins (Aptenodytes forsteri) were identified as the most vulnerable, followed by other sea birds and soil nematode worms. However, regional management strategies could benefit up to 74% of plants and animals at an estimated cost of 1.92 billion US dollars over the next 83 years, equating to 0.004% of global GDP in 2019. The regional management strategies identified as offering the greatest return on investment were minimizing the impacts of human activities, improving the planning and management of new infrastructure projects, and improving transport management.

As Antarctica faces increasing pressure from climate change and human activities, a combination of regional and global conservation efforts is needed to preserve Antarctic biodiversity and ecosystem services for future generations, the authors say.

Lee adds, “What this work shows is that climate change is the greatest threat to Antarctic species and what we need is global mitigation efforts to save them. This will not only help to secure their future, but also our own.”

Story Source:

Materials provided by PLOS. Note: Content may be edited for style and length.

“There are more than 150 species of known glassfrogs in the world, and yet we’re really just starting to learn about some of the really incredible ways they interact with their environment,” said co-lead author Jesse Delia, a Gerstner postdoctoral fellow in the Museum’s Department of Herpetology.

Glassfrogs, which live in the American tropics, are nocturnal amphibians that spend their days sleeping upside down on translucent leaves that match the color of their backs — a common camouflage tactic. Their tummies, however, show something surprising: translucent skin and muscle that allows their bones and organs to be visible, giving the glassfrog its common name. Recent research has proposed that this adaptation masks the frogs’ outlines on their leafy perches, making them harder for predators to spot.

Transparency is a common form of camouflage among animals that live in water, but it’s rare on land. In vertebrates, attaining transparency is difficult because their circulatory system is full of red blood cells that interact with light. Studies have shown that ice fish and larval eels achieve transparency by not producing hemoglobin and red blood cells. But glassfrogs use an alternative strategy, according to the findings of the new study.

“Glassfrogs overcome this challenge by essentially hiding red blood cells from view,” said Carlos Taboada, the study’s co-lead author from Duke University. “They almost pause their respiratory system during the day, even at high temperatures.”

At Duke, the researchers used a technique called photoacoustic imaging, which uses light to induce sound-wave propagation from red blood cells. This allows researchers to map the location of the cells within sleeping frogs without restraint, contrast agents, sacrifice, or surgical manipulation — particularly important to this study because glassfrog transparency is disrupted by activity, stress, anesthesia, and death.

The researchers focused on one particular species of glassfrog, Hyalinobatrachium fleischmanni. They found that resting glassfrogs increase transparency two- to threefold by removing nearly 90 percent of their red blood cells from circulation and packing them within their liver, which contains reflective guanine crystals. Whenever the frogs need to become active again, they bring the red blood cells back into the blood, which gives the frogs the ability to move around — at which point, light absorption from these cells breaks transparency.

In most vertebrates, aggregating red blood cells can lead to potentially dangerous blood clots in veins and arteries. But glassfrogs don’t experience clotting, which raises a set of significant questions for biological and medical researchers.

“This is the first of a series of studies documenting the physiology of vertebrate transparency, and it will hopefully stimulate biomedical work to translate these frogs’ extreme physiology into novel targets for human health and medicine,” Delia said.

Other authors on the study include Maomao Chen, Chenshuo Ma, Xiaorui Peng, Xiaoyi Zhu, Tri Vu, Junjie Yao, and So?nke Johnsen from Duke University; Laiming Jiang and Qifa Zhou, from the University of Southern California, Los Angeles; and Lauren O’Connell, from Stanford University.

This study was supported in part by the National Geographic Society, grant # NGS-65348R-19; the Human Frontier Science Program postdoctoral fellowship # LT 000660/2018-L; the Gerstner Scholars Fellowship provided by the Gerstner Family Foundation and the Richard Gilder Graduate School at the American Museum of Natural History; start-up funds from Stanford University; start-up funds from Duke University; the National Institutes of Health, grant #s R01 EB028143, R01 NS111039, RF1 NS115581 BRAIN Initiative; a Duke Institute of Brain Science Incubator award; the American Heart Association Collaborative Sciences award 18CSA34080277; and a Chan Zuckerberg Initiative grant 2020- 226178.

The new findings, published Nov. 21 in Epigenetics & Chromatin, could eventually help scientists understand diseases caused by disruption of these enzymes and develop new treatments for them.

“Developing a better understanding of how enzymes impact the activity of our genomes offers valuable insights into biology and can help researchers design new therapeutic approaches for disease,” says Sean Taverna, Ph.D., associate professor of pharmacology and molecular sciences at the Johns Hopkins University School of Medicine.

The search began more than a decade ago, when Taverna was looking for factors that influence DNA activity in Tetrahymena thermophila — a one-celled, fresh water dwelling organism. During the original study, the research team found a previously unknown signal that the single-celled creature uses to “mark” genes it has turned off.

The location of the mark is on histone proteins, which act as spools that tightly wind DNA, often turning off genes and protecting DNA from damage. If Tetrahymena are not able to add the marks — a process called methylation, which adds chemical tags to a part of histones called H3K23 — the DNA becomes damaged and the cells grow poorly.

In a follow up study published in 2016, Taverna found that the H3K23 location is conserved between Tetrahymena and mammals, including humans. However, the enzymes that control how the chemical tags are placed on H3K23 differ between the species.

Without the identity of these enzymatic H3K23 “writers” of methylation, the researchers found it difficult to study H3K23’s role in human biology and disease.

So, Taverna, recent Ph.D. graduate David Vinson and Srinivasan Yegnasubramanian, M.D., Ph.D., professor of oncology and pathology at the Johns Hopkins Kimmel Cancer Center, led a new study to search for the mammalian enzymes that add the chemical tags to H3K23.

After screening many enzymes that write methylation, Vinson found just one pair of enzymes, EHMT1/GLP and EHMT2/G9a, which placed chemical tags on the H3K23 histone location.

When the researchers used drug inhibitors and genetic mutations directed against the enzyme pair in human brain cells (neurons) grown in the laboratory, the ability of the enzymes to place methylation tags on the H3K23 histone location reduced significantly.

“With this initial precedent established in human neuronal cells, the door is now wide open to study the role of these enzymes and the H3K23 modification in numerous contexts of health and disease, including human cancer,” says Yegnasubramanian.

Now that the researchers know that EHMT1/GLP and EHMT2/G9a place chemical tags on the H3K23 histone location, they are aiming to understand the precise mechanism of how they do so and develop drugs that target this activity.

“We want to better understand why diseases occur when these enzymes aren’t working correctly, and what their connections are to H3K23,” says Taverna.

In addition to Taverna, Yegnasubramanian and Vinson, other researchers who contributed to the study are Kimberly Stephens of the University of Arkansas for Medical Sciences; Robert N. O’Meally, Shri Bhat and Robert Cole of Johns Hopkins; and Blair Dancy of the Walter Reed Army Institute of Research.

Funding for the study was provided by the National Institutes of Health (R01GM118760, R01CA221306 and F31GM130114), the National Science Foundation, the Irving A. Hansen Memorial Foundation and the Commonwealth Foundation.

A team led by physicians Dr. Andrea Keppler-Hafkemeyer and Dr. Christine Greil from the Medical Center-University of Freiburgand virologist Prof. Oliver T. Keppler from LMU Munich has now characterized in detail the course over several months of the immune response of patients with blood cancer who had received a total of three vaccinations against COVID-19. The results allow inferences to be made about the protection that vaccination gives these patients against serious illness from SARS-CoV2.

Strong T cell response to COVID-19 vaccination

The study focused on patients with two kinds of blood cancer: B-cell lymphoma and multiple myeloma. “Our results show that almost all study participants had a strong T cell response to COVID-19 vaccination,” explains Dr. Andrea Keppler-Hafkemeyer. “This could be one reason why breakthrough infections turned out to be mild to moderately severe even in study participants who had been unable to form any specific antibodies after vaccination because of their therapy,” adds Dr. Christine Greil. The co-principal investigators and lead authors regularly look after blood cancer patients in the Department of Medicine I at the Medical Center — University of Freiburg.

The research group led by Prof. Oliver T. Keppler is specialized not only in analyzing the concentration of antibodies after vaccination, but also their quality. This depends particularly on the strength of the bonds between antibodies and the viral spike protein. In addition, the ability of antibodies to neutralize different SARS-CoV-2 variants in cell cultures plays a major role. As the next step, therefore, the scientists compared the quantity and quality of antibodies and T cell responses to the spike protein among blood cancer patients and healthy study participants after two and three COVID-19 vaccinations.

High-quality antibodies against different SARS-CoV-2 variants

The study revealed that patients who can form antibodies tend to produce antibodies of particularly high quality. After their second vaccination, they are already able to neutralize and thus deactivate different SARS-CoV-2 variants. This ability is considerably more pronounced in this patient cohort than in vaccinated healthy people.

“COVID-19 vaccination can generate very broad antiviral immunity — including highly potent neutralizing antibodies — in patients with various types of blood cancer. Consequently, multiple vaccine doses can be recommended for patients with B-cell lymphoma or multiple myeloma without interrupting therapy,” summarizes Prof. Oliver T. Keppler.

Story Source:

Materials provided by Ludwig-Maximilians-Universität München. Note: Content may be edited for style and length.

The study focuses on the subtle substitution of a conserved aromatic residue in SRY (tyrosine) by a closely related aromatic residue (phenylalanine). The clinical mutation, shared by a fertile XY father and his sterile XY daughter, positions the embryonic male switch at the borderline of genetic function. The two aromatic rings are seemingly interchangeable in the structure of the protein, but differ in their ability to anchor a bridging water molecule in the protein-DNA complex.

“Loss of a single atom in SRY, an oxygen atom in a critical tyrosine, impairs the robustness of male development,” said Michael Weiss, MD, PhD, chair of the Department of Biochemistry and Molecular Biology. “Normally, the father has XY chromosomes and the daughter has XX chromosomes but in some families, the daughters can have XY chromosomes because there is a mutation in SRY. Sex chromosomes can degenerate over evolutionary time scales, leading to new upstream switches being recruited as male-determining pathways grow backwards. Such initial steps can be tenuous in biochemical terms.”

In the study, researchers focused on position 72 in the DNA-binding domain of SRY, which was not previously considered of special interest. However, the researchers discovered that tyrosine at this position enables operation of a water-mediated kinetic clamp, extending the lifetime of the protein-DNA complex. This mechanism is conserved in all mammalian SRY factors and is broadly observed in a related family of switch factors in multicellular (and some unicellular) animals. The latter family, designated “SOX” (SRY-related HMG box) is fundamental to patterning and development in metazoans.

Researchers published two recent papers about their work in Frontiers in Endocrinology. The first describes their findings related to focusing on box 72, and the second describes how the water-mediated clamp mechanism works. Weiss said they call it a “humpty-dumpty” model because of accelerated disassembly of the male-determining protein-DNA complex in the absence of the water-mediated clamp.

“Because the normal and mutant version of SRY are so similar in standard experimental assays,” said Joseph D. Racca, PhD, Assistant Research Professor in the Department of Biochemistry and Molecular Biology and first author of the new study. “Uncovering the water-mediated mechanism took several years. Critical insight was provided by molecular dynamics (MD) simulations of boundary water molecules in this system.”

“In the MD simulations a distinctive water molecule is anchored by the tyrosine as a bridge to the DNA: this special site of hydration is occupied for thousands of picoseconds, and then it will leave,” Weiss said. “But then another water molecule in the bulk solvent will almost immediately hop in its place, restoring the bridge.”

The subtle change from tyrosine to phenylalanine alters such hydration, a perturbation that propagates from position 72 predicted to destabilize successive protein-DNA contacts in the tail of the domain. Detachment of the tail would hasten dissociation of the protein-DNA complex and presumably male-specific gene-regulatory assemblies at target genes.

XY female children with differences in sexual differentiation due to Swyer Syndrome lack functional ovaries and are at risk for rare forms of early-onset gonadal cancer. Recognition of this syndrome is important allowing surgical removal of the gonads before cancer begins. The affected woman otherwise has a normal uterus and birth canal, and so they may bear children following in vitro fertilization of a donated egg.

Weiss said analogous mutations can occur in SOX genes, causing a variety of birth defects or diseases.

“Swyer mutations provide clues to help us understand a broad range of SOX diseases and may give rise to much improved protocols for different areas of medicine, such as regenerative medicine or cancer,” Weiss said. “This discovery thus goes way beyond sex determination because SRY is a prototype switch.”

In addition to Weiss, other study authors from IU include Yen-Shan Chen, PhD, Joseph Racca, PhD, Deepak Chatterjee, PhD, Ratan Rai, PhD, Yanwu Yang, PhD and Millie Georgiadis, PhD. Elisha Haas, PhD of Bar Ilan University in Israel was also a coauthor.