Shining some light on the obscure proteome

Group Leader in Chemical Proteomics, Dr. Guillaume Médard, and his research group in the lab.
 Credit: Uli Benz / TUM

Mass-spectrometry based proteomics is the big-data science of proteins that allows to monitor the abundances of thousands of proteins in a sample at once. It is therefore a particularly well suited readout to discover which proteins are targeted by any small molecule. An international research team has investigated this using chemical proteomics.

Histone deacetylase (HDAC) inhibitors are a class of drugs used in oncology. An international research team involving scientists at the Technical University of Munich (TUM), Cornell University in Ithaca (USA), the German Cancer Research Center (DKFZ) in Heidelberg and Martin Luther University of Halle-Wittenberg has now investigated the effects of some HDAC drugs in more detail. The scientists wanted to know whether those epidrugs engage proteins other than the HDACs which they are designed to inhibit.

“To do so, target deconvolution by chemical proteomics is the method of choice. Hence, we first made new chemical tools - the so called affinity matrices - that would allow us to systematically profile the HDACs,” explains Dr. Guillaume Médard, group leader for chemical proteomics at the TUM chair of Proteomics and Bioanalytics led by Prof. Bernhard Küster.

“I profiled 53 drugs”, details Severin Lechner, doctoral candidate at the TUM School of Life Sciences. “Most of them, but not all, hit their intended HDAC target. However there were some surprises. Drugs used in hundreds of scientific studies were not as selective as assumed. Many had additional targets that were not previously known.

Research brings new light to unsolved genetic diseases in children

Asst Prof Xue and her team in NUS study the effects of maternal SMCHD1 gene mutations on offspring.
Source: National University of Singapore

The study highlights the role of genes inherited from mothers in genetic diseases in children, and improves the understanding of such diseases

The development of an embryo is a well-orchestrated string of processes, ensuring correct formation and positioning of vital organs of the growing organism. At the molecular level, these processes are controlled in a precise manner by switching on or off specific factors such as genes or proteins. Any errors in these processes could result in physical defects or disease in the newborn organism.

A team of scientists from the National University of Singapore (NUS) led by Assistant Professor Xue Shifeng from the Department of Biological Sciences has discovered a new way to interpret unsolved Mendelian diseases – diseases inherited from either parent due to gene mutations in the developing egg or sperm – through studying the inheritance of a protein known as SMCHD1 which is coded by the SMCHD1 gene. Mutations in the SMCHD1 gene can cause diseases such as facioscapulohumeral muscular dystrophy (FSHD) which is a muscle degenerative disorder, and Bosma arhinia microphthalmia syndrome (BAMS) which causes abnormalities of the nose and eyes.

The researchers found that SMCHD1 from mothers controls the expression of a group of genes in offspring, known as the HOX genes, which determines the position of body parts in an embryo along the axis from its head to tail. The researchers also found that the inactivation of SMCHD1 in female zebrafish results in alterations to HOX gene expression leading to skeletal defects in their offspring.

The study led by NUS researchers, in collaboration with A*STAR, Yale-NUS and Aix-Marseille University, was published in Nature Communications.

Student helps find world’s largest frog in Equatorial Guinea for first time in almost two decades

Left: Student Sam Hurley (left) with local guide Edu. Right: A goliath frog found in Monte Alén National Park, Equatorial Guinea
Source: University of Bristol

Field researchers from the University of Bristol and Bristol Zoological Society have found the world’s largest frog in Equatorial Guinea for the first time in almost two decades.

The most recent amphibian survey in the country’s Monte Alén National Park, which is one of the goliath frog's few known habitats, recorded no sign of it.

Goliath frogs can be as big as some housecats, measuring up to 34cm in length and weighing more than 3kg.

Concerned by the lack of recent evidence of the species in the national park, conservationists travelled to Equatorial Guinea to find evidence that the giant amphibian was not lost to the region.

Working in partnership with INDEFOR-AP, the national park service of Equatorial Guinea, the researchers conducted a survey along the Benito River.

Over 10 days in the forest, the researchers spotted the amphibian in a small waterfall. They had hoped to collect vocal recordings of the frog, however, the animal was not heard calling, perhaps confirming previous accounts that it is indeed a quiet, if not silent, amphibian. More study is needed.

Bernese researchers simulate defense of the earth

Info graphic which shows what effects the collision of DART could have on the orbit of Didymos B.
Credit: NASA / Johns Hopkins APL

NASA’s Double Asteroid Redirection Test (DART) mission is the world’s first full-scale planetary defense test against potential asteroid impacts on Earth. Researchers of the University of Bern and the National Centre of Competence in Research (NCCR) PlanetS now show that instead of leaving behind a relatively small crater, the impact of the DART spacecraft on its target could leave the asteroid near unrecognizable.

66 million years ago, a giant asteroid impact on the Earth likely caused the extinction of the dinosaurs. Currently no known asteroid poses an immediate threat. But if one day a large asteroid were to be discovered on a collision course with Earth, it might have to be deflected from its trajectory to prevent catastrophic consequences.

Last November, the DART space probe of the US space agency NASA was launched as a first full-scale experiment of such a manoeuvre: Its mission is to collide with an asteroid and to deflect it from its orbit, in order to provide valuable information for the development of such a planetary defense system.

In a new study published in The Planetary Science Journal, researchers of the University of Bern and the National Centre of Competence in Research (NCCR) PlanetS have simulated this impact with a new method. Their results indicate that it may deform its target far more severely than previously thought.

COVID-19 Fattens Up Our Body’s Cells to Fuel Its Viral Takeover

Illustration of a SARS-CoV-2 viral particle entering a cell. The particle pierces through a cell’s membrane, made of two layers of lipids.  A PNNL-OHSU team has shown how lipids are key to the ability of the virus to replicate.
Credit: Illustration by Michael Perkins | Pacific Northwest National Laboratory

The virus that causes COVID-19 undertakes a massive takeover of the body’s fat-processing system, creating cellular storehouses of fat that empower the virus to hijack the body’s molecular machinery and cause disease.

After scientists discovered the important role of fat for SARS-CoV-2, they used weight-loss drugs and other fat-targeting compounds to try to stop the virus in cell culture. Cut off from its fatty fuel, the virus stopped replicating within 48 hours.

The authors of the recent paper in Nature Communications caution that the results are in cell culture, not in people; much more research remains to see if such compounds hold promise for people diagnosed with COVID. But the scientists, from Oregon Health & Science University and the Department of Energy’s Pacific Northwest National Laboratory, call the work a significant step toward understanding the virus.

“This is exciting work, but it’s the start of a very long journey,” said Fikadu Tafesse, the corresponding author of the study and assistant professor of molecular microbiology and immunology at OHSU. “We have an interesting observation, but we have a lot more to learn about the mechanisms of this disease.”

How did vertebrates first evolve jaws?

A zebrafish showing the skeleton and jaw (magenta), the eye (green circle on the left), and gill-like pseudobranch and gills (green structures on the right).
Image resized using AI by SFLORG
Credit: Mathi Thiruppathy/Crump Lab

Five-hundred million years ago, it was relatively safe to go back in the water. That’s because creatures of the deep had not yet evolved jaws. In a new pair of studies in the journals eLife and Development, scientists reveal clues about the origin of this thrilling evolutionary innovation in vertebrates.

In the studies, Mathi Thiruppathy from Gage Crump’s laboratory at USC, and collaborator J. Andrew Gillis from the University of Cambridge and the Marine Biological Laboratory, looked to embryonic development as way to gain insight into evolution—an approach known as “evo-devo.”

In fishes, jaws share a common developmental origin with gills. During development, jaws and gills both arise from embryonic structures called “pharyngeal arches.” The first of these arches is called the mandibular arch because it gives rise to jaws, while additional arches develop into gills. There are also anatomical similarities: the gills are supported by upper and lower bones, which could be thought of as analogous to the upper and lower jaws.

“These developmental and anatomical observations led to the theory that the jaw evolved by modification of an ancestral gill,” said Thiruppathy, who is the eLife study’s first author and a PhD student in the Crump Lab. “While this theory has been around since the late 1800s, it remains controversial to this day.”

Highly antibiotic-resistant strain of MRSA that arose in pigs can jump to humans

Pig farm 
Credit: Mark Holmes

The strain, called CC398, has become the dominant type of MRSA in European livestock in the past fifty years. It is also a growing cause of human MRSA infections.

The study found that CC398 has maintained its antibiotic resistance over decades in pigs and other livestock. And it is capable of rapidly adapting to human hosts while maintaining this antibiotic resistance.

The results highlight the potential threat that this strain of MRSA poses to public health. It has been associated with increasing numbers of human infections, in people who have and have not had direct contact with livestock.

“Historically high levels of antibiotic use may have led to the evolution of this highly antibiotic resistant strain of MRSA on pig farms,” said Dr Gemma Murray, a lead author of the study, previously in the University of Cambridge’s Department of Veterinary Medicine and now at the Wellcome Sanger Institute.

She added: “We found that the antibiotic resistance in this livestock-associated MRSA is extremely stable – it has persisted over several decades, and also as the bacteria has spread across different livestock species.”

Rock art detection via machine learning model a breakthrough

A hypothetical example of possible rock art image detection on an image from Kakadu National Park.
 Source: Griffith University

Researchers have developed a way to detect the presence of rock art in remote, hard-to-reach areas in Australia’s rugged landscapes using Machine Learning (ML) methods.

Co-led by Dr Andrea Jalandoni, a digital archaeologist from Griffith University’s Centre for Social and Cultural Research, the study used hundreds of images of rock art found within Kakadu National Park to train a ML model to detect whether painted rock art was present within the image.

The model achieved an 89% success rate, meaning it determined which images contained rock art the vast majority of times.

“Some of these sites are not easily accessible, so alleviating some of the time, effort and expense to mount some explorative missions is of huge value to this type of archaeological research in some of the most remote areas of Australia,” Dr Jalandoni said.

“Once our ML model picks up whether an area photographed potentially contains previously undiscovered rock art, scientists can then go in and ground-truth the site to verify if there is rock art present and report on it further.”

Magnetic resonance in tabletop format revolutionizes diagnostics and material analysis

Magnetic resonance in table device format revolutionizes diagnostics and material analysis
 Credit: Amadeus Bramsiepe, KIT

In the SFB HyPERion, which is coordinated by the Karlsruhe Institute of Technology (KIT), researchers from KIT and the universities of Kaiserslautern, Konstanz and Stuttgart are jointly developing a technology for compact, high-performance magnetic resonance. In the future, this could be used in the chemical and pharmaceutical industry, in medical practices or at border crossings. The German Research Foundation (DFG) will support the interdisciplinary network from the 1st. July 2022 over four years with more than 10.6 million euros.

Magnetic resonance is the most chemically specific and at the same time the most versatile measurement method for detailed information on the structure and function of molecular matter. Therefore, it is the basic technique for chemical, biological or material science characterizations. The low sensitivity and the relatively high degree of specialization stand in the way of nationwide use. The Collaborative Research Center "Compact high-performance magnetic resonance systems - HyPERiON" (High Performance Compact Magnetic Resonance) wants to change this by questioning conventional concepts along the entire signal processing chain. The aim is to improve the sensitivity, resilience and applicability of magnetic resonance in equal measure. The team led by SFB spokesman Professor Jan G. Korvink from the KIT Institute for Microstructure Technology (IMT) wants to reduce the volume of high-performance magnetic resonance systems from two cubic meters to the size of a 10-liter bucket - more than a factor of 200. This would enable them to be used from the laboratory in chemical and pharmaceutical factories, medical practices or at border crossings, making the technology universally usable. "Ultimately, it is about researching new and exciting applications in the field of chemistry, biology and chemical process engineering," says Korvink.

Miniaturization also makes magnetic resonance usable for smaller budgets

In order to achieve its goals, the SFB focuses on the miniaturization of all components involved in magnetic resonance technology. These are superconducting magnets, cooling systems, high-speed electronics, magnetic resonance sensors, devices for ultra-fast data transmission as well as devices for hyperpolarizing the nuclear spin of materials and biological samples. "The integration of all these technologies into a modern, portable platform will mean that we can advance applications of social relevance, such as in the diagnosis of diseases, the use of medical implants or the discovery of medication," explains SFB spokesman Korvink . The participants in the SFB assume that their research results will make the fast and high-resolution characterization of materials available for smaller budgets by means of magnetic resonance and will drive developments in chemistry and materials science as a whole.

Quick search for the best materials

In many ways, social well-being depends crucially on access to optimal materials. But the requirements are complex and include not only the function of the material, but also its effects on our biology, on the environment and on how the material can be recovered or broken down. “If the material characterization can be carried out quickly and in high resolution for a very large number of variants with only tiny samples and we can also carry out the tests under operating conditions and examine degradation processes, then we have the chance to find the best starting materials that meet our expectations correspond. This applies in particular to a minimal carbon footprint."Jan Korvink is convinced:" HyPERiON will fundamentally change the possibilities of material characterization and train a new generation of young researchers and engineers in their application for social challenges."

In addition to HyPERiON, KIT is also involved in another new collaborative research center, which will also be. July 2022 starts: SFB 1537 "ECOSENSE" under the leadership of the University of Freiburg wants to identify and predict more precisely and quickly critical changes in the forest ecosystem that arise from climate change.

Source/Credit: Karlsruhe Institute of Technology

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United States Army And Sikorsky Strengthen Army Aviation Fleet With 10th H-60 Black Hawk Helicopters

Lockheed-Martin-Sikorsky-HH60M-Black-Hawk-June-2022 An HH-60M MEDEVAC takes flight at Sikorsky’s headquarters in Stratford, Connecticut. Sikorsky continues to modernize and enhance the Black Hawk thanks to a hot production line, mature well-established supply chain and digital factory.
 Photo courtesy Sikorsky, a Lockheed Martin company.

The United States government and Sikorsky, a Lockheed Martin company (NYSE: LMT), signed a five-year contract for a baseline of 120 H-60M Black Hawk helicopters, with options to reach a total of 255 aircraft to be delivered to the U.S. Army and Foreign Military Sales (FMS) customers. Sikorsky continues to modernize and enhance the Black Hawk to meet the Army's challenging and evolving missions by continuously delivering aircraft thanks to a hot production line, mature well-established supply chain and digital factory.

The "Multi-Year X" contract for UH-60M Black Hawk and HH-60M MEDEVAC aircraft marks the 10th multiple-year contract for Sikorsky and the U.S. government for H-60 helicopters. With more than 2,100 H-60 variants in the U.S. Army's inventory, the Black Hawk continues to be the workhorse and backbone of U.S. Army Aviation. As the Army continues to develop its Future Vertical Lift (FVL) capabilities, they will continue to operate the H-60M for the next several decades and alongside the future fleet.