Human Proteoform Project to map proteins in human body

Project will accelerate the development of precision diagnostics and therapeutics

Now that the Human Genome Project has officially wrapped, an international team of researchers will map the entire collection of proteins in the human body.

Plans and goals for the Human Proteoform Project were outlined in a paper published last in the journal Science Advances. The large undertaking will characterize known proteoforms (specific protein molecules) as well as aim to systematically discover and analyze new ones in human tissues, cells and fluids.

“We are all built of proteins, and most drugs target proteins,” said Northwestern University’s Neil Kelleher, a world-renowned proteomics pioneer and corresponding author of the paper. “But understanding proteins is an open frontier. Like other seminal moments in science and technology, this project will serve as a major achievement that can help us more fully understand proteins’ role in all types of disease, aging and new therapeutics.”

Sandia cooks material-storage containers to assess fire safety

A test where a stainless-steel container designed for the storage and transportation of hazardous materials is heated to 2000 degrees Fahrenheit for four hours at Sandia National Laboratories. The container did not catastrophically fail, instead small pinholes formed relieving the intense pressure. On the upper left-hand corner is an X-ray video from outside the container. The top middle image is a video from a pinhole camera inside the test chamber. The upper right-hand corner shows the outside of the test chamber. The bottom graph shows the pressure inside the container (white line) and the temperature of the container (in degrees Celsius) from nine different places (colored lines) during the test. 

Video Credit: Sandia National Laboratories

A team at Sandia National Laboratories has completed a series of tests on specially designed stainless-steel containers used by the Department of Energy for storage and transportation of hazardous materials.

The engineers, technologists and project managers were surprised to find that the containers did not split open when heated to 2000 degrees Fahrenheit. That is almost as hot as a cement kiln.

“These containers were welded shut and heated to 2000 degrees, so we assumed that they were going to split open, but they developed small pinholes instead,” said Walt Gill, the test director and Sandia mechanical engineer. “We think the material inside reacted with the container itself and produced the pinholes in the container. These tiny holes let out all of the superheated gas without the containers pressurizing and pulling themselves apart.”

The series of 10 tests were designed to mimic a hypothetical raging-hot fire burning at a DOE facility and engulfing a container that had been knocked on its side and left outside of its insulated packaging, which protects it from heat. Since these containers are not designed to withstand such a fire, the goal of the test was to determine how much, if any, material stored within the container would be released into the air during such an accident, said Gill and Austin Baird, the test engineer.

Map of Mouse Iris Offers New Look at the Eye

Branching nerve fibers (red) stretch across the mouse iris. Scientists have now built the first cell-by-cell map of this eye tissue.
Credit: J. Wang

A cell-by-cell map of the mouse iris lays the foundation to study eye disorders and engineer cell therapies to replace damaged eye tissue.

If vision science were a movie, the iris would be a supporting actor. It doesn’t get as much limelight as the retina, the eye’s light-sensing tissue. And it’s not as high-profile as the lens, which can cloud with cataracts as people age.

Though the iris – the colorful tissue that rings the pupil – comes in a rainbow of showy shades, for most scientists, “it was not the main attraction in the eye,” says Jeremy Nathans, a Howard Hughes Medical Institute Investigator at Johns Hopkins University School of Medicine. In fact, he has spent most of his career studying the molecular biology of the retina.

“The basic biology of the iris had kind of languished,” Nathans says. Not anymore. He and his colleagues Jie Wang and Amir Rattner have now developed a high-resolution map of the mouse iris that distinguishes individual cells by the activity of their genes. The trio was motivated by the beauty of the iris, the diversity of iris structure in different animals, and its importance for vision, Nathans says.

Strands of dilator muscles (red) weave through the mouse iris.
Sphincter cells (green) cluster in the pupil (right),
which expands and constricts to control the amount of light entering the eye.
Credit: J. Wang

His team identified eight types of iris cells and uncovered new information about iris cell development and the genes that switch on when the pupil dilates, they report November 16, 2021, in the journal eLife. The researchers’ cell-by-cell map of the iris could one day help identify genes involved in iris-related eye disorders. The work could also guide engineering of healthy iris cells used to replace diseased cells elsewhere in the eye.

Common blood pressure drug does not slow down the progression of more advanced Alzheimer’s

New research led by the University of Bristol, has shown the drug losartan, normally used to treat high blood pressure (hypertension), is not effective in slowing down the progression of Alzheimer’s disease (AD) in people with mild-to-moderate disease after 12 months of treatment. However, the drug could still be of benefit if prescribed for longer and if given to people with very early disease. The findings are from the phase 2 multi-center clinical trial known as RADAR ((Reducing pathology in Alzheimer’s Disease through Angiotensin taRgeting).

The double blinded placebo-controlled randomized trial (where participants and doctors don’t know what treatment people are on) investigated whether losartan, compared with a placebo, could reduce brain volume loss, as a measure of disease progression, in people clinically diagnosed with established AD.

The research, published in The Lancet Neurology and NIHR Efficacy and Mechanism Evaluation, is the first to evaluate the potential benefit of losartan, an angiotensin receptor blocker, which is a drug commonly used to treat high blood pressure and heart failure, in clinically diagnosed AD using brain imaging as a primary outcome.

Two-hundred and sixty-one people aged 55 years or older diagnosed with AD, who had not been prescribed similar hypertension drugs, and who had capacity to consent, were recruited from 23 UK National Health Service hospital trusts between 22 July 2014 and 17 May 2018.

The 211 eligible participants were then randomly allocated with 105 assigned to receive the study drug, 100 mg of losartan, and 106 to the placebo (an identical looking pill with no active medicine) once a day for 12 months. From the 197 (93%) participants who completed the study, primary outcome data were available for 171 (81%) participants.

Study sheds light on how bacteria control their detoxification

Bacteria need to constantly adapt to compete against other species for nutrient sources and to survive against threats such as antibiotics and toxins.

In an effort to understand how bacteria control and regulate this adaptation, University of Michigan researchers are examining how RNA polymerase—the enzyme that transcribes genetic information from DNA onto RNA—slows during transcription in a process called transcriptional pausing.

They found that a protein called N-utilizing substance A, or NusA, in concert with another control element called a riboswitch, fine-tunes the transcription speed in order to regulate gene expression. Gene expression is the process by which genetic information is converted into the building blocks of the bacterium.

The researchers say their work, published in the Proceedings of the National Academy of Sciences, expands our general understanding of the transcription process in bacteria, and could provide a target for developing new antibiotics.

“NusA is specific to bacteria. It’s not found in human cells or in yeast, so that it can be a target for the design of new antibiotics or drugs that will affect pathogenic bacteria but not our own cells,” said Adrien Chauvier, lead author of the study and postdoctoral researcher in the Nils Walter laboratory in the U-M Department of Chemistry and the Center for RNA Biomedicine.

When bacteria undergo gene expression, RNA polymerase synthesizes RNA. As RNA is produced, it undergoes a process called co-transcriptional RNA folding, adopting a dynamic structure that researchers think influences the timing of gene expression. To examine this process, Chauvier, together with undergraduate researcher Pujan Ajmera, looked at an element called a riboswitch, a segment of the transcribed messenger RNA that regulates gene expression through modulation of the RNA conformation. This structural change is triggered when a specific metabolite or ion called a “ligand” binds to the riboswitch.

Air filter significantly reduces presence of airborne SARS-CoV-2 in COVID-19 wards

Image: Dr Vilas Navapurkar in ICU beside an air filter

While the discovery could have implications for improving the safety of repurposed ‘surge wards’, the researchers say it also opens up the possibility of being able to set standards for cleaner air to reduce the risk of airborne transmission of infections.

Over the duration of the pandemic there has been a steady rise in the evidence that the SARS-CoV-2 virus can be transmitted through the air in small droplets (aerosols). But as hospitals have seen their capacity overwhelmed, they have been forced to manage many of their COVID-19 patients in repurposed ‘surge’ wards, which often lack the ability to change the air with a high frequency. While the use of appropriate personal protective equipment (PPE) protects staff and patients significantly reduces the risk of transmission, there are still reports of patient-to-healthcare worker transmission of the virus, potentially through the inhalation of viral particles.

A team at the University of Cambridge and Cambridge University Hospitals (CUH) NHS Foundation Trust investigated whether portable air filtration/UV sterilization devices could reduce airborne SARS- CoV-2 in general wards that had been repurposed as a COVID ward and a COVID Intensive Care Unit (ICU). The results are published in Clinical Infectious Diseases.

Dr Vilas Navapurkar, a Consultant in Intensive Care Medicine at CUH, who led the study, said: “Reducing airborne transmission of the coronavirus is extremely important for the safety of both patients and staff. Effective PPE has made a huge difference, but anything we can do to reduce the risk further is important.”

“Because of the numbers of patients being admitted with COVID-19, hospitals have had to use wards not designed for managing respiratory infections. During an intensely busy time, we were able to pull together a team from across the hospital and University to test whether portable air filtration devices, which are relatively inexpensive, might remove airborne SARS-CoV-2 and make these wards safer.”

Air pollution clouds brain performance and workforce productivity

Credit: SFLORG

Even short-term exposure to air pollution impacts our brain performance and capacity to work, according to researchers from The University of Queensland and Carnegie Mellon University.

Dr Andrea La Nauze from UQ’s School of Economics said a data study indicated that air pollution damaged cognitive function in working-age adults.

“Our research used data from Lumosity brain training games to investigate the impact of air pollution on adults living in the United States,” Dr La Nauze said.

“The games we studied targeted seven cognitive functions: memory, verbal ability, attention, flexibility, math's ability, speed and problem-solving.

“We found that exposure to moderately high levels of fine particulate matter (PM2.5) caused a player to drop by almost six points in a 100-point scale where 100 represents the score of the top one per cent of cognitive performers.

“In fact, if you’re under 30 years old and you’re exposed to this level of pollution, your cognitive function declines by the same amount as ageing by 15 years."

PM2.5 are tiny particles 2.5 microns or less in size.

If inhaled, PM2.5 can penetrate the lungs, enter the bloodstream and cause serious health problems, including heart disease and respiratory issues.

Dr La Nauze said while the health effects of PM2.5 were widely understood, this research was the first to use brain training data to study the potential impact on cognitive performance.

Climate change impact on Earth’s ‘life zones’ on track to accelerate

All of Earth's 'life zones' have undergone climate-change-
fueled change since the early 1900s.
Credit: Mike Fouque

Scientists have revealed that climate change has already impacted all of Earth’s ‘life zones’ and the effects are set to triple under business-as-usual emissions growth.

A University of Queensland and Wildlife Conservation Society-led (WCS) research team assessed the impact of global warming across the world’s 45 different ‘life zones’ – distinct biogeographic regions characterized by differences in temperature, precipitation, and aridity along with the species and ecosystems that live within them.

UQ’s Professor James Watson said all areas have undergone change since the early 1900s.

“We found that 27 million square kilometers, or 18.3 per cent of earth’s land mass had been impacted,” Professor Watson said.

“Fundamental shifts in these life zones have occurred most notably in boreal forests, temperate coniferous forests, and tropical coniferous forested systems.

“So, Canada, the United States, Russia and those in northern Europe have experienced some of the biggest changes.

“Boundaries between life zones have shifted poleward and towards higher elevations, leading to expansions of zones associated with tropical climates and contractions of zones associated with temperate climates.”

Scientists have developed gene-edited barley that could better your beer

Germination in the non-mutated barley was almost complete,
while the gene-edited barley did not germinate at all.
This shows that the gene-edited barley had been dormant for longer
(images taken 7 days after imbibition).
Credit: Hiroshi Hisano from Okayama University

After a spell of unexpected rain, before the harvest season, a farmer may be faced with the unpredictable problem of untimely sprouting of barley. Sprouted barley fetches considerably low market prices and poses an economic burden on farmers and corporations that are at the mercy of nature to survive in the agriculture industry. The aggravation of climate change has not made this situation any better too.

The problem of pre-harvest sprouting, thus, has kept agricultural researchers occupied for long. Pre-harvest sprouting can be avoided by prolonged grain dormancy through genetic manipulation. However, such dormancy can interfere with malt production, and also cause non-uniform germination upon sowing. Balancing these issues is necessary for high-quality barley production, therefore.

Now, a team of scientists, led by Associate Professor Dr. Hiroshi Hisano from Okayama University, Japan, offer a solution to this age-old problem. To achieve the ‘perfect’ barley, they looked to the latest gene manipulation technology—CRISPR/Cas9-based gene editing. Speaking about their motivation to pursue the art of perfecting barley, Dr. Hisano says, “We recognized the need to strategically manipulate crops to weather the effects of steadily exacerbating climate change. Since our collaborative research group had already developed expertise in precision genome editing of barley, we decided to go with the same initially. Also, previous studies have pinpointed specific grain and seed dormancy genes in barley, called Qsd1, and Qsd2. Hence, our modus operandi was pretty clear.” Their findings have been published as a research article in Plant Biotechnology Journal.

Researchers train computers to predict the next designer drugs

Credit: Raimond Klavins / Unsplash

UBC researchers have trained computers to predict the next designer drugs before they are even on the market, technology that could save lives.

Law enforcement agencies are in a race to identify and regulate new versions of dangerous psychoactive drugs such as bath salts and synthetic opioids, even as clandestine chemists work to synthesize and distribute new molecules with the same psychoactive effects as classical drugs of abuse.

Identifying these so-called “legal highs” within seized pills or powders can take months, during which time thousands of people may have already used a new designer drug.

But new research is already helping law enforcement agencies around the world to cut identification time down from months to days, crucial in the race to identify and regulate new versions of dangerous psychoactive drugs.

“The vast majority of these designer drugs have never been tested in humans and are completely unregulated. They are a major public health concern to emergency departments across the world,” says UBC medical student Dr. Michael Skinnider, who completed the research as a doctoral student at UBC’s Michael Smith Laboratories.