Shutting down backup genes leads to cancer remission in mice

Abhinav Achreja, PhD, Research Fellow at the University of Michigan Biomedical Engineering and Deepak Nagrath, Ph.D. Associate Professor of Biomedical Engineering works on ovarian cancer cell research in the bio-engineering lab at the North Campus Research Center (NCRC).
Image credit: Marcin Szczepanski, Michigan Engineering

The way that tumor cells enable their uncontrolled growth is also a weakness that can be harnessed to treat cancer, researchers at the University of Michigan and Indiana University have shown.

Their machine-learning algorithm can identify backup genes that only tumor cells are using so that drugs can target cancer precisely.

“Most cancer drugs affect normal tissues and cells. However, our strategy allows specific targeting of cancer cells.”

Deepak Nagrath

The team demonstrated this new precision medicine approach for treating ovarian cancer in mice. Moreover, the cellular behavior that exposes these vulnerabilities is common across most forms of cancer, meaning the algorithms could provide better treatment plans for a host of malignancies.

“This could revolutionize the precision medicine field because the drug targeting will only affect and kill cancer cells and spare the normal cells,” said Deepak Nagrath, a U-M associate professor of biomedical engineering and senior author of the study in Nature Metabolism. “Most cancer drugs affect normal tissues and cells. However, our strategy allows specific targeting of cancer cells.”

Ocean scientists measure sediment plume stirred up by deep-sea-mining vehicle

The Launch and Recovery System deploying the Patania II pre-prototype collector vehicle from the surface operations vessel MV Normand Energy.
Credit: Global Sea Mineral Resources

What will be the impact to the ocean if humans are to mine the deep sea? It’s a question that’s gaining urgency as interest in marine minerals has grown.

The ocean’s deep-sea bed is scattered with ancient, potato-sized rocks called “polymetallic nodules” that contain nickel and cobalt — minerals that are in high demand for the manufacturing of batteries, such as for powering electric vehicles and storing renewable energy, and in response to factors such as increasing urbanization. The deep ocean contains vast quantities of mineral-laden nodules, but the impact of mining the ocean floor is both unknown and highly contested.

Now MIT ocean scientists have shed some light on the topic, with a new study on the cloud of sediment that a collector vehicle would stir up as it picks up nodules from the seafloor.

The study, appearing today in Science Advances, reports the results of a 2021 research cruise to a region of the Pacific Ocean known as the Clarion Clipperton Zone (CCZ), where polymetallic nodules abound. There, researchers equipped a pre-prototype collector vehicle with instruments to monitor sediment plume disturbances as the vehicle maneuvered across the seafloor, 4,500 meters below the ocean’s surface. Through a sequence of carefully conceived maneuvers. the MIT scientists used the vehicle to monitor its own sediment cloud and measure its properties.

Their measurements showed that the vehicle created a dense plume of sediment in its wake, which spread under its own weight, in a phenomenon known in fluid dynamics as a “turbidity current.” As it gradually dispersed, the plume remained relatively low, staying within 2 meters of the seafloor, as opposed to immediately lofting higher into the water column as had been postulated.

A new understanding of the neurobiology of impulsivity News

Photo Credit: Vitolda Klein

While not all impulsive behavior speaks of mental illness, a wide range of mental health disorders which often emerge in adolescence, including depression and substance abuse, have been linked to impulsivity. So, finding a way to identify and treat those who may be particularly vulnerable to impulsivity early in life is especially important.

A group of researchers, led by scholars at McGill University, have developed a genetically based score which could help identify, with a high degree of accuracy (greater than that of any impulsivity scores currently in use), the young children who are most at risk of impulsive behavior.

Their findings are especially compelling because the score they have developed was able to detect those at a higher risk of impulsivity within three ethnically diverse community samples of children, from a cohort of close to 6,000 children.

This discovery of a novel score for impulsivity in early life can inform prevention strategies and programs for children and adolescents who are at risk for psychiatric disorders. In addition, by describing the function of the gene networks comprising the score, the study can stimulate the development of new therapies in the future.

“COVID Time” is a real thing, and it’s not good

Credit: xaviandrew

Have you ever noticed that time seems to slow down sometimes? Like when you are waiting in line at a bank or grocery checkout, and it just seems to take forever?

During the peak of the pandemic, and mid-lockdown, many people reported they felt their days dragged on, inducing fatigue and making some tasks almost unbearable during “COVID time.”

An interdisciplinary team of researchers studied this effect of the COVID-19 pandemic, called Blursday, to understand how our perception of time is malleable and influenced by many factors. Blursday was the altered sense of time and difficulty in determining the day of the week during the lockdown.

Dr. Fuat Balci, a UM biologist and part of the research team, notes: “A new lingo emerged during the COVID-19 pandemic to capture the altered psychological state under the extraordinary conditions imposed by the pandemic such as the lockdown and social isolation, including doomscrolling and Blursday.”

The researchers had volunteers answer a questionnaire and perform 15 behavioral tasks, such as estimating how long they had been logged on to the study’s website. They were also asked to guess if a stated time interval was shorter or longer than they experienced to test how the pandemic affected temporal awareness.

Sifting through cellular recycling centers

A cartoon representation of the new method, which allows scientists to isolate the lysosomes (left) of any cell in a mouse to analyze and identify using mass spectrometry (right) all the molecules inside them.
Image credit: Cindy Lin

A new method allows scientists to determine all the molecules present in the lysosomes – the cell’s recycling centers – of mice. This could bring new understanding and treatment of neurodegenerative disorders.

Small but mighty, lysosomes play a surprisingly important role in cells despite their diminutive size. Making up only 1-3% of the cell by volume, these small sacs are the cell’s recycling centers, home to enzymes that break down unneeded molecules into small pieces that can then be reassembled to form new ones. Lysosomal dysfunction can lead to a variety of neurodegenerative or other diseases, but without ways to better study the inner contents of lysosomes, the exact molecules involved in diseases – and therefore new drugs to target them – remain elusive.

A new method, reported in Nature on Sept. 21, allows scientists to determine all the molecules present in the lysosomes of any cell in mice. Studying the contents of these molecular recycling centers could help researchers learn how the improper degradation of cellular materials leads to certain diseases. Led by Stanford University’s Monther Abu-Remaileh, institute scholar at Sarafan ChEM-H, the study’s team also learned more about the cause for a currently untreatable neurodegenerative disease known as Batten disease, information that could lead to new therapies.

Newly Discovered Barrier Prevents Immunity from Reaching Smell-Sensing Cells

Circulating antibody (white) is prevented from accessing olfactory epithelium (green) by a previously unknown blood-olfactory barrier, the BOB.
Credit: Ashley Moseman Lab, Duke University

Duke scientists have identified a previously unknown barrier that separates the bloodstream from smelling cells in the upper airway of mice, likely as a way to protect the brain.

But this barrier also ends up keeping some of the larger molecules of the body’s immune system out, and that may be hindering the effectiveness of vaccines.

It makes sense to have a protective barrier for the olfactory cells lining the nose, because they offer a direct path to the olfactory bulb of the brain, making them effectively extensions of the brain itself, said lead researcher Ashley Moseman, an assistant professor of immunology in the Duke School of Medicine.

However, the new barrier, which his team has dubbed the BOB – the blood-olfactory barrier -- also might be keeping vaccines against respiratory viruses from being more effective by preventing those antibodies from reaching the mucous on the surface of the nose, the first barrier a virus encounters.

The team was trying to understand better how the immune system protects the upper respiratory tract by infecting mice with a virus called vesicular stomatitis virus, or VSV, that is known to penetrate to the central nervous system. Once inhaled, VSV readily infects the olfactory sensing cells and rapidly replicates, reaching the olfactory bulb of the brain within a day. Although it can lead to paralysis and death, it is usually cleared by a T cell response.

Study finds high levels of PFAS in school uniforms

In yet another example of the prevalence of the hazardous chemicals known as PFAS (per- and polyfluoroalkyl substances) in consumer products, industrial products and textiles, researchers have found notably high levels in school uniforms sold in North America.

In a study published in Environmental Science and Technology Letters, scientists at the University of Notre Dame, Indiana University, the University of Toronto and the Green Science Policy Institute analyzed a variety of children’s textiles. Fluorine was detected in 65 percent of samples tested.

But concentrations were highest in school uniforms — and higher in those uniforms labeled as 100 percent cotton as opposed to synthetics.

“What was surprising about this group of samples was the high detection frequency of PFAS in the garments required for children to wear,” said Graham Peaslee, professor of physics at Notre Dame and a co-author of the study. “Children are a vulnerable population when it comes to chemicals of concern, and nobody knows these textiles are being treated with PFAS and other toxic chemicals.”

An estimated 20 percent of public schools in the United States require students to wear uniforms —meaning millions of children could be at risk of exposure to the toxic compounds.

Known as “forever chemicals,” PFAS are known to accumulate in the bloodstream and have been linked to an increased risk of several health problems including weakened immune systems, asthma, obesity, and neurodevelopmental and behavioral problems. The National Health and Nutrition Examination Surveys from the Centers for Disease Control and Prevention routinely find PFAS in blood samples of children between the ages of 3 and 11.

No evidence that dehorning black rhinos negatively impacts the species’ reproduction or survival

A sedated black rhino in the process of being dehorned, with a cap over its eye to protect it from the dust
Credit: Piet Beytell, Namibian Ministry of Environment, Forestry and Tourism

There are no statistically significant differences in key factors of population growth - breeding, birth, survival, life span and death - between dehorned or horned black rhinos new research, conducted by the University of Bristol Vet School, Namibian Ministry of Environment, Forestry and Tourism, and Save the Rhino Trust has found.

The black rhino is critically endangered, with poaching one of several threats to the species’ survival. Many reserves across a number of African countries, including Namibia, South Africa, and Zimbabwe, now dehorn their rhinos in an attempt to reduce poaching but few studies have looked at the impacts of dehorning, particularly in black rhinos.

The study aimed to build on existing knowledge of population productivity between dehorned and horned individuals in four sub-populations of black rhino (of the sub-species Diceros bicornis bicornis) in Namibia.

Three of the populations had undergone some level of dehorning at least once while one of the populations had never been dehorned. The measures investigated included: age of females at the birth of their first calf (age at first reproduction or AFR); average time between the birth of calves for each female (inter-calving interval); birth sex ratios, calf survival, life span and cause of death

Octopuses prefer certain arms when hunting and adjust tactics to prey

A California two-spot octopus hunts a shrimp in an experiment, striking with its second arm.
Credit: Wardill Lab, University of Minnesota

Famous for their eight arms, octopuses leverage all of their appendages to move, jet through the water and capture prey. But their movements can look awkward and seemingly unplanned at times, more closely resembling aliens than earthly creatures.

“Normally when you look at an octopus for a short while, nothing is repeatable. They squirm around and just look weird in their exploratory movements,” said Trevor Wardill, an assistant professor in the College of Biological Sciences who studies octopuses and other cephalopods.

For a new study in Current Biology, Wardill and colleagues investigated whether octopuses preferred certain arms over others when hunting, rather than using each arm equally. A better understanding of how they use their arms will aid efforts to develop next-generation, highly-manipulative soft robots.

The research team studied the California two-spot octopus, which live for about two years and grow to the size of tennis balls. Octopus arms are numbered on each side of its body, starting at the center. Researchers dropped different types of prey, including crabs and shrimp, into the tanks and recorded video as the octopuses, who were hiding in ornamental SpongeBob “dens” with one eye facing outward, lunged for the snack. Because crabs move slowly while shrimp can flick their tails to escape quickly, each type of prey potentially requires different hunting tactics.

Mysterious soil virus gene seen for first time

Crystals of the soil virus AMG product (chitosanase) at 400x magnification. Individual crystals were cryo-cooled in liquid nitrogen before being exposed to the powerful SSRL X-rays beams for structure analysis.
Credit: Clyde Smith/SLAC National Accelerator Laboratory

In every handful of soil, there are billions of bacteria, fungi, and viruses, all working to sustain the cycle of life. Understanding how these microorganisms interact with one another helps scientists analyze soil health, soil carbon and nutrient cycling, and even the ways in which dead insects decompose.

Soil viruses contain genes that appear to have some metabolic function, but they are clearly not required for normal viral replication. These genes are called auxiliary metabolic genes (AMGs) and they produce proteins, some of which are enzymes that have a variety of functions. Until now, scientists have wondered whether some AMG proteins play a role in critical soil processes, like carbon cycling. To find out more about soil AMGs, researchers determined the atomic structure of a protein that is expressed by a particular AMG.

Specifically, researchers irradiated fragile crystallized protein samples with high-brightness X-rays generated by the Stanford Synchrotron Radiation Lightsource’s (SSRL) Beam Line 12-2 at the Department of Energy’s (DOE) SLAC National Accelerator Laboratory. The X-rays struck the proteins within the crystal samples, revealing their molecular structures and a bit of the mystery behind their makeup.

AMGs do not, like many viral genes, help a virus replicate. Instead, they encode a variety of proteins, each with their own predicted function. The AMG that was expressed was a putative enzyme that plays a key role in how soils process and cycle carbon in the biosphere.