With Discovery, Oxygen's Role in Growth of Tumors Reconsidered

Structure of the HIF1A protein. Based on PyMOL rendering of PDB 1h2k Illustration
Credit: Emw
CC BY-SA 3.0

Yale researchers have made a discovery that changes conventional thinking about the role that oxygen plays in the growth of tumors—an area of cancer research that has been intensely studied in recent years.

The results, from the lab of Andre Levchenko, the John C. Malone Professor of Biomedical Engineering, are published in Cell Systems. Other groups collaborating on this study were directed by Chi V. Dang (Johns Hopkins University) and Kshitiz (University of Connecticut).

When tumors start running out of oxygen, they can switch on hypoxia-inducible factor (HIF-1alpha)—a transcription factor, which is a protein that controls the activity of genes. As a result of HIF-1alpha activation, the expression of hundreds of genes can change and dramatically alter the behavior of cancer cells. Although the increase in HIF-1alpha is thought to be steady, the new study led by Levchenko discovered that the levels of this molecule can also repeatedly rise and fall in small groups of cells, particularly in areas of high cell density. The effects of this oscillation are profound, as it allows cancer cells starving for oxygen to resume division and growth. It can also promote pro-cancer genes and inhibit anti-cancer genes.

Researchers find the snake clitoris

A death adder snake, also known as acanthophis antarcticus.
Photo Credit: Luke Allen.

An international team of researchers, led by the University of Adelaide has provided the first anatomical description of the female snake clitoris, in a first-of-its-kind study.

PhD Candidate Megan Folwell from the School of Biological Sciences, University of Adelaide, led the research.

“Across the animal kingdom female genitalia are overlooked in comparison to their male counterparts,” said Ms Folwell.

“Our study counters the long-standing assumption that the clitoris (hemiclitores) is either absent or non-functional in snakes.”

The research involved examination of female genitalia in adult snake specimens across nine species, compared to adult and juvenile male snake genitalia.

Associate Professor Kate Sanders, School of Biological Sciences, University of Adelaide, said: “We found the heart-shaped snake hemiclitores is composed of nerves and red blood cells consistent with erectile tissue - which suggests it may swell and become stimulated during mating. This is important because snake mating is often thought to involve coercion of the female – not seduction.”

Molecules found in mucus could prevent cholera infection

Scanning electron microscope image of Vibrio cholerae bacteria, which infects the digestive system.
Image Credit: Zeiss DSM 962 SEM T.J. Kirn, M.J. Lafferty, C.M.P Sandoe and R.K. Taylor,

MIT researchers have identified molecules found in mucus that can block cholera infection by interfering with the genes that cause the microbe to switch into a harmful state.

These protective molecules, known as glycans, are a major constituent of mucins, the gel-forming polymers that make up mucus. The MIT team identified a specific type of glycan that can prevent Vibrio cholerae from producing the toxin that usually leads to severe diarrhea.

If these glycans could be delivered to the site of infection, they could help strengthen the mucus barrier and prevent cholera symptoms, which affect up to 4 million people per year. Because glycans disarm bacteria without killing them, they could be an attractive alternative to antibiotics, the researchers say.

“Unlike antibiotics, where you can evolve resistance pretty quickly, these glycans don’t actually kill the bacteria. They just seem to shut off gene expression of its virulence toxins, so it’s another way that one could try to treat these infections,” says Benjamin Wang PhD ’21, one of the lead authors of the study.

Aging is driven by unbalanced genes

Northwestern University researchers have discovered a previously unknown mechanism that drives aging.

In a new study, researchers used artificial intelligence to analyze data from a wide variety of tissues, collected from humans, mice, rats and killifish. They discovered that the length of genes can explain most molecular-level changes that occur during aging.

All cells must balance the activity of long and short genes. The researchers found that longer genes are linked to longer lifespans, and shorter genes are linked to shorter lifespans. They also found that aging genes change their activity according to length. More specifically, aging is accompanied by a shift in activity toward short genes. This causes the gene activity in cells to become unbalanced.

Surprisingly, this finding was near universal. The researchers uncovered this pattern across several animals, including humans, and across many tissues (blood, muscle, bone and organs, including liver, heart, intestines, brain and lungs) analyzed in the study.

The new finding potentially could lead to interventions designed to slow the pace of — or even reverse — aging.

New findings on how to avert excessive weight loss from COVID-19

Professor Yihai Cao.
Photo Credit: Dr. Muyi Yang.

Losing too much weight when infected with COVID-19 has been linked to worse outcomes. Now, researchers at Karolinska Institutet have discovered that SARS-CoV-2 infection fuels blood vessel formation in fat tissues, thus revving up the body’s thermogenic metabolism. Blocking this process by using an existing drug curbed weight loss in mice and hamsters that were infected with the virus, according to the study published in the journal Nature Metabolism.

“Our study proposes a completely new concept for treating COVID-19 associated weight loss by targeting the blood vessels in the fat tissues,” says Yihai Cao, professor at the Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, and the study’s corresponding author.

The researchers examined how different types of fat, including brown fat and visceral and subcutaneous white fat, reacted when exposed to SARS-CoV-2 and how it impacted weight in mice and hamsters. They found that the animals lost significant amounts of weight in four days and that this weight loss was preceded by the activation of brown fat and the browning of both types of white fat. These fat tissues also contained more microvessels and high levels of a signaling protein called vascular endothelial growth factor (VEGF), which promotes the growth of new blood vessels.

Very fast, but not a supersonic

The computer model of the dinosaur tail used and a diplodocide
Image Credit: Simone Conti / Zachi Evenor

An international research team with the participation of the Department of Biology at the University of Hamburg has analyzed the mobility of dinosaur tails using computer models and methods from engineering. According to a study published in Scientific Reports, the researchers found that these tails could be moved more than 100 kilometers per hour. Unlike previously assumed, however, they did not reach supersonic speed.

Diplodocids were large herbivorous dinosaurs with long necks and long tails. In a previous study, it was believed that a hypothetical structure at the end of a diplodocid's tail, similar to the end of a whip, could move faster than the speed of sound (340 meters per second) and produce a supersonic bang.

To test this hypothesis, the international research team simulated the movements of the tail of diplodocids using a model based on five fossil diplodocid skeletons. The virtual tail model is over 12 meters long, would weigh 1,446 kilograms in real terms and consists of 82 cylinders, which are supposed to represent vertebrae and are attached to an immovable, virtual basin.

“Research was quite a challenge, because we had to tackle the problem with two methods, that are normally used in aerospace technology: multi-body simulation and the estimation of the resilience of the materials”, reports the first author of the study, Simone Conti from the Universidade NOVA de Lisboa and the Politecnico di Milano.

Argentine ants will do anything for sugar, but they won’t do this

 An Argentine ant tending aphids, plant parasites that secrete a sugar-rich substance the ants consume.
 Photo Credit: UCLA/Noa Pinter-Wollman

It might seem like common sense that a starving animal is more likely to take dangerous risks to obtain food than one with a full belly. But new research from UCLA shows that groups of Argentine ants, who forage boldly when they’re well fed, exercise far more caution when they’ve been deprived of carbohydrates and the risks from competitors are high.

This counterintuitive foraging strategy might contribute to the success of these insects, known as Linepithema humile, an invasive species that displaces native ant populations in California and elsewhere and has become a significant agricultural pest, the researchers said.

Their findings, published in the journal Current Zoology, suggest that the unwillingness of Argentine ants to expose themselves to danger when weakened by hunger could possibly give them a competitive edge over other species by helping to preserve their colonies’ foraging capabilities.

“While not foraging may lead to a reduction in food stores when those stores are already low, foraging in a high-risk environment exposes the colony to potential loss of foragers,” said the study’s senior author, Noa Pinter-Wollman, a UCLA professor of ecology and evolutionary biology. “So reduced foraging could be interpreted as individual foragers not taking unnecessary risks.”

The Superpowers of the Female Locust

Elongation of the body of the female locust while laying eggs in the ground
Illustration Credit: Tel Aviv University

Every mother will do anything to know that her offspring are in a safe place. The female locust, however, takes it to a whole new level: A new Tel Aviv University study has discovered that these females have superpowers. The female locust’s central nervous system has elastic properties, allowing her to stretch up to two or three times her original length when laying her eggs in the ground, without causing any irreparable damage.

“We are not aware of a similar ability in almost any living creature,” say the researchers. “Nerves in the human nervous system, for example, can stretch only up to 30% without tearing or being permanently damaged. In the future, these findings may contribute to new developments in the field of regenerative medicine, as a basis for nerve restoration and the development of synthetic tissues.”

“The superpower of the locust is almost something out of science fiction. There are only two other known examples in nature of a similar phenomenon: the tongue of the sperm whale, and a certain type of sea snail whose nervous systems are able to extend significantly due to an accordion-like mechanism they have." Prof. Amir Ayali

Many genes linked to alcohol and tobacco use are shared among diverse ancestries

Penn State College of Medicine researchers co-led a large genetic study that identified more than 2,300 genes predicting alcohol and tobacco use. They said that many of these genes were similar among people with diverse ancestries.
Photo Credit: Pavel Danilyuk

Penn State researchers co-led a large genetic study that identified more than 2,300 genes predicting alcohol and tobacco use after analyzing data from more than 3.4 million people. They said a majority of these genes were similar among people with European, African, American and Asian ancestries.

Alcohol and tobacco use are associated with approximately 15% and 5% of deaths worldwide, respectively, and are linked with chronic conditions like cancer and heart disease. Although the environment and culture can affect a person’s use and the likelihood of becoming addicted to these substances, genetics is also a contributing factor, according to Penn State College of Medicine researchers. They helped identify around 400 genes that are associated with certain alcohol and tobacco use behaviors in people in a prior research study.

“We’ve now identified more than 1,900 additional genes that are associated with alcohol and tobacco use behaviors,” said Dajiang Liu, professor and vice chair for research in the Department of Public Health Sciences. “A fifth of the samples used in our analysis were from non-European ancestries, which increases the relevance of these findings to a diverse population.”

Developmental genetics: How germ cells cut the cord from their parent

An adult specimen of the worm C. elegans and an embryo are shown. In the adult worm, the protein BCC-1 was labelled with a fluorescent protein (GFP) to track its activity.
Photo Credit: Uni Halle / AG Christian Eckmann

For the first cell to develop into an entire organism, genes, RNA molecules and proteins have to work together in a complex way. First, this process is indirectly controlled by the mother. At a certain point in time, the protein GRIF-1 ensures that the offspring cut themselves off from this influence and start their own course of development. A research team from Martin Luther University Halle-Wittenberg (MLU) details how this process works in the journal Science Advances.

When a new organism starts to develop, the mother calls the shots. During fertilization, the egg cell and sperm fuse to form a single new cell. However, the course of cell division, and thus how a new living being forms, is initially determined by the mother cell. "Regardless of the organism, cell division is initially pre-programmed by the mother," explains geneticist Professor Christian Eckmann from MLU. The mother’s cell provides a developmental starter set that includes the first proteins as well as the RNA molecules that serve as blueprints for further proteins. All this is necessary to jump start cell division and an organism’s development.

How do worms develop their gut?

a juvenile C. angaria larva, about 150 microns long.
Photo Credit: Maduro lab/UCR

Were it not for the COVID-19 pandemic, an important discovery about the development of nematodes — elongated cylindrical worms — might not have been made.

With most classes and meetings at universities and schools having moved online in 2020-2021, a husband-and-wife research team at the University of California, Riverside, finally found some time to explore a question they had been mulling over for a long time: How do nematodes distantly related to the best-studied one, Caenorhabditis elegans, make their gut, given that the genes responsible for specifying the gut in C. elegans are absent in other nematodes?

“The pandemic freed up some time for us to think about what research we would like to move forward with when the pandemic eased,” said Morris Maduro, a professor of molecular, cell and systems biology and the corresponding author of the study published in Development, a journal. “Fortunately, an experiment we conducted generated a surprising result. It turns out a simpler gene network seems to be involved in specifying the gut in nematodes related to C. elegans. An ancestral species of C. elegans appears to have duplicated and expanded this simpler gene network to make one that is more complicated, and that complicated network is the one we have been studying all this time in C. elegans.”

Positively charged nanomaterials treat obesity anywhere you want

Illustration of depot-specific targeting of fat by cationic nanomaterials
Illustration Credit: Nicoletta Barolini/Columbia University

Researchers have long been working on how to treat obesity, a serious condition that can lead to hypertension, diabetes, chronic inflammation, and cardiovascular diseases. Studies have also revealed a strong correlation of obesity and cancer--recent data show that smoking, drinking alcohol, and obesity are the biggest contributors to cancer worldwide.

The development of fat cells, which are produced from a tiny fibroblast-like progenitor, not only activates the fat cells’ specific genes but also grows them by storing more lipids (adipocytes and adipose tissue). In fact, lipid storage is the defining function of a fat cell. But the storage of too much lipid can make fat cells unhealthy and lead to obesity.

Challenges in targeting fat cells

The ability to target fat cells and safely uncouple unhealthy fat formation from healthy fat metabolism would be the answer to many peoples’ prayers. A major challenge in obesity treatment is that fat tissue, which is not continuous in the body but is found piece by piece in “depots,” has been difficult to target in a depot-specific manner, pinpointed at the exact location.

There are two main kinds of fat: visceral fat, internal tissues that surround the stomach, liver, and intestines, and subcutaneous fat, found under the skin anywhere in the body. Visceral fat produces potbellies; subcutaneous fat can create chin jowls, arm fat, etc. To date, there has been no way to specifically treat visceral adipose tissue. And current treatments for subcutaneous fat like liposuction are invasive and destructive.

Development of the immune system before and after birth

What influence does a premature birth have on the development of the immune system? And how can the immune system be supported to ensure an optimal start in life? The researchers in the SFB/TRR PILOT are dealing with these and many other questions.
Photo Credit: University Medical Centre Freiburg

The newborn's immune system is suddenly confronted with microorganisms, food and numerous environmental influences at birth. How do the baby's immune cells prepare for this moment during pregnancy and birth? How do external influences shape the immune system immediately after birth? And what influence does an event like a premature birth have? These and many other questions about the development of the child's immune system around birth are being investigated by scientists from the Facult of Medicine at the University of Freiburg together with researchers from the LMU Munich, the University Hospital RWTH Aachen and other institutions in the Collaborative Research Center/Transregio “Perinatal Development of Immune Cell Topology (PILOT).” PILOT was approved by the German Research Foundation (DFG) on November 25, 2022, and will be funded with a total of 12 million euros for an initial period of four years starting January 1, 2023.

New clues about how carbon dioxide affects bumble bee reproduction

In addition to inducing a calming effect, carbon dioxide also can trigger a range of other physiological responses in bumble bees, according to a Penn State researcher.
Photo Credit: Eduardo Goody

While a beekeeper puffing clouds of carbon dioxide into a hive to calm the insects is a familiar image to many, less is known about its other effects on bees. A recent study revealed clues about how the chemical compound affects bee physiology, including reproduction.

The research team, led by an entomologist in Penn State’s College of Agricultural Sciences, set out to disentangle how carbon dioxide seems to bypass diapause, a phase similar to hibernation during which bees sleep over the winter, to trigger the reproductive process in bumblebee queens.

The researchers found that carbon dioxide first induced a change in metabolism, which then triggered secondary effects on reproduction. The findings, recently published in Insect Biochemistry and Molecular Biology, were contrary to previous hypotheses.

“Previously, it was believed that CO2 directly affected reproduction, but this study is some of the first evidence showing this is likely not the case,” said Etya Amsalem, associate professor of entomology. “We found that CO2 changes the way macronutrients are stored and reallocated in the body. The fact that the reproductive process is then kickstarted is just an artifact of these processes.”

Smallest mobile lifeform created

The origin of all biological movements, including walking, swimming, or flying, can be traced back to cellular movements; however, little is known about how cell motility arose in evolution.

A research team led by graduate student Hana Kiyama, from the Graduate School of Science at Osaka City University, and Professor Makoto Miyata, from the Graduate School of Science at Osaka Metropolitan University, introduced seven proteins, believed to be directly involved in allowing Spiroplasma bacteria to swim into a synthetic bacterium named syn3—through genetic engineering. syn3 was designed and chemically synthesized to have the smallest genomic DNA possible including the minimum essential genetic information required for growth from the smallest genomes of naturally occurring Mycoplasma bacteria.

“Studying the world’s smallest bacterium with the smallest functional motor apparatus could be used to develop movement for cell-mimicking microrobots or protein-based motors,” said Professor Miyata.

This genetically re-engineered syn3 changed from its normal spherical shape into a spiraling helix, which was able to swim by reversing the helix’s direction just like Spiroplasma. Further investigation revealed that only two of these newly added proteins were required to make syn3 capable of minimal swimming.

“Our swimming syn3 can be said to be the ‘smallest mobile lifeform’ with the ability to move on its own,” said Professor Miyata. “The results of this research are expected to advance how we understand the evolution and origins of cell motility.”

Published:

In the journal Science Advances

Source/Credit:  Osaka Metropolitan University

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Male orb-weaving spiders fight less in female-dominated colonies

 Orb-weaving spiders spin webs connected to each other in vast networks; within their colonies, individual spiders guard their own webs from intruders and often fight each other over food and mates.
Photo Credit: Gregory Grether/UCLA

Birds do it. Bees do it. Even spiders in their webs do it: cooperate for more peaceful colonies.

That’s one of the surprising findings of a new study by UCLA undergraduates of orb-weaving spiders in Peru.

The study also revealed that when there are more females than males in colonies of orb-weaving spiders, males fight less with each other — and that females fight less in female-dominated colonies than in male-dominated ones, leading to colonies that are somewhat more peaceful. The spiders also showed little hostility to individuals from different colonies, a discovery that has not been previously documented for colonial spiders.

The research was published in the Journal of Arachnology.

“We’re used to thinking of animals like honeybees and elephants living cooperatively,” said the paper’s senior author, Gregory Grether, a UCLA professor of ecology and evolutionary biology. “But spiders usually live solitarily, so we were excited to study these colonial spiders and find out how they interact with colony mates as well as with individuals from other colonies.”

Tropical wildlife follow the same daily patterns worldwide

An elephant faces a camera trap in one of millions of photos analyzed for a new study led by a Rice University visiting student. The study found striking similarities in how rainforest animals across the world spend their days.
Resized Image using AI by SFLORG
Photo Credit: Courtesy of Lydia Beaudrot/Conservation International

How do animals in the wild use their time? A researcher at Rice University is part of a new study that shows what motivates the daily ramble of tropical populations.

The study by an international team that includes Rice bioscientist Lydia Beaudrot and is led by Andrea Vallejo-Vargas, a graduate student at the Norwegian University of Life Sciences and currently a visiting scholar at Rice, found that communities of mammals across the wet tropics divide their days in similar ways, all generally geared toward finding their next meal. (Or avoiding being the next meal.)

Using millions of images from camera trap networks in 16 protected forests around the world, they examined the relationship of mammal activities to body sizes and feeding routines to find common characteristics among diverse populations.

Their open-access study in Nature Communications confirms that despite their diversity, similar patterns dominate the days of wildlife in Africa, Asia and the Americas.

The study showed that the activity of herbivores and insectivores was largely influenced by temperature in the environment (in study-speak, “thermoregulatory constraints”). For instance, large African herbivores are seven times more likely to be nocturnal than smaller herbivores.

How giant-faced owls snag voles hidden in snow

Video Credit: Sylvain Eckhardt

Hovering over a target helps giant-faced Great Gray owls pinpoint prey hidden beneath as much as two feet of snow.

Several of the owls’ physical features, especially parts of their wings and face, help them correct for sonic distortions caused by the snow, enabling them to find their moving food with astonishing accuracy, according to a new UC Riverside study.

While most owls fly straight at their prey, this species hovers just above a target area before dropping straight down and punching through the snow with its talons.

“These aren’t the only birds to hunt this way, but in some ways, they are the most extreme because they can locate prey so far beneath the snow cover,” said UC Riverside biologist Christopher Clark, who led the study. “This species is THE snow hunting specialist.”

Clark and his team conducted a series of experiments in the forests of Manitoba, Canada, this year to better understand the owls’ precision despite snow-limited visibility and sounds. Their observations are documented in a new Proceedings of the Royal Society B paper.

A key finding relates to the owls’ broad disc-like face, which they use like radar to find food. The fleshy part of our ears works the way their facial features do. An opening under their feathers funnels sound toward their ears, which are located near the center of their faces.

Sex roles in the animal kingdom are driven by the ratio of females to males

A female (left) and a male (right) red-fronted lemur with an infant (center).
Photo Credit: Louise Peckre

How picky should females and males be when they choose a mate? How fiercely should they compete for mates? And how much should they engage in raising their offspring? The answers to these questions largely depend on the ratio of adult females to males in the social group, population or species. This is the conclusion of a review by a scientific team with the participation of the German Primate Center – Leibniz Institute for Primate Research (DPZ), the Max Planck Institute for Biological Intelligence, in foundation, and the Leibniz Institute for Zoo and Wildlife Research (Leibniz-IZW). The paper is published in the journal Biological Reviews.

In species with separate sexes, females and males often differ in their morphology, physiology and behavior. Such sex-specific adaptations imply differences between females and males in the degree of mate competition, mate choice and parental care. Empirical research showed that females generally tend to be choosier than males about whom to mate with, and males are more likely than females to compete for mating opportunities. This pattern is often referred to as “conventional” sex roles. But the opposite pattern (“reversed” sex roles) also exists and there generally is a lot of variation in sex roles both between and within species. How can this surprisingly large variation in sex roles be explained? The team led by Peter Kappeler from the German Primate Center now reviewed the sex roles literature in animals and found that the ratio of adult males to females in a population likely is a strong evolutionary driver of sex roles. The scientific paper also identifies unanswered questions and proposes research that can lead to a better understanding of sexual selection and the evolution of sex roles.

Machine learning model builds on imaging methods to better detect ovarian lesions

(From left) The top row shows an ultrasound image of a malignant lesion, the blood oxygen saturation, and hemoglobin concentration. The bottom row is an ultrasound image of a benign lesion, the blood oxygen saturation, and hemoglobin concentration.
Image Credit: Zhu lab

Although ovarian cancer is the deadliest type of cancer for women, only about 20% of cases are found at an early stage, as there are no real screening tests for them and few symptoms to prompt them. Additionally, ovarian lesions are difficult to diagnose accurately — so difficult, in fact that there is no sign of cancer in more than 80% of women who undergo surgery to have lesions removed and tested.

Quing Zhu, the Edwin H. Murty Professor of Biomedical Engineering at Washington University in St. Louis’ McKelvey School of Engineering, and members of her lab have applied a variety of imaging methods to diagnose ovarian cancer more accurately. Now, they have developed a new machine learning fusion model that takes advantage of existing ultrasound features of ovarian lesions to train the model to recognize whether a lesion is benign or cancerous from reconstructed images taken with photoacoustic tomography. Machine learning traditionally has been focused on single modality data. Recent findings have shown that multi-modality machine learning is more robust in its performance over unimodality methods. In a pilot study of 35 patients with more than 600 regions of interest, the model’s accuracy was 90%.