Novel sex-determination mechanism revealed in mammals

Amami spiny rat
Photo Credit: Asato Kuroiwa

In mammals, the distinction between male and female at the chromosomal level is due to the X and Y chromosomes. Typically, females have two X chromosomes (XX) while males have an X and a Y chromosome (XY). The Sry gene on the Y chromosome triggers the formation of the testes. However, there exist a handful of rodent species in which the Y chromosome has disappeared, taking with it the Sry gene. The mechanism by which testes development occurs in these species is not fully understood, and is subject to much research.

A team of researchers led by Professor Asato Kuroiwa at Hokkaido University has uncovered the genetic basis for sexual differentiation in the Amami spiny rat, one of the species the lacks a Y chromosome and the Sry gene. Their discoveries were published in the journal Proceedings of the National Academy of Sciences.

The Amami spiny rat is an endangered rodent found only on Amami Oshima, Japan. It is one of just four mammals known to lack a Y chromosome, alongside its close relative the Tokunoshima spiny rat, as well as the Transcaucasian mole vole and the Zaisan mole vole. In the Amami spiny rat, the the Sry gene is completely absent; thus, it has evolved a novel, unknown sex-determining mechanism independent of Sry.

Study finds that big rains bring big algae blooms… eventually

Center for Limnology system engineer Mark Gahler, right, co-author of a new study on the relationship between big storms and algae blooms, and colleague Jonathon Thom collect Lake Mendota data from instruments aboard David Buoy.
Photo Credit: Paul Schramm / University of Wisconsin–Madison

In the lake-rich regions of the world, algae blooms are a growing problem. Not only are the floating green scums a nuisance for anyone hoping to enjoy the water, they can turn toxic and threaten public health.

The main driver behind these blooms is phosphorus, an element used widely in agriculture to fertilize crops, that can run from the land and into lakes — especially during heavy rains. A new study from the University of Wisconsin–Madison shows how soon after a storm phosphorous “loading” sparks algae explosions, but also describes the many other factors that weigh on when and whether the lake reaches a tipping point.

“The fact that you just had a big storm doesn’t mean now you’re going to get a big [algae] bloom. The blooms are much more complicated.” says Steve Carpenter, lead author of a report published in the Proceedings of the National Academy of the Sciences.

Squirrel sperm and feet tell a different climate change story

Cape ground squirrels are ecosystem engineers
Photo Credit: Gary Simons

Perhaps it’s time to replace the canary in a coal mine metaphor with a squirrel in the ground. Because two University of Manitoba studies found that climate change is altering ground squirrels’ sperm and feet, and this warns of big consequences potentially coming to endangered ecosystems.

These subtle squirrel changes concern UM researchers Jane Waterman and Miya Warrington, who tuned into them only recently and published their latest findings in the latest Journal of Mammalogy.

It began last year when they found that some male Richardson’s ground squirrels, a species found throughout the Canadian prairies, emerged from hibernation during a particularly warm winter with non-motile sperm. This non-lethal effect of climate change fortunately did not result in fewer young that year, although other negative consequences of males “shooting blanks” may emerge in other species or situations.

Intrigued by this finding, they then looked at what non-lethal affects climate change was having on African ground squirrels in the grasslands of South Africa.

Localizing BRCA gene mutations to better treat ovarian cancer

Dr. Intidhar Labidi-Galy
Researcher at the Translational Research Centre in Onco-hematology at the UNIGE Faculty of Medicine and a physician at the HUG.
Credit: University of Geneva /  Intidhar Labidi-Galy

Mutations of BRCA1 and BRCA2 genes, which are inherited by 1 in 400 and 1 in 800 people respectively, significantly increase the risk of certain cancers such as ovarian, breast, pancreatic and prostate cancer. In 2016, a new class of drugs, the PARP inhibitors, was found to be highly effective against BRCA mutation-related tumors. However, almost half of women with ovarian cancer experience a recurrence of the disease within 5 years. An international team led by the University of Geneva (UNIGE), the Geneva University Hospitals (HUG), the Centre Léon Bérard in Lyon, the Curie Institute, the French collaborative group ARCAGY- GINECO and the European consortium ENGOT, examined the genetic data of 233 patients enrolled in the pre-marketing phase III clinical trial of olaparib, a PARP inhibitor added to bevacizumab, a drug already used to treat ovarian cancer. The researchers found that the success of PARP inhibitors depends on the precise location of the mutation on the gene. These results, that can be read in the journal Annals of Oncology, demonstrate that a very high precision medicine is possible in oncology.

The BRCA1 and BRCA2 genes code for proteins involved in the repair of DNA double-strand breaks, a particularly severe form of DNA damage, and thus play an essential role in maintaining the genomic stability of cells. When they are mutated, cells are less able to repair damaged DNA, a phenomenon that promotes the development of cancers.

Protein Spheres Protect the Genome of Cancer Cells

MYC proteins are colored green in this figure. In normally growing cells, they are homogeneously distributed in the cell nucleus (left). In diverse stress situations, as they occur in cancer cells, they rearrange themselves, form sphere-like structures and thus surround particularly vulnerable sections of the genome.
Image Credit: Team Martin Eilers / Universität Würzburg

Hollow spheres made of MYC proteins open new doors in cancer research. Würzburg scientists have discovered them and report about this breakthrough in the journal "Nature".

MYC genes and their proteins play a central role in the emergence and development of almost all cancers. They drive uncontrolled growth and altered metabolism of tumor cells. And they help tumors hide from the immune system.

MYC proteins also show an activity that was previously unknown – and which is now opening new doors for cancer research: They form hollow spheres that protect particularly sensitive parts of the genome. If these MYC spheres are destroyed, cancer cells will die.

This was reported by a research team led by Martin Eilers and Elmar Wolf from the Institute of Biochemistry and Molecular Biology at Julius-Maximilians-Universität Würzburg (JMU, Bavaria, Germany) in the journal Nature. The researchers are convinced that their discovery is a game changer for cancer research, an important breakthrough on the way to new therapeutic strategies.

New CRISPR-based tool inserts large DNA sequences at desired sites in cells

Building on the CRISPR gene-editing system, MIT researchers designed a new tool that can snip out faulty genes and replace them with new ones.
Image Credit: Sangharsh Lohakare

Building on the CRISPR gene-editing system, MIT researchers have designed a new tool that can snip out faulty genes and replace them with new ones, in a safer and more efficient way.

Using this system, the researchers showed that they could deliver genes as long as 36,000 DNA base pairs to several types of human cells, as well as to liver cells in mice. The new technique, known as PASTE, could hold promise for treating diseases that are caused by defective genes with a large number of mutations, such as cystic fibrosis.

“It’s a new genetic way of potentially targeting these really hard to treat diseases,” says Omar Abudayyeh, a McGovern Fellow at MIT’s McGovern Institute for Brain Research. “We wanted to work toward what gene therapy was supposed to do at its original inception, which is to replace genes, not just correct individual mutations.”

The new tool combines the precise targeting of CRISPR-Cas9, a set of molecules originally derived from bacterial defense systems, with enzymes called integrases, which viruses use to insert their own genetic material into a bacterial genome.

Old World flycatchers’ family tree mapped

European robin in snow. A new study of Old World flycatcher family, to which these birds belong. The study comprises 92 per cent of the more than 300 species in this family. 
Photo Credit: Tomas Carlberg

The European robin’s closest relatives are found in tropical Africa. The European robin is therefore not closely related to the Japanese robin, despite their close similarity in appearance. This is confirmed by a new study of the Old World flycatcher family, to which these birds belong. The study comprises 92 per cent of the more than 300 species in this family.

“The fact that the European and Japanese robins are so similar-looking despite not being closely related is one of many examples of so-called convergent evolution in this group of birds. Similarities in appearance can evolve in distant relatives, e.g., as a result of similarities in lifestyle,” says Per Alström from Uppsala University, who is one of the researchers behind the study published in Molecular Phylogenetics and Evolution.

Genome studies uncover a new branch in fungal evolution

In a class of their own: The earth tongue is one of 600 “oddball” fungi that were found to share a common ancestor dating back 300 million years, according to U of A researchers.
Full Size Original
Photo Credit: Alan Rockefeller, CC-BY-SA-4.0

About 600 seemingly disparate fungi that never quite found a fit along the fungal family tree have been shown to have a common ancestor, according to a University of Alberta-led research team that used genome sequencing to give these peculiar creatures their own classification home.

“They don't have any particular feature that you can see with the naked eye where you can say they belong to the same group. But when you go to the genome, suddenly this emerges,” says Toby Spribille, principal investigator on the project and associate professor in the Department of Biological Sciences.

“I like to think of these as the platypus and echidna of the fungal world.”

Spribille, Canada Research Chair in Symbiosis, is referring to Australia’s famed Linnaean classification system-defying monotremes — which produce milk and have nipples, but lay eggs — that were the source of debate as to whether they were even real.

Human evolution wasn’t just the sheet music, but how it was played

The fluorescent glow of mouse brain cells on the right indicates the effectiveness of a human-derived gene enhancer, HAQER0059, versus a 6-million-year-old version of the enhancer at left.
Image Credit: Riley Mangan, Duke University

A team of Duke researchers has identified a group of human DNA sequences driving changes in brain development, digestion and immunity that seem to have evolved rapidly after our family line split from that of the chimpanzees, but before we split with the Neanderthals.

Our brains are bigger, and our guts are shorter than our ape peers.

“A lot of the traits that we think of as uniquely human, and human-specific, probably appear during that time period,” in the 7.5 million years since the split with the common ancestor we share with the chimpanzee, said Craig Lowe, Ph.D., an assistant professor of molecular genetics and microbiology in the Duke School of Medicine.

Specifically, the DNA sequences in question, which the researchers have dubbed Human Ancestor Quickly Evolved Regions (HAQERS), pronounced like hackers, regulate genes. They are the switches that tell nearby genes when to turn on and off. The findings appear Nov.23 in the journal Cell.

The rapid evolution of these regions of the genome seems to have served as a fine-tuning of regulatory control, Lowe said. More switches were added to the human operating system as sequences developed into regulatory regions, and they were more finely tuned to adapt to environmental or developmental cues. By and large, those changes were advantageous to our species.

World’s oldest meal offers food for thought

Professor Jochen Brocks (left) and Dr Ilya Bobrovskiy
Photo Credit: ANU

The contents of the last meal consumed by the earliest animals known to inhabit Earth more than 550 million years ago has unearthed new clues about the physiology of our earliest animal ancestors, according to scientists from The Australian National University (ANU).

Ediacara biota are the world's oldest large organisms and were first discovered in the Ediacara Hills in South Australia's Flinders Ranges. They date back 575 million years.

ANU researchers found the animals ate bacteria and algae that was sourced from the ocean floor. The findings, published in Current Biology, reveal more about these strange creatures, including how they were able to consume and digest food.

The scientists analyzed ancient fossils containing preserved phytosterol molecules -- a type of fat found in plants -- that remained from the animals' last meal. By examining the molecular remains of what the animals ate, the researchers were able to confirm the slug-like organism, known as Kimberella, had a mouth and a gut and digested food the same way modern animals do. The researchers say it was likely one of the most advanced creatures of the Ediacarans.

New Omicron subvariant BQ.1.1 resistant to all therapeutic antibodies

The Omicron subvariants BA.1, BA.4, BA.5 as well as Q.1.1 have a high number of mutations in the spike protein. Some of these mutations are escape mutations that allow the virus to escape neutralization by antibodies. In addition, resistance to biotechnologically produced antibodies, which are administered to high-risk patients as a preventive measure or as therapy for a diagnosed SARS-CoV-2 infection, is also developing. Omicron sub-lineage BQ.1.1 is the first variant resistant to all antibody therapies currently approved by the EMA (European Medicines Agency) and/or FDA (US Food and Drug Administration).
Figure Credit: Markus Hoffmann, German Primate Center – Leibniz Institute for Primate Research.

Are the currently approved antibody therapies used to treat individuals at increased risk for severe COVID-19 disease also effective against currently circulating viral variants? A recent study by researchers at the German Primate Center (DPZ) – Leibniz Institute for Primate Research and Friedrich-Alexander University Erlangen-Nürnberg shows that the Omicron sub-lineage BQ.1.1, currently on the rise worldwide, is resistant to all approved antibody therapies. published in the journal Lancet Infectious Diseases.

Covid-19: the Spike protein is no longer the only target

Possible mechanism of action of a drug targeting Nsp1 of SARS-CoV-2. In infected cells, Nsp1 blocks the ribosome mRNA canal by acting as a "cap" that prevents the expression of the host's mRNA. Linking a ligand to the proposed cryptic pocket highlighted in purple could prevent blockage mediated by Nsp1 and, ultimately, restore the ability of the ribosome to initiate the translation of the mRNA.
Photo Credit: UNIGE Alberto Borsatto

A research team led by the UNIGE reveals a hidden cavity on a key SARS-CoV-2 protein to which drugs could bind.

With the continuous emergence of new variants and the risk of new strains of the virus, the development of innovative therapies against SARS-CoV-2 remains a major public health challenge. Currently, the proteins that are on the surface of the virus and/or are involved in its replication are the preferred therapeutic targets, like the Spike protein targeted by vaccines. One of them, the non-structural protein Nsp1, had been studied little until now. A team from the University of Geneva (UNIGE), in collaboration with University College London (UCL) and the University of Barcelona, has now revealed the existence of a hidden ''pocket’ on its surface. A potential drug target, this cavity opens the way to the development of new treatments against Covid-19 and other coronaviruses. These results can be found in the journal eLife.

Immune cells in ALS patients can predict the course of the disease

Solmaz Yazdani, PhD student at KI.
Photo Credit: Filip Mestanov

ALS is a disease in which nerve cells in the brain, brain stem and spinal cord die. 

By measuring immune cells in the spinal cord fluid when diagnosing ALS, it is possible to predict how the course of the disease will go, according to a study from the Karolinska Institutet published in Nature Communications.

The study shows that a high proportion of so-called effector T cells are associated with a low survival rate. At the same time, the study shows that a high proportion of activated regulatory T cells are protective against the disease. The findings provide new evidence of T-cell involvement in the course of the disease and show that certain types of effector T cells accumulate in the spinal cord fluid in ALS patients.

Genetic ‘Hitchhikers’ Can Be Directed Using CRISPR

NC State researchers expand the CRISPR toolbox with possible agricultural implications.
Photo Credit: Atlas Green

In a new study, North Carolina State University researchers characterize a range of molecular tools to rewrite – not just edit – large chunks of an organism’s DNA, based on CRISPR-Cas systems associated with selfish genetic “hitchhikers” called transposons.

The researchers investigate diverse Type I-F CRISPR-Cas systems and engineer them to add genetic cargo – up to 10,000 additional genetic code letters – to the transposon’s cargo to make desired changes to a bacterium – in this case, E. coli.

The findings expand the CRISPR toolbox and could have significant implications in the manipulation of bacteria and other organisms at a time of need for flexible genome editing in therapeutics, biotechnology and more sustainable and efficient agriculture.

Bacteria use CRISPR-Cas as adaptive immune systems to withstand attacks from enemies like viruses. These systems have been adapted by scientists to remove or cut and replace specific genetic code sequences in a variety of organisms. The new finding shows that exponentially larger amounts of genetic code can be moved or added, potentially increasing CRISPR’s functionality.

Intestinal microorganisms influence white blood cell levels in blood

Under normal conditions (steady state) neutrophils regulate the gut microbiota. When the number of neutrophils drops (neutropenia), the composition of the gut microbiota changes, stimulating T cells to produce IL-17A. IL-17-A in turn stimulates the production of neutrophils in the bone marrow (reactive granulopoiesis).
Illustration Credit: Daigo Hashimoto

White blood cells, or granulocytes, are cells that are part of the innate immune system. The most common type of granulocyte is the neutrophil, a phagocyte that destroys microbes in the body. Low neutrophil counts in the blood is called neutropenia; this condition is commonly seen in cases of leukemia or following chemotherapy. It is known that neutropenia induces granulopoiesis, the process formation of granulocytes. However, the exact mechanisms by which neutropenia drives granulopoiesis are not fully understood.

A team of researchers led by Associate Professor Daigo Hashimoto and Professor Takanori Teshima at Hokkaido University’s Faculty of Medicine have discovered that the gut microbiome plays a critical role in driving granulopoiesis in mice models. Their findings were published in the journal Proceedings of the National Academy of Sciences.

Zebrafish are smarter than we thought

A new study from MIT and Harvard University suggests that the brains of the seemingly simple zebrafish are more sophisticated than previously thought. The researchers found that larval zebrafish can use visual information to create three-dimensional maps of their physical surroundings.
Photo Credit: Petr Kuznetsov

A new study from MIT and Harvard University suggests that the brains of the seemingly simple zebrafish are more sophisticated than previously thought. The researchers found that larval zebrafish can use visual information to create three-dimensional maps of their physical surroundings — a feat that scientists didn’t think was possible.

In the new study, the researchers discovered that zebrafish can move around environmental barriers while escaping predators. The findings suggest that zebrafish are “much smarter than we thought,” and could be used as a model to explore many aspects of human visual perception, the researchers say.

“These results show you can study one of the most fundamental computational problems faced by animals, which is perceiving a 3D model of the environment, in larval zebrafish,” says Vikash Mansinghka, a principal research scientist in MIT’s Department of Brain and Cognitive Sciences and an author of the new study.

Andrew Bolton, an MIT research scientist and a research associate at Harvard University, is the senior author of the new study, which appears in the journal Current Biology. Hanna Zwaka, a Harvard postdoc, and Olivia McGinnis, a recent Harvard graduate who is now a graduate student at the Oxford University, are the paper’s lead authors.

Amphibian Population Decreased Rapidly in the Last Three Years

Lake frogs are among the largest modern amphibians.
Photo Credit: Ilya Safarov

Biologists have recorded severe simultaneous drops in the numbers of three different species of frogs and newts - rare and widespread. The largest population declines occurred among juveniles, but the scientists noted that adults and egg clutches were also affected. The description and results of the study are published in the journal Conservation Science and Practice.

"We believe that a wide range of anthropogenic adverse factors combined with natural fluctuations are responsible for the population decline. Among the causes are global warming, pathogenic infections, habitat loss and exposure to agro-industrial chemicals. But the main reason is drought: reduced precipitation led to a shortage of water in reservoirs and increased water temperature, which ultimately affected the amphibian population," explains Vladimir Vershinin, co-author of the work, Head of the Department of Biodiversity and Bioecology of Ural Federal University, Head of the Laboratory of Functional Ecology of Terrestrial Animals of the Institute of Plant and Animal Ecology of Ural Branch of Russian Academy of Science.

Newly Developed Gene Classifier Identifies Risk of Breast Pre-Cancer Progression

Photo Credit: Angiola Harry

A team of researchers mapping a molecular atlas for ductal carcinoma in situ (DCIS) has made a major advance toward distinguishing whether the early pre-cancers in the breast will develop into invasive cancers or remain stable.

Analyzing samples from patients who had undergone surgery to remove areas of DCIS, the team identified 812 genes associated with cancer progression. Using this gene classifier, they were then able to predict the risk of cancer cells recurring or progressing.

The study, which was published this week in the journal Cancer Cell, was led by E. Shelley Hwang, M.D., of the Duke Cancer Institute, and Rob West, M.D., Ph.D., of the Stanford University Medical Center. Their work is part of the Human Tumor Atlas Network under the Moonshot Initiative funded by the National Cancer Institute.

“There has been a long-standing debate over whether DCIS is cancer or a high-risk condition,” Hwang said. “In the absence of a way to make that determination, we currently treat everyone with surgery, radiation, or both.

“DCIS is diagnosed in more than 50,000 women a year, and about a third of those women have a mastectomy, so we are increasingly concerned that we might be overtreating many women,” Hwang said. “We need to understand the biology of DCIS better, and that’s what our research has been designed to do.”

Researchers may have found a new biomarker for covid-19

Patients with acute COVID-19 infection have increased levels of the cytokine IL-26 in their blood.
Photo Credit: Louis Reed

Researchers at Karolinska Institutet have shown that patients with acute COVID-19 infection have increased levels of the cytokine IL-26 in their blood. Moreover, high IL-26 levels correlate with an exaggerated inflammatory response that signifies severe cases of the disease. The findings, which are presented in Frontiers in Immunology, indicate that IL-26 is a potential biomarker for severe COVID-19.

Vaccines for SARS-CoV-2 have proved effective at reducing the number of cases of severe COVID-19. However, the emergence of new viral variants, limited distribution of the vaccine and declining immunity are problems that drive scientists to find more efficacious treatments for the disease.

“We need to understand more about underlying immunological mechanisms in order to find better treatments. There is also a need for improved diagnostics in COVID 19-patients,” says Eduardo Cardenas, postdoc researcher at the Institute of Environmental Medicine, Karolinska Institutet, and principal author of the new pilot study.

Tick-borne pathogens increasingly widespread in Central Canada

Image Credit: 13smok

Tick-borne pathogens, known for causing illnesses such as Lyme disease, are on the rise in Central Canada – presenting new risks in areas where they were never previously detected.

The findings from researchers at McGill University and the University of Ottawa demonstrate the need for more comprehensive testing and tracking to detect the spread and potential risk of tick-borne pathogens to human and wildlife populations throughout Canada.

“Most people know that diseases can be transmitted to humans through the bite of infected ticks. Ticks can carry and spread several disease agents, called pathogens, that can make people and animals sick,” explains Kirsten Crandall, a PhD candidate under the joint supervision of McGill University Professor Virginie Millien and University of Ottawa Professor Jeremy Kerr.

“While the bacteria that causes Lyme disease is the most common tick-borne pathogen in Canada, other tick-borne pathogens are moving in,” she adds.

To investigate the presence and prevalence of several emerging tick-borne pathogens, Crandall and her team analyzed small mammals and ticks collected in Ontario and Quebec. The researchers found that five emerging pathogens were present across their study sites in Central Canada, including the pathogens causing Lyme disease and babesiosis, a malaria-like parasitic disease.