It’s possible that I shall make an ass of myself. But in that case one can always get out of it with a little dialectic. I have, of course, so worded my proposition as to be right either way (K.Marx, Letter to F.Engels on the Indian Mutiny)
Tuesday, March 31, 2026
University of York scientists solve 40-year-old biological mystery behind Sleeping Sickness
Scientists at the University of York have cracked a 40-year-old biological cold case by revealing how the parasite that causes Sleeping Sickness stays one step ahead of the human immune system
To survive in the human bloodstream, the African trypanosome parasite wears a “cloak” made of proteins known as a variant surface glycoprotein (VSG). The study, published in Nature Microbiology, identifies the protein that allows the parasite to fine-tune this “cloak”.
The newly discovered ESB2 protein acts as a “molecular shredder”, allowing the parasite to avoid detection by destroying specific parts of its genetic instructions with surgical precision as they are being produced.
By understanding how the parasite manages to do this with such incredible precision, researchers can now identify new vulnerabilities in its life cycle. This opens the door for future treatments for Sleeping Sickness, a disease that continues to have a devastating impact on communities across sub-Saharan Africa.
Transmitted by the bite of the tsetse fly, if left untreated the parasites invade the central nervous system, causing neurological issues including severe sleep disruptions, confusion, and coma.
Dr Joana Faria, senior author of the study and leader of the research group at the University of York, said: “We’ve discovered that the parasite’s secret to staying invisible isn’t just what it prints, but what it chooses to redact. By placing a “molecular shredder” directly inside its “protein factory”, the parasite can edit its genetic manual in real-time.
“This suggests a fundamental shift in how we view infection: survival for many organisms may depend less on how they issue genetic instructions and more on how they destroy them at the source.”
The discovery provides an answer to a bizarre quirk in the parasite’s biology that has baffled scientists for 40 years. The genetic manual for the “cloak” also contains several “helper genes” needed for survival and immune evasion. Logic suggests that when the parasite follows these genetic instructions, it should produce equal amounts of each protein. However, the parasite somehow produces a mountain of cloak proteins but only a tiny amount of helper proteins.
By identifying the ESB2 protein, the York team discovered that the parasite controls its genetic messages through destruction rather than just production.
ESB2 sits directly inside the parasite’s protein factory, known as the Expression Site Body. As the genetic manual is being printed, ESB2 acts as a “molecular blade” that instantly shreds the helper sections while leaving the cloak instructions intact. This real-time redaction ensures the parasite expresses exactly what it needs to remain hidden from the host’s immune system.
The breakthrough marks the first major output for Dr Faria’s new laboratory at the University of York, representing a significant addition to the city’s growing reputation as a global hub for life sciences.
The project was funded by a Sir Henry Dale Fellowship – a partnership between the Wellcome Trust and the Royal Society – and brought together expertise from the United Kingdom, Portugal, the Netherlands, Germany, Singapore and Brazil.
Lianne Lansink, first author of the study, said: “When we first saw the molecular shredder localised in the microscope, we knew we had found something special.”
Dr Faria added: “This discovery is a real full-circle moment for me. The mystery of how this parasite manages the asymmetric expression of its genetic manual has been a cold case in the back of my mind since my days as a postdoc. To finally solve it now, as the first major output of my own lab here at York, is incredibly rewarding. It’s a testament to what a fresh lab and a diverse group of scientists can achieve when they look at an old problem from a completely new angle.”
A new study, co-led by researchers at the Icahn School of Medicine at Mount Sinai and published March 30 in Nature Medicine[https://doi.org/ 10.1038/s41591-026-04228-6], demonstrates that genes associated with autism risk are largely the same across people of different ancestries.
The findings, based on one of the largest genomic studies of Latin American individuals to date, provide strong evidence that the genetic architecture of autism is consistent across diverse populations. They underscore the importance of expanding genetic research beyond individuals of European ancestry.
Over the past decade, scientists have identified numerous rare genetic variants that confer substantial risk for autism and other neurodevelopmental disorders. However, most of these discoveries were made in cohorts composed predominantly of individuals of European ancestry, leaving open the question of whether autism’s genetic underpinnings differ across populations. This knowledge gap has contributed to disparities in genetic testing, including higher rates of inconclusive results among non-European individuals due to limited reference data.
To address this issue, the research team analyzed exome and genome sequencing data from more than 15,000 Latin American individuals across North, Central, and South America, including approximately 4,700 individuals diagnosed with autism. Latin American populations represent the largest recently mixed-ancestry group globally, with heritage that frequently includes Indigenous American, West African, and European origins. This rich genetic diversity provides a powerful opportunity to refine gene-disease associations, which can improve health outcomes for all populations.
The study examined more than 18,000 genes for enrichment of rare, deleterious coding variants—genetic changes that can have immediate and profound clinical implications for diagnosis, treatment, and family counseling.
Consistent with prior research, rare, deleterious variants in highly conserved genes—genes that remain similar across species and populations over long periods of time—were disproportionately observed in individuals with autism. Researchers identified 35 genes significantly associated with autism in the Latin American cohort. These genes showed extensive overlap with those previously identified in genome-wide studies of individuals of European ancestry. The findings also provide support for several recently identified “emerging” autism-associated genes.
“Our results indicate that the core genetic architecture of autism is shared across ancestries,” said study senior author Joseph D. Buxbaum, PhD, Director of the Seaver Autism Center for Research and Treatment at Mount Sinai. “This suggests that the biology underlying autism is universal and reinforces the importance of ensuring that diverse populations are represented in genetic research.”
The study also evaluated widely used metrics that assess evolutionary conservation of genes, an important tool for prioritizing genes in clinical genetic analyses of neurodevelopmental disorders. The researchers found that these metrics, which were again largely derived from European-ancestry datasets, may overestimate conservation overall due to limited ancestral diversity in European populations. However, the metrics remain highly accurate for the most strongly conserved genes—including those most relevant to autism and other neurodevelopmental disorders.
The authors note that continued sequencing of diverse populations will further improve conservation metrics, particularly for less conserved genes, ultimately enhancing the accuracy of clinical genetic testing.
“These findings provide a road map for improving genetic diagnosis across ancestral groups,” said Dr. Buxbaum. “Expanding genomic research in underrepresented populations is essential to reducing health disparities and advancing precision medicine for autism and related conditions across all ancestral populations.”
The study’s results align with growing evidence that both rare and common genetic risk factors for complex disorders are shared across diverse populations. By demonstrating broad overlap in autism risk genes across ancestries, the research supports more inclusive approaches to genomic medicine and reinforces the universal biological foundations of autism.
About the Mount Sinai Health System Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with 48,000 employees working across seven hospitals, more than 400 outpatient practices, more than 600 research and clinical labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time—discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.
Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 9,000 primary and specialty care physicians and 10 free-standing joint-venture centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida. Hospitals within the System are consistently ranked by Newsweek’s® “The World’s Best Smart Hospitals, Best in State Hospitals, World Best Hospitals and Best Specialty Hospitals” and by U.S. News & World Report’s® “Best Hospitals” and “Best Children’s Hospitals.” The Mount Sinai Hospital is on the U.S. News & World Report® “Best Hospitals” Honor Roll for 2025-2026.
Autism has a significant and enduring sex bias, with roughly four boys diagnosed for every girl. For many years, experts have believed this disparity arises primarily from diagnostic inequities because much of autism research — and the screening tools that grew out of it — has historically focused on boys, effectively setting a male standard for what autism “looks like.” As a result, girls and women are more likely to be overlooked, misdiagnosed, or diagnosed much later in life.
This disparity has also shaped the science around autism. When fewer females with the condition are identified, fewer are included in research studies, creating a feedback loop where scientific understanding of autism in females remains limited. Because of this underrepresentation of females, it has been difficult for scientists to disentangle how much of the sex bias in autism reflects social inequities versus underlying biological differences between the sexes.
While the search for biological explanations has largely lagged behind, one leading theory, known as the “female protective effect,” proposes that females may be biologically buffered against developing autism in a way males aren’t.
The idea can be traced back to studies showing that females diagnosed with autism tend to carry a higher number of genetic mutations or “hits” than males with the condition, meaning that they require a higher load of the same genetic mutations for autism to manifest. But, until now, there’s been little clarity on the exact biological mechanism behind this apparent resilience.
Now, a perspective from the lab of Whitehead Institute Member David Page, published March 30 in Nature Genetics, proposes a genetic explanation for the female protective effect and suggests that biological differences between males and females contribute to autism’s strong sex bias.
The work is one of many projects from the Page lab uncovering the biological underpinnings of sex bias in everything from heart health and autoimmune disease to certain cancers.
“The fact that we see sex biases in disease all across the body gives credence to the notion that the sex bias in autism isn’t simply emerging from diagnostic inequities and gendered expectations of what the conditions looks like,” says Page, who is also a professor of biology at Massachusetts Institute of Technology and an investigator at the Howard Hughes Medical Institute (HHMI).
The researchers propose that this protective effect extends beyond autism, and could help explain why 17 other congenital and developmental disorders predominately affect males. By characterizing the biological factors that make one sex more or less likely to develop certain health conditions, scientists see an opportunity to improve how these conditions are diagnosed and how people receive care.
Page and Harvard-MIT MD-PhD student Maya Talukdar trace the female protective effect to the X chromosome. Talukdar is a graduate student in Page’s lab and the lead author of the perspective.
Most females have two X chromosomes (XX) while most males have one X and one Y chromosome (XY). Sex chromosomes can dial up and down the expression of thousands of genes on the other 22 pairs of chromosomes in a cell, impacting cell function across the entire body.
Historically, scientists believed that the second X chromosome in females is largely inactive. But, in recent years, research out of the Page lab has shown that the so-called “inactive X,” also called Xi, plays a crucial role in regulating gene expression on the active X chromosome, and the rest of the chromosomes.
In this perspective, the researchers point to a subset of genes that are expressed from both the active and inactive X chromosome — often known as genes that “escape” X chromosome inactivation. Many of these genes are dosage-sensitive regulators of key cellular processes. These processes influence thousands of other genes across the genome, including many linked to autism.
Because females have an extra copy of these regulatory genes expressed from Xi, Page and Talukdar propose that they may be better able to buffer the effects of autism-associated mutations than males.
The female protective effect beyond autism
This mechanism, the researchers say, extends beyond autism to a range of congenital and developmental diseases with a male bias.
“Many of the other congenital or developmental conditions we’re pointing to aren’t subject to diagnostic inequities in the way autism is,” says Talukdar. “This strengthens the idea that the female protective effect is emerging from genetic differences in males and females.”
One example is pyloric stenosis, which like autism, affects four boys for every girl. Infants with the condition experience severe vomiting due to thickening of the pyloric sphincter, the passage between the stomach and small intestine. As with autism, girls with pyloric stenosis appear to require more genetic “hits” in order to develop the condition.
The researchers’ new framework of looking at Xi to understand sex differences in disease could impact treatment and care not just for conditions that predominately affect males, but also for those that are more common in women, such as autoimmune diseases.
“Our biology isn’t one-size-fits-all,” Talukdar says “Sex differences clearly play a huge role in health, and it’s so important that we understand them.”
ABOUT WHITEHEAD INSTITUTE FOR BIOMEDICAL RESEARCH Whitehead Institute is a nonprofit, independent biomedical research institute founded in 1982. The institute advances pioneering research in cancer, developmental biology, genetics, genomics, and related fields, with a mission to pursue bold, curiosity-driven science that deepens our understanding of life and improves human health. Led by 24 principal investigators and a global community of trainees and scholars, Whitehead Institute maintains a teaching affiliation with Massachusetts Institute of Technology (MIT) but is fully independent in its research programs, governance, and finances.
Researchers, including those from the University of Tokyo, combine various past climate data to investigate the impacts of ancient volcanic eruptions. They explored eruptions in the tropics over the last 1,000 years and found some large eruptions have far-reaching climatic consequences. Preserved tree rings, as well as climate models, show evidence that some monsoon activity is reduced following particularly large tropical eruptions. This research could impact current climate models, eruption simulations, and even influence long-term disaster preparedness given the potential impact eruptions can have on monsoon-dependent crop supplies.
Volcanoes are both captivating and disastrous. Most are likely familiar with the common short-term dangers associated with them: explosive forces, lava, and even atmospheric particles disrupting air traffic. But researchers also explore longer-term impacts of eruptions, as their contributions to broader climate patterns are important, but not well understood. For example, it’s known that ejected material can reach high into the atmosphere and cause local or even global cooling to some degree. Assistant Professor Kanon Kino from the Department of Civil Engineering at the University of Tokyo and her international team are now able to connect past tropical volcanic eruptions with historical large-scale droughts across parts of Asia documented over the last millennium.
“A visiting Ph.D. student, Wenzheng Nie, was working on reconstructing Earth's past hydroclimate by using preserved tree-ring patterns,” said Kino. “As tree ring patterns reflect local variations in hydroclimate, we combined existing tree-ring derived data and climate model simulation datasets to reconstruct large-scale hydroclimate variability and atmospheric circulation patterns in the past. When you do this, you can reconstruct atmospheric circulation variability, including remote simultaneous patterns called teleconnections, such as the circumglobal teleconnection (CGT), which is a large-scale atmospheric wave pattern that modulates rainfall across Eurasia. In particular, its negative phase is associated with reduced precipitation over northern East and South Asia. But what surprised us is that drought-causing negative phases of the CGT repeatedly occurred after large tropical volcanic eruptions.”
This relationship does not arise simply from the transport of cooler or drier air. Instead, the key mechanism lies in how volcanic cooling alters atmospheric heating. Large eruptions inject sulfate aerosols into the stratosphere, reducing incoming solar radiation and cooling the surface. This cooling suppresses monsoon convection over South Asia, weakening the release of latent heat into the atmosphere. The reduction in this heating triggers a large-scale atmospheric pattern resembling the negative phase of the CGT. After particularly large eruptions, and depending on other atmospheric conditions, a drought in Asia might occur during the first boreal summer following the eruption. This response is strongest in the first year following a large eruption. This mechanism appears to arise directly from volcanic effects, rather than depending on other climate fluctuations.
“The last negative CGT following a volcanic eruption seemed to take place in the 1960s. And while it could happen again, we now know that the atmospheric response typically peaks in the first boreal summer following a major eruption, it ought to give affected regions time to prepare when it does,” said Kino. “Reconstructing past extreme weather events and understanding the mechanisms is challenging, but climate proxies, such as tree rings, help tackle these problems. I would like to reconstruct more past extreme weather events from even deeper in Earth’s history. I think doing so can help us better understand our changing climate.”
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Journal: Wenzheng Nie, Jun Xia, Kanon Kino, Dunxian She, and Taikan Oki, “Tropical volcanism triggers pan-Asian monsoon droughts via circumglobal teleconnection”, Nature Communications, DOI: 10.1038/s41467-026-70710-x, https://www.nature.com/articles/s41467-026-70710-x
Funding: This work was supported by the National Key Research and Development Program of China (grant No. 2023YFC3206605 to D.S.) and the National Natural Science Foundation of China (grant No. U2340213 to J.X.), the Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant No. 24K20915 to K.K.). This work was performed as part of the IAHS HELPING Working Group on "Development & application of river basin simulators".
Research Contact:
Assistant Professor Kanon Kino
Department of Civil Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, JAPAN kanon@hydra.t.u-tokyo.ac.jp
The University of Tokyo is Japan's leading university and one of the world's top research universities. The vast research output of some 6,000 researchers is published in the world's top journals across the arts and sciences. Our vibrant student body of around 15,000 undergraduate and 15,000 graduate students includes over 5,000 international students. Find out more at www.u-tokyo.ac.jp/en/ or follow us on X (formerly Twitter) at @UTokyo_News_en.
Ticks are major vectors of infectious diseases, affecting both animals and humans. Their ability to remain attached to a host and feed on their blood over the course of several days derives from their saliva, which prevents blood clotting and reduces the host's immune defences.
Previous work on tick saliva have primarily focused on identifying its involved in suppressing the host defence system and facilitating pathogen transmission. One question remained: how does the tick control its salivation process?
Using computer models and microscopy techniques, the research team found that the tick’s nervous system can precisely regulate the activity of its salivary glands during blood feeding. This control is achieved through two distinct yet complementary signalling pathways involving receptors sensitive to the neurotransmitter acetylcholine. To explore the roles of these pathways, the researchers tested 37 substances — including pilocarpine and atropineine(which are alkaloids) — identifying compounds that either activated or blocked one or both receptors. The findings revealed that one pathway governs the continuous secretion of salivary fluid, while both pathways must work in tandem to produce the full salivary cocktail, including key proteins needed for blood feeding. This dual control enables the tick to finely tune the quantity and composition of its saliva while attached to a host.
A key contribution of this study is providing evidence that acetylcholine, a compound naturally present in ticks, is a powerful natural stimulator of salivation in female ticks. Moreover, the team discovered that one of the identified receptors is specific to invertebrates and absent in mammals including humas, suggesting the potential for developing targeted strategies to disrupt tick feeding without harming the host.
Better understanding the enemy to develop effective countermeasures
Inhibiting salivation is a crucial step in preventing both blood feeding and pathogen transmission. Targeting the tick's nervous system and its connection to the salivary glands presents a particularly promising strategy for future control efforts. This foundational research rests on a simple principle: understanding the enemy enables more effective and targeted control measures. A deeper understanding of these mechanisms—which are likely shared across different tick species worldwide—could lead to more universal and sustainable control strategies.
