Here in Austria, as in many other places, it’s been a hot end to another unusually warm month (this year, only May has been cooler than average). Blistering heatwaves like the one expected to peak in Europe this week are just one consequence of climate change. Another is the spread of vector-borne diseases, as mosquitoes and other vectors expand into new regions. For example, mosquito-borne flaviviruses causing diseases like dengue fever, Zika, and West Nile fever already infect over 400 million people a year and are set to continue spreading to temperate regions. There are currently no effective antiviral drugs for flaviviruses.

Unlike mammals and birds, some scaled reptiles are resistant to flavivirus infection, but the mechanisms underlying this resistance are unknown. A recent preprint reported a screen for viral resistance genes in iguanas, identifying a TRIM-family E3 ubiquitin ligase that reduces dengue virus replication in human cells ~10,000-fold. The authors provide evidence that the E3 ligase targets the viral capsid protein for degradation, a strategy distinct from known anti-flavivirus strategies. Crucially, flaviviruses depend on (non-degradative) capsid ubiquitylation for infection, so it might be difficult for them to evolve TRIM resistance without losing infectivity. Indeed, the authors used experimental evolution to show how flaviviruses might be forced into an evolutionary corner: TRIM resistance (enabled by mutations in ubiquitin-modifiable capsid residues) came at the cost of reduced fitness in human cells.

Finally, the authors identified a whole family of similar genes in reptiles with varied antiviral activity, “highlighting the vast potential of querying diverse animal genomes for discovering new defenses to pandemic viruses.”

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A trove of antiviral TRIM family E3 ligases in reptiles
In bioRxiv, 25 June 2025

From the group of Nels Elde, University of Utah and Howard Hughes Medical Institute

Snippet by Katrina Woolcock.

Image credit: Figure 1 from Boys et al. cited above (CC-BY-NC 4.0).

Seventeen years ago, when I was pregnant with my daughter, I was diagnosed with gestational diabetes. I assumed it would go away after delivery, as it does for many people. But it didn’t. Today, like about 1 in 3 American adults, I live with prediabetes, marked by elevated HbA1c—a quiet signal that my blood sugar regulation is off. What’s more troubling is that most people with prediabetes don’t know they have it. And the consequences aren’t trivial: about 70% of people with prediabetes eventually develop type 2 diabetes, and even before that, the spikes and swings in blood sugar can fuel inflammation, high blood pressure, cardiovascular disease, kidney damage, and more. Here’s how a recent Nature Medicine paper frames one of the challenges in its opening sentences:

Elevated postprandial glycemic responses (PPGRs) are associated with type 2 diabetes and cardiovascular disease. PPGRs to the same foods have been shown to vary between individuals, but systematic characterization of the underlying physiologic and molecular basis is lacking.

That is: we’ve known for a while that some foods spike blood sugar more than others, but we haven’t fully understood why the same food can spike one person’s glucose dramatically, while barely nudging another’s. This study took a rigorous look at that mystery. The researchers gave 55 people seven different carbohydrate-rich meals—rice, bread, potatoes, pasta, beans, grapes, and berries—and then tracked their glucose levels. They also performed an in-depth analysis of their metabolic health.
As expected, blood sugar responses to the same foods varied hugely between individuals. For example, rice produced the biggest spike in most people, but others spiked more with potatoes, bread, or even grapes. But these response patterns weren’t random—they reflected underlying physiology. People who spiked most after potatoes were often insulin resistant and had weaker beta cell function, whereas “grape-spikers” were generally more metabolically healthy. Another key insight: “mitigators” like fiber, protein, or fat—when consumed just 10 minutes before a meal—could blunt glucose spikes, but only in people with good metabolic health. For insulin-resistant individuals like me, these strategies were less effective.

The takeaway is both sobering and empowering: glycemic responses are personal, shaped by your unique metabolic profile. Blood sugar is easy to monitor, and can expose dysfunction that traditional labs might miss. Many of us are trying to be pro-active about health – and this kind of personalized insight could be a key to staying on the right side of the tipping point.

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Individual variations in glycemic responses to carbohydrates and underlying metabolic physiology
In Nature Medicine, 4 June 2025
From the groups of Tracey McLaughlin at Michael P. Snyder at the Stanford Diabetes Research Center of Stanford University.

Snippet by Angela Andersen

Image credit: Figure 1a from Wu et al. cited above (CC BY-NC-ND)

Among my favorite characters in the Marvel Cinematic Universe (MCU) is King T’Challa, the title character in Black Panther (2018) who appears in other MCU movies. T’Challa was portrayed by the brilliant Chadwick Boseman—even if you are not a fan of the MCU, you might know Boseman from his portrayal of Jackie Robinson in 42 or of Thurgood Marshall in Marshall. He worked on Black Panther while terminally ill, somehow keeping this fact largely unknown and keeping it from stopping his work. He died in 2020 at the age of 43, and he was killed by early-onset colon cancer.

That cancer is on the rise. Here is how a new paper in Nature frames the problem in the first sentences of the abstract:

Incidence rates of colorectal cancer vary geographically and have changed over time. Notably, in the past two decades, the incidence of early-onset colorectal cancer, which affects individuals below 50 years of age, has doubled in many countries. The reasons for this increase are unknown.

Two things to notice about those opening sentences: 1) they clearly outline the background and the urgency of the problem; and 2) they starkly state the knowledge gap. Even without mentioning the devastating human cost, the authors compel us to read on. When we do that, we learn that they undertook a vast international quest to identify mutations that underlie this menace, and how the mutations vary (widely) across continents and in people of different ages. One major finding: colibactin, a mutagen produced by gut bacteria (certain strains of E. coli), likely explains some of the patterns of mutation that cause early-onset colorectal cancer. Interestingly, we know from previous work that the use of antibiotics and the presence of clean water seem to favor the mutagen-making bacteria, and these factors are associated with the alarming increase in this cancer in some parts of the world but not others. These clues offer hope!

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Geographic and age variations in mutational processes in colorectal cancer
In Nature, 23 April 2025
From the groups of Ludmil Alexandrov (UCSD), Mike Stratton (Wellcome Sanger Institute), and Paul Brennan (International Agency for Research on Cancer (IARC/WHO)), with collaborators and co-authors from throughout the world.

Snippet by Stephen Matheson

Image credit: Figure 1a from Díaz-Gay et al. cited above (CC BY)

Misuse and overuse of antimicrobials have led to a global health crisis: antimicrobial resistance (AMR), including multidrug-resistant superbugs. Common misconceptions that contribute to the problem have proven difficult to dispel; for example, 30% of Europeans believe that antibiotics are effective against colds (Eurobarometer 2022). One important arm of the multipronged strategy to tackle AMR is surveillance, but the current focus on clinical settings is too narrow. Microbes – including bacteria carrying antibiotic resistance genes (ARGs) – are everywhere, and environments like wastewater are hotspots for ARG exchange. A recent preprint, conducted as part of the SEARCHER project, used metagenomics and functional metagenomics on environmental samples to identify genes conferring resistance to cefiderocol, a last-resort antibiotic used against multidrug-resistant bacteria. Metagenomics is a technique that analyzes all the genetic material in a complex environmental sample, enabling identification of known ARGs. Functional metagenomics goes a step further, identifying ARGs based on their activity rather than their sequence. The authors used functional metagenomics to analyze freshwater, wastewater, and soil samples from Sweden, Germany, and Pakistan. By expressing sampled DNA in cefiderocol-sensitive host bacteria exposed to the antibiotic, they uncovered four ARGs not previously linked to cefiderocol resistance, two of which are not in current ARG databases. The paper showcases the importance of a ‘One Health’ surveillance strategy – i.e., one that recognizes the interconnectedness of human health, animal health, and the environment – to provide early warning of emerging AMR threats.

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Environmental reservoir of resistance genes for the last resort antibiotic Cefiderocol
In bioRxiv, 28 May 2025

From the group of Etienne Ruppé, INSERM, France, and collaborators at the SEARCHER (Surveillance for Emerging Antimicrobial Resistance through Characterization of the uncharted Environmental Resistome) program.

Snippet by Katrina Woolcock.

Image credit: Figure 5 from Gschwind et al. cited above (CC BY-NC-ND).

When food shopping, I tend to opt for organic products. These often have an extra label touting their GMO-free status, since organic farming prohibits the use of genetically modified organisms. That includes organisms created with “new genomic techniques” (NGTs) like CRISPR. But there’s a paradox: plants bred using conventional mutagenesis (i.e., random mutagenesis with chemicals and radiation) are generally allowed in organic farming, even though these techniques are more likely than modern gene editing to produce unintended mutations in the final product.

NGTs allow for precise and targeted changes that could, in theory, occur naturally. The technology is moving fast; for example, base editing and prime editing (techniques derived from CRISPR technology) enable precise changes without cutting both strands of the DNA and come with even lower risk of unintended mutations. Both techniques have been in the news recently because of their therapeutic use: on May 15, we learned that base editing was used for the first personalized CRISPR therapy, while on May 19, it was announced that prime editing has been used to treat a person for the first time. Going back to plants, base and prime editing have been successfully applied in several important cereal crops (e.g., rice, wheat, maize) but not yet in sorghum. A recent preprint reported a high-efficiency genome editing toolkit for sorghum, paving the way for use of base and prime editing in this important crop. The authors conclude: “These advancements provide a streamlined approach to generating diverse genetic variation, facilitating crop improvement efforts that address food security challenges and contribute to carbon capture initiatives that are addressing climate change.”

This year, the EU is set to relax strict regulation of NGT plants (which are currently treated like GMO plants containing foreign DNA), marking a long-awaited and scientifically-supported shift in focus away from the breeding method and towards the characteristics of the final product. However, the paradox persists: NGT plants will still be excluded from organic farming, while those bred using conventional mutagenesis can stay.

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High-frequency Wus2-integrated transformation toolkit enhances Cas9 editing efficiency and expands capability with SpRY in sorghum
In bioRxiv, 24 January 2025
From the group of Peggy Lemaux in the Department of Plant and Microbial Biology, University of California, Berkeley.

Snippet by Katrina Woolcock

Image credit: Figure 1 from Kantor et al., International Journal of Molecular Sciences, 2020 (CC BY)

Chronic stress is not just unpleasant; it degrades human health in several ways. One effect of chronic stress is increased susceptibility to depression, which itself exerts damaging effects on health and wellbeing. Neither of these conditions is deeply understood, and so perhaps it is unsurprising that the link between chronic stress and depression is unclear.

A recent paper in Nature provides interesting and useful clues to that link, in a set of experiments that journey from effects of antidepressants to basics of neuronal cell biology. The connection is in the machinery of autophagy (literally “self eating”) in which parts of a cell are digested in a recycling and reclamation process. The authors show that autophagy is central to stress and depression, specifically in neurons of an emotion-related brain region (the lateral habenula, or LHb). They find that acute stress activates autophagy in that region, but chronic stress (a model of depression in mice) does the opposite. Consistent with that fact, they show that autophagy in the LHb underlies antidepressant effects of various drugs, from antidepressant drugs themselves to metabolic inhibitors that (interestingly) also exert antidepressant actions. They then show that genetically inactivating autophagy—specifically in the LHb—causes depression-like effects. After several additional great experiments, the authors conclude: “our study proposes a fascinating possibility that LHb autophagy serves as a new cellular target of rapid antidepressants.”

Basic research by hard-working scientists all over the world is steadily eroding the power of scourges like depression.

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Stress dynamically modulates neuronal autophagy to gate depression onset
In Nature, 9 April 2025
From the groups of Yihui Cui and Xiangnan Zhang at Zhejiang University.

Snippet by Stephen Matheson

Image credit: Extended data Figure 15 from Yang et al. cited above (CC BY-NC-ND)

I am regularly awestruck by the feats accomplished by our fellow animals. Here’s one that might not seem particularly praiseworthy: eating your body weight in a single meal. This is regularly achieved by ticks, and that’s a second reason you might want to stop reading, but hear me out. A tick gorges itself on blood (perhaps yours) until it has ballooned to at least ONE HUNDRED TIMES its pre-meal body weight. How is this even possible? Specifically, how does this animal’s gut accommodate the vast expansion that results from a blood feast?

A new paper in Cell Reports asked that question, focusing on the muscles of the tick’s gut. The authors looked at two interesting consequences of feeding in the gut: proliferation of gut stem cells, and fission (splitting) of mitochondria. Stem cell proliferation seems a reasonable path toward the necessary expansion of the gut, but when the authors inhibited that process, ticks happily gorged themselves to the same extent. But inhibition of mitochondrial fission disrupts feeding, and the authors show why: more mitochondria are needed for ATP, which is needed for upregulation of a muscle protein called troponin T (delightfully abbreviated TNT). Experimental reduction of TNT expression inhibits muscle function, and ruins the tick’s meal. Sad.

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Mitochondrial fission regulates midgut muscle assembly and tick feeding capacity
In Cell Reports, 22 April 2025
From the group of Jingwen Wang at Fudan University

Snippet by Stephen Matheson

Image credit: graphical abstract from Zhong et al. (CC BY-NC)

Autism is extremely heterogeneous. It is shaped by a complex interplay of genetic and environmental factors, which have been studied for decades, making RFK Jr’s pledge to determine “what has caused the autism epidemic” by September highly questionable. Some worry that the effort will be biased towards vaccine-autism theories, which have been repeatedly and thoroughly debunked. The strongest known contributors to autism risk are genetic, but there is reasonable evidence that environmental factors during pregnancy can affect autism risk in offspring (and, of course, these factors may interact with genetic predispositions). For example, activation of the mother’s immune system during pregnancy has been linked to increased autism risk. Proving causation in humans is tricky, so much of the evidence on this “maternal immune activation” comes from animal models. A recent preprint sheds light on the potential molecular mechanisms, suggesting that changes in DNA methylation disrupt neural circuit formation in the offspring of mice treated with a viral mimetic (poly(I:C), or PIC) during pregnancy.

The authors are careful to make the distinction between the immune activation in their experiments and the immune activation occurring upon mild infection or vaccination: “The cytokine levels post-PIC injection are comparable to those produced during a cytokine storm due to influenza or other serious infections. Such levels of proinflammatory cytokines are not produced during common cold infections or after immunizations.” So, if anything, vaccines before and during pregnancy might reduce autism risk by protecting against serious infections.

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Maternal Immune Activation Disrupts Epigenomic and Functional Maturation of Cortical Excitatory Neurons
In bioRxiv, 29 April 2025
From the groups of Margarita Behrens, Eran Mukamel, and Joseph Ecker

Snippet by Katrina Woolcock

Image credit: Figure 1 from Lai et al. linked above (CC-BY-NC-ND)

Last month, the UK Supreme Court ruled that the legal definition of a woman is based on biological sex. Snippets are not the place for discussing legal rulings and their ramifications, but I want to focus on one quote from the decision: “the concept of sex is binary, a person is either a woman or a man”. Such simplicity might be convenient in terms of legal clarity but is at odds with the reality of human biology. Biological sex is by no means strictly binary: for example, intersex people are born with physical sex characteristics that do not fit typical definitions of male or female. A vast array of “differences in sex development” (DSDs) often underlie such variation, with much remaining to be discovered about the biological mechanisms. A recent preprint from the Institut Pasteur in France sheds light on a DSD called 46,XY sex-reversal, whereby an individual with male chromosomes develops female genitalia and reproductive structures. DHX37, a gene encoding an RNA helicase, is one of several genes implicated in 46,XY sex-reversal. Among other experiments, the authors analyzed RNA transcripts physically interacting with wild-type and mutant DHX37 proteins, providing insights into how DHX37 mutations might disrupt early testicular development. Such studies will help unravel the vast natural variation in sex development, hopefully changing oversimplified ‘either/or’ views of sex.

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Altered RNA-processing provides a mechanistic framework delineating human sex-reversal associated with pathogenic variants in the RNA-helicase DHX37
In bioRxiv, 13 January 2025
From the group of Anu Bashamboo

Snippet by Katrina Woolcock

Image credit: Figure 4A-4D from Elzaiat et al. linked above (CC-BY)

mRNA vaccines have been administered billions of times worldwide and their importance was underscored by the 2023 Nobel Prize in Physiology or Medicine, awarded to Katalin Karikó and Drew Weissman “for their discoveries concerning nucleoside base modifications that enabled the development of effective mRNA vaccines against COVID-19”. Nonetheless, mRNA vaccines have been the subject of controversy, some of it rooted in misinformation. For example, false claims and conspiracy theories about mRNA vaccines altering DNA gained traction, spreading fear of long-term consequences. Far from it, mRNA does not enter the nucleus and, even if it did, would not be able to interact with or change DNA. In fact, mRNA is highly unstable, making the effectiveness of mRNA vaccines rather surprising. A recent paper in Nature helps explain how the vaccine mRNAs manage to stick around long enough to produce the protein needed for an immune response. The authors found that an enzyme called TENT5A extends the mRNA poly(A) tails, which are crucial for mRNA stability and translation. The findings will aid the design of future mRNA therapeutics, which are under investigation for treating a range of diseases, from flu to cancer. The authors are particularly proud that the paper is exclusively a product of Polish institutions; yet the path to publication wasn’t easy – it took more than two years and multiple rounds of revision before their manuscript was accepted.

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Re-adenylation by TENT5A enhances efficacy of SARS-CoV-2 mRNA vaccines
In Nature, 16 April 2025
From the groups of Andrzej Dziembowski and Seweryn Mroczek, International Institute of Molecular and Cell Biology and University of Warsaw

Snippet by Katrina Woolcock

Image credit: Figure 3 from Krawczyk et al. linked above (CC-BY)