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.”

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.

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!

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.

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).