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Striking the balance: Complexity, simplicity, and credibility in mathematical biology

Climate change amplifies neurotoxic methylmercury threat to Asian fish consumers

Climate change is intricately influencing the accumulation of neurotoxic methylmercury (MeHg) in human food webs, potentially leading to uneven exposure risks across regions. Here, we reveal that climate change will elevate MeHg risks in China, with implications for regional inequalities in Asia through a climate-mercury-food-health nexus. Using a compiled fish mercury dataset from 13,000 samples and machine learning, we find that freshwater wild fish—an essential component of the Asian diet—is an underappreciated MeHg source. Specifically, MeHg concentrations in freshwater wild fish are 2.9 to 6.2 times higher than in freshwater farmed fish and 1.7 times higher than in marine wild fish. Individual climate factors influence MeHg accumulation differently, while their combined effects significantly increase MeHg concentrations in freshwater wild fish. Under SSP2–4.5 and SSP5–8.5 by 2031 to 2060, national average MeHg concentrations in freshwater wild fish are projected to increase by about 60%, adding a maximum annual economic loss of US$18 million (2022 USD) from intelligence quotient decrements in Chinese newborns. This loss may vary regionally within China and among Asian countries, disproportionately affecting less developed areas. Coordinating climate action with mercury emission reduction strategies could mitigate these overlooked regional risks, reduce regional inequalities in food safety, and ultimately contribute to sustainable development.

A national megastudy shows that email nudges to elementary school teachers boost student math achievement, particularly when personalized

In response to the alarming recent decline in US math achievement, we conducted a national megastudy in which 140,461 elementary school teachers who collectively taught 2,992,027 students were randomly assigned to receive a variety of behaviorally informed email nudges aimed at improving students’ progress in math. Specifically, we partnered with the nonprofit educational platform Zearn Math to compare the impact of 15 different interventions with a reminder-only megastudy control condition. All 16 conditions entailed weekly emails delivered to teachers over 4-wk in the fall of 2021. The best-performing intervention, which encouraged teachers to log into Zearn Math for an updated report on how their students were doing that week, produced a 5.06% increase in students’ math progress (3.30% after accounting for the winner’s curse). In exploratory analyses, teachers who received any behaviorally informed email nudge (vs. a reminder-only megastudy control) saw their students’ math progress boosted by an average of 1.89% during the 4-wk intervention period; emails referencing personalized data (i.e., classroom-specific statistics) outperformed emails that did not by 2.26%. While small in size, these intervention effects were consistent across school socioeconomic status and school type (public, private, etc.) and, further, persisted in the 8-wk post-intervention period. Collectively, these findings underscore both how difficult it is to change behavior and the need for large-scale, rigorous, empirical research of the sort undertaken in this megastudy.

Competition response of cloud supersaturation explains diminished Twomey effect for smoky aerosol in the tropical Atlantic

The Twomey effect brightens clouds by increasing aerosol concentrations, which activates more droplets and decreases cloud supersaturation in response to more competition for water vapor. To quantify this competition response, we used marine low cloud observations in clean and smoky conditions at Ascension Island in the tropical South Atlantic during the Layered Aerosol Smoke Interactions with Cloud (LASIC) campaign. These observations show similar increases in droplet number for increased accumulation-mode particles from surface-based and satellite cloud retrievals, demonstrating the importance of below-cloud aerosol measurements for retrieving aerosol–cloud interactions (ACI) in clean and smoky aerosol conditions. Four methods for estimating cloud supersaturation from aerosol–cloud measurements were compared, with cloud scene-based and parcel-based methods showing sufficient variability for a strong dependence on both aerosol accumulation number concentration and cloud-base updraft velocities. Decomposing aerosol-related changes in cloud albedo and optical depth shows the calculated competition response accounts for dampening the activation response by 12 to 35%, explaining the diminished Twomey effect at high aerosol concentrations observed for smoky conditions at LASIC and previously around the world. This result was consistent for independent supersaturation retrievals by cloud scene-based droplet number and cloud condensation nuclei and parcel-based multimode size-resolving Lagrangian methods. Translating aerosol effects to local radiative forcing with clean conditions as a proxy for preindustrial and smoky conditions for present-day showed that the competition response reduces cooling from the Twomey radiative forcing by 12 to 35%, providing an essential process-specific constraint for improving the representation of aerosol competition in climate model simulation of indirect aerosol forcing.

Targeted degradation of α-Synuclein using an evolved botulinum toxin protease

There is considerable interest in the targeted degradation of proteins implicated in human disease. The use of sequence-specific proteases for this purpose is severely limited by the difficulty in engineering the numerous enzyme–substrate interactions required to yield highly selective proteases while maintaining catalytic activity. Herein, we report a strategy to evolve a protease for the programmed degradation of α-Synuclein, a presynaptic protein closely linked to Parkinson’s disease. Our structure-guided evolution campaign uses the protease from botulinum neurotoxin and showcases the stepwise change of specificity from its native substrate SNAP25 to the selective degradation of α-Synuclein. The protease’s selectivity is further demonstrated in human cells where near complete degradation of overexpressed human α-Synuclein is observed with no significant effects on cell proliferation. This stepwise strategy may serve as a general approach to evolve highly selective proteases targeting dysregulated proteins.

Control of circadian muscle glucose metabolism through the BMAL1–HIF axis in obesity

Disruptions of circadian rhythms are widespread in modern society and lead to accelerated and worsened symptoms of metabolic syndrome. In healthy mice, the circadian clock factor BMAL1 is required for skeletal muscle function and metabolism. However, the importance of muscle BMAL1 in the development of metabolic diseases, such as diet-induced obesity (DIO), remains unclear. Here, we demonstrate that skeletal muscle–specific BMAL1-deficient mice exhibit worsened glucose tolerance upon high-fat diet feeding, despite no evidence of increased weight gain. Metabolite profiling from Bmal1 -deficient muscles revealed impaired glucose utilization specifically at early steps in glycolysis that dictate the switch between anabolic and catabolic glucose fate. We provide evidence that this is due to abnormal control of the nutrient stress–responsive hypoxia-inducible factor (HIF) pathway. Genetic HIF1α stabilization in muscle Bmal1 -deficient mice restores glucose tolerance and expression of 217/736 dysregulated genes during DIO, including glycolytic enzymes. Together, these data indicate that during DIO, skeletal muscle BMAL1 is an important regulator of HIF-driven glycolysis and metabolic flexibility, which influences the development of high-fat-diet-induced glucose intolerance.

Bacteria on steroids

Long-chain alkanes preserved in a Martian mudstone

Organic molecules preserved in ancient Martian rocks provide a critical record of the past habitability of Mars and could be chemical biosignatures. Experiments conducted by the Sample Analysis at Mars instrument onboard the Curiosity rover have previously reported several classes of indigenous chlorinated and sulfur-containing organic compounds in Gale crater sedimentary rocks, with chemical structures of up to six carbons. Here, we report the detection of decane (C 10 H 22 ), undecane (C 11 H 24 ), and dodecane (C 12 H 26 ) at the tens of pmol level, released from the Cumberland drilled mudstone sample, using a modified SAM analytical procedure optimized for the detection of larger organic molecules. Laboratory experiments support the hypothesis that the alkanes detected were originally preserved in the mudstone as long-chain carboxylic acids. The origin of these molecules remains uncertain, as they could be derived from either abiotic or biological sources.

Correction for Magesh et al., Co-zorbs: Motile, multispecies biofilms aid transport of diverse bacterial species

Correction for Quach et al., Deep learning–driven bacterial cytological profiling to determine antimicrobial mechanisms in <i>Mycobacterium tuberculosis</i>

Correction to Supporting Information for Walters et al., Identification of FSH-regulated and estrous stage–specific transcriptional networks in mouse ovaries

CERN releases detailed plans for supercollider — but no hints about funding

Large language models for identifying social determinants of health

Daily briefing: Mass layoffs across US health agencies

Correction to Supporting Information for Stransky et al., Toward a CRISPR-based mouse model of <i>Vhl</i> -deficient clear cell kidney cancer: Initial experience and lessons learned

Correction to Supporting Information for Struve et al., Systematic changes in circumpolar dust transport to the Subantarctic Pacific Ocean over the last two glacial cycles

Reply to Deter-Wolf et al.: Laser-stimulated fluorescence of Chancay tattoos

Laser imaging of ancient tattoos: New tools illuminate established knowledge

Reply to Wang: Improving large language model approaches for identifying social determinants of health from clinical notes

Xylem embolism refilling revealed in stems of a weedy grass

Plant hydraulic dysfunction by embolism formation can impair photosynthesis, growth, and reproduction and, in severe cases, lead to death. Embolism reversal, or “refilling,” is a hypothesized adaptive process in which xylem functionality is rapidly and sustainably restored. This study investigated xylem embolism refilling during recovery from severe drought stress using entirely noninvasive measurements of the same plants. These results were considered in relation to functional traits to address long-standing gaps in understanding the consequences of severe drought stress. Leaf and stem xylem embolism as well as transpiration, photosynthesis, and stem water potential were characterized nondestructively on intact barnyard grass plants during an acute drought event. Plants were rewatered and returned to growth conditions for 10 d, during which time recovery of stem xylem embolism and transpiration were monitored. Leaf xylem embolism and declines in leaf gas exchange occurred mostly between −1.0 MPa and −2.0 MPa, whereas stem xylem embolism occurred mostly between −3.0 MPa and −4.0 MPa. In all measured plants, which included embolism levels up to 88%, stem xylem embolism reversed completely within 24 h after rewatering, and this refilling supported recovery of transpiration and growth after plants were returned to growth conditions. This study provides direct evidence of complete and functional stem xylem refilling. These results present a clear need to elucidate underlying mechanisms and the adaptive significance of this phenomenon as well as its prevalence in nature.