Sanchez Garcia, L. | bioRxiv Science

bioRxiv2025

Seasonal biogeochemical variations in a modern microbialite reef under early Earth-like conditions

Microbialites are organosedimentary structures dating to the Precambrian that serve as archives of Earths environmental evolution. Today, they persist in only a few environments markedly different from those in which they first arose. Here, we report a modern microbialite reef in Laguna Pozo Bravo (Puna region, Argentina), exposed to high radiation, low oxygen pressure, and volcanic inputs reminiscent of early Earth. Through physicochemical, mineralogical, spectroscopic, electron microscopy, and metagenomic analyses, we identified diverse microbial communities with metabolic capacities that induce mineralisation. Seasonal environmental fluctuations drive cyclical changes in community composition, producing potential mineralisation patterns. Our findings suggest that carbon fixation and the metabolic drivers of alkalinity in microbialites evolved over time. Moreover, the variability in prokaryotic compositions among modern microbialites demonstrates that carbonate precipitation is governed by metabolic potential rather than taxonomy, reinforcing their role as dynamic records of environmental conditions.

microbiology↗

bioRxiv2024

Broad therapeutic benefit of myosin inhibition in hypertrophic cardiomyopathy

Myosin inhibitor mavacamten is the only targeted treatment available for hypertrophic cardiomyopathy (HCM), a disease caused by hundreds of genetic variants that affect mainly sarcomeric myosin and its negative regulator cardiac myosin-binding protein C (cMyBP-C, encoded by MYBPC3). Here, we have examined whether the reported limited efficacy of mavacamten in a fraction of HCM patients can result from dissimilar HCM pathomechanisms triggered by different genetic variants, a scenario particularly relevant for MYBPC3-associated HCM. To this aim, we have generated knock-in mice including missense pathogenic variant cMyBP-C p.R502W, which, different from patients who carry truncations in the protein, develop progressive pathogenic myocardial remodeling in the absence of alterations of cMyBP-C levels and localization. Mechanistically, we find that mutation R502W reduces the binding affinity of cMyBP-C for myosin without inducing a shift towards more active myosin conformations as observed when cMyBP-C levels are reduced. Despite these diverging molecular alterations, we show that mavacamten blunts myocardial remodeling both in R502W and cMyBP-C-deficient, knock-out hearts. These beneficial effects are accompanied by improved tolerance to exercise only in R502W animals. Hence, our results indicate that myosin inhibition is effective to treat HCM caused by both truncating and missense variants in MYBPC3 regardless of the primary pathomechanisms they elicit.

physiology↗