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PLOS Biology: New Articles

  • Sub-daily virus sampling at the Bermuda Atlantic Time Series reveals diel and depth-structured population dynamics without community-level shifts

    by Alfonso Carrillo, Emily Hageman, Lauren Chittick, Anna I. Mackey, Kimberley S. Ndlovu, Funing Tian, Naomi E. Gilbert, Daniel Muratore, Dean Vik, Gary R. LeCleir, Christine Sun, Ho B. Jang, Ricardo R. Pavan, Joshua S. Weitz, Steven W. Wilhelm, Matthew B. Sullivan

    Ocean microbes contribute to biogeochemical cycles and ecosystem function, but they do so under top-down pressure imposed by viruses. While viruses are increasingly understood spatially and beginning to be incorporated into predictive modeling, high-frequency ocean virus dynamics remain understudied due to methodological challenges. Here we sampled stratified Bermuda Atlantic Time Series (BATS) waters for 112 hours at sub-daily 4- (surface) or 12- (deep chlorophyll maximum) hour intervals, purified viral particles from these samples, sequenced their metagenomes, and used the resulting data to characterize high-frequency virus community dynamics. Aggregated community diversity metrics changed with depth, but were not statistically significant temporally at a fixed location. However, finer-scale population-level analyses revealed both depth and temporal change, including physicochemical depth-driven differences and, in surface waters, thousands of viral populations that exhibited statistically significant diel rhythms. Statistical analyses revealed three main archetypes of temporal dynamics that themselves differed in abundance patterns, host predictions, viral taxonomy, and gene functions. Among these, highlights include viruses resembling an archetype with a night peaking pattern in activity that include an over-representation of viruses that putatively infect Prochlorococcus, a phototrophic cyanobacteria. Together, these efforts provide baseline community- and population-scale short-time-frame observations relevant to future climate state modeling.

  • The adaptor protein TASL is required for age-related B cell emergence and lupus-like disease development in mice

    by Julia C. Johnstone, Robert Mitchell, Timothy J. Vyse, Alexander J. Clarke

    The autoimmune disease systemic lupus erythematosus (SLE) is associated with genetic variants in the X-linked gene CXORF21, which encodes the protein TASL. TASL acts as an adaptor in the IRF5 pathway and is necessary for the phosphorylation of IRF5 in response to TLR7 or TLR9 stimulation. Here, we investigate the role of TASL in the humoral immune response, and in the development of lupus in the B6.MRLlpr murine model of SLE. We find that while TASL is dispensable for their development, it is required for the full activation of B cells via TLR9 stimulation, and consequent interferon signaling and inflammatory cytokine expression. Additionally, TASL is crucial for the emergence of age-associated B cells (ABCs), a B cell population derived from the extrafollicular response that increases with age and is expanded in autoimmune disease, and the production of IgG2c antibodies. We also find that deletion of TASL prevents the onset of autoimmunity in the genetically-determined B6.MRLlpr model of lupus.

  • Gpc3 selectively suppresses subcutaneous adipogenesis in diet-induced obesity

    by Yan Li, Ming Tao, Carlos F. Ibáñez, Meng Xie

    Subcutaneous and visceral adipose depots employ distinct expansion strategies in response to dietary cues, yet the molecular regulators underlying these depot-specific adaptations remain poorly understood. Through integrated proteomic profiling of human subcutaneous and visceral adipose tissues from paired obese/non-obese donors and temporal transcriptomic analysis of mouse adipose stem and progenitor cells (ASPCs) during dietary transitions, we identified Glypican 3 (Gpc3) as an obesity-responsive gene exhibiting reciprocal expression patterns between depots. ASPC-specific Gpc3 deletion in mice amplified high-fat diet-induced weight and fat mass gain, with a selective enhancement of expansion in inguinal white adipose tissue (WAT) without affecting epididymal WAT. Mechanistically, Gpc3 loss biased ASPC fate toward adipogenesis over proliferation through depot-specific modulation of canonical Wnt signaling. These findings establish Gpc3 as a regulator for regional adipose plasticity, offering a molecular target for reprogramming pathological fat distribution in obesity and related metabolic disorders.

  • Developing monoclonal antibody therapies for measles could lead to adverse pathogen evolution

    by David A. Kennedy

    Monoclonal antibody therapies are being developed to treat measles in response to its recent resurgence. These therapies risk driving measles virus evolution in ways that might undermine the protection offered by vaccination, outweighing potential benefits. Monoclonal antibody therapies are being developed to treat measles in response to its recent resurgence. This Perspective argues that such therapies risk driving measles virus evolution in ways that might undermine the protection offered by vaccination.

  • Magnesium depletion by <i>Candida albicans</i> unleashes two unusual modes of colistin resistance in <i>Pseudomonas aeruginosa</i> with different fitness costs

    by Yu-Ying Phoebe Hsieh, Ian P. O’Keefe, Zeqi Wang, Wanting Sun, Hyojik Yang, Linda M. Vu, Nicole E. Smalley, Robert K. Ernst, Ajai A. Dandekar, Harmit S. Malik

    Increasing bacterial resistance to colistin, a vital last-resort antibiotic, is an urgent challenge. Previous studies have shown that Mg2+ depletion enables Pseudomonas aeruginosa to become resistant to colistin. Here, we show that magnesium sequestration by Candida albicans also enables P. aeruginosa to evolve a nearly hundredfold higher level of colistin resistance through genetic changes in lipid A biosynthesis-modification pathways and a putative magnesium transporter. These mutations synergize with the Mg2+-sensing PhoPQ two-component signaling system to remodel lipid A structures of the bacterial outer membrane in previously uncharacterized ways. One predominant mutational pathway involves early mutations in htrB2, a non-essential gene involved in lipid A biosynthesis, which enhances resistance but compromises outer membrane integrity, resulting in fitness costs and increased susceptibility to other antibiotics. A second pathway achieves increased colistin resistance independently of htrB2 mutations without compromising membrane integrity. In both cases, reduced colistin binding to the bacterial membrane underlies resistance. Our findings reveal that Mg2+ scarcity triggers novel evolutionary trajectories, leading to extremely high colistin resistance in P. aeruginosa.