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Biology subjects

Whitman, M.

Publications and source records attributed to Whitman, M..

3 recordsLinked to original sources

From field naturalism to Bayesian models: fog-frost interaction shapes growth form partitioning along Himalayan gradient

AO_SCPLOWBSTRACTC_SCPLOWMountain gradients facilitate our understanding of species range limits, competition dynamics, stress-resilience trade-offs, and determinants of vegetation zone boundaries. Forest compositional models often use altitude as the main predictor, a proxy for temperature that is defensible where floristic transitions are gradual and climate relationships are linear. However, mountains with distinct assemblages, representing tropical gradients or areas with complex biogeographic history, require a modeling framework that reflects non-linear dynamics or interactions between environmental factors, including outlier events (rather than mean conditions). Our study system encompasses both tropical and temperate forests along a broad ([~]3000 m) altitudinal gradient, positioned within a narrow latitudinal band (< 1{degrees}) and composed of mature, continuous forest in the Bhutan Himalaya. To represent the breadth of climatic conditions experienced over a trees lifetime, we used a Bayesian modeling paradigm and integrated multi-generational field knowledge to develop a priori hypotheses and informed priors, with consideration of monsoon seasonality and possible ecophysiological thresholds. Our approach followed three stages (the Pattern, the Mechanism, the Test). Specifically, we interpolated microclimate data and derived custom metrics based on thermodynamics, propagating uncertainty into subsequent models to test whether climate posteriors outperformed altitude in explaining growth form partitioning. For spatial patterns, we identified six distinct vegetation zones (encompassing 145 species from 57 families), with a mid-gradient peak in richness at the tropical-temperate transition zone, and convergence of deciduousness at either end of the gradient. For individual growth forms, abundance was tied to different ecological mechanisms, explained by adaptations to climatic stressors and competition trade-offs. For instance, evergreen broad-leaved dominance was linked to ephemeral cloud immersion, whereas tropical deciduous species were affiliated with higher vapor pressure deficit at lower altitudes. Most importantly, compositional (between-group) models showed that the interaction between frost events and fog probability (air saturation prior to the dry season) governed growth form partitioning more than any single factor; temperate deciduous species, confined to a narrow altitudinal band, exemplified this finding. Our methodological approach is transferable to other data-sparse mountain systems, and our results highlight the vulnerability of unique habitat types and montane endemics under climate change scenarios that alter the fog-frost dynamics. Second abstract in DzongkhaTo see the second abstract in Dzongkha, the official language of Bhutan, please visit our Zenodo site: https://doi.org/10.5281/zenodo.19081441.

ecology↗

Amino Acid Stress Induces Non-AUG Initiation of c-myc Translation

Initiation of translation at non-AUG start codons can generate novel isoforms of important cellular regulators, with activities or localization distinct from their AUG-initiated counterparts. Ribosomes scanning the 5UTR upstream of canonical AUG starts recognize near-cognate starts inefficiently, however, and the mechanisms by which non-canonical starts might be regulated physiologically are poorly understood. We show here that the restriction of utilization of individual amino acid induces a switch in expression of c-myc from its AUG-initiated isoform, c-myc-2, to an upstream CUG-initiated isoform, c-myc-1. This switch is enhanced in cells lacking GCN2, the protein kinase linking amino acid stress to phosphorylation and inhibition of eif2. Induction of upstream CUG start site usage in c-myc by restriction of proline utilization depends on the proximity of proline codons downstream of the canonical AUG start site. These observations support a model in which the stalling of an elongating ribosome near a canonical start leads to the accumulation of a ribosome queue that facilitates initiation at an upstream non-canonical start site. We find similar effects associated with deprivation of amino acids other than proline, and isoform changes with ATF-3 as well as c-myc. These findings suggest a broad mechanism by which amino acid stress can regulate translation initiation site use to modify the N-terminal proteome.

cell biology↗

The secreted tyrosine kinase VLK is essential for normal platelet activation and thrombus formation

Tyrosine phosphorylation of extracellular proteins is observed in cell cultures and in vivo, but little is known about the functional roles of tyrosine phosphorylation of extracellular proteins. Vertebrate Lonesome Kinase (VLK) is a broadly expressed secretory pathway tyrosine kinase present in platelet [a]-granules. It is released from platelets upon activation and phosphorylates substrates extracellularly. Its role in platelet function, however, has not been previously studied. In human platelets, we identified phosphorylated tyrosines mapped to luminal or extracellular domains of transmembrane and secreted proteins implicated in the regulation of platelet activation. To determine the role of VLK in extracellular tyrosine phosphorylation and platelet function, we generated mice with a megakaryocyte/platelet-specific deficiency of VLK. Platelets from these mice are normal in abundance and morphology, but have dramatic changes in function both in vitro and in vivo. Resting and thrombin-stimulated VLK-deficient platelets demonstrate a significant decrease of several tyrosine phosphobands. Functional testing of VLK-deficient platelets shows decreased PAR4- and collagen-mediated platelet aggregation, but normal responses to ADP. Dense granule and -granule release are reduced in these platelets. Furthermore, VLK-deficient platelets exhibit decreased PAR4-mediated Akt (S473) and Erk1/2(T202/Y204) phosphorylation, indicating altered proximal signaling. In vivo, mice lacking VLK in megakaryocytes/platelets demonstrate strongly reduced platelet accumulation and fibrin formation following laser-injury of cremaster arterioles compared to controls. These studies demonstrate that the secretory pathway tyrosine kinase VLK is critical for stimulus-dependent platelet activation and thrombus formation, providing the first evidence that a secreted protein kinase is required for normal platelet function.

cell biology↗