Extracellular Vesicles – the next frontier in endocrinology

Extracellular vesicles (EVs) including exosomes are emerging as important carriers of signals in normal and patho- physiology. As EVs are a long-range communication or signaling modality – just like hormones are, the field of endocrinology is uniquely poised to offer insight into their functional biology and regulation. EVs are membrane bound particles secreted by many different cell types and can have local or systemic effects, being transported in body fluids. They express trans-membrane proteins, some of which are shared between EVs and some being specific to the tissue of origin, that can interact with target cells directly (much like hormones can). They also contain cargo within them that includes DNA, RNA, miRNA and various metabolites. They can fuse with target cells to empty their cargo and alter their target cell physiology in this way too. Similar to the endocrine system, the EV system is likely to be under homeostatic control, making the regulation of their biogenesis and secretion important aspects to study. In this review, we briefly highlight select examples of how EVs are implicated in normal physiology and disease states. We also discuss what is known about their biogenesis and regulation of secretion. We hope that this paper inspires the endocrinology field to use our collective expertise to explore these new multi-modal ‘hormones’.

Functional biology in its natural context: A search for emergent simplicity

The immeasurable complexity at every level of biological organization creates a daunting task for understanding biological function. Here, we highlight the risks of stripping it away at the outset and discuss a possible path toward arriving at emergent simplicity of understanding while still embracing the ever-changing complexity of biotic interactions that we see in nature.

Insights into SARS-CoV-2: Medicinal Chemistry Approaches to Combat Its Structural and Functional Biology

Coronavirus disease 2019, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still a pandemic around the world. Currently, specific antiviral drugs to control the epidemic remain deficient. Understanding the details of SARS-CoV-2 structural biology is extremely important for development of antiviral agents that will enable regulation of its life cycle. This review focuses on the structural biology and medicinal chemistry of various key proteins (Spike, ACE2, TMPRSS2, RdRp and Mpro) in the life cycle of SARS-CoV-2, as well as their inhibitors/drug candidates. Representative broad-spectrum antiviral drugs, especially those against the homologous virus SARS-CoV, are summarized with the expectation they will drive the development of effective, broad-spectrum inhibitors against coronaviruses. We are hopeful that this review will be a useful aid for discovery of novel, potent anti-SARS-CoV-2 drugs with excellent therapeutic results in the near future.

Direct and biometrical estimates of the closing force of major claws of the sand fiddler crab Leptuca pugilator (Bosc, 1801) (Decapoda: Brachyura: Ocypodidae): Support for the weakening combatant hypothesis

Many conclusions concerning the functional biology of crab claws rely upon biometrical estimates of closing force, based upon measures of muscle cross-sectional area and mechanical advantage. Fiddler crab closing force patterns show variation with body size, claw size, location of the opposing claw tips, and physiological condition, so we have measured closing force of the sand fiddler crab Leptuca pugilator (Bosc, 1801) as a function of claw size, force exerted at claw tips, and at the commonly well-developed pollex tooth. Leptuca pugilator has an elongated claw with gracile dactyl and pollex. As predicted by biometrical proportions, closing force is greater at the pollex tooth than at the claw tip. The pollex tooth does shift with increasing claw size in relative position toward the claw hinge. Mechanical advantage at the pollex tooth and dactyl tip both decline with increasing claw length. But there is no difference in slope of log closing force as a function of log claw length between the pollex position and terminus of the dactyl, which demonstrates that force exerted at the pollex tooth has no impact on proportional change in closing force with increasing claw size. The log-log slope is ~0.9, reflecting the proportionally decreasing muscle cross-sectional area and lowering mechanical advantage with increasing claw size. For both the pollex tooth and the claw tip, mechanical advantage decreases very slightly with increasing claw size, but closing force proportionally decreases with increasing claw size, supporting the weakening combatant hypothesis for this species.

Developmental innovations promote species diversification in mushroom-forming fungi

Fungi evolved complex fruiting body (‘mushroom’) morphologies as adaptations to efficient spore dispersal in terrestrial habitats. Mushroom-forming fungi (Agaricomycetes) display a graded series of developmental innovations related to fruiting body morphology, however, how these evolved is largely unknown, leaving the functional biology and evolutionary principles of complex multicellularity in the third largest multicellular kingdom poorly known. Here, we show that developmental innovations of mushroom-forming fungi that enclose the spore-producing surface (hymenophore) in a protected environment display significant asymmetry in their evolution and are associated with increased diversification rates. ‘Enclosed’ development and related tissues (partial and universal veils) evolved convergently and became a widespread developmental type in clades in which it emerged. This probably mirrors increased fitness for protected fruiting body initials in terrestrial habitats, by better coping with environmental factors such as desiccation or predators, among others. We observed similar patterns in the evolution of complex hymenophore architectures, such as gills, pores or teeth, which optimize biomass-to-propagule number ratios and were found to spur diversification in mushrooms. Taken together, our results highlight new morphological traits associated with the adaptive radiation of mushroom-forming fungi and present formal phylogenetic testing of hypotheses on the reproductive ecology of a poorly known but hyperdiverse clade.