Solid-phase synthesis of a library based on biphenyl-containing trypsin-like serine protease inhibitors

The solid-phase synthesis of a library based on an unusual biphenyl-containing trypsin-like serine protease inhibitor is described. Key to this effort was the synthesis of a highly functionalized aryl boronic acid reagent which required the development of a novel and efficient method to convert a triflate to a pinacolboronate in large scale.     

Variation in rod spectral sensitivity of fishes is best predicted by habitat and depth

Rod spectral sensitivity data (λ_max), measured by microspectrophotometry, were compiled for 403 species of ray-finned fishes in order to examine four hypothesized predictors of rod spectral sensitivity (depth, habitat, diet and temperature). From this database, a subset of species that were known to be adults and available on a published phylogeny (n = 210) were included in analysis, indicating rod λ_max values averaging 503 nm and ranging from 477 to 541 nm. Linear models that corrected for phylogenetic relatedness showed that variation in rod sensitivity was best predicted by habitat and depth, with shorter wavelength λ_max values occurring in fishes found offshore or in the deep sea. Neither diet, nor the interaction of diet and habitat, had significant explanatory power. Although temperature significantly correlated with rod sensitivity, in that fishes in temperate latitudes had longer wavelength rod λ_max values than those in tropical latitudes, sampling inequity and other confounds require the role of the temperature to be studied further. Together, these findings indicate that fish rod λ_max is influenced by several ecological factors, suggesting that selection can act on even small differences in fish spectral sensitivity.     

The Case of Heinrich Wilhelm Poll (1877–1939): A German-Jewish Geneticist, Eugenicist, Twin Researcher, and Victim of the Nazis

This paper uses a reconstruction of the life and career of Heinrich Poll as a window into developments and professional relationships in the biological sciences in Germany in the period from the beginning of the twentieth century to the Nazi seizure of power in 1933. Poll’s intellectual work involved an early transition from morphometric physical anthropology to comparative evolutionary studies, and also found expression in twin research – a field in which he was an acknowledged early pioneer. His advocacy of eugenics led to participation in state-sponsored committees convened to advise on social policy, one of which debated sterilisation and made recommendations that led eventually to the establishment of the notorious Kaiser Wilhelm Institute for Anthropology, Human Heredity and Eugenics. However, his status as a prominent geneticist and, in particular, as a eugenicist had an ironic and ultimately tragic dimension. Heinrich Poll was of Jewish birth, and this resulted in his career being destroyed by an application of the population policies he had helped put in place.     

Negative Coupling as a Mechanism for Signal Propagation between C2 Domains of Synaptotagmin I

Synaptotagmin I (Syt I) is a vesicle-localized protein implicated in sensing the calcium influx that triggers fast synchronous release of neurotransmitter. How Syt I utilizes its two C2 domains to integrate signals and mediate neurotransmission has continued to be a controversial area of research, though prevalent hypotheses favor independent function. Using differential scanning calorimetry and fluorescence lifetime spectroscopy in a thermodynamic denaturation approach, we tested an alternative hypothesis in which both domains interact to cooperatively disseminate binding information. The free energy of stability was determined for C2A, C2B, and C2AB constructs by globally fitting both methods to a two-state model of unfolding. By comparing the additive free energies of C2A and C2B with C2AB, we identified a negative coupling interaction between the C2 domains of Syt I. This interaction not only provides a mechanistic means for propagating signals, but also a possible means for coordinating the molecular events of neurotransmission.     

Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein

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Inertia in an ombrotrophic bog ecosystem in response to 9 years' realistic perturbation by wet deposition of nitrogen,separated by form

Wet deposition of nitrogen (N) occurs in oxidized (nitrate) and reduced (ammonium) forms. Whether one form drives vegetation change more than the other is widely debated, as field evidence has been lacking. We are manipulating N form in wet deposition to an ombrotrophic bog, Whim (Scottish Borders), and here report nine years of results. Ammonium and nitrate were provided in rainwater spray as NH₄Cl or NaNO₃ at 8, 24 or 56 kg N ha^?1 yr^?1, plus a rainwater only control, via an automated system coupled to site meteorology. Detrimental N effects were observed in sensitive nonvascular plant species, with higher cumulative N loads leading to more damage at lower annual doses. Cover responses to N addition, both in relation to form and dose, were species specific and mostly dependent on N dose. Some species were generally indifferent to N form and dose, while others were dose sensitive. Calluna vulgaris showed a preference for higher N doses as ammonium N and Hypnum jutlandicum for nitrate N. However, after 9 years, the magnitude of change from wet deposited N on overall species cover is small, indicating only a slow decline in key species. Nitrogen treatment effects on soil N availability were likewise small and rarely correlated with species cover. Ammonium caused most N accumulation and damage to sensitive species at lower N loads, but toxic effects also occurred with nitrate. However, because different species respond differently to N form, setting of ecosystem level critical loads by N form is challenging. We recommend implementing the lowest value of the critical load range where communities include sensitive nonvascular plants and where ammonium dominates wet deposition chemistry. In the context of parallel assessment at the same site, N treatments for wet deposition showed overall much smaller effects than corresponding inputs of dry deposition as ammonia.