Pinto, T. | Search bioRxiv

bioRxiv2020

Species traits predict extinction risk across the Tree of Life

SummaryBiodiversity is eroding at unprecedented rates due to human activity1. Species’ trajectories towards extinction are shaped by multiple factors, including life-history traits2 as well as human pressures3. Previous studies linking these factors to extinction risk have been narrow in their taxonomic and geographic scope4, thus limiting the ability for identifying global predictors. We studied the relation between 12 traits and the extinction risk of almost 900 species representing 15 groups across the tree of life (vertebrates, invertebrates and plants) at a global scale. We show that threatened species share narrow habitat breadth, poor dispersal ability, low fecundity, small altitudinal range, and are affected by a large human footprint. Other traits either show contrasting responses among groups (body size, offspring size, and change in human footprint), or relations were found for only a limited number of taxa (generation length, diet breadth, microhabitat). Our study suggests that in the absence of data on the precise distribution and population trends of species, traits can be used as predictors of extinction risk and thus help guide future research, monitoring and conservation efforts.Competing Interest StatementThe authors have declared no competing interest.View Full Text

ecology↗

bioRxiv2020

Fast isolation of sub-nanomolar affinity alpaca nanobody against the Spike RBD of SARS-CoV-2 by combining bacterial display and a simple single-step density gradient selection

Despite unprecedented global efforts to rapidly develop SARS-CoV-2 treatments, in order to reduce the burden placed on health systems, the situation remains critical. Effective diagnosis, treatment, and prophylactic measures are urgently required to meet global demand: recombinant antibodies fulfill these requirements and have marked clinical potential. Here, we describe the fast-tracked development of an alpaca Nanobody specific for the receptor-binding-domain (RBD) of the SARS-CoV-2 Spike protein with therapeutic potential applicability. We present a rapid method for nanobody isolation that includes an optimized immunization regimen coupled with VHH library E. coli surface display, which allows single-step selection of high-affinity nanobodies using a simple density gradient centrifugation of the bacterial library. The selected single and monomeric Nanobody, W25, binds to the SARS-CoV-2 S RBD with sub-nanomolar affinity and efficiently competes with ACE-2 receptor binding. Furthermore, W25 potently neutralizes SARS-CoV-2 wild type and the D614G variant with IC50 values in the nanomolar range, demonstrating its potential as antiviral agent.

molecular biology↗

bioRxiv2019

Binding of Filamentous Actin to CaMKII as a Potential Mechanism for the Regulation of Bidirectional Synaptic Plasticity by betaCaMKII in Cerebellar Purkinje Cells

Calcium-calmodulin dependent protein kinase II (CaMKII) regulates many forms of synaptic plasticity, but little is known about its functional role during plasticity induction in the cerebellum. Experiments have indicated that the {beta} isoform of CaMKII controls the bidirectional inversion of plasticity at parallel fibre (PF)-Purkinje cell (PC) synapses in cerebellar cortex. Because the cellular events that underlie these experimental findings are still poorly understood, we developed a simple computational model to investigate how {beta}CaMKII regulates the direction of plasticity in cerebellar PCs. We present the first model of AMPA receptor phosphorylation that simulates the induction of long-term depression (LTD) and potentiation (LTP) at the PF-PC synapse. Our simulation results suggest that the balance of CaMKII-mediated phosphorylation and protein phosphatase 2B (PP2B)-mediated dephosphorylation of AMPA receptors can determine whether LTD or LTP occurs in cerebellar PCs. The model replicates experimental observations that indicate that {beta}CaMKII controls the direction of plasticity at PF-PC synapses, and demonstrates that the binding of filamentous actin to CaMKII can enable the {beta} isoform of the kinase to regulate bidirectional plasticity at these synapses.\n\nAuthor SummaryMany molecules and the complex interactions between them are involved in synaptic plasticity in the cerebellum. However, the exact relationship between cerebellar plasticity and the different signalling cascades remains unclear. Calcium-calmodulin dependent protein kinase II (CaMKII) is an important component of the signalling network that is responsible for plasticity in cerebellar Purkinje cells (PCs). The CaMKII holoenzyme contains different isoforms such as CaMKII and {beta}CaMKII. Experiments with Camk2b knockout mice that lack the {beta} isoform of CaMKII demonstrated that {beta}CaMKII regulates the direction of plasticity at parallel fibre (PF)-PC synapses. Stimulation protocols that induce long-term depression in wild-type mice, which contain both and {beta}CaMKII, lead to long-term potentiation in knockout mice without {beta}CaMKII, and vice versa. We developed a kinetic simulation of the phosphorylation and dephosphorylation of AMPA receptors by CaMKII and protein phosphatase 2B to investigate how {beta}CaMKII can control bidirectional synaptic plasticity in cerebellar PCs. Our simulation results demonstrate that the binding of filamentous actin to {beta}CaMKII can contribute to the regulation of bidirectional plasticity at PF-PC synapses. Our computational model of intracellular signalling significantly advances the understanding of the mechanisms of synaptic plasticity induction in the cerebellum.

neuroscience↗