ChanFAD: A Functional Annotation Database for Ion Channels.

Ion channels are integral membrane protein complexes critical for regulation of membrane potential, cell volume, and other signaling events. As complex molecular assemblies with many interacting partners, ion channels have multiple structural and functional domains. While channel sequence and functional data are readily available across multiple online resources, there is an unmet need for functional annotation directly relating primary sequence information, 2D interactions, and three-dimensional protein structure. To this end, we present ChanFAD (Channel Functional Annotation Database), to provide the research community with a centralized resource for ion channel structure and functional data. ChanFAD provides functional annotation of PDB structures built on the National Center for Biotechnology Information's iCn3D structure viewing tool while providing additional information such as primary sequence, organism, and relevant links to other databases. Here we provide a brief tour of ChanFAD functionality while showing example use cases involving drug-channel interactions and structural changes based on mutation. ChanFAD is freely available and can be accessed at https://www.chanfad.org/.

CoV-RBD121-NP Vaccine Candidate Protects against Symptomatic Disease following SARS-CoV-2 Challenge in K18-hACE2 Mice and Induces Protective Responses That Prevent COVID-19-Associated Immunopathology.

We developed a SARS-CoV-2 vaccine candidate (CoV-RBD121-NP) comprised of a tobacco mosaic virus-like nanoparticle conjugated to the receptor-binding domain of the spike glycoprotein of SARS-CoV-2 fused to a human IgG1 Fc domain. CoV-RBD121-NP elicits strong antibody responses in C57BL/6 mice and is stable for up to 12 months at 2-8 or 22-28 °C. Here, we showed that this vaccine induces a strong neutralizing antibody response in K18-hACE2 mice. Furthermore, we demonstrated that immunization protects mice from virus-associated mortality and symptomatic disease. Our data indicated that a sufficient pre-existing pool of neutralizing antibodies is required to restrict SARS-CoV-2 replication upon exposure and prevent induction of inflammatory mediators associated with severe disease. Finally, we identified a potential role for CXCL5 as a protective cytokine in SARS-CoV-2 infection. Our results suggested that disruption of the CXCL5 and CXCL1/2 axis may be important early components of the inflammatory dysregulation that is characteristic of severe cases of COVID-19.

Stability of plasmid and viral banks supporting the cGMP manufacture of Q-Griffithsin from a TMV-based viral vector.

The "whole genome" TMV-based expression system, Geneware®, was used in the cGMP production of the plant-made pharmaceutical Q-Griffithsin and demonstrates stable expression for up to a two-year period. Virion and plasmid banks which contained viral cDNA and a Q-Griffithsin sequence were able to produce >200 g of Q-Griffithsin. Data assessing the quality and stability of the product banks were measured through functional assessments of visual symptomology and product expression.

The bi-pedal ape: plasticity and asymmetry in footedness.

A strong preference for using the right foot for skilled activities parallels a similar side bias for hand use. However, many neuropsychologists, sports scientists and sports commentators argue that right-foot bias in soccer is reduced or even eliminated by practice. This sort of plasticity is an important component of the principle genetic theories of handedness, yet very little is known about the relative asymmetries in the many unipedal skills required in soccer at amateur or professional levels. The first study examined self-report of hand and foot bias in a sample (n=400) of amateur soccer players, in addition to information about their practice with the non-preferred foot. A second study quantified foot use on the pitch in a large sample (n=426) of professional soccer players. The majority of the amateurs reported a right-foot bias that is very similar to that seen in the general population ( approximately 80%). However they only endorse strong biases for "closed" (self-paced) soccer actions like penalty and other free kicks, which give players unlimited time and space for preparation and execution. Although there was a very slight tendency for less right-foot bias in the professionals ( approximately 75%), as assessed by actual foot use rather than questionnaire, few players show anything like what could be described as two-footed play. This bias, unlike in the reports of amateurs, were for all of the behaviours investigated, not just so-called "skilled" behaviours. Finally, when outcomes of preferred and non-preferred foot behaviours were contrasted, the professionals were remarkably adept on those rare occasions when they use their non-preferred foot, suggesting that skill cannot explain asymmetry of choice. These results are discussed in terms of 1) limitations of self-report on questionnaires for predicting actual on the field behaviour, 2) the surprising absence of plasticity in foot use, given the importance of learning, experience and culture in models of handedness and footedness, and 3) a left hemisphere lateralised intentional system as important for the selection of movements as for their execution.