RCSB Protein Data Bank: Enabling biomedical research and drug discovery

Analyses of publicly available structural data reveal interesting insights into the impact of the three‐dimensional (3D) structures of protein targets important for discovery of new drugs (e.g., G‐protein‐coupled receptors, voltage‐gated ion channels, ligand‐gated ion channels, transporters, and E3 ubiquitin ligases). The Protein Data Bank (PDB) archive currently holds > 155,000 atomic‐level 3D structures of biomolecules experimentally determined using crystallography, nuclear magnetic resonance spectroscopy, and electron microscopy. The PDB was established in 1971 as the first open‐access, digital‐data resource in biology, and is now managed by the Worldwide PDB partnership (wwPDB; wwPDB.org ). US PDB operations are the responsibility of the Research Collaboratory for Structural Bioinformatics PDB (RCSB PDB). The RCSB PDB serves millions of RCSB.org users worldwide by delivering PDB data integrated with ～40 external biodata resources, providing rich structural views of fundamental biology, biomedicine, and energy sciences. Recently published work showed that the PDB archival holdings facilitated discovery of ～90% of the 210 new drugs approved by the US Food and Drug Administration 2010–2016. We review user‐driven development of RCSB PDB services, examine growth of the PDB archive in terms of size and complexity, and present examples and opportunities for structure‐guided drug discovery for challenging targets (e.g., integral membrane proteins).     

Reconstruction of the absorption spectrum of Synechocystis sp. PCC 6803 optical mutants from the in vivo signature of individual pigments

Photosynthesis Research - In this work, we reconstructed the absorption spectrum of different Synechocystis sp. PCC 6803 optical strains by summing the computed signature of all pigments present in...     

Follicular growth and sex steroids in adult females of the endemic Amazonian freshwater stingray Potamotrygon wallacei (Chondrichthyes,Potamotrygonidae)

Environmental Biology of Fishes - This study evaluated how the plasma steroid hormones testosterone (T) and 17β-estradiol (E2) are related to follicular development in regenerating females of...     

Conventional single-chamber pacemakers versus transcatheter pacing systems in a “real world” cohort of patients: A comparative prospective single-center study

PurposeDespite the developments in conventional transvenous pacemakers (VVI-PM), the procedure is still associated with significant complications. Although there are no prospective clinical trials that compared VVI-PM with transcatheter pacemaker systems (TPS).MethodsThis is a prospective, observational, single-center study that included all patients with an indication for a single-chamber pacemaker implant within a 4-year period. All clinical, ECG and echocardiographic characteristics at implant, electrical parameters, associated complications and mortality were analyzed. A Cox survival model and a Bayesian cohort analysis were performed for differences in complication rates between groups.ResultsThere were 443 patients included (198 TPS and 245 VVI-PM). The mean age was 81.5 years (TPS group, 79.2 ± 6.6 years; VVI-PM group, 83.5 ± 8.9 years). There was a male predominance in TPS group (123, 62.1% vs. 67, 27.3%; p < 0.001). The presence of systolic dysfunction and renal insufficiency were more frequent in VVI-PM group than in TPS patients. Mean follow-up was 22.3 ± 15.9 months. In a multivariable paired data the TPS group presented fewer complications than VVI-PM group (HR = 0.39 [0.15–0.98], p-value 0.013), but major complications were not different (6, 3% vs 14, 5.6% respectively, p = 0.1761). There was no difference in the mortality rate between the groups. The TPS group had less risk than VVI-PM group to have a complication, with a 96% of probability.ConclusionsTPS patients had a lower overall complication rate than VVI-PM patients including matched-pair samples using a Bayesian analysis. These results confirm the safety profile of TPS in clinical practice.     

A new species of pikeblenny (Blenniiformes: Chaenopsidae: Chaenopsis) from the tropical eastern Pacific and a key to all species

The genus Chaenopsis presently includes 10 species, four in the eastern Pacific and six in the western Atlantic. Five individuals of an undescribed species of this genus were obtained at Gorgona Island in the eastern Pacific of Colombia, in depths between 3 and 5 m. This new species differs from all the Eastern Pacific species in an array of traits including meristic, coloration and morphometric characters. Chaenopsis celeste new species differs from its only sympatric species, C. deltarrhis, in having fewer pectoral rays, fewer dorsal spines and more dorsal-fin soft rays and anal-fin elements. This new species is found over shallow sandy, rubble and small rocks bottoms from Costa Rica to Colombia.     

Molecular dating for phylogenies containing a mix of populations and species by using Bayesian and RelTime approaches

Simultaneous molecular dating of population and species divergences is essential in many biological investigations, including phylogeography, phylodynamics and species delimitation studies. In these investigations, multiple sequence alignments consist of both intra‐ and interspecies samples (mixed samples). As a result, the phylogenetic trees contain interspecies, interpopulation and within‐population divergences. Bayesian relaxed clock methods are often employed in these analyses, but they assume the same tree prior for both inter‐ and intraspecies branching processes and require specification of a clock model for branch rates (independent vs. autocorrelated rates models). We evaluated the impact of a single tree prior on Bayesian divergence time estimates by analysing computer‐simulated data sets. We also examined the effect of the assumption of independence of evolutionary rate variation among branches when the branch rates are autocorrelated. Bayesian approach with coalescent tree priors generally produced excellent molecular dates and highest posterior densities with high coverage probabilities. We also evaluated the performance of a non‐Bayesian method, RelTime, which does not require the specification of a tree prior or a clock model. RelTime's performance was similar to that of the Bayesian approach, suggesting that it is also suitable to analyse data sets containing both populations and species variation when its computational efficiency is needed.     

A Highlights from MBoC Selection: β1 integrin regulates Arg to promote invadopodial maturation and matrix degradation

β1 integrin has been shown to promote metastasis in a number of tumor models, including breast, ovarian, pancreatic, and skin cancer; however, the mechanism by which it does so is poorly understood. Invasive membrane protrusions called invadopodia are believed to facilitate extracellular matrix degradation and intravasation during metastasis. Previous work showed that β1 integrin localizes to invadopodia, but its role in regulating invadopodial function has not been well characterized. We find that β1 integrin is required for the formation of mature, degradation-competent invadopodia in both two- and three-dimensional matrices but is dispensable for invadopodium precursor formation in metastatic human breast cancer cells. β1 integrin is activated during invadopodium precursor maturation, and forced β1 integrin activation enhances the rate of invadopodial matrix proteolysis. Furthermore, β1 integrin interacts with the tyrosine kinase Arg and stimulates Arg-dependent phosphorylation of cortactin on tyrosine 421. Silencing β1 integrin with small interfering RNA completely abrogates Arg-dependent cortactin phosphorylation and cofilin-dependent barbed-end formation at invadopodia, leading to a significant decrease in the number and stability of mature invadopodia. These results describe a fundamental role for β1 integrin in controlling actin polymerization–dependent invadopodial maturation and matrix degradation in metastatic tumor cells.