Interactive molecular dynamics in virtual reality for accurate flexible protein-ligand docking

Simulating drug binding and unbinding is a challenge, as the rugged energy landscapes that separate bound and unbound states require extensive sampling that consumes significant computational resources. Here, we describe the use of interactive molecular dynamics in virtual reality (iMD-VR) as an accurate low-cost strategy for flexible protein-ligand docking. We outline an experimental protocol which enables expert iMD-VR users to guide ligands into and out of the binding pockets of trypsin, neuraminidase, and HIV-1 protease, and recreate their respective crystallographic protein-ligand binding poses within 5 - 10 minutes. Following a brief training phase, our studies shown that iMD-VR novices were able to generate unbinding and rebinding pathways on similar timescales as iMD-VR experts, with the majority able to recover binding poses within 2.15 Angstrom RMSD of the crystallographic binding pose. These results indicate that iMD-VR affords sufficient control for users to carry out the detailed atomic manipulations required to dock flexible ligands into dynamic enzyme active sites and recover crystallographic poses, offering an interesting new approach for simulating drug docking and generating binding hypotheses.Comment: PLOS ON

'Mindless markers of the nation': The routine flagging of nationhood across the visual environment

The visual environment has increasingly been used as a lens with which to understand wider processes of social and economic change with studies employing in-depth qualitative approaches to focus on, for example, gentrification or trans-national networks. This exploratory paper offers an alternative perspective by using a novel method, quantitative photo mapping, to examine the extent to which a particular socio-cultural marker, the nation, is ‘flagged’ across three contrasting sites in Britain. As a multi-national state with an increasingly diverse population, Britain offers a particularly fruitful case study, drawing in debates around devolution, European integration and Commonwealth migration. In contributing to wider debates around banal nationalism, the paper notes the extent to which nations are increasingly articulated through commerce, consumption and market exchange and the overall significance of everyday markers (signs, objects, infrastructure) in naturalising a national view of the world

Bird’s-eye view of chromosomic evolution in Class Aves

Birds (Aves) are the most speciose of terrestrial vertebrates, displaying Class-specific characteristics yet incredible external phenotypic diversity. Critical to agriculture and as model organisms, birds have adapted to many habitats. The only extant examples of dinosaurs, birds emerged ~150 mya and >10% are currently threatened with extinction

A bird's-eye view of chromosomic evolution in the Class Aves

Birds (Aves) are the most speciose of terrestrial vertebrates, displaying Class-specific characteristics yet incredible external phenotypic diversity. Critical to agriculture and as model organisms, birds have adapted to many habitats. The only extant examples of dinosaurs, birds emerged ~150 mya and >10% are currently threatened with extinction. This review is a comprehensive overview of avian genome (“chromosomic”) organization research based mostly on chromosome painting and BAC-based studies. We discuss traditional and contemporary tools for reliably generating chromosome-level assemblies and analyzing multiple species at a higher resolution and wider phylogenetic distance than previously possible. These results permit more detailed investigations into inter- and intrachromosomal rearrangements, providing unique insights into evolution and speciation mechanisms. The ‘signature’ avian karyotype likely arose ~250 mya and remained largely unchanged in most groups including extinct dinosaurs. Exceptions include Psittaciformes, Falconiformes, Caprimulgiformes, Cuculiformes, Suliformes, occasional Passeriformes, Ciconiiformes, and Pelecaniformes. The reasons for this remarkable conservation may be the greater diploid chromosome number generating variation (the driver of natural selection) through a greater possible combination of gametes and/or an increase in recombination rate. A deeper understanding of avian genomic structure permits the exploration of fundamental biological questions pertaining to the role of evolutionary breakpoint regions and homologous synteny blocks

How Do Price Minimizing Behaviors Impact Smoking Cessation? Findings from the International Tobacco Control (ITC) Four Country Survey

This paper examines how price minimizing behaviors impact efforts to stop smoking. Data on 4,988 participants from the International Tobacco Control Policy Evaluation (ITC) Four-Country Survey who were smokers at baseline (wave 5) and interviewed at a 1 year follow-up were used. We examined whether price minimizing behaviors at baseline predicted: (1) cessation, (2) quit attempts, and (3) successful quit attempts at one year follow up using multivariate logistic regression modeling. A subset analysis included 3,387 participants who were current smokers at waves 5 and 6 and were followed through wave 7 to explore effects of changing purchase patterns on cessation. Statistical tests for interaction were performed to examine the joint effect of SES and price/tax avoidance behaviors on cessation outcomes. Smokers who engaged in any price/tax avoidance behaviors were 28% less likely to report cessation. Persons using low/untaxed sources were less likely to quit at follow up, those purchasing cartons were less likely to make quit attempts and quit, and those using discount cigarettes were less likely to succeed, conditional on making attempts. Respondents who utilized multiple behaviors simultaneously were less likely to make quit attempts and to succeed. SES did not modify the effects of price minimizing behaviors on cessation outcomes. The data from this paper indicate that the availability of lower priced cigarette alternatives may attenuate public health efforts aimed at to reduce reducing smoking prevalence through price and tax increases among all SES groups

Dinosaurs

According to Britannica, dinosaurs are described as “Triceratops, contemporary birds, their most recent common ancestor and all of their descendants.” However, for biologists, it could be simpler to picture dinosaurs as reptiles with hind limbs held erect beneath the trunk, similar to how mammals’ hind limbs are held

Dinosaurs: comparative cytogenomics of their reptile cousins and avian descendants

Simple Summary Dinosaurs have been in scientific and popular culture since early fossil discoveries, but increased interest, particularly in their genomes, is expanding. Birds are reptiles, specifically theropod dinosaurs, meaning that if we compare the genomes of related reptile relations, we can get an idea of what the extinct dinosaur genomes looked like. In all animals/plants/fungi, we think of genome organization in terms of chromosomes. Genes sit on chromosomes and each cell of each individual of each species has its own unique organization. Every gene is in exactly the same spot on each chromosome, organized like continents and islands, with the genes as the cities/ towns/villages. All reptiles apart from crocodilians have both big and small chromosomes in their genomes but birds particularly so, like the Philippines or Polynesia. Birds have ~80 chromosomes (far more than most organisms) and this is very consistent in most species. Recent studies suggest that this pattern was probably established ~255 million years ago as it is also mostly present in some turtles. In other words, most dinosaurs probably had chromosomes (genome organization) like chickens or emus. In this paper, we present ideas of how this may have contributed to dinosaurs being so diverse in appearance and function. Abstract Reptiles known as dinosaurs pervade scientific and popular culture, while interest in their genomics has increased since the 1990s. Birds (part of the crown group Reptilia) are living theropod dinosaurs. Chromosome‐level genome assemblies cannot be made from long‐extinct biological material, but dinosaur genome organization can be inferred through comparative genomics of related extant species. Most reptiles apart from crocodilians have both macro‐ and microchromosomes; comparative genomics involving molecular cytogenetics and bioinformatics has established chromosomal relationships between many species . The capacity of dinosaurs to survive multiple extinction events is now well established, and birds now have more species in comparison with any other terrestrial vertebrate. This may be due, in part, to their karyotypic features, including a distinctive karyotype of around n = 40 (~10 macro and 30 microchromosomes). Similarity in genome organization in distantly related species suggests that the common avian ancestor had a similar karyotype to e.g., the chicken/emu/zebra finch. The close karyotypic similarity to the soft‐shelled turtle (n = 33) suggests that this basic pattern was mostly established before the Testudine–Archosaur divergence, ~255 MYA. That is, dinosaurs most likely had similar karyotypes and their extensive phenotypic variation may have been mediated by increased random chromosome segregation and genetic recombination, which is inherently higher in karyotypes with more and smaller chromosomes

The failure of suicide prevention in primary care: family and GP perspectives - a qualitative study

Background Although Primary care is crucial for suicide prevention, clinicians tend to report completed suicides in their care as non-preventable. We aimed to examine systemic inadequacies in suicide prevention from the perspectives of bereaved family members and GPs.Methods Qualitative study of 72 relatives or close friends bereaved by suicide and 19 General Practitioners who have experienced the suicide of patients.Results Relatives highlight failures in detecting symptoms and behavioral changes and the inability of GPs to understand the needs of patients and their social contexts. A perceived overreliance on anti-depressant treatment is a major source of criticism by family members. GPs tend to lack confidence in the recognition and management of suicidal patients, and report structural inadequacies in service provision.Conclusions Mental health and primary care services must find innovative and ethical ways to involve families in the decision-making process for patients at risk of suicide