Manipulation of subsurface carbon nanoparticles in Bi2Sr2CaCu2O8+δ using a scanning tunneling microscope

We present evidence that subsurface carbon nanoparticles in Bi2Sr2CaCu2O8+δ can be manipulated with nanometer precision using a scanning tunneling microscope. High-resolution images indicate that most of the carbon particles remain subsurface after transport observable as a local increase in height as the particle pushes up on the surface. Tunneling spectra in the vicinity of these protrusions exhibit semiconducting characteristics with a band gap of approximately 1.8 eV, indicating that the incorporation of carbon locally alters the electronic properties near the surface

Toxin release by conditional remodelling of ParDE1 from Mycobacterium tuberculosis leads to gyrase inhibition

Mycobacterium tuberculosis, the causative agent of tuberculosis, is a growing threat to global health, with recent efforts towards its eradication being reversed in the wake of the COVID-19 pandemic. Increasing resistance to gyrase-targeting second-line fluoroquinolone antibiotics indicates the necessity to develop both novel therapeutics and our understanding of M. tuberculosis growth during infection. ParDE toxin–antitoxin systems also target gyrase and are regulated in response to both host-associated and drug-induced stress during infection. Here, we present microbiological, biochemical, structural, and biophysical analyses exploring the ParDE1 and ParDE2 systems of M. tuberculosis H37Rv. The structures reveal conserved modes of toxin–antitoxin recognition, with complex-specific interactions. ParDE1 forms a novel heterohexameric ParDE complex, supported by antitoxin chains taking on two distinct folds. Curiously, ParDE1 exists in solution as a dynamic equilibrium between heterotetrameric and heterohexameric complexes. Conditional remodelling into higher order complexes can be thermally driven in vitro. Remodelling induces toxin release, tracked through concomitant inhibition and poisoning of gyrase activity. Our work aids our understanding of gyrase inhibition, allowing wider exploration of toxin–antitoxin systems as inspiration for potential therapeutic agents

Relational practices and reflexivity: Exploring the responses of women entrepreneurs to changing household dynamics

This qualitative study explores how and why women, positioned as mothers, wives, or carers, navigate changing household dynamics, related to care and reproductive resources, and become entrepreneurial. Drawing on relational reflexivity, we show how women’s embodied, intimate relations with important others in the household form the focal point for entrepreneurial activities and offer evidence of their entrepreneurial agency. Our analysis reveals the emergence of three relational practices that result in a new venture as the entrepreneurial response of women. We critically evaluate normative analyses on gender, entrepreneurship, and household

Physical activity as a treatment for depression: the TREAD randomised trial protocol

Depression is one of the most common reasons for consulting a General Practitioner (GP) within the UK. Whilst antidepressants have been shown to be clinically effective, many patients and healthcare professionals would like to access other forms of treatment as an alternative or adjunct to drug therapy for depression. A recent systematic review presented some evidence that physical activity could offer one such option, although further investigation is needed to test its effectiveness within the context of the National Health Service.The aim of this paper is to describe the protocol for a randomised, controlled trial (RCT) designed to evaluate an intervention developed to increase physical activity as a treatment for depression within primary care

Identification of Novel Proteins in Neospora caninum Using an Organelle Purification and Monoclonal Antibody Approach

Neospora caninum is an important veterinary pathogen that causes abortion in cattle and neuromuscular disease in dogs. Neospora has also generated substantial interest because it is an extremely close relative of the human pathogen Toxoplasma gondii, yet does not appear to infect humans. While for Toxoplasma there are a wide array of molecular tools and reagents available for experimental investigation, relatively few reagents exist for Neospora. To investigate the unique biological features of this parasite and exploit the recent sequencing of its genome, we have used an organelle isolation and monoclonal antibody approach to identify novel organellar proteins and develop a wide array of probes for subcellular localization. We raised a panel of forty-six monoclonal antibodies that detect proteins from the rhoptries, micronemes, dense granules, inner membrane complex, apicoplast, mitochondrion and parasite surface. A subset of the proteins was identified by immunoprecipitation and mass spectrometry and reveal that we have identified and localized many of the key proteins involved in invasion and host interaction in Neospora. In addition, we identified novel secretory proteins not previously studied in any apicomplexan parasite. Thus, this organellar monoclonal antibody approach not only greatly enhances the tools available for Neospora cell biology, but also identifies novel components of the unique biological characteristics of this important veterinary pathogen

Psychological distress during pregnancy in a multi-ethnic community: findings from the born in Bradford cohort study

Purpose: Antenatal anxiety and depression are predictive of future mental distress, which has negative effects on children. Ethnic minority women are more likely to have a lower socio-economic status (SES) but it is unclear whether SES is an independent risk factor for mental health in pregnancy. We described the association between maternal mental distress and socio-demographic factors in a multi-ethnic cohort located in an economically deprived city in the UK. Methods: We defined eight distinct ethno-language groups (total N = 8,454) and classified a threshold of distress as the 75th centile of within-group GHQ-28 scores, which we used as the outcome for univariate and multivariate logistic regression for each ethnic group and for the sample overall. Results: Financial concerns were strongly and independently associated with worse mental health for six out of the eight ethnic groups, and for the cohort overall. In some groups, factors such as working status, education and family structure were associated with worse mental health, but for others these factors were of little importance. Conclusions: The diversity between and within ethnic groups in this sample underlines the need to take into consideration individual social, migration and economic circumstances and their potential effect on mental health in ethnically diverse areas

Overt Visual Attention as a Causal Factor of Perceptual Awareness

Our everyday conscious experience of the visual world is fundamentally shaped by the interaction of overt visual attention and object awareness. Although the principal impact of both components is undisputed, it is still unclear how they interact. Here we recorded eye-movements preceding and following conscious object recognition, collected during the free inspection of ambiguous and corresponding unambiguous stimuli. Using this paradigm, we demonstrate that fixations recorded prior to object awareness predict the later recognized object identity, and that subjects accumulate more evidence that is consistent with their later percept than for the alternative. The timing of reached awareness was verified by a reaction-time based correction method and also based on changes in pupil dilation. Control experiments, in which we manipulated the initial locus of visual attention, confirm a causal influence of overt attention on the subsequent result of object perception. The current study thus demonstrates that distinct patterns of overt attentional selection precede object awareness and thereby directly builds on recent electrophysiological findings suggesting two distinct neuronal mechanisms underlying the two phenomena. Our results emphasize the crucial importance of overt visual attention in the formation of our conscious experience of the visual world

Generalised Anxiety Disorder – A Twin Study of Genetic Architecture, Genome-Wide Association and Differential Gene Expression

Generalised Anxiety Disorder (GAD) is a common anxiety-related diagnosis, affecting approximately 5% of the adult population. One characteristic of GAD is a high degree of anxiety sensitivity (AS), a personality trait which describes the fear of arousal-related sensations. Here we present a genome-wide association study of AS using a cohort of 730 MZ and DZ female twins. The GWAS showed a significant association for a variant within the RBFOX1 gene. A heritability analysis of the same cohort also confirmed a significant genetic component with h2 of 0.42. Additionally, a subset of the cohort (25 MZ twins discordant for AS) was studied for evidence of differential expression using RNA-seq data. Significant differential expression of two exons with the ITM2B gene within the discordant MZ subset was observed, a finding that was replicated in an independent cohort. While previous research has shown that anxiety has a high comorbidity with a variety of psychiatric and neurodegenerative disorders, our analysis suggests a novel etiology specific to AS

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio