Attachment style moderates partner presence effects on pain : A laser-evoked potentials study

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly citedSocial support is crucial for psychological and physical well-being. Yet, in experimental and clinical pain research, the presence of others has been found to both attenuate and intensify pain. To investigate the factors underlying these mixed effects, we administered noxious laser stimuli to 39 healthy women while their romantic partner was present or absent, and measured pain ratings and laser-evoked potentials to assess the effects of partner presence on subjective pain experience and underlying neural processes. Further, we examined whether individual differences in adult attachment style, alone or in interaction with the partner's level of attentional focus (manipulated to be either on or away from the participant) might modulate these effects. We found that the effects of partner presence versus absence on pain-related measures depended on adult attachment style but not partner attentional focus. The higher participants' attachment avoidance, the higher pain ratings and N2 and P2 local peak amplitudes were in the presence compared to the absence of the romantic partner. As laser-evoked potentials are thought to reflect activity relating to the salience of events, our data suggest that partner presence may influence the perceived salience of events threatening the body, particularly in individuals who tend to mistrust others.Peer reviewedFinal Published versio

Global Scale Dissemination of ST93: A Divergent Staphylococcus aureus Epidemic Lineage That Has Recently Emerged From Remote Northern Australia.

Background: In Australia, community-associated methicillin-resistant Staphylococcus aureus (MRSA) lineage sequence type (ST) 93 has rapidly risen to dominance since being described in the early 1990s. We examined 459 ST93 genome sequences from Australia, New Zealand, Samoa, and Europe to investigate the evolutionary history of ST93, its emergence in Australia and subsequent spread overseas. Results: Comparisons with other S. aureus genomes indicate that ST93 is an early diverging and recombinant lineage, comprising of segments from the ST59/ST121 lineage and from a divergent but currently unsampled Staphylococcal population. However, within extant ST93 strains limited genetic diversity was apparent with the most recent common ancestor dated to 1977 (95% highest posterior density 1973-1981). An epidemic ST93 population arose from a methicillin-susceptible progenitor in remote Northern Australia, which has a proportionally large Indigenous population, with documented overcrowded housing and a high burden of skin infection. Methicillin-resistance was acquired three times in these regions, with a clade harboring a staphylococcal cassette chromosome mec (SCCmec) IVa expanding and spreading to Australia's east coast by 2000. We observed sporadic and non-sustained introductions of ST93-MRSA-IVa to the United Kingdom. In contrast, in New Zealand, ST93-MRSA-IVa was sustainably transmitted with clonal expansion within the Pacific Islander population, who experience similar disadvantages as Australian Indigenous populations. Conclusion: ST93 has a highly recombinant genome including portions derived from an early diverging S. aureus population. Our findings highlight the need to understand host population factors in the emergence and spread of antimicrobial resistant community pathogens

<i>HLA</i> and autoantibodies define scleroderma subtypes and risk in African and European Americans and suggest a role for molecular mimicry

Systemic sclerosis (SSc) is a clinically heterogeneous autoimmune disease characterized by mutually exclusive autoantibodies directed against distinct nuclear antigens. We examined HLA associations in SSc and its autoantibody subsets in a large, newly recruited African American (AA) cohort and among European Americans (EA). In the AA population, the African ancestry-predominant HLA-DRB1*08:04 and HLA-DRB1*11:02 alleles were associated with overall SSc risk, and the HLA-DRB1*08:04 allele was strongly associated with the severe antifibrillarin (AFA) antibody subset of SSc (odds ratio = 7.4). These African ancestry-predominant alleles may help explain the increased frequency and severity of SSc among the AA population. In the EA population, the HLA-DPB1*13:01 and HLA-DRB1*07:01 alleles were more strongly associated with antitopoisomerase (ATA) and anticentromere antibody-positive subsets of SSc, respectively, than with overall SSc risk, emphasizing the importance of HLA in defining autoantibody subtypes. The association of the HLA-DPB1*13:01 allele with the ATA+ subset of SSc in both AA and EA patients demonstrated a transancestry effect. A direct correlation between SSc prevalence and HLA-DPB1*13:01 allele frequency in multiple populations was observed (r = 0.98, P = 3 × 10−6). Conditional analysis in the autoantibody subsets of SSc revealed several associated amino acid residues, mostly in the peptide-binding groove of the class II HLA molecules. Using HLA &#x3B1; / &#x3B2; allelic heterodimers, we bioinformatically predicted immunodominant peptides of topoisomerase 1, fibrillarin, and centromere protein A and discovered that they are homologous to viral protein sequences from the Mimiviridae and Phycodnaviridae families. Taken together, these data suggest a possible link between HLA alleles, autoantibodies, and environmental triggers in the pathogenesis of SSc

Meraculous: De Novo Genome Assembly with Short Paired-End Reads

We describe a new algorithm, meraculous, for whole genome assembly of deep paired-end short reads, and apply it to the assembly of a dataset of paired 75-bp Illumina reads derived from the 15.4 megabase genome of the haploid yeast Pichia stipitis. More than 95% of the genome is recovered, with no errors; half the assembled sequence is in contigs longer than 101 kilobases and in scaffolds longer than 269 kilobases. Incorporating fosmid ends recovers entire chromosomes. Meraculous relies on an efficient and conservative traversal of the subgraph of the k-mer (deBruijn) graph of oligonucleotides with unique high quality extensions in the dataset, avoiding an explicit error correction step as used in other short-read assemblers. A novel memory-efficient hashing scheme is introduced. The resulting contigs are ordered and oriented using paired reads separated by ∼280 bp or ∼3.2 kbp, and many gaps between contigs can be closed using paired-end placements. Practical issues with the dataset are described, and prospects for assembling larger genomes are discussed

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels

Sequence element enrichment analysis to determine the genetic basis of bacterial phenotypes

Peer reviewe

Atlas of group A streptococcal vaccine candidates compiled using large-scale comparative genomics.

Group A Streptococcus (GAS; Streptococcus pyogenes) is a bacterial pathogen for which a commercial vaccine for humans is not available. Employing the advantages of high-throughput DNA sequencing technology to vaccine design, we have analyzed 2,083 globally sampled GAS genomes. The global GAS population structure reveals extensive genomic heterogeneity driven by homologous recombination and overlaid with high levels of accessory gene plasticity. We identified the existence of more than 290 clinically associated genomic phylogroups across 22 countries, highlighting challenges in designing vaccines of global utility. To determine vaccine candidate coverage, we investigated all of the previously described GAS candidate antigens for gene carriage and gene sequence heterogeneity. Only 15 of 28 vaccine antigen candidates were found to have both low naturally occurring sequence variation and high (>99%) coverage across this diverse GAS population. This technological platform for vaccine coverage determination is equally applicable to prospective GAS vaccine antigens identified in future studies

Measuring factors that influence the utilisation of preventive care services provided by general practitioners in Australia

Background: Relatively little research attention has been given to the development of standardised and psychometrically sound scales for measuring influences relevant to the utilisation of health services. This study aims to describe the development, validation and internal reliability of some existing and new scales to measure factors that are likely to influence utilisation of preventive care services provided by general practitioners in Australia.----- Methods: Relevant domains of influence were first identified from a literature review and formative research. Items were then generated by using and adapting previously developed scales and published findings from these. The new items and scales were pre-tested and qualitative feedback was obtained from a convenience sample of citizens from the community and a panel of experts. Principal Components Analyses (PCA) and internal reliability testing (Cronbach's alpha) were then conducted for all of the newly adapted or developed scales utilising data collected from a self-administered mailed survey sent to a randomly selected population-based sample of 381 individuals (response rate 65.6 per cent).----- Results: The PCA identified five scales with acceptable levels of internal consistency were: (1) social support (ten items), alpha 0.86; (2) perceived interpersonal care (five items), alpha 0.87, (3) concerns about availability of health care and accessibility to health care (eight items), alpha 0.80, (4) value of good health (five items), alpha 0.79, and (5) attitudes towards health care (three items), alpha 0.75.----- Conclusion The five scales are suitable for further development and more widespread use in research aimed at understanding the determinants of preventive health services utilisation among adults in the general population

HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures.

Approximately 1-5% of breast cancers are attributed to inherited mutations in BRCA1 or BRCA2 and are selectively sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors. In other cancer types, germline and/or somatic mutations in BRCA1 and/or BRCA2 (BRCA1/BRCA2) also confer selective sensitivity to PARP inhibitors. Thus, assays to detect BRCA1/BRCA2-deficient tumors have been sought. Recently, somatic substitution, insertion/deletion and rearrangement patterns, or 'mutational signatures', were associated with BRCA1/BRCA2 dysfunction. Herein we used a lasso logistic regression model to identify six distinguishing mutational signatures predictive of BRCA1/BRCA2 deficiency. A weighted model called HRDetect was developed to accurately detect BRCA1/BRCA2-deficient samples. HRDetect identifies BRCA1/BRCA2-deficient tumors with 98.7% sensitivity (area under the curve (AUC) = 0.98). Application of this model in a cohort of 560 individuals with breast cancer, of whom 22 were known to carry a germline BRCA1 or BRCA2 mutation, allowed us to identify an additional 22 tumors with somatic loss of BRCA1 or BRCA2 and 47 tumors with functional BRCA1/BRCA2 deficiency where no mutation was detected. We validated HRDetect on independent cohorts of breast, ovarian and pancreatic cancers and demonstrated its efficacy in alternative sequencing strategies. Integrating all of the classes of mutational signatures thus reveals a larger proportion of individuals with breast cancer harboring BRCA1/BRCA2 deficiency (up to 22%) than hitherto appreciated (∼1-5%) who could have selective therapeutic sensitivity to PARP inhibition