Identification of T-cell antigens specific for latent mycobacterium tuberculosis infection.

BACKGROUND: T-cell responses against dormancy-, resuscitation-, and reactivation-associated antigens of Mycobacterium tuberculosis are candidate biomarkers of latent infection in humans. METHODOLOGY/PRINCIPAL FINDINGS: We established an assay based on two rounds of in vitro restimulation and intracellular cytokine analysis that detects T-cell responses to antigens expressed during latent M. tuberculosis infection. Comparison between active pulmonary tuberculosis (TB) patients and healthy latently M. tuberculosis-infected donors (LTBI) revealed significantly higher T-cell responses against 7 of 35 tested M. tuberculosis latency-associated antigens in LTBI. Notably, T cells specific for Rv3407 were exclusively detected in LTBI but not in TB patients. The T-cell IFNgamma response against Rv3407 in individual donors was the most influential factor in discrimination analysis that classified TB patients and LTBI with 83% accuracy using cross-validation. Rv3407 peptide pool stimulations revealed distinct candidate epitopes in four LTBI. CONCLUSIONS: Our findings further support the hypothesis that the latency-associated antigens can be exploited as biomarkers for LTBI

Lipid-Based Passivation in Nanofluidics

Stretching DNA in nanochannels is a useful tool for direct, visual studies of genomic DNA at the single molecule level. To facilitate the study of the interaction of linear DNA with proteins in nanochannels, we have implemented a highly effective passivation scheme based on lipid bilayers. We demonstrate virtually complete long-term passivation of nanochannel surfaces to a range of relevant reagents, including streptavidin-coated quantum dots, RecA proteins, and RecA-DNA complexes. We show that the performance of the lipid bilayer is significantly better than that of standard bovine serum albumin-based passivation. Finally, we show how the passivated devices allow us to monitor single DNA cleavage events during enzymatic degradation by DNase I. We expect that our approach will open up for detailed, systematic studies of a wide range of protein-DNA interactions with high spatial and temporal resolution

The DINGO dataset: a comprehensive set of data for the SAMPL challenge

Part of the latest SAMPL challenge was to predict how a small fragment library of 500 commercially available compounds would bind to a protein target. In order to assess the modellers’ work, a reasonably comprehensive set of data was collected using a number of techniques. These included surface plasmon resonance, isothermal titration calorimetry, protein crystallization and protein crystallography. Using these techniques we could determine the kinetics of fragment binding, the energy of binding, how this affects the ability of the target to crystallize, and when the fragment did bind, the pose or orientation of binding. Both the final data set and all of the raw images have been made available to the community for scrutiny and further work. This overview sets out to give the parameters of the experiments done and what might be done differently for future studies

Aboriginal and Torres Strait Islander Suicide in Context

Aboriginal and Torres Strait Islander suicide has been an issue of national public health and mental health concern for only one decade, having increased dramatically from levels that were very low in the late 1980s to levels of young adult male suicide that are now substantially higher than for the non-indigenous population. In this review the authors socially and historically contextualize these changes, identifying the causal frameworks adopted in developing interventions, and present an explanation in narrative and pictorial form that draws on critical family-centered trauma

Health Industries in the Twentieth Century. Introduction

This article is the introduction to the special issue' Health Industries in the Twentieth Century'. It offers a broad literature review of scholarly works about the history of health and medicine, and stresses the opportunities for business historians to tackle the field of healthcare

The State Socialist Mortality Syndrome

Death rates for working-age men in European state socialist countries deviated from general improvements in survival observed in the rest of Europe during the 20th century. The magnitude of structural labor force changes across countries correlates with lagged increases in death rates for men in the working ages. This pattern is consistent with a hypothesis that hyper-development of heavy industry and stagnation (even contraction) of the service sector created anomic conditions leading to unhealthy lifestyles and self-destructive behavior among men moving from primary-sector to secondary-sector occupations. Occupational contrasts within countries similarly show concentration of rising male death rates among blue collar workers. Collapse of state socialist systems produced rapid corrections in labor force structure after 1990, again correlated with a fading of the state socialist mortality syndrome in following decades

The landscape of genetic aberrations in myxofibrosarcoma

Myxofibrosarcoma (MFS) is a rare subtype of sarcoma, whose genetic basis is poorly understood. We analyzed 69 MFS cases using whole-genome (WGS), whole-exome (WES), and/or targeted-sequencing (TS). Newly sequenced genomic data were combined with additional deposited 116 MFS samples. WGS identified a high number of structural variations (SVs) per tumor most frequently affecting the TP53 and RB1 loci, 40% of tumors showed a BRCAness-associated mutation signature, and evidence of chromothripsis was found in all cases. Most frequently mutated /copy number altered genes affected known disease drivers such as TP53 (56.2%), CDKN2A/B (29.7%), RB1 (27.0%), ATRX (19.5%), and HDLBP (18.9%). Several previously unappreciated genetic aberrations including MUC17, FLG, and ZNF780A were identified in more than 20% of patients. Longitudinal analysis of paired diagnosis and relapse time points revealed a 1.2-fold mutation number increase accompanied with substantial changes in clonal composition over time. This study highlights the genetic complexity underlying sarcomagenesis of MFS

Socioeconomic disadvantage in childhood as a predictor of excessive gestational weight gain and obesity in midlife adulthood

BACKGROUND: Lower childhood socioeconomic position is associated with greater risk of adult obesity among women, but not men. Pregnancy-related weight changes may contribute to this gender difference. The objectives of this study were to determine the associations between: 1. childhood socioeconomic disadvantage and midlife obesity; 2. excessive gestational weight gain (GWG) and midlife obesity; and 3. childhood socioeconomic disadvantage and excessive GWG, among a representative sample of childbearing women. METHODS: We constructed marginal structural models for seven measures of childhood socioeconomic position for 4780 parous women in the United States, using National Longitudinal Survey of Youth (1979–2010) data. Institute of Medicine definitions were used for excessive GWG; body mass index ≥30 at age 40 defined midlife obesity. Analyses were separated by race/ethnicity. Additionally, we estimated controlled direct effects of childhood socioeconomic disadvantage on midlife obesity under a condition of never gaining excessively in pregnancy. RESULTS: Low parental education, but not other measures of childhood disadvantage, was associated with greater midlife obesity among non-black non-Hispanic women. Among black and Hispanic mothers, childhood socioeconomic disadvantage was not consistently associated with midlife obesity. Excessive GWG was associated with greater midlife obesity in all racial/ethnic groups. Childhood socioeconomic disadvantage was not statistically significantly associated with excessive GWG in any group. Controlled direct effects were not consistently weaker than total effects. CONCLUSIONS: Childhood socioeconomic disadvantage was associated with adult obesity, but not with excessive gestational weight gain, and only for certain disadvantage measures among non-black non-Hispanic mothers. Prevention of excessive GWG may benefit all groups through reducing obesity, but excessive GWG does not appear to serve as a mediator between childhood socioeconomic position and adult obesity in women