Proteome-Scale Antibody Responses and Outcome of Mycobacterium tuberculosis Infection in Nonhuman Primates and in Tuberculosis Patients

Background.Biomarkers of progression from latent Mycobacterium tuberculosis infection to active tuberculosis are needed. We assessed correlations between infection outcome and antibody responses in macaques and humans by high-throughput, proteome-scale serological studies. Methods.Mycobacterium tuberculosis proteome microarrays were probed with serial sera from macaques representing various infection outcomes and with single-point human sera from tuberculosis suspects. Fluorescence intensity data were analyzed by calculating Z scores and associated P values. Temporal changes in macaque antibody responses were analyzed by polynomial regression. Correlations between human responses and sputum bacillary burden were assessed by quantile and hurdle regression. Results.Macaque outcome groups exhibited distinct antibody profiles: early, transient responses in latent infection and stable antibody increase in active and reactivation disease. In humans, antibody levels and reactive protein numbers increased with bacillary burden. Responses to a subset of 10 proteins were more tightly associated with disease state than reactivity to the broader reactive proteome. Conclusions.Integration of macaque and human data reveals dynamic properties of antibody responses in relation to outcome and leads to actionable findings for translational research. These include the potential of antibody responses to detect acute infection and preclinical tuberculosis and to identify serodiagnostic proteins for the spectrum of bacillary burden in tuberculosis.     

Recruitment of medial prefrontal cortex neurons during alcohol withdrawal predicts cognitive impairment and excessive alcohol drinking

Chronic intermittent access to alcohol leads to the escalation of alcohol intake, similar to binge drinking in humans. Converging lines of evidence suggest that impairment of medial prefrontal cortex (mPFC) cognitive function and overactivation of the central nucleus of the amygdala (CeA) are key factors that lead to excessive drinking in dependence. However, the role of the mPFC and CeA in the escalation of alcohol intake in rats with a history of binge drinking without dependence is currently unknown. To address this issue, we examined FBJ murine osteosarcoma viral oncogene homolog (Fos) expression in the mPFC, CeA, hippocampus, and nucleus accumbens and evaluated working memory and anxiety-like behavior in rats given continuous (24 h/d for 7 d/wk) or intermittent (3 d/wk) access to alcohol (20% vol/vol) using a two-bottle choice paradigm. The results showed that abstinence from alcohol in rats with a history of escalation of alcohol intake specifically recruited GABA and corticotropin-releasing factor (CRF) neurons in the mPFC and produced working memory impairments associated with excessive alcohol drinking during acute (24–72 h) but not protracted (16 –68 d) abstinence. Moreover, abstinence from alcohol was associated with a functional disconnection of the mPFC and CeA but not mPFC and nucleus accumbens. These results show that recruitment of a subset of GABA and CRF neurons in the mPFC during withdrawal and disconnection of the PFC–CeA pathway may be critical for impaired executive control over motivated behavior, suggesting that dysregulation of mPFC interneurons may be an early index of neuroadaptation in alcohol dependence.     

HIV-related conspiracy beliefs and its relationships with HIV testing and unprotected sex among men who have sex with men in Tshwane (Pretoria), South Africa

The objective of this study was to determine extent of HIV conspiracy belief endorsement among men who have sex with men (MSM) in Pretoria, and assess whether endorsement of HIV conspiracy beliefs are associated with inconsistent condom use and never testing for HIV. A cross-sectional survey using respondent-driven sampling was conducted between February and August 2009. A high proportion of respondents endorsed HIV conspiracy beliefs. MSM commonly endorsed beliefs related to AIDS information being held back from the general public (51.0%), HIV being a man-made virus (25.5%), and people being used as guinea pigs in HIV research and with HIV treatments (approximately 20%). Bisexually- or heterosexually-identified MSM were significantly more likely to endorse conspiracy beliefs compared to homosexually-identified MSM (38.5% vs. 14.7%). Endorsing conspiracy beliefs was not associated with unprotected anal intercourse; however, it was significantly associated with not having been HIV tested (AOR: 2.4; 95% CI: 1.1-5.7). Endorsing beliefs in HIV conspiracies reflects a mistrust in government institutions and systems which could be an impediment to seeking HIV-related services, including HIV counseling and testing.     

Electrodeposited nickel–graphene nanocomposite coating: effect of graphene nanoplatelet size on its microstructure and hardness

In this study, the effect of graphene nanoplatelet (GNP) size on the microstructure and hardness of the electrodeposited nickel–graphene nanocomposite coatings were investigated. GNPs with different sizes were prepared by using a high energy ball milling technique. The experimental result revealed the high energy ball milling technique could reduce the size, increase the surface area, and improve the dispersion ability of GNPs. The microstructure, hardness, and components of the nanocomposite coatings were greatly affected by GNP sizes. The highest microhardness was measured to be 273 HV for the nanocomposite coatings containing 5 h-milled GNPs, which is increased up to ∼47% compared to pristine Ni coating. The enhancement in the hardness is attributed to the uniform dispersion of the small GNP sizes inside the Ni matrix and the Ni grain size reduction when using milled GNPs.

The effect of graphene nanoplatelet size on the microstructure and hardness of electrodeposited nickel–graphene nanocomposite coatings was investigated.     

Association between granzyme B and perforin I polymorphisms and allograft outcomes in Hispanic kidney transplant recipients

Granzyme B (GZMB) and perforin 1 gene (PRF1) are key effector molecules of cytotoxic T lymphocytes, in causing acute and chronic solid organ transplant rejection. In this study, we analyzed the impact of GZMB and PRF1 polymorphism on kidney allograft outcomes. In all, 527 de novo kidney Hispanic allograft recipients were genotyped for PRF1 (rs10999426, rs35947132) and GZMB (rs8192917, rs7144366). PRF1 (rs10999426, rs35947132) G alleles and GG genotypes were negatively associated with allograft rejection, demonstrating protection against allograft rejection (OR = 0.61, p = 0.005 for rs1099946; OR = 0.4, p = 0.01 for rs 35947132). On the other hand, the GA heterozygosity of PRF1 was found marginally associated with the rejection group (OR = 1.53, p = 0.05 for rs10999426; OR = 2.24, p = 0.07 for rs35947132). There was a significant increase in allograft survival in time period studied for the PRF1 (rs10999426) GG genotype, while the GA heterozygosity was associated with graft failure. We found no association for polymorphic markers in GZMB gene with allograft rejection. Survival was significantly improved for patients who were homozygous TT for the GZMB (rs8192917) (TT vs. CC/TT, p = 0.041). The result suggests that PRF1 and GZMB gene polymorphisms may determine the incidence of acute rejection or graft survival among Hispanic allograft recipients.     

The Effect of Court Location and Available Time on the Tactical Shot Selection of Elite Squash Players

No previous research in squash has considered the time between shots or the proximity of the ball to a wall, which are two important variables that influence shot outcomes. The aim of this paper was to analyse shot types to determine the extent to which they are played in different court areas and a more detailed analysis to determine whether the time available had an influence on the shot selected. Ten elite matches, contested by fifteen of the world’s top right handed squash players (age 27 ± 3.2, height 1.81 ± 0.06 m, weight 76.3 ± 3.7 kg), at the men’s World Team Championships were processed using the SAGIT/Squash tracking system with shot information manually added to the system. Results suggested that shot responses were dependent upon court location and the time between shots. When these factors were considered repeatable performance existed to the extent that one of two shots was typically played when there was limited time to play the shot (< 1.20s). For example, it was clear that when players did not have a lot of time to hit the ball (low time i.e. < 1.06s, and mid time i.e. 1.06 - 1.20s) in the front left corner close to the side wall, the crosscourt lob was used frequently (44.30% and 36.31% respectively) whereas when there was more time this shot was seldom used (13.64%). Consequently variant and invariant behaviour were shown to exist in elite squash although for the first time it was suggested that the availability of time to play a shot contributed to which of these behaviours was evident. This analysis could be extended by adopting a case study approach to see how individual differences in strategy and tactics affect shot selections.

Key points

• Previous research has suggested that a playing strategy, elements decided in advance of the match, may be evident for elite players by examining court location and preceding shot type, however these parameters alone are unlikely to be sufficient predictors.
• At present there is no known analysis in squash, or indeed in any of the racket sports, that has quantified the time available to respond to different shot types. An understanding of the time interval between shots and the movement characteristics of the player responding to different shots according to the court positions might facilitate a better understanding of the dynamics that determine shot selection.
• Some elements of a general playing strategy were evident e.g. predominately hitting to the back left of the court, but tactical differences in shot selection were also evident on the basis of court location and time available to play a shot.

Key words: Strategy, tactics, SAGIT, invariant behaviour.