Susceptibility to a sexually transmitted disease in a wild koala population shows heritable genetic variance but no inbreeding depression

The koala, one of the most iconic Australian wildlife species, is facing several concomitant threats that are driving population declines. Some threats are well known and have clear methods of prevention (e.g., habitat loss can be reduced with stronger land-clearing control), whereas others are less easily addressed. One of the major current threats to koalas is chlamydial disease, which can have major impacts on individual survival and reproduction rates and can translate into population declines. Effective management strategies for the disease in the wild are currently lacking, and to date we know little about the determinants of individual susceptibility to disease. Here we investigated the genetic basis of variation in susceptibility to chlamydia using one of the most intensively studied wild koala populations. We combined data from veterinary examinations, chlamydia testing, genetic sampling and movement monitoring. Out of our sample of 342 wild koalas, 60 were found to have chlamydia. Using genotype information on 5007 SNPs to investigate the role of genetic variation in determining disease status, we found no evidence of inbreeding depression, but a heritability of 0.11 (95%CI = 0.05 – 0.23) for the probability that koalas had chlamydia. Heritability of susceptibility to chlamydia could be relevant for future disease management, as it suggests adaptive potential for the population

Effect of Disorder on Ultrafast Exciton Dynamics Probed by Single Molecule Spectroscopy

We present a single-molecule study unraveling the effect of static disorder on the vibrational-assisted ultrafast exciton dynamics in multichromophoric systems. For every single complex, we probe the initial exciton relaxation process by an ultrafast pump-probe approach and the coupling to vibrational modes by emission spectra, while fluorescence lifetime analysis measures the amount of static disorder. Exploiting the wide range of disorder found from complex to complex, we demonstrate that static disorder accelerates the dephasing and energy relaxation rate of the exciton

On the Early History of Current Algebra

The history of Current Algebra is reviewed up to the appearance of the Adler-Weisberger sum rule. Particular emphasis is given to the role current algebra played for the historical struggle in strong interaction physics of elementary particles between the S-matrix approach based on dispersion relations and field theory. The question whether there are fundamental particles or all hadrons are bound or resonant states of one another played an important role in this struggle and is thus also regarded.Comment: 17 page

Socio-cultural, environmental and behavioural determinants of obesity in black South African women

South Africa (SA) is undergoing a rapid epidemiological transition and has the highest prevalence of obesity in sub- Saharan Africa (SSA), with black women being the most affected (obesity prevalence 31.8%). Although genetic factors are important, socio-cultural, environmental and behavioural factors, as well as the influence of socio-economic status, more likely explain the high prevalence of obesity in black SA women. This review examines these determinants in black SA women, and compares them to their white counterparts, black SA men, and where appropriate, to women from SSA. Specifically this review focuses on environmental factors influencing obesity, the influence of urbanisation, as well as the interaction with socio-cultural and socio-economic factors. In addition, the role of maternal and early life factors and cultural aspects relating to body image are discussed. This information can be used to guide public health interventions aimed at reducing obesity in black SA women.Department of HE and Training approved lis

Characterization of the 6-methyl isoxanthopterin (6-MI) base analog dimer, a spectroscopic probe for monitoring guanine base conformations at specific sites in nucleic acids

We here characterize local conformations of site-specifically placed pairs of guanine (G) residues in RNA and DNA, using 6-methyl isoxanthopterin (6-MI) as a conformational probe. 6-MI is a base analog of G and spectroscopic signals obtained from pairs of adjacent 6-MI residues reflect base–base interactions that are sensitive to the sequence context, local DNA conformation and solvent environment of the probe bases. CD signals show strong exciton coupling between stacked 6-MI bases in double-stranded (ds) DNA; this coupling is reduced in single-stranded (ss) DNA sequences. Solvent interactions reduce the fluorescence of the dimer probe more efficiently in ssDNA than dsDNA, while self-quenching between 6-MI bases is enhanced in dsDNA. 6-MI dimer probes closely resemble adjacent GG residues, in that these probes have minimal effects on the stability of dsDNA and on interactions with solvent additive betaine. They also serve as effective template bases, although further polymerase-dependent extension of DNA primers past 6-MI template bases is significantly inhibited. These probes are also used to monitor DNA ‘breathing’ at model replication forks. The 6-MI dimer probe can serve in many contexts as a useful tool to investigate GG conformations at specific sites within the nucleic acid frameworks of functioning macromolecular machines in solution

Meeting physical activity guidelines is associated with reduced risk for cardiovascular disease in black South African women; a 5.5-year follow-up study

Background: Low levels of physical activity (PA) have been associated with increased risk for cardiovascular disease (CVD) and type 2 diabetes (T2D), but few studies have examined whether meeting international PA guidelines is associated with reduced risk in a black South African (SA) population. The aims of this study were to compare body composition and cardio-metabolic risk factors for CVD and T2D between active and inactive groups (part 1, cross-sectional analysis) and, to determine whether PA level predicts changes in body composition and cardio-metabolic risk factors for CVD and T2D at follow-up after 5.5-years (part 2, longitudinal analysis). Methods: Part 1 included a sample of 240 apparently healthy black SA women (26 ± 7 years) who underwent the following measurements at baseline: PA (Global Physical Activity Questionnaire (GPAQ)), body composition and regional fat distribution (dual-energy x-ray absorptiometry and computerised tomography), blood pressure, fasting glucose, insulin and lipid concentrations. For part 2, a sub-sample of women (n = 57) underwent the same measurements after a 5.5-year period. Results: At baseline, 61% of women were classified as meeting the guidelines for moderate- to vigorous-intensity physical activity (MVPA) according to GPAQ. Women who were active had significantly lower body weight (p < 0.001), body fat (BMI, fat mass, % body fat, waist circumference, central and appendicular fat mass, all p < 0.001), and measures of insulin resistance (fasting serum insulin and HOMA-IR, both p = 0.01), and higher high-density lipoprotein cholesterol (p = 0.041), compared to the inactive group. At follow-up, all body fat measures increased significantly in both groups and diastolic blood pressure decreased significantly in those who were active at baseline, but did not change in those who were inactive. Conclusions: Meeting PA guidelines was associated with decreased risk for CVD and T2D in black SA women, but did not prevent the increase in body fat over time. Interventions promoting physical activity to specifically address obesity in this high-risk group are recommended

Signatures of exciton coupling in paired nanoemitters

An exciton formed by the delocalized electronic excitation of paired nanoemitters is interpreted in terms of the electromagnetic emission of the pair and their mutual coupling with a photodetector. A formulation directly tailored for fluorescence detection is identified, giving results which are strongly dependent on geometry and selection rules. Signature symmetric and antisymmetric combinations are analyzed and their distinctive features identified

Bright ligand-activatable fluorescent protein for high-quality multicolor live-cell super-resolution microscopy

We introduce UnaG as a green-to-dark photoswitching fluorescent protein capable of high-quality super-resolution imaging with photon numbers equivalent to the brightest photoswitchable red protein. UnaG only fluoresces upon binding of a fluorogenic metabolite, bilirubin, enabling UV-free reversible photoswitching with easily controllable kinetics and low background under Epi illumination. The on- and off-switching rates are controlled by the concentration of the ligand and the excitation light intensity, respectively, where the dissolved oxygen also promotes the off-switching. The photo-oxidation reaction mechanism of bilirubin in UnaG suggests that the lack of ligand-protein covalent bond allows the oxidized ligand to detach from the protein, emptying the binding cavity for rebinding to a fresh ligand molecule. We demonstrate super-resolution single-molecule localization imaging of various subcellular structures genetically encoded with UnaG, which enables facile labeling and simultaneous multicolor imaging of live cells. UnaG has the promise of becoming a default protein for high-performance super-resolution imaging. Photoconvertible proteins occupy two color channels thereby limiting multicolour localisation microscopy applications. Here the authors present UnaG, a new green-to-dark photoswitching fluorescent protein for super-resolution imaging, whose activation is based on a noncovalent binding with bilirubin

Spot sputum samples are at least as good as early morning samples for identifying Mycobacterium tuberculosis

Supported by the Global Alliance for TB Drug Development with support from the Bill and Melinda Gates Foundation, the European and Developing Countries Clinical Trials Partnership (Grant IP.2007.32011.011), US Agency for International Development, UK Department for International Development, Directorate General for International Cooperation of the Netherlands, Irish Aid, Australia Department of Foreign Affairs and Trade, National Institutes of Health, AIDS Clinical Trials Group. The study was also supported by grants from the National Institute of Allergy and Infectious Diseases (NIAID) (UM1AI068634, UM1 AI068636, and UM1AI106701) and by NIAID grants to the University of KwaZulu Natal, South Africa, AIDS Clinical Trials Group (ACTG) site 31422 (1U01AI069469); to the Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, South Africa, ACTG site 12301 (1U01AI069453); and to the Durban International Clinical Trials Unit, South Africa, ACTG site 11201 (1U01AI069426). Bayer Healthcare for donated moxifloxacin and Sanofi donated rifampin.Background:  The use of early morning sputum samples (EMS) to diagnose tuberculosis (TB) can result in treatment delay given the need for the patient to return to the clinic with the EMS, increasing the chance of patients being lost during their diagnostic workup. However, there is little evidence to support the superiority of EMS over spot sputum samples. In this new analysis of the REMoxTB study, we compare the diagnostic accuracy of EMS with spot samples for identifying Mycobacterium tuberculosis pre- and post-treatment. Methods:  Patients who were smear positive at screening were enrolled into the study. Paired sputum samples (one EMS and one spot) were collected at each trial visit pre- and post-treatment. Microscopy and culture on solid LJ and liquid MGIT media were performed on all samples; those missing corresponding paired results were excluded from the analyses. Results:  Data from 1115 pre- and 2995 post-treatment paired samples from 1931 patients enrolled in the REMoxTB study were analysed. Patients were recruited from South Africa (47%), East Africa (21%), India (20%), Asia (11%), and North America (1%); 70% were male, median age 31 years (IQR 24–41), 139 (7%) co-infected with HIV with a median CD4 cell count of 399 cells/μL (IQR 318–535). Pre-treatment spot samples had a higher yield of positive Ziehl–Neelsen smears (98% vs. 97%, P = 0.02) and LJ cultures (87% vs. 82%, P = 0.006) than EMS, but there was no difference for positivity by MGIT (93% vs. 95%, P = 0.18). Contaminated and false-positive MGIT were found more often with EMS rather than spot samples. Surprisingly, pre-treatment EMS had a higher smear grading and shorter time-to-positivity, by 1 day, than spot samples in MGIT culture (4.5 vs. 5.5 days, P < 0.001). There were no differences in time to positivity in pre-treatment LJ culture, or in post-treatment MGIT or LJ cultures. Comparing EMS and spot samples in those with unfavourable outcomes, there were no differences in smear or culture results, and positive results were not detected earlier in Kaplan–Meier analyses in either EMS or spot samples. Conclusions:  Our data do not support the hypothesis that EMS samples are superior to spot sputum samples in a clinical trial of patients with smear positive pulmonary TB. Observed small differences in mycobacterial burden are of uncertain significance and EMS samples do not detect post-treatment positives any sooner than spot samples.Publisher PDFPeer reviewe