Influence of carbon and nitrogen sources on glutathione catabolic enzymes inCandida albicans during dimorphism

The effect of carbon sources, glucose and sucrose, and nitrogen sources such as ammonia, glutamate andl-citrulline on the activities of glutathione metabolic enzymes has been studied. Yeast and mycelial cells were used to identify changes in activity levels of glutathione reductase (GSSGR), glutathione transferase (GST), glutathione peroxidase (GPX) and -glutamyl transpeptidase (GGT). Enzyme activities from cells grown in sucrose media were lower than in glucose media regardless of the enzyme tested, morphological form, or the growth interval. In all enzymes except GST, activity was higher in yeast form than in mycelia, regardless of nitrogen source, with lower activity from 24 to 72 h than at 96 h. In citrulline media, yeast form showed the maximum GST, GGT, and GPX activity. In ammonia-amended media, mycelia showed maximum activity in GGT, whereas in glutamate media, mycelia showed the maximum activity in GST. Also, the type of nitrogen source had no effect on GPX activity in the mycelial form. Finally, changing the nitrogen source showed no significant effect on GSSGR activity, either in the yeast or mycelial form.     

Precipitation of the warmest quarter and temperature of the warmest month are key to understanding the effect of climate change on plant species diversity in Southern African savannah

In this study, we test for the key bioclimatic variables that significantly explain the current distribution of plant species richness in a southern African ecosystem as a preamble to predicting plant species richness under a changed climate. We used 54,000 records of georeferenced plant species data to calculate species richness and spatially interpolated climate data to derive nineteen bioclimatic variables. Next, we determined the key bioclimatic variables explaining variation in species richness across Zimbabwe using regression analysis. Our results show that two bioclimatic variables, that is, precipitation of the warmest quarter (R² = 0.92, P < 0.001) and temperature of the warmest month (R² = 0.67, P < 0.001) significantly explain variation in plant species richness. In addition, results of bioclimatic modelling using future climate change projections show a reduction in the current bio‐climatically suitable area that supports high plant species richness. However, in high‐altitude areas, plant richness is less sensitive to climate change while low‐altitude areas show high sensitivity. Our results have important implications to biodiversity conservation in areas sensitive to climate change; for example, high‐altitude areas are likely to continue being biodiversity hotspots, as such future conservation efforts should be concentrated in these areas.     

The Risk and Timing of Tuberculosis Diagnosed in Smear-Negative TB Suspects: A 12 Month Cohort Study in Harare,Zimbabwe

Background

Cases of smear-negative TB have increased dramatically in high prevalence HIV settings and pose considerable diagnostic and management challenges.

Methods and Findings

Between February 2006 and July 2007, a cohort study nested within a cluster-randomised trial of community-based case finding strategies for TB in Harare, Zimbabwe was undertaken. Participants who had negative sputum smears and remained symptomatic of TB were follow-up for one year with standardised investigations including HIV testing, repeat sputum smears, TB culture and chest radiography. Defaulters were actively traced to the community. The objectives were to investigate the incidence and risk factors for TB. TB was diagnosed in 218 (18.2%) participants, of which 39.4% was bacteriologically confirmed. Most cases (84.2%) were diagnosed within 3 months, but TB incidence remained high thereafter (111.3 per 1000 person-years, 95% CI: 86.6 to 146.3). HIV prevalence was 63.3%, and HIV-infected individuals had a 3.5-fold higher risk of tuberculosis than HIV-negative individuals.

Conclusion

We found that diagnosis of TB was insensitive and slow, even with early radiography and culture. Until more sensitive and rapid diagnostic tests become widely available, a much more proactive and integrated approach towards prompt initiation of ART, ideally from within TB clinics and without waiting for TB to be excluded, is needed to minimise the risk and consequences of diagnostic delay.     

Antiretroviral Therapy Outcomes among Adolescents and Youth in Rural Zimbabwe

Around 2 million adolescents and 3 million youth are estimated to be living with HIV worldwide. Antiretroviral outcomes for this group appear to be worse compared to adults. We report antiretroviral therapy outcomes from a rural setting in Zimbabwe among patients aged 10–30 years who were initiated on ART between 2005 and 2008. The cohort was stratified into four age groups: 10–15 (young adolescents) 15.1–19 years (adolescents), 19.1–24 years (young adults) and 24.1–29.9 years (older adults). Survival analysis was used to estimate rates of deaths and loss to follow-up stratified by age group. Endpoints were time from ART initiation to death or loss to follow-up. Follow-up of patients on continuous therapy was censored at date of transfer, or study end (31 December 2008). Sex-adjusted Cox proportional hazards models were used to estimate hazard ratios for different age groups. 898 patients were included in the analysis; median duration on ART was 468 days. The risk of death were highest in adults compared to young adolescents (aHR 2.25, 95%CI 1.17–4.35). Young adults and adolescents had a 2–3 times higher risk of loss to follow-up compared to young adolescents. When estimating the risk of attrition combining loss to follow-up and death, young adults had the highest risk (aHR 2.70, 95%CI 1.62–4.52). This study highlights the need for adapted adherence support and service delivery models for both adolescents and young adults.     

Defining resonance Raman spectral responses to substrate binding by cytochrome P450 from Pseudomonas putida

Resonance Raman spectra are reported for substrate-free and camphor-bound cytochrome P450cam and its isotopically labeled analogues that have been reconstituted with protoheme derivatives that bear -CD(3) groups at the 1, 3, 5, and 8-positions (d12-protoheme) or deuterated methine carbons (d4-protoheme). In agreement with previous studies of this and similar enzymes, substrate binding induces changes in the high frequency and low frequency spectral regions, with the most dramatic effect in the low frequency region being activation of a new mode near 367 cm(-1). This substrate-activated mode had been previously assigned as a second "propionate bending" mode (Chen et al., Biochemistry, 2004, 43, 1798-1808), arising in addition to the single propionate bending mode observed for the substrate-free form at 380 cm(-1). In this work, this newly activated mode is observed to shift by 8 cm(-1) to lower frequency in the d12-protoheme reconstituted enzyme (i.e., the same shift as that observed for the higher frequency "propionate bending" mode) and is therefore consistent with the suggested assignment. However, the newly acquired data for the d4-protoheme substituted analogue also support an earlier alternate suggestion (Deng et al., Biochemistry, 1999, 38, 13699-13706) that substrate binding activates several heme out-of-plane modes, one of which (gamma(6)) is accidentally degenerate with the 367 cm(-1) propionate bending mode. Finally, the study of the enzyme reconstituted with the protoheme-d4, which shifts the macrocycle nu(10) mode, has now allowed a definitive identification of the vinyl C==C stretching modes. (c) 2008 Wiley Periodicals, Inc. Biopolymers 89: 1045-1053, 2008.This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com.     

Spatial distribution of <Emphasis Type="Italic">Vachellia karroo</Emphasis> in Zimbabwean savannas (southern Africa) under a changing climate

Climate change projections in southern Africa show a drier and a warmer future climate. It is not yet clear how these changes are going to affect the suitable habitat of bush encroacher woody species in southern African savannas. Maximum Entropy niche modelling technique was used to test the extent to which climate change is likely to affect the suitable habitat of Vachellia karroo in Zimbabwe based on six Global Climate Models (GCMs) from Coupled Model Intercomparison Project Phase 5 (CMIP5) and two Representative Concentration Pathways (RCPs) for the 2070s. An overlay analysis was then performed in a Geographic Information System based on the current and future bioclimatically suitable areas for the respective GCMs and RCPs. This was done to determine the potential effect of climate change on the focal species. Results show that temperature related variables are more important in explaining the spatial distribution of V. karroo than precipitation related variables. In addition, results indicate an overall increase in the modelled suitable habitat for V. karroo by the 2070s across the GCMs and RCPs considered in this study. Specifically, the suitable habitat of V. Karroo is projected to increase by a maximum of 57,594 km² signifying a 69% increase from the current suitable habitat (83,674 km²). The suitable areas are projected to increase in eastern, western and south eastern parts of Zimbabwe. These results imply that improved understanding of the response of woody species to a changing climate is important for managing bush encroachment in savanna ecosystems.     

An Investigation of the Shortcomings of the CONSORT 2010 Statement for the Reporting of Group Sequential Randomised Controlled Trials: A Methodological Systematic Review

Background

It can be argued that adaptive designs are underused in clinical research. We have explored concerns related to inadequate reporting of such trials, which may influence their uptake. Through a careful examination of the literature, we evaluated the standards of reporting of group sequential (GS) randomised controlled trials, one form of a confirmatory adaptive design.

Methods

We undertook a systematic review, by searching Ovid MEDLINE from the 1^st January 2001 to 23^rd September 2014, supplemented with trials from an audit study. We included parallel group, confirmatory, GS trials that were prospectively designed using a Frequentist approach. Eligible trials were examined for compliance in their reporting against the CONSORT 2010 checklist. In addition, as part of our evaluation, we developed a supplementary checklist to explicitly capture group sequential specific reporting aspects, and investigated how these are currently being reported.

Results

Of the 284 screened trials, 68(24%) were eligible. Most trials were published in “high impact” peer-reviewed journals. Examination of trials established that 46(68%) were stopped early, predominantly either for futility or efficacy. Suboptimal reporting compliance was found in general items relating to: access to full trials protocols; methods to generate randomisation list(s); details of randomisation concealment, and its implementation. Benchmarking against the supplementary checklist, GS aspects were largely inadequately reported. Only 3(7%) trials which stopped early reported use of statistical bias correction. Moreover, 52(76%) trials failed to disclose methods used to minimise the risk of operational bias, due to the knowledge or leakage of interim results. Occurrence of changes to trial methods and outcomes could not be determined in most trials, due to inaccessible protocols and amendments.

Discussion and Conclusions

There are issues with the reporting of GS trials, particularly those specific to the conduct of interim analyses. Suboptimal reporting of bias correction methods could potentially imply most GS trials stopping early are giving biased results of treatment effects. As a result, research consumers may question credibility of findings to change practice when trials are stopped early. These issues could be alleviated through a CONSORT extension. Assurance of scientific rigour through transparent adequate reporting is paramount to the credibility of findings from adaptive trials. Our systematic literature search was restricted to one database due to resource constraints.     

Zimbabwe Culture before Mapungubwe: New Evidence from Mapela Hill,South-Western Zimbabwe

Across the globe, the emergence of complex societies excites intense academic debate in archaeology and allied disciplines. Not surprisingly, in southern Africa the traditional assumption that the evolution of socio-political complexity began with ideological transformations from K2 to Mapungubwe between CE1200 and 1220 is clouded in controversy. It is believed that the K2−Mapungubwe transitions crystallised class distinction and sacred leadership, thought to be the key elements of the Zimbabwe culture on Mapungubwe Hill long before they emerged anywhere else. From Mapungubwe (CE1220–1290), the Zimbabwe culture was expressed at Great Zimbabwe (CE1300–1450) and eventually Khami (CE1450–1820). However, new fieldwork at Mapela Hill, when coupled with a Bayesian chronology, offers tremendous fresh insights which refute this orthodoxy. Firstly, Mapela possesses enormous prestige stone-walled terraces whose initial construction date from the 11^th century CE, almost two hundred years earlier than Mapungubwe. Secondly, the basal levels of the Mapela terraces and hilltop contain élite solid dhaka (adobe) floors associated with K2 pottery and glass beads. Thirdly, with a hilltop and flat area occupation since the 11^th century CE, Mapela exhibits evidence of class distinction and sacred leadership earlier than K2 and Mapungubwe, the supposed propagators of the Zimbabwe culture. Fourthly, Mapungubwe material culture only appeared later in the Mapela sequence and therefore post-dates the earliest appearance of stone walling and dhaka floors at the site. Since stone walls, dhaka floors and class distinction are the essence of the Zimbabwe culture, their earlier appearance at Mapela suggests that Mapungubwe can no longer be regarded as the sole cradle of the Zimbabwe culture. This demands not just fresh ways of accounting for the rise of socio-political complexity in southern Africa, but also significant adjustments to existing models.