NDP52 acts as a redox sensor in PINK1/Parkin‐mediated mitophagy

Mitophagy, the elimination of mitochondria via the autophagy‐lysosome pathway, is essential for the maintenance of cellular homeostasis. The best characterised mitophagy pathway is mediated by stabilisation of the protein kinase PINK1 and recruitment of the ubiquitin ligase Parkin to damaged mitochondria. Ubiquitinated mitochondrial surface proteins are recognised by autophagy receptors including NDP52 which initiate the formation of an autophagic vesicle around the mitochondria. Damaged mitochondria also generate reactive oxygen species (ROS) which have been proposed to act as a signal for mitophagy, however the mechanism of ROS sensing is unknown. Here we found that oxidation of NDP52 is essential for the efficient PINK1/Parkin‐dependent mitophagy. We identified redox‐sensitive cysteine residues involved in disulphide bond formation and oligomerisation of NDP52 on damaged mitochondria. Oligomerisation of NDP52 facilitates the recruitment of autophagy machinery for rapid mitochondrial degradation. We propose that redox sensing by NDP52 allows mitophagy to function as a mechanism of oxidative stress response.     

Glucuronoarabinoxylan structure in the walls of Aechmea leaf chlorenchyma cells is related to wall strength

In CAM-plants rising levels of malic acid in the early morning cause elevated turgor pressures in leaf chlorenchyma cells. Under specific conditions this process is lethal for sensitive plants resulting in chlorenchyma cell burst while other species can cope with these high pressures and do not show cell burst under comparable conditions. The non-cellulosic polysaccharide composition of chlorenchyma cell walls was investigated and compared in three cultivars of Aechmea with high sensitivity for chlorenchyma cell burst and three cultivars with low sensitivity. Chlorenchyma layers were cut from the leaf and the non-cellulosic carbohydrate fraction of the cell wall fraction was analyzed by gas-liquid chromatography. Glucuronoarabinoxylans (GAXs) were the major non-cellulosic polysaccharides in Aechmea. The fine structure of these GAXs was strongly related to chlorenchyma wall strength. Chlorenchyma cell walls from cultivars with low sensitivity to cell burst were characterized by an A/X ratio of ca. 0.13 while those from cultivars with high sensitivity showed an A/X ratio of ca. 0.23. Xylose chains from cultivars with high cell burst sensitivity were ca. 40% more substituted with arabinose compared to cultivars with low sensitivity for cell burst. The results indicate a relationship in vivo between glucuronoarabinoxylan fine structure and chlorenchyma cell wall strength in Aechmea. The evidence obtained supports the hypothesis that GAXs with low degrees of substitution cross-link cellulose microfibrils, while GAXs with high degrees of substitution do not. A lower degree of arabinose substitution on the xylose backbone implies stronger cell walls and the possibility of withstanding higher internal turgor pressures without cell bursting.     

The Impact of Company-Level ART Provision to a Mining Workforce in South Africa: A Cost–Benefit Analysis

BackgroundHIV impacts heavily on the operating costs of companies in sub-Saharan Africa, with many companies now providing antiretroviral therapy (ART) programmes in the workplace. A full cost–benefit analysis of workplace ART provision has not been conducted using primary data. We developed a dynamic health-state transition model to estimate the economic impact of HIV and the cost–benefit of ART provision in a mining company in South Africa between 2003 and 2022.ConclusionsWorkplace ART provision can be cost-saving for companies in high HIV prevalence settings due to reductions in healthcare costs, absenteeism, and staff turnover. Company-sponsored HIV counselling and voluntary testing with ensuing treatment of all HIV-positive employees and family members should be implemented universally at workplaces in countries with high HIV prevalence.     

A model of the complex response of Staphylococcus aureus to methicillin

It is widely accepted that β-lactam antimicrobials cause cell death through a mechanism that interferes with cell wall synthesis. Later studies have also revealed that β-lactams modify the autolysis function (the natural process of self-exfoliation of the cell wall) of cells. The dynamic equilibrium between growth and autolysis is perturbed by the presence of the antimicrobial. Studies with Staphylococcus aureus to determine the minimum inhibitory concentration (MIC) have revealed complex responses to methicillin exposure. The organism exhibits four qualitatively different responses: homogeneous sensitivity, homogeneous resistance, heterogeneous resistance and the so-called ‘Eagle-effect’. A mathematical model is presented that links antimicrobial action on the molecular level with the overall response of the cell population to antimicrobial exposure. The cell population is modeled as a probability density function F(x,t) that depends on cell wall thickness x and time t. The function F(x,t) is the solution to a Fokker-Planck equation. The fixed point solutions are perturbed by the antimicrobial load and the advection of F(x,t) depends on the rates of cell wall synthesis, autolysis and the antimicrobial concentration. Solutions of the Fokker-Planck model are presented for all four qualitative responses of S. aureus to methicillin exposure.     

THE ULTRASTRUCTURE OF PYRAMIMONAS PSEUDOPARKEAE SP. NOV. (PRASINOPHYCEAE) FROM SOUTH AFRICA1

The ultrastructure of Pyramimonas pseudoparkeae sp. nov., a member of the class Prasinophyceae occurring in tidal pools along the east, south and west coast of South Africa, is described. The cell surface is covered by three distinctive body scales whilst the flagellar surfaces possess four types of scales. The structure of these scales is described. P. pseudoparkeae resembles Pyramimonas parkeae Norris and Pearson but differs in the structure of the type 2 body scale. The symmetry and ultrastructure of the cell are described with special attention given to the flagellar apparatus. Preliminary information on the life cycle of this species is presented. This new species is compared with other closely related members of the genus Pyramimonas.     

ULTRASTRUCTURE OF PRYMNESIUM NEMAMETHECUM SP. NOV. (PRYMNESIOPHYCEAE)1

Based on material collected from Cape Town, a new sand-dwelling, marine species of Prymnesium is described. Using light and electron microscopy, Prymnesium nemamethecum sp. nov. has been found to resemble other species of the genus in size, organelle arrangement, and swimming behavior. It differs from other described species in that it has three types of scales, one of which is confined to the region of appendage insertion and forms a sheath of simple plate scales over the haptonema. In addition, the scales constituting the proximal body scale layer(s) are unusual because they are not simple plate scales but are specifically ornamented.     

The Evolution of Conservation Management Philosophy: Science, Environmental Change and Social Adjustments in Kruger National Park

In this ‘perspectives’ article, we share experiences gained from the century-old Kruger National Park (KNP) in South Africa to illustrate the dynamic complexity of biophysical and socio-political systems, the interactions that occur between them, and the consequences for ecosystem-scale functions and resources and for their management. As in KNP, the social-ecological milieu surrounding many national parks and protected areas is changing rapidly. There will be significant managerial adjustments as human populations grow and the needs for resources accelerate. The changes, driven largely by global-scale environmental shifts as well as by new knowledge, are intimately intertwined with evolving societal perceptions, values, and expectations. Many KNP resource-related issues of the past century originated more internally and were largely environmental, whereas the emerging issues are more external and largely social. Here, we illustrate how interrelated scientific and managerial advances in integrating biophysical and social systems are acting to conserve and rehabilitate resources within KNP, and to aid in their conservation. Where appropriate, we relate these advances to similar examples in the region or other protected areas in the world. Strategies to address emerging issues are identified and discussed—and their combined effects on resource conservation and management are evaluated. In our experience the approach to conservation within KNP has been successful, despite well-intended but damaging management actions in the past. We believe that the perceived success stems from a willingness to continually incorporate new knowledge into management, to foster close working and personal associations among scientists, managers, and rangers, to acquire an intimate knowledge and understanding of the social-ecological system by the administrators as well as by the staff, and to be actively ‘forward’ thinking in an increasingly complex and uncertain world. We accept that many decisions taken today will be challenged by future managers and scientists, and we expect that some will be found wanting as emerging knowledge and continued learning shape future decisions. Further, evolving political, social, and environmental contexts may mean that protected areas will need to be managed in different ways. Therefore, we emphasize the importance of minimizing the permanency and impact of decisions so that today’s actions do not compromise future decisions when meaningful changes need to be made.

Functional capacity of Mycobacterium tuberculosis-specific T cell responses in humans is associated with mycobacterial load

High Ag load in chronic viral infections has been associated with impairment of Ag-specific T cell responses; however, the relationship between Ag load in chronic Mycobacterium tuberculosis infection and functional capacity of M. tuberculosis-specific T cells in humans is not clear. We compared M. tuberculosis-specific T cell-associated cytokine production and proliferative capacity in peripheral blood from adults with progressively higher mycobacterial loads-that is, persons with latent M. tuberculosis infection (LTBI), with smear-negative pulmonary tuberculosis (TB), and smear-positive TB. Patients with smear-positive TB had decreased polyfunctional IFN-γ(+)IL-2(+)TNF-α(+) and IL-2-producing specific CD4 T cells and increased TNF-α single-positive cells, when compared with smear-negative TB and LTBI. TB patients also had increased frequencies of M. tuberculosis-specific CD8 T cells, compared with LTBI. M. tuberculosis-specific CD4 and CD8 T cell proliferative capacity was profoundly impaired in individuals with smear-positive TB, and correlated positively with ex vivo IFN-γ(+)IL-2(+)TNF-α(+) CD4 T cells, and inversely with TNF-α single-positive CD4 T cells. During 6 mo of anti-TB treatment, specific IFN-γ(+)IL-2(+)TNF-α(+) CD4 and CD8 T cells increased, whereas TNF-α and IFN-γ single-positive T cells decreased. These results suggest progressive impairment of M. tuberculosis-specific T cell responses with increasing mycobacterial load and recovery of responses during therapy. Furthermore, these data provide a link between specific cytokine-producing subsets and functional capacity of M. tuberculosis-specific T cells, and between the presence of specific CD8 T cells ex vivo and active TB disease. These data have potentially significant applications for the diagnosis of TB and for the identification of T cell correlates of TB disease progression.     

Evolutionary stable sex ratios with non‐facultative male‐eggs first sex allocation in fig wasps

Sex allocation theory has long generated insights into the nature of natural selection. Classical models have elucidated causal phenomena such as local mate competition and inbreeding on the degree of female bias exhibited by various invertebrates. Typically, these models assume mothers facultatively adjust sex allocation using predictive cues of future offspring mating conditions. Here we relax this assumption by developing a sex allocation model for haplodiploid mothers experiencing local mate competition that lay a fixed number of male eggs first. Female egg number is determined by remaining oviposition sites or remaining eggs of the mother, depending on which is exhausted first. Our model includes parameters for variation in foundress number, patch size, fecundity and offspring mortality that allow us to generate secondary sex ratio predictions based on specific parameterizations for natural populations. Simulations show that: 1) in line with classical models, factors that increase sib‐mating result in mothers laying relatively more female eggs; 2) high offspring mortality leads to relatively more males as fertilization insurance; 3) unlike classical model predictions, sub‐optimal predictions, such as more males than females are possible. In addition, our model provides the first quantitative predictions for the expected number of males and females in a patch where typically only one mother utilizes a given patch. We parameterized the model with data obtained from seven species of southern African fig wasps to predict expected means and variances for numbers of male and female offspring for typical numbers of mothers utilizing a patch. These predictions were compared to secondary sex ratio data from single foundress patches, the most commonly encountered situation for these species. Our predictions matched both the observed number and variance of male and female offspring with a high degree of accuracy suggesting that facultative adjustment is not required to produce evolutionary stable sex ratios.     

Synaptic Protein Alterations in Parkinson’s Disease

Alterations occur within distal neuronal compartments, including axons and synapses, during the course of neurodegenerative diseases such as Parkinson’s disease (PD). These changes could hold important implications for the functioning of neural networks, especially since research studies have shown a loss of dendritic spines locating to medium spiny projection neurons and impaired axonal transport in PD-affected brains. However, despite ever-increasing awareness of the vulnerability of synapses and axons, inadequate understanding of the independent mechanisms regulating non-somatic neurodegeneration prevails. This has resulted in limited therapeutic strategies capable of targeting these distinct cellular compartments. Deregulated protein synthesis, folding and degrading proteins, and protein quality-control systems have repeatedly been linked with morphological and functional alterations of synapses in the PD-affected brains. Here, we review current understanding concerning the proteins involved in structural and functional changes that affect synaptic contact-points in PD. The collection of studies discussed emphasizes the need for developing therapeutics aimed at deregulated protein synthesis and degradation pathways operating at axonal and dendritic synapses for preserving “normal” circuitry and function, for as long as possible.