Secondary metabolites produced by endophytic fungi, Alternaria alternata, as potential inhibitors of the human immunodeficiency virus

Antiretroviral treatment has significantly reduced human immunodeficiency virus infection and mortality. However, the current treatment regimen is limited by adverse side effects, the emergence of drug resistance, and the inability to eliminate viral reservoirs. Here, fifteen endophytic fungi were isolated from Sclerocarya birrea and Hypoxis plants. Crude extracts of Alternaria alternata (strain ID PO4PR1, PO4PR2, and PO2PL1) of the fifteen isolate’s crude extracts showed anti-HIV-1 activity in TZM-bl cell line at inhibitory concentration (IC50) values ranging from 0.017 to 1.170 μg/ml. The three crude extracts also maintained the virus replication inhibition profile on PBMCs and CD4+ T cells at concentrations ranging from 0.3 to 50.2 ng/ml. Partial purification using the solid phase extraction and analysis with Gas Chromatography-Mass spectrophotometry showed a diverse profile. The bioactive compounds were identified based on peak area, retention time, similarity index. The major compounds from GC-MS analysis of A. Alternata revealed the existence of cyclotrisiloxane octamethyl (22.92%); Propaninitrile (16,67%); Pyrrolol[1,2-a]pyrazine-1,4-dione, hexahydro-3-(2-methyl propyl) (10.42%); Silane, diethylethoxy(2-ethoxyethyloxy) (4.17%); Coumarin, 3,4-dihydro-4,5,7-trimethyl- 4,5,7-Trimethyl-2-chromanone (13.7%) and 1,2-Cyclobutanedicarbonitrile (2.08%) with previously reported biological activities such as antimicrobial, anti-inflammatory and antioxidant properties. Therefore, these bioactive compounds from A. alternata fungal endophytes could be repurposed as potential anti-HIV agents. This study showed the potential of endophytic fungi, Alternaria alternata from S. birrea, and Hypoxis species as producers of anti-HIV compounds

Evaluating South African Weather Service information on Idai tropical cyclone and KwaZulu-Natal flood events

Severe weather events associated with strong winds and flooding can cause fatalities, injuries and damage to property. Detailed and accurate weather forecasts that are issued and communicated timeously, and actioned upon, can reduce the impact of these events. The responsibility to provide such forecasts usually lies with government departments or state-owned entities; in South Africa that responsibility lies with the South African Weather Service (SAWS). SAWS is also a regional specialised meteorological centre and therefore provides weather information to meteorological services within the Southern African Development Community (SADC). We evaluated SAWS weather information using near real-time observations and models on the nowcasting to short-range forecasting timescales during two extreme events. These are the Idai tropical cyclone in March 2019 which impacted Mozambique, Zimbabwe and Malawi resulting in over 1000 deaths, and the floods over the KwaZulu-Natal (KZN) province in April 2019 that caused over 70 deaths. Our results show that weather models gave an indication of these systems in advance, with warnings issued at least 2 days in advance in the case of Idai and 1 day in advance for the KZN floods. Nowcasting systems were also in place for detailed warnings to be provided as events progressed. Shortcomings in model simulations were shown, in particular on locating the KZN flood event properly and over/-underestimation of the event. The impacts experienced during the two events indicate that more needs to be done to increase weather awareness, and build disaster risk management systems, including disaster preparedness and risk reduction.Significance: This paper is relevant for all South Africans and the SADC region at large because it provides information on: the weather forecasting processes followed at the South African Weather Service, available early warning products in South Africa and for the SADC region made possible through the public purse, the performance of nowcasting and modelling systems in the case of predicting two extreme weather events that had adverse impacts on southern African society, and the dissemination of warnings of future extreme weather events

Conducting sexualities research: An outline of emergent issues and case studies from ten wellcome-funded projects [version 1; peer review: 3 approved]

© 2019 Kneale D et al. This letter seeks to synthesise methodological challenges encountered in a cohort of Wellcome Trust-funded research projects focusing on sexualities and health. The ten Wellcome Trust projects span a diversity of gender and sexual orientations and identities, settings; institutional and non-institutional contexts, lifecourse stages, and explore a range of health-related interventions. As researchers, we originate from a breadth of disciplinary traditions, use a variety of research methods and data sources. Despite this breadth, four common themes are found across the projects: (i) inclusivity representations and representativeness, (ii) lumping together of diverse groups, (iii) institutions and closed settings (iv) ethical and governance barriers

Health-related quality of life among people living with HIV in the era of universal test and treat: Results from a cross-sectional study in KwaZulu-Natal, South Africa

Background: The World Health Organization’s (WHO) key population-based strategy for ending the human immunodeficiency virus (HIV) epidemic is universal HIV test and treat (UTT) along with pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP). Despite the successful scale-up of the UTT strategy in sub-Saharan Africa, the quality of life (QoL) of people living with HIV (PLHIV) remains sub-optimal. Poor quality of life in PLHIV may threaten the UNAIDS 95-95-95 programme targets. Monitoring QoL of PLHIV has become a key focus of HIV research among other outcomes so as to understand health-related quality of life (HRQoL) profiles and identify interventions to improve programme performance. This study aimed to describe HRQoL profiles and identify their predictors in PLHIV in KwaZulu Natal, South Africa. Methods: We conducted a secondary data analysis of a cross-sectional survey conducted between May and June 2022 among PLHIV (n=105) accessing HIV services at an outpatient clinic in KwaZulu-Natal, South Africa. Socio-demographic, HRQoL (EQ-5D-5L index scores), clinical data, depressive symptoms (CES-D-10) and viral load data were collected from all participants. We examined predictors of HRQoL using generalised linear models controlling for age and sex. Results: The mean age of the participants was 45 years (SD= 13). The proportion of participants with disabilities and comorbidities was 3% and 18%, respectively. Depressive symptoms were present in 49% of the participants. Participant’s mean EQ-5D-5L index score was 0.87 (SD= 0.21) and ranged from 0.11 to 1.0. The mean general health state (EQ-VAS) was 74.7 (SD= 18.8) and ranged from 6 to 100. Factors that reduced HRQoL were disability (β=-0.607, p<0.001), comorbidities (β = - 0.23, p<0.05), presence of depressive symptoms (β = -0.10, p<0.05) and old age (β = -0.04, p<0.05). Factors that increased HRQoL were a good perceived health state (β = 0.147, p<0.001) and availability of social support (β = 0.098, p<0.05). Conclusion: A combination of old age (60 years and above), any disability and comorbidities had a considerable effect on HRQoL among PLHIV. Our findings support the recommendation for an additional fourth UNAIDS target that should focus on ensuring that 95% of PLHIV have the highest possible HRQoL. Psycho-social support interventions are recommended to improve the HRQoL of PLHIV

Conducting sexualities research: an outline of emergent issues and case studies from ten Wellcome-funded projects [version 1; peer review: awaiting peer review]

This letter seeks to synthesise methodological challenges encountered in a cohort of Wellcome Trust-funded research projects focusing on sexualities and health. The ten Wellcome Trust projects span a diversity of gender and sexual orientations and identities, settings; institutional and non-institutional contexts, lifecourse stages, and explore a range of health-related interventions.  As researchers, we originate from a breadth of disciplinary traditions, use a variety of research methods and data sources. Despite this breadth, four common themes are found across the projects: (i) inclusivity, representations and representativeness, (ii) lumping together of diverse groups, (iii) institutions and closed settings (iv) ethical and governance barriers

Evaluating South African weather service information on Idai tropical cyclone and KwaZulu- Natal flood events

Severe weather events associated with strong winds and flooding can cause fatalities, injuries and damage to property. Detailed and accurate weather forecasts that are issued and communicated timeously, and actioned upon, can reduce the impact of these events. The responsibility to provide such forecasts usually lies with government departments or state-owned entities; in South Africa that responsibility lies with the South African Weather Service (SAWS). SAWS is also a regional specialised meteorological centre and therefore provides weather information to meteorological services within the Southern African Development Community (SADC). We evaluated SAWS weather information using near real-time observations and models on the nowcasting to short-range forecasting timescales during two extreme events. These are the Idai tropical cyclone in March 2019 which impacted Mozambique, Zimbabwe and Malawi resulting in over 1000 deaths, and the floods over the KwaZulu-Natal (KZN) province in April 2019 that caused over 70 deaths. Our results show that weather models gave an indication of these systems in advance, with warnings issued at least 2 days in advance in the case of Idai and 1 day in advance for the KZN floods. Nowcasting systems were also in place for detailed warnings to be provided as events progressed. Shortcomings in model simulations were shown, in particular on locating the KZN flood event properly and over/underestimation of the event. The impacts experienced during the two events indicate that more needs to be done to increase weather awareness, and build disaster risk management systems, including disaster preparedness and risk reduction. Significance: This paper is relevant for all South Africans and the SADC region at large because it provides information on: • the weather forecasting processes followed at the South African Weather Service, • available early warning products in South Africa and for the SADC region made possible through the public purse, • the performance of nowcasting and modelling systems in the case of predicting two extreme weather events that had adverse impacts on southern African society, and • the dissemination of warnings of future extreme weather events.The Climate Research for Development (CR4D) Postdoctoral Fellowship CR4D-19-11 implemented by the African Academy of Sciences (AAS) in partnership with the United Kingdom’s Department for International Development (DfID) Weather and Climate Information Services for Africa (WISER) programme and the African Climate Policy Center (ACPC) of the United Nations Economic Commission for Africa (UNECA).http://www.sajs.co.zaam2022Geography, Geoinformatics and Meteorolog

Adaptation and pre-test of a shortened Stepping Stones and Creating Futures intervention focused on HIV for young men in rural South Africa

This is the final version. Available on open access from Public Library of Science via the DOI in this recordData Availability: All data are available via the AHRI data repository: https://data.ahri.org/index.php/home with access based on their guidelines.Men’s engagement in HIV prevention and treatment is suboptimal, including in South Africa. We sought to address this through adapting an evidence-based intervention, Stepping Stones and Creating Futures (SSCF), to strengthen its HIV content and provide a more scalable (shorter) intervention in rural South Africa. We then conducted a mixed methods pre-test of the intervention among young men aged 18–35 years. To adapt SSCF, we reviewed the current evidence base and worked with male Peer Navigators to update the SSCF theory of change (ToC) and manual. The revised intervention was ~45 hours (9 sessions) as opposed to ~63 hours and included a greater focus on HIV prevention and treatment technologies. Overall, 64% (n = 60) of men approached agreed to participate in the intervention, uptake (attending one session) among those who agreed was n = 35(58%) and retention (attending 6 or more sessions) was n = 25(71%). Qualitative data emphasized the intervention was acceptable, with young men describing it as something they liked. The qualitative data also broadly supported the intervention ToC, including the normalization of HIV in men’s lives, and the importance of health for men in achieving their life goals. However, it also highlighted the need to focus more on HIV-related stigma and fear, and the importance of HIV self-testing kits in encouraging testing. We revised the ToC and manual in light of this data. The adapted SSCF is acceptable and supports the ToC. Next steps is an evaluation to look at effectiveness of the intervention.Medical Research Council (MRC)Wellcome TrustNational Institutes of Health (NIH)South African Medical Research Counci

A molecular assay for sensitive detection of pathogen-specific T-cells.

Here we describe the development and validation of a highly sensitive assay of antigen-specific IFN-γ production using real time quantitative PCR (qPCR) for two reporters--monokine-induced by IFN-γ (MIG) and the IFN-γ inducible protein-10 (IP10). We developed and validated the assay and applied it to the detection of CMV, HIV and Mycobacterium tuberculosis (MTB) specific responses, in a cohort of HIV co-infected patients. We compared the sensitivity of this assay to that of the ex vivo RD1 (ESAT-6 and CFP-10)-specific IFN-γ Elispot assay. We observed a clear quantitative correlation between the two assays (P<0.001). Our assay proved to be a sensitive assay for the detection of MTB-specific T cells, could be performed on whole blood samples of fingerprick (50 uL) volumes, and was not affected by HIV-mediated immunosuppression. This assay platform is potentially of utility in diagnosis of infection in this and other clinical settings

Rainfall simulations of high-impact weather in South Africa with the conformal cubic atmospheric model (CCAM)

Warnings of severe weather with a lead time longer that two hours require the use of skillful numerical weather prediction (NWP) models. In this study, we test the performance of the Commonwealth Scientific and Industrial Research Organisation (CSIRO) Conformal Cubic Atmospheric Model (CCAM) in simulating six high-impact weather events, with a focus on rainfall predictions in South Africa. The selected events are tropical cyclone Dineo (16 February 2017), the Cape storm (7 June 2017), the 2017 Kwa-Zulu Natal (KZN) floods (10 October 2017), the 2019 KZN floods (22 April 2019), the 2019 KZN tornadoes (12 November 2019) and the 2020 Johannesburg floods (5 October 2020). Three configurations of CCAM were compared: a 9 km grid length (MN9km) over southern Africa nudged within the Global Forecast System (GFS) simulations, and a 3 km grid length over South Africa (MN3km) nudged within the 9 km CCAM simulations. The last configuration is CCAM running with a grid length of 3 km over South Africa, which is nudged within the GFS (SN3km). The GFS is available with a grid length of 0.25 , and therefore, the configurations allow us to test if there is benefit in the intermediate nudging at 9 km as well as the effects of resolution on rainfall simulations. The South AfricanWeather Service (SAWS) station rainfall dataset is used for verification purposes. All three configurations of CCAM are generally able to capture the spatial pattern of rainfall associated with each of the events. However, the maximum rainfall associated with two of the heaviest rainfall events is underestimated by CCAM with more than 100 mm. CCAM simulations also have some shortcomings with capturing the location of heavy rainfall inland and along the northeast coast of the country. Similar shortcomings were found with other NWP models used in southern Africa for operational forecasting purposes by previous studies. CCAM generally simulates a larger rainfall area than observed, resulting in more stations reporting rainfall. Regarding the different configurations, they are more similar to one another than observations, however, with some suggestion that MN3km outperforms other configurations, in particular with capturing the most extreme events. The performance of CCAM in the convective scales is encouraging, and further studies will be conducted to identify areas of possible improvement.The AIMS NEI Women in Climate Change Science (WiCCS) fellowship and the Water Research Commission.https://www.mdpi.com/journal/atmospheream2023Geography, Geoinformatics and Meteorolog

Comparative genomics of Cluster O mycobacteriophages

Mycobacteriophages - viruses of mycobacterial hosts - are genetically diverse but morphologically are all classified in the Caudovirales with double-stranded DNA and tails. We describe here a group of five closely related mycobacteriophages - Corndog, Catdawg, Dylan, Firecracker, and YungJamal - designated as Cluster O with long flexible tails but with unusual prolate capsids. Proteomic analysis of phage Corndog particles, Catdawg particles, and Corndog-infected cells confirms expression of half of the predicted gene products and indicates a non-canonical mechanism for translation of the Corndog tape measure protein. Bioinformatic analysis identifies 8-9 strongly predicted SigA promoters and all five Cluster O genomes contain more than 30 copies of a 17 bp repeat sequence with dyad symmetry located throughout the genomes. Comparison of the Cluster O phages provides insights into phage genome evolution including the processes of gene flux by horizontal genetic exchange