Genetic polymorphisms linked to susceptibility to malaria

The influence of host genetics on susceptibility to Plasmodium falciparum malaria has been extensively studied over the past twenty years. It is now clear that malaria parasites have imposed strong selective forces on the human genome in endemic regions. Different genes have been identified that are associated with different malaria related phenotypes. Factors that promote severity of malaria include parasitaemia, parasite induced inflammation, anaemia and sequestration of parasitized erythrocytes in brain microvasculature

PDGF Upregulates Mcl-1 Through Activation of β-Catenin and HIF-1α-Dependent Signaling in Human Prostate Cancer Cells

BACKGROUND: Aberrant platelet derived growth factor (PDGF) signaling has been associated with prostate cancer (PCa) progression. However, its role in the regulation of PCa cell growth and survival has not been well characterized. METHODOLOGY/PRINCIPAL FINDINGS: Using experimental models that closely mimic clinical pathophysiology of PCa progression, we demonstrated that PDGF is a survival factor in PCa cells through upregulation of myeloid cell leukemia-1 (Mcl-1). PDGF treatment induced rapid nuclear translocation of β-catenin, presumably mediated by c-Abl and p68 signaling. Intriguingly, PDGF promoted formation of a nuclear transcriptional complex consisting of β-catenin and hypoxia-inducible factor (HIF)-1α, and its binding to Mcl-1 promoter. Deletion of a putative hypoxia response element (HRE) within the Mcl-1 promoter attenuated PDGF effects on Mcl-1 expression. Blockade of PDGF receptor (PDGFR) signaling with a pharmacological inhibitor AG-17 abrogated PDGF induction of Mcl-1, and induced apoptosis in metastatic PCa cells. CONCLUSIONS/SIGNIFICANCE: Our study elucidated a crucial survival mechanism in PCa cells, indicating that interruption of the PDGF-Mcl-1 survival signal may provide a novel strategy for treating PCa metastasis

Synthesis, crystal structure and mono-dimensional thallium ion conduction of TlFe(0.22)Al(0.78)As(2)O(7)

A new solid solution TlFe0.22Al0.78As2O7 has been synthesized by a solid-state reaction. The structure of the title compound has been determined from a single-crystal X-ray diffraction and refined to final values of the reliability factors: R(F2) ¼ 0.030 and wR(F2) ¼ 0.081 for 1343 independent reflections with I42s(I). It crystallizes in the triclinic space group P-1, with a ¼ 6.296(2)A ˚ , b ¼ 6.397(2)A ˚ , c ¼ 8.242(2)A ˚ , a ¼ 96.74(2)1, b ¼ 103.78(2)1, g ¼ 102.99(3)1, V ¼ 309.0(2)A ˚ 3 and Z ¼ 2. The structure can be described as a threedimensional framework containing (Fe/Al)O6 octahedra connected through As2O7 groups. The metallic units and diarsenate groups share oxygen corners to form a three-dimensional framework with interconnected tunnels parallel to the a, b and c directions, where Tl+ cations are located. The ionic conductivity measurements are performed on pellets of the polycrystalline powder. At 683 K, The conductivity value is 5.23106 S cm1 and the ionic jump activation energy is 0.656 eV. The bond valence analysis reveals that the ionic conductivity is ensured by Tl+ along the [001] directio

Assessment of the capacity for flood monitoring and early warning in Enlargement and Eastern/ Southern Neighbourhood countries of the European Union

Flooding is a natural disaster that can damage large areas in the vicinity of rivers, and in the case of flash floods, also in the vicinity of smaller streams. The Global Risks Report 2017 lists extreme weather events, of which flooding is the main risk in most countries, as the risk with the second highest potential impact and the highest likelihood of occurrence. It furthermore seems likely that climate change will aggravate flood impacts in many regions. This report presents an assessment of the capacity for flood monitoring and early flood warning in 17 of the 22 countries which belong to the Eastern and Southern neighbourhood policy of the European Union and the enlargement candidate countries. Many of these receive external funding to improve their systems, but this is often on an ad hoc basis and through individual projects.JRC.E.1-Disaster Risk Managemen

Training during the COVID-19 lockdown : knowledge, beliefs, and practices of 12,526 athletes from 142 countries and six continents

OBJECTIVE Our objective was to explore the training-related knowledge, beliefs, and practices of athletes and the influence of lockdowns in response to the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS Athletes (n = 12,526, comprising 13% world class, 21% international, 36% national, 24% state, and 6% recreational) completed an online survey that was available from 17 May to 5 July 2020 and explored their training behaviors (training knowledge, beliefs/attitudes, and practices), including specific questions on their training intensity, frequency, and session duration before and during lockdown (March–June 2020). RESULTS Overall, 85% of athletes wanted to “maintain training,” and 79% disagreed with the statement that it is “okay to not train during lockdown,” with a greater prevalence for both in higher-level athletes. In total, 60% of athletes considered “coaching by correspondence (remote coaching)” to be sufficient (highest amongst world-class athletes). During lockdown, < 40% were able to maintain sport-specific training (e.g., long endurance [39%], interval training [35%], weightlifting [33%], most (83%) training for “general fitness and health maintenance” during lockdown. Athletes trained alone (80%) and focused on bodyweight (65%) and cardiovascular (59%) exercise/training during lockdown. Compared with before lockdown, most athletes reported reduced training frequency (from between five and seven sessions per week to four or fewer), shorter training sessions (from ≥ 60 to < 60 min), and lower sport-specific intensity (~ 38% reduction), irrespective of athlete classification. CONCLUSIONS COVID-19-related lockdowns saw marked reductions in athletic training specificity, intensity, frequency, and duration, with notable within-sample differences (by athlete classification). Higher classification athletes had the strongest desire to “maintain” training and the greatest opposition to “not training” during lockdowns. These higher classification athletes retained training specificity to a greater degree than others, probably because of preferential access to limited training resources. More higher classification athletes considered “coaching by correspondence” as sufficient than did lower classification athletes. These lockdown-mediated changes in training were not conducive to maintenance or progression of athletes’ physical capacities and were also likely detrimental to athletes’ mental health. These data can be used by policy makers, athletes, and their multidisciplinary teams to modulate their practice, with a degree of individualization, in the current and continued pandemic-related scenario. Furthermore, the data may drive training-related educational resources for athletes and their multidisciplinary teams. Such upskilling would provide athletes with evidence to inform their training modifications in response to germane situations (e.g., COVID related, injury, and illness).A specific funding was provided by the National Sports Institute of Malaysia for this study.The National Sports Institute of Malaysia.https://www.springer.com/journal/40279am2023Sports Medicin

COVID-19 lockdown : a global study investigating athletes’ sport classification and sex on training practices

PURPOSE : To investigate differences in athletes’ knowledge, beliefs, and training practices during COVID-19 lockdowns with reference to sport classification and sex. This work extends an initial descriptive evaluation focusing on athlete classification. METHODS : Athletes (12,526; 66% male; 142 countries) completed an online survey (May–July 2020) assessing knowledge, beliefs, and practices toward training. Sports were classified as team sports (45%), endurance (20%), power/technical (10%), combat (9%), aquatic (6%), recreational (4%), racquet (3%), precision (2%), parasports (1%), and others (1%). Further analysis by sex was performed. RESULTS : During lockdown, athletes practiced body-weight-based exercises routinely (67% females and 64% males), ranging from 50% (precision) to 78% (parasports). More sport-specific technical skills were performed in combat, parasports, and precision (∼50%) than other sports (∼35%). Most athletes (range: 50% [parasports] to 75% [endurance]) performed cardiorespiratory training (trivial sex differences). Compared to prelockdown, perceived training intensity was reduced by 29% to 41%, depending on sport (largest decline: ∼38% in team sports, unaffected by sex). Some athletes (range: 7%–49%) maintained their training intensity for strength, endurance, speed, plyometric, change-of-direction, and technical training. Athletes who previously trained ≥5 sessions per week reduced their volume (range: 18%–28%) during lockdown. The proportion of athletes (81%) training ≥60 min/session reduced by 31% to 43% during lockdown. Males and females had comparable moderate levels of training knowledge (56% vs 58%) and beliefs/attitudes (54% vs 56%). CONCLUSIONS : Changes in athletes’ training practices were sport-specific, with few or no sex differences. Team-based sports were generally more susceptible to changes than individual sports. Policy makers should provide athletes with specific training arrangements and educational resources to facilitate remote and/or home-based training during lockdown-type events.https://journals.humankinetics.com/view/journals/ijspp/ijspp-overview.xmlhj2023Sports Medicin

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century