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We describe system verification tests and early science results from the pulsar processor (PTUSE) developed for the newly-commissioned 64-dish SARAO MeerKAT radio telescope in South Africa. MeerKAT is a high-gain (~2.8 K/Jy) low-system temperature (~18 K at 20cm) radio array that currently operates from 580-1670 MHz and can produce tied-array beams suitable for pulsar observations. This paper presents results from the MeerTime Large Survey Project and commissioning tests with PTUSE. Highlights include observations of the double pulsar J0737-3039A, pulse profiles from 34 millisecond pulsars from a single 2.5h observation of the Globular cluster Terzan 5, the rotation measure of Ter5O, a 420-sigma giant pulse from the Large Magellanic Cloud pulsar PSR J0540-6919, and nulling identified in the slow pulsar PSR J0633-2015. One of the key design specifications for MeerKAT was absolute timing errors of less than 5 ns using their novel precise time system. Our timing of two bright millisecond pulsars confirm that MeerKAT delivers exceptional timing. PSR J2241-5236 exhibits a jitter limit of <4 ns per hour whilst timing of PSR J1909-3744 over almost 11 months yields an rms residual of 66 ns with only 4 min integrations. Our results confirm that the MeerKAT is an exceptional pulsar telescope. The array can be split into four separate sub-arrays to time over 1000 pulsars per day and the future deployment of S-band (1750-3500 MHz) receivers will further enhance its capabilities.

The diverse aquaculture sector makes important contributions toward achieving the Sustainable Development Goals (SDGs)/Agenda 2030, and can increasingly do so in the future. Its important role for food security, nutrition, livelihoods, economies, and cultures is not clearly visible in the Agenda 21 declaration. This may partly reflect the state of development of policies for aquaculture compared with its terrestrial counterpart, agriculture, and possibly also because aquaculture production has historically originated from a few key hotspot regions/countries. This review highlights the need for better integration of aquaculture in global food system dialogues. Unpacking aquaculture's diverse functions and generation of values at multiple spatiotemporal scales enables better understanding of aquaculture's present and future potential contribution to the SDGs. Aquaculture is a unique sector that encompasses all aquatic ecosystems (freshwater, brackish/estuarine, and marine) and is also tightly interconnected with terrestrial ecosystems through, for example, feed resources and other dependencies. Understanding environmental, social, and economic characteristics of the multifaceted nature of aquaculture provides for more context‐specific solutions for addressing both opportunities and challenges for its future development. This review includes a rapid literature survey based on how aquaculture links to the specific SDG indicators. A conceptual framework is developed for communicating the importance of context specificity related to SDG outcomes from different types of aquaculture. The uniqueness of aquaculture's contributions compared with other food production systems are discussed, including understanding of species/systems diversity, the role of emerging aquaculture, and its interconnectedness with supporting systems. A selection of case studies is presented to illustrate: (1) the diversity of the aquaculture sector and what role this diversity can play for contributions to the SDGs, (2) examples of methodologies for identification of aquaculture's contribution to the SDGs, and (3) trade‐offs between farming systems’ contribution to meeting the SDGs. It becomes clear that decision‐making around resource allocation and trade‐offs between aquaculture and other aquatic resource users needs review of a wide range of established and emergent systems. The review ends by highlighting knowledge gaps and pathways for transformation that will allow further strengthening of aquaculture's role for contributing to the SDGs. This includes identification and building on already existing monitoring that can enable capturing SDG‐relevant aquaculture statistics at a national level and discussion of how a cohesive and comprehensive aquaculture strategy, framed to meet the SDGs, may help countries to prioritize actions for improving well‐being.

The X chromosome and X-linked variants have largely been ignored in genome-wide and candidate association studies of infectious diseases due to the complexity of statistical analysis of the X chromosome. This exclusion is significant, since the X chromosome contains a high density of immune-related genes and regulatory elements that are extensively involved in both the innate and adaptive immune responses. Many diseases present with a clear sex bias, and apart from the influence of sex hormones and socioeconomic and behavioural factors, the X chromosome, X-linked genes and X chromosome inactivation mechanisms contribute to this difference. Females are functional mosaics for X-linked genes due to X chromosome inactivation and this, combined with other X chromosome inactivation mechanisms such as genes that escape silencing and skewed inactivation, could contribute to an immunological advantage for females in many infections. In this review, we discuss the involvement of the X chromosome and X inactivation in immunity and address its role in sexual dimorphism of infectious diseases using tuberculosis susceptibility as an example, in which male sex bias is clear, yet not fully explored.

After nearly two decades of substantial investment in the field of nanomedicine within South Africa, this study undertakes an investigation into the specific diseases that have been targeted for research and development, as well as the key actors and collaborative networks involved in this burgeoning field. To accomplish this, the study adopts a mixed-method approach, combining bibliometric and scientometric techniques alongside a comprehensive review of existing literature. The study’s findings illuminate that the diseases selected for emphasis in nanomedicine research closely align with the prevalent health challenges faced by South Africa. Notably, these ailments encompass cancer, bacterial infections, and tuberculosis, all of which significantly contribute to the country’s disease burden. Furthermore, the investigation highlights that research-intensive South African universities play a pivotal role as the primary actors in advancing nanomedicine initiatives. Over time, collaborative endeavors among these key actors have seen a noteworthy upswing. These collaborations have fostered robust connections between South African institutions and counterparts in Asian nations and the Middle East. It is worth emphasizing that nanomedicine is a resource-intensive field, necessitating substantial capital investment. Collaborative initiatives have, in turn, granted access to critical infrastructure and materials that would have otherwise been beyond the reach of some participating entities. Remarkably, these collaborative partnerships have not only facilitated scientific progress but have also cultivated social capital and trust among involved stakeholders. These valuable intangible assets hold great potential as South Africa advances towards more exploitative phases of technology development within the domain of nanomedicine. Moreover, South Africa is strategically positioning itself to cultivate a critical mass of expertise in nanomedicine, recognising the significance of skilled human resources in harnessing the full potential of this technology in the future. Systematic Review Registration: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173875/

Acetyl-CoA carboxylase (ACCase) catalyzes the committed step of de novo fatty acid biosynthesis. In prokaryotes, green algae, and most plants, this enzyme is a heteromeric complex requiring four different subunits for activity. The plant complex is recalcitrant to conventional purification schemes and hence the structure and composition of the full assembly have been unclear. In vivo coimmunoprecipitation using subunit-specific antibodies identified a novel family of proteins in Arabidopsis thaliana annotated as biotin/lipoyl attachment domain containing (BADC) proteins. Results from yeast two-hybrid and coexpression in Escherichia coli confirmed that all three BADC isoforms interact with the two biotin carboxyl carrier protein (BCCP) isoforms of Arabidopsis ACCase. These proteins resemble BCCP subunits but are not biotinylated due to a mutated biotinylation motif. We demonstrate that BADC proteins significantly inhibit ACCase activity in both E. coli and Arabidopsis. Targeted gene silencing of BADC isoform 1 in Arabidopsis significantly increased seed oil content when normalized to either mass or individual seed. We conclude the BADC proteins are ancestral BCCPs that gained a new function as negative regulators of ACCase after initial loss of the biotinylation motif. A functional model is proposed.

4′-Ethynyl-2-fluoro-2′-deoxyadenosine (EFdA) is the most potent nucleoside analog inhibitor of HIV reverse transcriptase (RT). It retains a 3′-OH yet acts as a chain-terminating agent by diminishing translocation from the pretranslocation nucleotide-binding site (N site) to the posttranslocation primer-binding site (P site). Also, facile misincorporation of EFdA-monophosphate (MP) results in difficult-to-extend mismatched primers. To understand the high potency and unusual inhibition mechanism of EFdA, we solved RT crystal structures (resolutions from 2.4 to 2.9 Å) that include inhibition intermediates (i) before inhibitor incorporation (catalytic complex, RT/DNA/EFdA-triphosphate), (ii) after incorporation of EFdA-MP followed by dT-MP (RT/DNAEFdA-MPP•dT-MPN ), or (iii) after incorporation of two EFdA-MPs (RT/DNAEFdA-MPP•EFdA-MPN ); (iv) the latter was also solved with EFdA-MP mismatched at the N site (RT/DNAEFdA-MPP•EFdA-MP*N ). We report that the inhibition mechanism and potency of EFdA stem from interactions of its 4′-ethynyl at a previously unexploited conserved hydrophobic pocket in the polymerase active site. The high resolution of the catalytic complex structure revealed a network of ordered water molecules at the polymerase active site that stabilize enzyme interactions with nucleotide and DNA substrates. Finally, decreased translocation results from favorable interactions of primer-terminating EFdA-MP at the pretranslocation site and unfavorable posttranslocation interactions that lead to observed localized primer distortions.

Orthopaedic devices comprise a significant portion of the medical devices that are imported into South Africa. Through case studies, we investigated the effect of contextual factors on knowledge development and exchange in the orthopaedic device innovation system, using the technological innovation systems framework. Our findings revealed that the drivers of knowledge development and exchange were inter-sectoral collaboration, availability of resources, affordability of available devices, creating legitimacy for devices, and the positive externalities of allied innovation systems. The main barriers identified were those that hindered inter-sectoral collaboration. The critical roles of the university and of healthcare actors were also highlighted. These findings may be used proactively to address problems in the innovation systems and to develop policy and institutional mechanisms that are aimed at building the domestic medical devices industry.

We recently reported that non-preconditioned hearts from diet-induced obese rats showed, compared to controls, a significant reduction in infarct size after ischaemia/reperfusion, whilst ischaemic preconditioning was without effect. In view of the high circulating FFA concentration in diet rats, the aims of the present study were to: (i) compare the effect of palmitate on the preconditioning potential of hearts from age-matched controls and diet rats (ii) elucidate the effects of substrate manipulation on ischaemic preconditioning. Substrate manipulation was done with dichloroacetate (DCA), which enhances glucose oxidation and decreases fatty acid oxidation. Isolated hearts from diet rats, age-matched controls or young rats, were perfused in the working mode using the following substrates: glucose (10 mM); palmitate (1.2 mM)/3% albumin) + glucose (10 mM) (HiFA + G); palmitate (1.2 mM/3% albumin) (HiFA); palmitate (0.4 mM/3% albumin) + glucose(10 mM) (LoFA + G); palmitate (0.4 mM/3% albumin) (LoFA). Hearts were preconditioned with 3 × 5 min ischaemia/reperfusion, followed by 35 min coronary ligation and 60 min reperfusion for infarct size determination (tetrazolium method) or 20 min global ischaemia/10 or 30 min reperfusion for Western blotting (ERKp44/42, PKB/Akt). Preconditioning of glucose-perfused hearts from age-matched control (but not diet) rats reduced infarct size, activated ERKp44/42 and PKB/Akt and improved functional recovery during reperfusion (ii) perfusion with HiFA + G abolished preconditioning and activation of ERKp44/42 (iii) DCA pretreatment largely reversed the harmful effects of HiFA. Hearts from non-preconditioned diet rats exhibited smaller infarcts, but could not be preconditioned, regardless of the substrate. Similar results were obtained upon substrate manipulation of hearts from young rats. Abolishment of preconditioning in diet rats may be due to altered myocardial metabolic patterns resulting from changes in circulating FA. The harmful effects of HiFA were attenuated by stimulation of glycolysis and inhibition of FA oxidation.