The bii4africa dataset of faunal and floral population intactness estimates across Africa's major land uses.

Sub-Saharan Africa is under-represented in global biodiversity datasets, particularly regarding the impact of land use on species' population abundances. Drawing on recent advances in expert elicitation to ensure data consistency, 200 experts were convened using a modified-Delphi process to estimate 'intactness scores': the remaining proportion of an 'intact' reference population of a species group in a particular land use, on a scale from 0 (no remaining individuals) to 1 (same abundance as the reference) and, in rare cases, to 2 (populations that thrive in human-modified landscapes). The resulting bii4africa dataset contains intactness scores representing terrestrial vertebrates (tetrapods: ±5,400 amphibians, reptiles, birds, mammals) and vascular plants (±45,000 forbs, graminoids, trees, shrubs) in sub-Saharan Africa across the region's major land uses (urban, cropland, rangeland, plantation, protected, etc.

How colonization bottlenecks, tissue niches, and transmission strategies shape protozoan infections.

Protozoan pathogens such as Plasmodium spp., Leishmania spp., Toxoplasma gondii, and Trypanosoma spp.

CRISPR-based oligo recombineering prioritizes apicomplexan cysteines for drug discovery.

Nucleophilic amino acids are important in covalent drug development yet underutilized as anti-microbial targets. Chemoproteomic technologies have been developed to mine chemically accessible residues via their intrinsic reactivity towards electrophilic probes but cannot discern which chemically reactive sites contribute to protein function and should therefore be prioritized for drug discovery. To address this, we have developed a CRISPR-based oligo recombineering (CORe) platform to support the rapid identification, functional prioritization and rational targeting of chemically reactive sites in haploid systems.

Cellular barcoding of protozoan pathogens reveals the within-host population dynamics of host colonization.

Cellular barcoding techniques are powerful tools to understand microbial pathogenesis. However, barcoding strategies have not been broadly applied to protozoan parasites, which have unique genomic structures and virulence strategies compared with viral and bacterial pathogens. Here, we present a CRISPR-based method to barcode protozoa, which we successfully apply to and .

Malaria parasite evades mosquito immunity by glutaminyl cyclase-mediated posttranslational protein modification.

Glutaminyl cyclase (QC) modifies N-terminal glutamine or glutamic acid residues of target proteins into cyclic pyroglutamic acid (pGlu). Here, we report the biochemical and functional analysis of QC. We show that sporozoites of QC-null mutants of rodent and human malaria parasites are recognized by the mosquito immune system and melanized when they reach the hemocoel.

No acetyl-CoA keeps Plasmodium at bay.

Acetyl-coenzyme A is an important metabolite and regulates diverse cellular processes, including metabolism and epigenetics. In this issue of Cell Chemical Biology, Summers et al. (2022) describe an essential parasite enzyme, acetyl-coenzyme A synthetase, as a target of two antimalarial small molecules active against liver and blood stages of the parasite.

An Extracellular Redox Signal Triggers Calcium Release and Impacts the Asexual Development of .

The ability of an organism to sense and respond to environmental redox fluctuations relies on a signaling network that is incompletely understood in apicomplexan parasites such as . The impact of changes in redox upon the development of this intracellular parasite is not known. Here, we provide a revised collection of 58 genes containing domains related to canonical antioxidant function, with their encoded proteins widely dispersed throughout different cellular compartments.

Ecological basis and genetic architecture of crypsis polymorphism in the desert clicker grasshopper (Ligurotettix coquilletti).

Color polymorphic species can offer exceptional insight into the ecology and genetics of adaptation. Although the genetic architecture of animal coloration is diverse, many color polymorphisms are associated with large structural variants and maintained by biotic interactions. Grasshoppers are notably polymorphic in both color and karyotype, which makes them excellent models for understanding the ecological drivers and genetic underpinnings of color variation.

Live imaging and biophysical modeling support a button-based mechanism of somatic homolog pairing in .

Three-dimensional eukaryotic genome organization provides the structural basis for gene regulation. In , genome folding is characterized by somatic homolog pairing, where homologous chromosomes are intimately paired from end to end; however, how homologs identify one another and pair has remained mysterious. Recently, this process has been proposed to be driven by specifically interacting 'buttons' encoded along chromosomes.

Rapid evolution of blood-brain-barrier-penetrating AAV capsids by RNA-driven biopanning.

Therapeutic payload delivery to the central nervous system (CNS) remains a major challenge in gene therapy. Recent studies using function-driven evolution of adeno-associated virus (AAV) vectors have successfully identified engineered capsids with improved blood-brain barrier (BBB) penetration and CNS tropism in mouse. However, these strategies require transgenic animals and thus are limited to rodents.

Activity- and reactivity-based proteomics: Recent technological advances and applications in drug discovery.

Activity-based protein profiling (ABPP) is recognized as a powerful and versatile chemoproteomic technology in drug discovery. Central to ABPP is the use of activity-based probes to report the activity of specific enzymes or reactivity of amino acid types in complex biological systems. Over the last two decades, ABPP has facilitated the identification of new drug targets and discovery of lead compounds in human and infectious disease.

CRISPR-TAPE: protein-centric CRISPR guide design for targeted proteome engineering.

Rational molecular engineering of proteins with CRISPR-based approaches is challenged by the gene-centric nature of gRNA design tools. To address this, we have developed CRISPR-TAPE, a protein-centric gRNA design algorithm that allows users to target specific residues, or amino acid types within proteins. gRNA outputs can be customized to support maximal efficacy of homology-directed repair for engineering purposes, removing time-consuming post hoc curation, simplifying gRNA outputs and reducing CPU times.

Horizon scanning for South African biodiversity: A need for social engagement as well as science.

A horizon scan was conducted to identify emerging and intensifying issues for biodiversity conservation in South Africa over the next 5-10 years. South African biodiversity experts submitted 63 issues of which ten were identified as priorities using the Delphi method. These priority issues were then plotted along axes of social agreement and scientific certainty, to ascertain whether issues might be "simple" (amenable to solutions from science alone), "complicated" (socially agreed upon but technically complicated), "complex" (scientifically challenging and significant levels of social disagreement) or "chaotic" (high social disagreement and highly scientifically challenging).

Efficacy of an incentive intervention on secondary prophylaxis for young people with rheumatic fever: a multiple baseline study.

Background: Acute rheumatic fever in New Zealand persists and is a barometer of equity as its burden almost exclusively falls on Māori and Pacific Island populations. The primary objective of this study is to determine whether an incentive programme will result in increased secondary prophylaxis injections over a one-year period compared to a baseline period prior to the intervention.

Methods: The evaluation used a multiple baseline study to determine whether an incentive consisting of a mobile phone and monthly "top-up" (for data/calls) resulted in increased injections, increased texts/calls with nurses, reduced number of visits to get a successful injection, less medicine wasted, and increased nurse satisfaction.

Radical transformation pathway towards sustainable electricity via evolutionary steps.

A transition towards long-term sustainability in global energy systems based on renewable energy resources can mitigate several growing threats to human society simultaneously: greenhouse gas emissions, human-induced climate deviations, and the exceeding of critical planetary boundaries. However, the optimal structure of future systems and potential transition pathways are still open questions. This research describes a global, 100% renewable electricity system, which can be achieved by 2050, and the steps required to enable a realistic transition that prevents societal disruption.

A framework to measure the wildness of managed large vertebrate populations.

As landscapes continue to fall under human influence through habitat loss and fragmentation, fencing is increasingly being used to mitigate anthropogenic threats and enhance the commercial value of wildlife. Subsequent intensification of management potentially erodes wildness by disembodying populations from landscape-level processes, thereby disconnecting species from natural selection. Tools are needed to measure the degree to which populations of large vertebrate species in formally protected and privately owned wildlife areas are self-sustaining and free to adapt.

Activity-Based Protein Profiling for the Study of Parasite Biology.

Parasites exist within most ecological niches, often transitioning through biologically and chemically complex host environments over the course of their parasitic life cycles. While the development of technologies for genetic engineering has revolutionised the field of functional genomics, parasites have historically been less amenable to such modification. In light of this, parasitologists have often been at the forefront of adopting new small-molecule technologies, repurposing drugs into biological tools and probes.

Development of an activity-based probe for acyl-protein thioesterases.

Protein palmitoylation is a dynamic post-translational modification (PTM) important for cellular functions such as protein stability, trafficking, localization, and protein-protein interactions. S-palmitoylation occurs via the addition of palmitate to cysteine residues via a thioester linkage, catalyzed by palmitoyl acyl transferases (PATs), with removal of the palmitate catalyzed by acyl protein thioesterases (APTs) and palmitoyl-protein thioesterases (PPTs). Tools that target the regulators of palmitoylation-PATs, APTs and PPTs-will improve understanding of this essential PTM.

Toxoplasma DJ-1 Regulates Organelle Secretion by a Direct Interaction with Calcium-Dependent Protein Kinase 1.

Human DJ-1 is a highly conserved and yet functionally enigmatic protein associated with a heritable form of Parkinson's disease. It has been suggested to be a redox-dependent regulatory scaffold, binding to proteins to modulate their function. Here we present the X-ray crystal structure of the orthologue DJ-1 (TgDJ-1) at 2.

Building capacity in implementation science research training at the University of Nairobi.

Background: Health care systems in sub-Saharan Africa, and globally, grapple with the problem of closing the gap between evidence-based health interventions and actual practice in health service settings. It is essential for health care systems, especially in low-resource settings, to increase capacity to implement evidence-based practices, by training professionals in implementation science. With support from the Medical Education Partnership Initiative, the University of Nairobi has developed a training program to build local capacity for implementation science.

Global Analysis of Palmitoylated Proteins in Toxoplasma gondii.

Post-translational modifications (PTMs) such as palmitoylation are critical for the lytic cycle of the protozoan parasite Toxoplasma gondii. While palmitoylation is involved in invasion, motility, and cell morphology, the proteins that utilize this PTM remain largely unknown. Using a chemical proteomic approach, we report a comprehensive analysis of palmitoylated proteins in T.

A small-molecule antivirulence agent for treating Clostridium difficile infection.

Clostridium difficile infection (CDI) is a worldwide health threat that is typically triggered by the use of broad-spectrum antibiotics, which disrupt the natural gut microbiota and allow this Gram-positive anaerobic pathogen to thrive. The increased incidence and severity of disease coupled with decreased response, high recurrence rates, and emergence of multiple antibiotic-resistant strains have created an urgent need for new therapies. We describe pharmacological targeting of the cysteine protease domain (CPD) within the C.