Baobab Index

Understanding how dietary compounds affect human health is challenged by their molecular complexity and cell-type-specific effects. Conventional multi-cell type (bulk) analyses obscure cellular heterogeneity, while animal and standard

Although coccidial infection is often asymptomatic in sheep, both clinical and subclinical forms of the disease are linked to considerable production losses, mainly in young lambs. Studies aiming to identify genetic markers for use in selection programs towards increasing genetic resistance to coccidiosis are lacking and have yet to be performed in Portuguese Merino sheep. The purpose of this study was to identify genomic regions associated with resistance to coccidiosis by conducting a genome-wide association study (GWAS) in Portuguese Merino sheep. From an initial population of 1,022 sheep having known phenotypic characteristics, 206 and 202 distinct animals were genotyped using 50 K and 600 K Single Nucleotide Polymorphism (SNP) arrays, respectively. After the 50 K array was imputed using a 600 K array as reference, an association analysis was performed for faecal oocyst counts (FOC). We identified 12 SNPs that were significantly associated with resistance by using a chromosome-wide significance threshold. The significant SNPs were related to Ccser1, Thsd4, Eci1, Tnfrsf12a, Chrm3 and Slc20a2 genes. We identified 80 candidate genes located in the proximity of the significant SNPs using the defined confidence regions. Two types of gene set enrichment analyses were performed. Enrichment based on the set of candidate genes, identified the terms virus receptor activity and exogenous protein binding to be enriched, both due to two claudins, CLDN6 and CLDN9. Enrichment based on gene interactions, showed enrichment of terms related to transport vesicles, mainly due to the presence of Rab proteins. Given the role that Rab and Claudins play in host-parasite relationships, these results suggest the existence of reliable markers associated with resistance to coccidiosis. These markers should be explored in future studies to further validate their use in marker assisted selection, with the goal of enhancing sustainability of the breed conservation-management program.

Cancer is an increasing public health burden, including in Sub-Saharan African (SSA) populations, where cancer incidence is predicted to increase by around 140% between 2022 and 2050. These rates require a better understanding of the epidemiological, clinical, and genetic/molecular characteristics of cancer in SSA populations. There is an urgent need to improve the genomic characterization of SSA tumour samples and also to establish suitable in vitro models for hypothesis testing. In fact, even though thousands of cancer cell lines (CCLs) have been established employing different methods of cell immortalization and have been included in deep molecular characterization panels, SSA ancestry is limited to only ~6% (mostly African Americans, who represent limited diversity in the context of the African continent) of publicly available CCLs. This disparity needs to be addressed by using next-generation immortalization methods such as conditional reprogramming to establish CCLs derived from SSA cancer patients that also represent the diversity within the African continent. Research in SSA oncobiology has the potential to add essential information to better understand the diverse molecular pathways leading to cancer and to find promising therapeutic avenues. We also discuss the challenges to conducting oncobiology studies with cell modelling derived from SSA patients in low-to-middle-income African countries, such as Portuguese-speaking African countries.

African populations remain substantially under-represented in research studies and global genomic databases. As the ancestral home of anatomically modern humans, Africa holds pride of place regarding human genetic diversity, with a deep and complex evolution over hundreds of thousands of years of human migration, admixture, and exposure to climate changes and infectious agents. Yet our present view of genomic diversity in Africa is sparse and poorly captures the rich variation across its more than 2,000 ethnolinguistic groups. To enhance representation, the Assessing Genetic Diversity in Africa (AGenDA) project, under the umbrella of the Human Heredity and Health in Africa (H3Africa) consortium, identified under-represented groups across nine different African countries for human whole-genome sequencing, with a view to enriching global datasets. Here we share our processes, including community engagement, obtaining ethics approvals, navigating legal compliance and developing a common governance framework. AGenDA is a testament to the determination of the scientific community to undertake research in challenging environments. It is led from Africa by African investigators who are the decision-makers in data-sharing processes. AGenDA is a step towards greater African representation in global genomic datasets to advance genomic research towards enabling precision medicine for Africa and the world.

ObjectivesTetralogy of Fallot (TOF) repair is associated with low mortality in high-performance centers, but outcomes are worse in low- and middle-income countries (LMICs). Prior studies have not demonstrated a strong link between Technical Performance Score (TPS) and mortality. The aim of this was to evaluate risk factors for mortality and complications after TOF repair in a high-volume LMIC heart center with a focus on surgical performance.MethodsWe retrospectively reviewed children undergoing TOF repair between 2015 and 2022. Patients over two years of age or with complex defects beyond atrial septal defect and persistent ductus arteriosus were excluded. Preoperative factors included age, weight, genetic syndromes, urgency, and pulmonary artery z-scores. Intraoperative variables included transannular patch use, cardiopulmonary bypass and cross-clamp times, surgeon, and TPS classification. Postoperative variables included delayed sternal closure (DSC), extracorporeal membrane oxygenation (ECMO), and Vasoactive Inotropic Score (VIS) during the first 24 h. Outcomes included mortality, complications, and length of stay (LOS). Analyses included logistic regression and Kaplan-Meier estimates.ResultsAmong 255 patients, in-hospital mortality was 7.5% (n = 19). Technical Performance Score class 3 was an independent predictor of mortality (

Amodiaquine-artesunate is one of the recommended options by the Angolan National Malaria Control Program for the treatment of uncomplicated malaria and for malaria seasonal chemoprevention. CYP2C8 is a critical enzyme in the metabolism of amodiaquine. The CYP2C8 gene harbors alleles coding for less active enzymes that have been linked to amodiaquine-associated adverse events. In this work, we analyzed the prevalences of the CYP2C8 main alleles in a sample of the Angolan population. We found an expected robust frequency of a very-low-activity allele, CYP2C8*2 (18.2%) but also the unusual presence of alleles CYP2C8*3 (1%) and CYP2C8*4 (0.5%). Together, these alleles were seen in a non-negligible group of Plasmodium falciparum malaria patients and children under amodiaquine-based therapies and prophylactic strategies.

The majority of SARS-CoV-2 genomes obtained during the pandemic were derived by amplifying overlapping windows of the genome ('tiled amplicons'), reconstructing their sequences and fitting them together. This leads to systematic errors in genomes unless the software is both aware of the amplicon scheme and of the error modes of amplicon sequencing. Additionally, over time, amplicon schemes need to be updated as new mutations in the virus interfere with the primer binding sites at the end of amplicons. Thus, waves of variants swept the world during the pandemic and were followed by waves of systematic errors in the genomes, which had significant impacts on the inferred phylogenetic tree.Here we reconstruct the genomes from all public data as of June 2024 using an assembly tool called Viridian ( https://github.com/iqbal-lab-org/viridian ), developed to rigorously process amplicon sequence data. With these high-quality consensus sequences we provide a global phylogenetic tree of 4,471,579 samples, viewable at https://viridian.taxonium.org . We provide simulation and empirical validation of the methodology, and quantify the improvement in the phylogeny.

Salix suchowensis is an important species of Salix, known for its rapid growth property and wide application in environmental construction, ecological restoration, wicker production, and biomass energy production. Due to its significance as a sustainable biological resource, S. suchowensis has been the centre of intensive breeding. However, rapid improvement of growth and biomass has been hindered by a lack of genomic resources. To address this limitation, we designed a liquid-phase probe array by genotyping by target sequencing technology. Using whole-genome resequencing data, a total of 39,076 SNPs were selected for the array panel, consisting of trait-associated SNPs, intragenic SNPs, and intergenic SNPs. This panel was validated by genotyping 550 new samples, demonstrating high call rates and effective capture of the population structure. Genome-wide association analysis identified 72 SNPs associated with plant height and ground diameter. Additionally, the array panel shows a high potential for genomic selection, with high prediction accuracy for various traits. These results highlight the efficiency of this panel in capturing genomic variations that are highly valuable for future genetic research and breeding applications.

Plasmodium falciparum malaria remains a leading cause of mortality in Angola, with emerging antimalarial resistance threatening treatment and prevention strategies. Efficacy of artemether-lumefantrine has been reported below 90% in two provinces, underscoring the need for routine resistance surveillance. This study aimed to provide a geographically comprehensive and up-to-date overview of antimalarial drug resistance markers in Angola. Between March and July 2023, dried blood spots and demographic data were collected from P. falciparum-positive participants at 14 health facilities across 7 provinces. Multiplexed amplicon sequencing was used to characterize single nucleotide polymorphisms in 12 genes linked with resistance, estimate allele frequencies, and detect coinfecting non-falciparum Plasmodium species. Sequence data from 820 samples revealed significant geographic variation in resistance markers. In the southeast, artemisinin partial resistance markers (k13 P574L, P441L) were detected at very low prevalence (<0.1%), whereas the quintuple dhps/dhfr haplotype, linked to sulfadoxine-pyrimethamine resistance, was very prevalent (>35% of samples). In the northwest, the sextuple dhps/dhfr haplotype, a marker of higher sulfadoxine-pyrimethamine resistance, was most prevalent in the Zaire province (14.2%). The chloroquine resistance marker crt C72/V73/M74I/N75E/K76T (CVIET) haplotype had a national prevalence of 17.7%, detected in over 48% of samples from the northern sites. The mdr1 N86 genotype, linked to reduced lumefantrine susceptibility, was detected in 99.2% of samples. Coinfections of P. falciparum and non-falciparum species were rare, with no Plasmodium vivax coinfections detected. These findings highlight the need for continued monitoring to safeguard treatment efficacy, reinforcing the importance of molecular surveillance in malaria control strategies.

Migration to Europe has been rising in recent years and is associated with higher HIV vulnerability due to overlapping social and structural barriers. New cases among migrants have been steadily increasing, and for the first time in Portugal, there were more cases among migrants than among non-migrants in 2023. This study aims to compare sociodemographic, behavioural, clinical, and viral genomic characteristics of non-migrant and migrant MSM newly diagnosed with HIV-1 in Portugal (2023-2024), as well as the composition of Transmission Clusters (TC) to which they belong. Between June 2023 and December 2024, 60 MSM were recruited upon HIV-1 reactive screening in a community centre in Lisbon. Sociodemographic and behavioural data were collected through a questionnaire. A blood sample was collected for viral load measurement and HIV-1 genomic sequencing. TC were identified using a branch support ≥ 90% and iterating between 1.5%, 2.5%, 3.5%, 4.5%, 5.5% and 6.5% genetic distances. Among the 60 MSM newly diagnosed with HIV in our 2023-2024 community-based sample, 70% were migrants, of whom 60% were from Latin America and 10% from other regions. The results showed significant differences in age at diagnosis, district of residence, and HIV-1 subtype between non-migrants and migrants, while sexual behaviours, testing patterns, and STI prevalence were similar across the two groups. No difference between the proportion of non-migrant and migrant MSM in TC was found. Notably, phylogenetic analysis suggests that migrant MSM are mainly related to other migrant MSM and outside Portugal. In contrast, non-migrant MSM were more frequently found in mixed clusters. All Surveillance drug resistance mutations (SDRM) in TC were related to migrant MSM. Findings from this single community-based centre suggest that recent HIV-1 epidemiology among MSM has shifted towards an increased proportion of migrants in MSM HIV diagnosis, who are primarily involved in sexual networks with other migrants. To effectively address these current dynamics, Portugal should explore strategies to improve early and accessible PrEP, STI, and HIV testing for the migrant MSM communities.