Genetic Characterization of a New HIV-1 Sub-Subtype A in Cabo Verde, Denominated A8.
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ABSTRACT:
SUBMITTER: Mendes Da Silva RK
PROVIDER: S-EPMC8230070 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectivesWe used an individual-based model to evaluate the effects of hypothetical prevention interventions on HIV incidence trajectories in a concentrated, mixed epidemic setting from 2011 to 2021, and using Cabo Verde as an example.MethodsSimulations were conducted to evaluate the extent to which early HIV treatment and optimization of care, HIV testing, condom distribution, and substance abuse treatment could eliminate new infections (i.e., reduce incidence to less than 10 cases per 10,000 person-years) among non-drug users, female sex workers (FSW), and people who use drugs (PWUD).ResultsScaling up all four interventions resulted in the largest decreases in HIV, with estimates ranging from 1.4 (95 % CI 1.36-1.44) per 10,000 person-years among non-drug users to 8.2 (95 % CI 7.8-8.6) per 10,000 person-years among PWUD in 2021. Intervention scenarios prioritizing FWS and PWUD also resulted in HIV incidence estimates at or below 10 per 10,000 person-years by 2021 for all population sub-groups.ConclusionsOur results suggest that scaling up multiple interventions among entire population is necessary to achieve elimination. However, prioritizing key populations with this combination prevention strategy may also result in a substantial decrease in total incidence.
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Project description:From the 15th to the 19th century, the Trans-Atlantic Slave-Trade (TAST) influenced the genetic and cultural diversity of numerous populations. We explore genomic and linguistic data from the nine islands of Cabo Verde, the earliest European colony of the era in Africa, a major Slave-Trade platform between the 16th and 19th centuries, and a previously uninhabited location ideal for investigating early admixture events between Europeans and Africans. Using local-ancestry inference approaches, we find that genetic admixture in Cabo Verde occurred primarily between Iberian and certain Senegambian populations, although forced and voluntary migrations to the archipelago involved numerous other populations. Inter-individual genetic and linguistic variation recapitulates the geographic distribution of individuals' birth-places across Cabo Verdean islands, following an isolation-by-distance model with reduced genetic and linguistic effective dispersals within the archipelago, and suggesting that Kriolu language variants have developed together with genetic divergences at very reduced geographical scales. Furthermore, based on approximate bayesian computation inferences of highly complex admixture histories, we find that admixture occurred early on each island, long before the 18th-century massive TAST deportations triggered by the expansion of the plantation economy in Africa and the Americas, and after this era mostly during the abolition of the TAST and of slavery in European colonial empires. Our results illustrate how shifting socio-cultural relationships between enslaved and non-enslaved communities during and after the TAST, shaped enslaved-African descendants' genomic diversity and structure on both sides of the Atlantic.
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Project description:Conus ateralbus is a cone snail endemic to the west side of the island of Sal, in the Cabo Verde Archipelago off West Africa. We describe the isolation and characterization of the first bioactive peptide from the venom of this species. This 30AA venom peptide is named conotoxin AtVIA (δ-conotoxin-like). An excitatory activity was manifested by the peptide on a majority of mouse lumbar dorsal root ganglion neurons. An analog of AtVIA with conservative changes on three amino acid residues at the C-terminal region was synthesized and this analog produced an identical effect on the mouse neurons. AtVIA has homology with δ-conotoxins from other worm-hunters, which include conserved sequence elements that are shared with δ-conotoxins from fish-hunting Conus. In contrast, there is no comparable sequence similarity with δ-conotoxins from the venoms of molluscivorous Conus species. A rationale for the potential presence of δ-conotoxins, that are potent in vertebrate systems in two different lineages of worm-hunting cone snails, is discussed.
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Project description:Mortality analysis studies in Cabo Verde are scarce and those available are limited to short periods of analysis and to specific population groups. National mortality data reports do not quantify the burden of disease associated with premature mortality. This study estimated the years of potential life lost (YPLL), years of potential productive life lost (YPPLL) and the costs associated with them in Cabo Verde from 2016 to 2020 and aimed to determine trends of early mortality due to all causes of death. Mortality data were obtained from the Ministry of Health, Cabo Verde. Deaths that occurred from 2016 to 2020, in individuals aged between one (1) and 73 years old were analyzed by sex, age group, municipality and cause of death. YPLL, YPPLL and cost of productivity lost (CPL) were estimated using life expectancy and the human capital approach methods, respectively. There were 6100 deaths recorded in the sample population and males represented 68.1% (n = 4,154) of the reported deaths. The number of deaths verified corresponded to 145,544 YPLL, of which 69.0% (n = 100,389) were attributed to males. There were 4,634 deaths among individuals of working age, which resulted in 80 965 YPPLL, with males contributing 72.1% (n = 58,403) of the total YPPLL. The estimated CPL due to premature death was 98,659,153.23 USD. Injuries and external causes together accounted for 21,580,954.42 USD (21.9%) of CPL, while diseases of the circulatory system 18,843,260.42 USD (19.1%) and certain infectious and parasitic diseases accounted for 16,633,842.70 USD (16.9%). The study demonstrated the social and economic burden of premature mortality. The YPLL, YPPLL and CPL measures can be used to complement measures traditionally used to demonstrate the burden and loss of productivity due to premature mortality and to support resource allocation and public health decision making in Cabo Verde.
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Project description:Botulism is a severe neurological disease caused by the complex family of botulinum neurotoxins (BoNT). Based on the different serotypes known today, a classification of serotype variants termed subtypes has been proposed according to sequence diversity and immunological properties. However, the relevance of BoNT subtypes is currently not well understood. Here we describe the isolation of a novel Clostridium botulinum strain from a food-borne botulism outbreak near Chemnitz, Germany. Comparison of its botulinum neurotoxin gene sequence with published sequences identified it to be a novel subtype within the BoNT/A serotype designated BoNT/A8. The neurotoxin gene is located within an ha-orfX+ cluster and showed highest homology to BoNT/A1, A2, A5, and A6. Unexpectedly, we found an arginine insertion located in the HC domain of the heavy chain, which is unique compared to all other BoNT/A subtypes known so far. Functional characterization revealed that the binding characteristics to its main neuronal protein receptor SV2C seemed unaffected, whereas binding to membrane-incorporated gangliosides was reduced in comparison to BoNT/A1. Moreover, we found significantly lower enzymatic activity of the natural, full-length neurotoxin and the recombinant light chain of BoNT/A8 compared to BoNT/A1 in different endopeptidase assays. Both reduced ganglioside binding and enzymatic activity may contribute to the considerably lower biological activity of BoNT/A8 as measured in a mouse phrenic nerve hemidiaphragm assay. Despite its reduced activity the novel BoNT/A8 subtype caused severe botulism in a 63-year-old male. To our knowledge, this is the first description and a comprehensive characterization of a novel BoNT/A subtype which combines genetic information on the neurotoxin gene cluster with an in-depth functional analysis using different technical approaches. Our results show that subtyping of BoNT is highly relevant and that understanding of the detailed toxin function might pave the way for the development of novel therapeutics and tailor-made antitoxins.
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Project description:Due to their great species and ecological diversity as well as their capacity to produce hundreds of different toxins, cone snails are of interest to evolutionary biologists, pharmacologists and amateur naturalists alike. Taxonomic identification of cone snails still relies mostly on the shape, color, and banding patterns of the shell. However, these phenotypic traits are prone to homoplasy. Therefore, the consistent use of genetic data for species delimitation and phylogenetic inference in this apparently hyperdiverse group is largely wanting. Here, we reconstruct the phylogeny of the cones endemic to Cabo Verde archipelago, a well-known radiation of the group, using mitochondrial (mt) genomes.The reconstructed phylogeny grouped the analyzed species into two main clades, one including Kalloconus from West Africa sister to Trovaoconus from Cabo Verde and the other with a paraphyletic Lautoconus due to the sister group relationship of Africonus from Cabo Verde and Lautoconus ventricosus from Mediterranean Sea and neighboring Atlantic Ocean to the exclusion of Lautoconus endemic to Senegal (plus Lautoconus guanche from Mauritania, Morocco, and Canary Islands). Within Trovaoconus, up to three main lineages could be distinguished. The clade of Africonus included four main lineages (named I to IV), each further subdivided into two monophyletic groups. The reconstructed phylogeny allowed inferring the evolution of the radula in the studied lineages as well as biogeographic patterns. The number of cone species endemic to Cabo Verde was revised under the light of sequence divergence data and the inferred phylogenetic relationships.The sequence divergence between continental members of the genus Kalloconus and island endemics ascribed to the genus Trovaoconus is low, prompting for synonymization of the latter. The genus Lautoconus is paraphyletic. Lautoconus ventricosus is the closest living sister group of genus Africonus. Diversification of Africonus was in allopatry due to the direct development nature of their larvae and mainly triggered by eustatic sea level changes during the Miocene-Pliocene. Our study confirms the diversity of cone endemic to Cabo Verde but significantly reduces the number of valid species. Applying a sequence divergence threshold, the number of valid species within the sampled Africonus is reduced to half.
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Project description:Raised blood pressure (BP) is the biggest contributor to mortality and disease burden in Cabo Verde. May Measurement Month (MMM) is a global campaign set up in 2017 to raise awareness of high BP. In 2018, we aimed to expand the campaign by including a greater number of centres to increase awareness. Nine islands participated in MMM 2018. Volunteers (≥18 years) were recruited through opportunistic sampling at a variety of screening sites. Each participant had three BP measurements and completed a questionnaire on demographic, lifestyle, and environmental factors. Hypertension was defined as a systolic BP ≥140 mmHg and/or diastolic BP ≥90 mmHg, or taking antihypertensive medication. In total, 98.0% of screenees provided three BP readings and multiple imputation using chained equations was used to impute missing readings. A total of 8008 individuals (mean age 40.4 years; 68.5% female) were screened. After multiple imputation, 2666 (33.3%) individuals had hypertension, of whom 74.8% were aware of their previous diagnosis and 55.8% were taking antihypertensive medication. Of those on medication, 39.1% were controlled and of all hypertensives, 21.8% were controlled. We detected 44.2% of individuals with untreated hypertension and 60.9% of treated individuals were inadequately treated. The Cape Verdean population is ageing and consequently cardiovascular disease is increasing, with hypertension being an important risk factor. Corrective actions need to be taken by the government. MMM is an ideal initiative to reach the public by raising awareness of this major cardiovascular risk factor.
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Project description:Humans have undergone large migrations over the past hundreds to thousands of years, exposing ourselves to new environments and selective pressures. Yet, evidence of ongoing or recent selection in humans is difficult to detect. Many of these migrations also resulted in gene flow between previously separated populations. These recently admixed populations provide unique opportunities to study rapid evolution in humans. Developing methods based on distributions of local ancestry, we demonstrate that this sort of genetic exchange has facilitated detectable adaptation to a malaria parasite in the admixed population of Cabo Verde within the last ~20 generations. We estimate that the selection coefficient is approximately 0.08, one of the highest inferred in humans. Notably, we show that this strong selection at a single locus has likely affected patterns of ancestry genome-wide, potentially biasing demographic inference. Our study provides evidence of adaptation in a human population on historical timescales.
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