Pharmacological challenge with a serotonin 1D agonist in alcohol dependence

BACKGROUND: Both animal and clinical studies have implicated serotonergic dysfunction in the pathogenesis of alcohol abuse and dependence. However the exact mechanisms involved remain unknown. Theoretically, low serotonin promotes alcohol seeking behavior. Sumatriptan is a serotonin1D agonist. It is postulated that sumatriptan's agonism at this terminal autoreceptor increases negative feedback, creating a net effect of decreased serotonergic neurotransmission. Administration of sumatriptan should therefore produce a craving for alcohol and the desire to drink. METHODS: Fifteen patients with alcohol dependence who had undergone detoxification were recruited. Sumatriptan (100 mg) and placebo was administered in cross-over fashion on 2 separate days 72 hours apart. Both patients and raters were blind to all treatments. Patients were assessed on the following scales at -30, 0, 30, 90, 150 and 210 minutes: A 6-item scale designed to rate the patient's intention to drink; The Sensation Scale; a 13-item affect analog scale designed to rate the pattern and extent of emotional changes; and an 8-item scale designed to rate the patient's craving for alcohol RESULTS: No significant differences were found between the placebo and sumatriptan groups and no significant cross over effects were found. CONCLUSION: The general lack of efficacy of sumatriptan in producing alcohol-like symptoms or a desire to drink alcohol may suggest that the 5HT1D receptor plays little role in the pathophysiology of alcoholism

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.) and intensities (e.g., large-scale vs smallholder cropland). This dataset was co-produced as part of the Biodiversity Intactness Index for Africa Project. Additional uses include assessing ecosystem condition; rectifying geographic/ taxonomic biases in global biodiversity indicators and maps; and informing the Red List of Ecosystems

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

Early Bactericidal Activity and Pharmacokinetics of PA-824 in Smear-Positive Tuberculosis Patients▿ †

PA-824 is a novel nitroimidazo-oxazine being evaluated for its potential to improve tuberculosis (TB) therapy. This randomized study evaluated safety, tolerability, pharmacokinetics, and extended early bactericidal activity of PA-824 in drug-sensitive, sputum smear-positive, adult pulmonary tuberculosis patients. Fifteen patients per cohort received 1 of 4 doses of oral PA-824: 200, 600, 1,000, or 1,200 mg per day for 14 days. Eight subjects received once daily standard antituberculosis treatment as positive control. The primary efficacy endpoint was the mean rate of change in log CFU of Mycobacterium tuberculosis in sputum incubated on agar plates from serial overnight sputum collections, expressed as log10 CFU/day/ml (± standard deviation [SD]). The drug demonstrated increases that were dose linear but less than dose proportional in serum concentrations in doses from 200 to 1,000 mg daily. Dosing of 1,200 mg gave no additional exposure compared to 1,000 mg daily. The mean daily CFU fall under standard treatment was 0.148 (±0.055), consistent with that found in previous studies. The mean daily fall under PA-824 was 0.098 (±0.072) and was equivalent for all four dosages. PA-824 appeared safe and well tolerated; the incidence of adverse events potentially related to PA-824 appeared dose related. We conclude that PA-824 demonstrated bactericidal activity over the dose range of 200 to 1,200 mg daily over 14 days. Because maximum efficacy was unexpectedly achieved at the lowest dosage tested, the activity of lower dosages should now be explored

Subtle structures with not-so-subtle functions: A dataset of arthropod constructs and their host plants

The construction of shelters on plants by arthropods might influence other organisms via changes in colonization, community richness, species composition and functionality. Arthropods, including beetles, caterpillars, sawflies, spiders, and wasps often interact with host plants via the construction of shelters, building a variety of structures such as leaf ties, tents, rolls, and bags; leaf and stem galls, and hollowed out stems. Such constructs might have both an adaptive value in terms of protection (i.e., serve as shelters) but may also exert a strong influence on terrestrial community diversity in the engineered and neighboring hosts via colonization by secondary occupants. While different traits of the host plant (e.g., physical, chemical and architectural features) may affect the potential for ecosystem engineering by insects, such effects have been, to a certain degree, overlooked. Further analyses of how plant traits affect the occurrence of shelters may thus enrich our understanding of the organizing principles of plant-based communities. This dataset includes more than a thousand unique records of ecosystem engineering by arthropods, in the form of structures built on plants. All records have been published in the literature, and span both natural structures (90.6% of the records) and structures artificially created byresearchers (9% of the records). The data were gathered between 1932 and 2021, across more than 50 countries and several ecosystems, ranging from polar to tropical zones. Besides data on host plants and engineers, we aggregated data on the type of constructs and the identity of inquilines using these structures. This dataset highlights the importance of these subtle structures for the organization of terrestrial arthropod communities, enabling hypotheses testing in ecological studiesaddressing ecosystem engineering and facilitation mediated by constructs.Fil: Pereira, Cássio Cardoso. Universidade Federal de Minas Gerais; BrasilFil: Novais, Samuel. Instituto de Ecología; MéxicoFil: Barbosa, Milton. Universidade Federal de Minas Gerais; BrasilFil: Negreiros, Daniel. Universidade Federal de Minas Gerais; BrasilFil: Gonçalves Souza, Thiago. Universidade Federal de Pernambuco; BrasilFil: Roslin, Tomas. Swedish University Of Agricultural Sciences; SueciaFil: Marquis, Robert. University of Missouri; Estados UnidosFil: Marino, Nicholas. Universidade Federal do Rio de Janeiro; BrasilFil: Novotny, Vojtech. Biology Centre of the Academy of Sciences of the Czech Republic; República ChecaFil: Orivel, Jerome. Universite de Guyane; GuyanaFil: Sui, Shen. New Guinea Binatang Research Center; GuineaFil: Aires, Gustavo. Universidade Federal de Pernambuco; BrasilFil: Antoniazzi, Reuber. University of Texas at Austin; Estados UnidosFil: Dáttilo, Wesley. Instituto de Ecología; MéxicoFil: Breviglieri, Crasso. Universidade Estadual de Campinas; BrasilFil: Busse, Annika. Bavarian Forest National Park; AlemaniaFil: Gibb, Heloise. La Trobe University. Department Of Ecology, Environment And Evolution; AustraliaFil: Izzo, Thiago. Universidade Federal do Mato Grosso do Sul; BrasilFil: Kadlec, Tomas. Czech University Of Life Sciences Prague; República ChecaFil: Kemp, Victoria. Queen Mary University of London; Reino UnidoFil: Kersch Becker, Monica. University of Alabama at Birmingahm; Estados UnidosFil: Knapp, Michal. Czech University Of Life Sciences Prague; República ChecaFil: Kratina, Pavel. Queen Mary University of London; Reino UnidoFil: Luke, Rebecca. Royal Holloway University of London; Reino UnidoFil: Majnari, Stefan. University Of Zagreb, Faculty Of Science; CroaciaFil: Maritz, Robin. University of the Western Cape; SudáfricaFil: Martins, Paulo Mateus. Universidade Federal de Pernambuco; BrasilFil: Mendesil, Esayas. Jimma University; EtiopíaFil: Michalko, Jaroslav. Slovak Academy of Sciences; EslovaquiaFil: Mrazova, Anna. Biology Centre of the Academy of Sciences of the Czech Republic; República ChecaFil: Peri, Mirela Serti. University Of Zagreb. Faculty Of Science; CroaciaFil: Petermann, Jana. University Of Salzburg. Department Of Biosciences; AustriaFil: Ribeiro, Sérvio. Universidade Federal de Ouro Preto; BrasilFil: Sam, Katerina. University of Missouri; Estados UnidosFil: Trzcinski, M. Kurtis. University of British Columbia; CanadáFil: Vieira, Camila. Universidade Federal de Uberlândia; BrasilFil: Westwood, Natalie. University of British Columbia; CanadáFil: Bernaschini, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Carvajal, Valentina. Universidad de Caldas; ColombiaFil: González, Ezequiel. Czech University of Life Sciences Prague; República ChecaFil: Jausoro, Mariana. Universidad Nacional de Chilecito. Departamento de Ciencias Basicas y Tecnologicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Kaensin, Stanis. New Guinea Binatang Research Center; GuineaFil: Ospina, Fabiola. Universidad de Caldas; ColombiaFil: Pérez, Jacob Cristóbal. Universidad Autónoma del Estado de México; MéxicoFil: Quesada, Mauricio. Universidad Autónoma del Estado de México; MéxicoFil: Rogy, Pierre. University of British Columbia; CanadáFil: Srivastava, Diane S.. University of British Columbia; CanadáFil: Szpryngiel, Scarlett. The Swedish Museum of Natural History; SueciaFil: Tack, Ayco J. M.. Stockholms Universitet; SueciaFil: Teder, Tiit. University of Tartu; EstoniaFil: Videla, Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Viljur, Mari Liis. University of Tartu; EstoniaFil: Koricheva, Julia. Royal Holloway University of London; Reino UnidoFil: Fernandes, Geraldo Wilson Afonso. Universidade Federal de Minas Gerais; BrasilFil: Romero, Gustavo Q.. Universidade Estadual de Campinas; BrasilFil: Cornelissen, Tatiana. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas; Brasi

bii4africa dataset

The bii4africa dataset is presented in a multi-spreadsheet .xlsx file. The raw data spreadsheet (‘Scores_Raw’) includes 31,313 individual expert estimates of the impact of a sub-Saharan African land use on a species response group of terrestrial vertebrates or vascular plants. Estimates are reported as intactness scores - the remaining proportion of an ‘intact’ reference (pre-industrial or contemporary wilderness area) population of a species response group in a land use, on a scale from 0 (no individuals remain) through 0.5 (half the individuals remain), to 1 (same as the reference population) and, in limited cases, to 2 (two or more times the reference population). For species that thrive in human-modified landscapes, scores could be greater than 1 but not exceeding 2 to avoid extremely large scores biasing aggregation exercises. Expert comments are included alongside respective estimates

bi4africa dataset - open source

The bii4africa dataset is presented in a multi-spreadsheet .ods file. The raw data spreadsheet (‘Scores_Raw’) includes 31,313 individual expert estimates of the impact of a sub-Saharan African land use on a species response group of terrestrial vertebrates or vascular plants. Estimates are reported as intactness scores - the remaining proportion of an ‘intact’ reference (pre-industrial or contemporary wilderness area) population of a species response group in a land use, on a scale from 0 (no individuals remain) through 0.5 (half the individuals remain), to 1 (same as the reference population) and, in limited cases, to 2 (two or more times the reference population). For species that thrive in human-modified landscapes, scores could be greater than 1 but not exceeding 2 to avoid extremely large scores biasing aggregation exercises. Expert comments are included alongside respective estimates