Evolutionary history and identification of conservation units in the giant otter, Pteronura brasiliensis.

The giant otter, Pteronura brasiliensis, occupies a range including the major drainage basins of South America, yet the degree of structure that exists within and among populations inhabiting these drainages is unknown. We sequenced portions of the mitochondrial DNA (mtDNA) cytochrome b (612 bp) and control region (383 bp) genes in order to determine patterns of genetic variation within the species. We found high levels of mtDNA haplotype diversity (h = 0.93 overall) and support for subdivision into four distinct groups of populations, representing important centers of genetic diversity and useful units for prioritizing conservation within the giant otter. We tested these results against the predictions of three hypotheses of Amazonian diversification (Pleistocene Refugia, Paleogeography, and Hydrogeology). While the phylogeographic pattern conformed to the predictions of the Refugia Hypothesis, molecular dating using a relaxed clock revealed the phylogroups diverged from one another between 1.69 and 0.84 Ma, ruling out the influence of Late Pleistocene glacial refugia. However, the role of Plio-Pleistocene climate change could not be rejected. While the molecular dating also makes the influence of geological arches according to the Paleogeography Hypothesis extremely unlikely, the recent Pliocene formation of the Fitzcarrald Arch and its effect of subsequently altering drainage pattern could not be rejected. The data presented here support the interactions of both climatic and hydrological changes resulting from geological activity in the Plio-Pleistocene, in shaping the phylogeographic structure of the giant otter

Tree genetic resources at risk in South America: A spatial threat assessment to prioritize populations for conservation

Background Humans threat the populations of tree species by overexploitation, deforestation, land use change, and climate change. We present a novel threat assessment at intraspecific level to support the conservation of genetic resources of 80 socioeconomically viable tree species in South America. In this assessment, we evaluate the threat status of Ecogeographic Range Segments (ERSs). ERSs are groups of populations of a specific species in a certain ecological zone of a particular grid cell of a species’ geographic occupancy. Methods We used species location records to determine the species distributions and species‐specific ERSs. We distinguished eight threat situations to assess the risk of extirpation of the ERSs of all 80 species. These threat situations were determined by large or little tree cover, low or high human pressure, and low or high climate change impact. Available layers of tree cover and threats were used to determine the levels of fragmentation and direct human pressure. Maxent niche modelling with two Global Circulation Models helped determining climate change impact by the 2050s. Results When all 80 species are considered, in total, 59% of the ERSs are threatened by little tree cover or high human pressure. When climate change is also considered, then 71‐73% of the ERSs are threatened. When an increased risk of extirpation of populations outside protected areas is considered, then 84–86% of the ERSs are threatened. Seven species warrant special attention because all their ERSs are threatened across their whole distribution in South America: Balfourondendron riedelianum, Cariniana legalis, Dalbergia nigra, Handroanthus pulcherrimus, Pachira quintana, Prosopis flexuosa, and Prosopis pallida. Conclusions Our results confirm the urgency to set up a regional action plan for the conservation of tree genetic resources in South America. With this threat assessment, we aim to support governments and organizations who are taking up this task

A phase 3 multicenter, prospective, open-label efficacy and safety study of immune globulin (human) 10% caprylate/chromatography purified in patients with myasthenia gravis exacerbations

Background: Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular transmission. Exacerbations may involve increasing bulbar weakness and/or sudden respiratory failure, both of which can be critically disabling. Management of MG exacerbations includes plasma exchange and intravenous immunoglobulin (IVIG); they are equally effective, but patients experience fewer side effects with IVIG. The objective of this study was to assess the efficacy and safety of immune globulin caprylate/chromatography purified (IGIV-C) in subjects with MG exacerbations. Methods: This prospective, open-label, non-controlled 28-day clinical trial was conducted in adults with MG Foundation of America class IVb or V status. Subjects received IGIV-C 2 g/kg over 2 consecutive days (1 g/kg/day) and were assessed for efficacy/safety on Days 7, 14, 21, and 28. The primary efficacy endpoint was the change from Baseline in quantitative MG (QMG) score to Day 14. Secondary endpoints of clinical response, Baseline to Day 14, included at least a 3-point decrease in QMG and MG Composite and a 2-point decrease in MG-activities of daily living (MG-ADL). Results: Forty-nine subjects enrolled. The change in QMG score at Day 14 was significant (p < 0.001) in the Evaluable (-6.4, n = 43) and Safety (-6.7, n = 49) populations. Among evaluable subjects, Day 14 response rates were 77, 86, and 88% for QMG, MG Composite, and MG-ADL, respectively. IGIV-C showed good tolerability with no serious adverse events. Conclusions: The results of this study show that IGIV-C was effective, safe, and well tolerated in the treatment of MG exacerbations

The COOH-Terminal Peptide of Platelet Factor-4 Variant (CXCL4L1/PF-4var47-70) Strongly Inhibits Angiogenesis and Suppresses B16 Melanoma Growth In vivo.

Chemokines influence tumor growth directly or indirectly via both angiogenesis and tumor-leukocyte interactions. Platelet factor-4 (CXCL4/PF-4), which is released from alpha-granules of activated platelets, is the first described angiostatic chemokine. Recently, it was found that the variant of CXCL4/PF-4 (CXCL4L1/PF-4var) could exert a more pronounced angiostatic and antitumoral effect than CXCL4/PF-4. However, the molecular mechanisms of the angiostatic activities of the PF-4 forms remain partially elusive. Here, we studied the biological properties of the chemically synthesized COOH-terminal peptides of CXCL4/PF-4 (CXCL4/PF-4(47-70)) and CXCL4L1/PF-4var (CXCL4L1/PF-4var(47-70)). Both PF-4 peptides lacked monocyte and lymphocyte chemotactic activity but equally well inhibited (25 nmol/L) endothelial cell motility and proliferation in the presence of a single stimulus (i.e., exogenous recombinant fibroblast growth factor-2). In contrast, when assayed in more complex angiogenesis test systems characterized by the presence of multiple mediators, including in vitro wound-healing (2.5 nmol/L versus 12.5 nmol/L), Matrigel (60 nmol/L versus 300 nmol/L), and chorioallantoic membrane assays, CXCL4L1/PF-4var(47-70) was found to be significantly (5-fold) more angiostatic than CXCL4/PF-4(47-70). In addition, low (7 mug total) doses of intratumoral CXCL4L1/PF-4var(47-70) inhibited B16 melanoma growth in mice more extensively than CXCL4/PF-4(47-70). This antitumoral activity was predominantly mediated through inhibition of angiogenesis (without affecting blood vessel stability) and induction of apoptosis, as evidenced by immunohistochemical and fluorescent staining of B16 tumor tissue. In conclusion, CXCL4L1/PF-4var(47-70) is a potent antitumoral and antiangiogenic peptide. These results may represent the basis for the design of CXCL4L1/PF-4var COOH-terminal-derived peptidomimetic anticancer drugs. Mol Cancer Res; 8(3); 322-34

Modelling for Taenia solium control strategies beyond 2020

The cestode Taenia solium is responsible for a considerable cross-sectoral health and economic burden due to human neurocysticercosis and porcine cysticercosis. The 2012 World Health Organization (WHO) roadmap for neglected tropical diseases called for the development of a validated strategy for control of T. solium; however, such a strategy is not yet available. In 2019, WHO launched a global consultation aimed at refining the post-2020 targets for control of T. solium for a new roadmap for neglected tropical diseases. In response, two groups working on taeniasis and cysticercosis mathematical models (cystiSim and EPICYST models), together with a range of other stakeholders organized a workshop to provide technical input to the WHO consultation and develop a research plan to support efforts to achieve the post-2020 targets. The workshop led to the formation of a collaboration, CystiTeam, which aims to tackle the population biology, transmission dynamics, epidemiology and control of T. solium through mathematical modelling approaches. In this paper, we outline developments in T. solium control and in particular the use of modelling to help achieve post-2020 targets for control of T. solium. We discuss the steps involved in improving confidence in the predictive capacities of existing mathematical and computational models on T. solium transmission, including model comparison, refinement, calibration and validation. Expanding the CystiTeam partnership to other research groups and stakeholders, particularly those operating in different geographical and endemic areas, will enhance the prospects of improving the applicability of T. solium transmission models to inform taeniasis and cysticercosis control strategies

Comparing the hierarchy of keywords in on-line news portals

The tagging of on-line content with informative keywords is a widespread phenomenon from scientific article repositories through blogs to on-line news portals. In most of the cases, the tags on a given item are free words chosen by the authors independently. Therefore, relations among keywords in a collection of news items is unknown. However, in most cases the topics and concepts described by these keywords are forming a latent hierarchy, with the more general topics and categories at the top, and more specialised ones at the bottom. Here we apply a recent, cooccurrence-based tag hierarchy extraction method to sets of keywords obtained from four different on-line news portals. The resulting hierarchies show substantial differences not just in the topics rendered as important (being at the top of the hierarchy) or of less interest (categorised low in the hierarchy), but also in the underlying network structure. This reveals discrepancies between the plausible keyword association frameworks in the studied news portals

Trends and seasonal variability in ammonia across major biomes in western and central Africa inferred from long-term series of ground-based and satellite measurements

Ammonia (NH3) is the most abundant alkaline component in the atmosphere. Changes in NH3 concentrations have important implications for atmospheric chemistry, air quality, and ecosystem integrity. We present a long-term ammonia (NH3) assessment in the western and central African regions within the framework of the International Network to study Deposition and Atmospheric chemistry in Africa (INDAAF) programme. We analyse seasonal variations and trends in NH3 concentrations and total column densities along an African ecosystem transect spanning dry savannas in Banizoumbou, Niger, and Katibougou, Mali; wet savannas in Djougou, Benin, and Lamto, Côte d'Ivoire; and forests in Bomassa, Republic of the Congo, and Zoétélé, Cameroon. We use a 21-year record of observations (1998–2018) from INDAAF passive samplers and an 11-year record of observations (2008–2018) of atmospheric vertical column densities from the Infrared Atmospheric Sounding Interferometer (IASI) to evaluate NH3 ground-based concentrations and total column densities, respectively. Climatic data (air temperature, rainfall amount, and leaf area index), as well as ammonia emission data of biomass combustion from the fourth version of the Global Fire Emissions Database (GFED4) and anthropogenic sources from the Community Emissions Data System (CEDS), were compared with total NH3 concentrations and total columns over the same periods. Annual mean ground-based NH3 concentrations are around 5.7–5.8 ppb in dry savannas, 3.5–4.7 ppb in wet savannas, and 3.4–5.6 ppb in forests. Annual IASI NH3 total column densities are 10.0–10.7 × 1015 molec. cm−2 in dry savanna, 16.0–20.9 × 1015 molec. cm−2 in wet savanna, and 12.4–13.8 × 1015 molec. cm−2 in forest stations. Non-parametric statistical Mann–Kendall trend tests applied to annual data show that ground-based NH3 concentrations increase at Bomassa (+2.56 % yr−1) but decrease at Zoétélé (−2.95 % yr−1) over the 21-year period. The 11-year period of IASI NH3 total column density measurements show yearly increasing trends at Katibougou (+3.46 % yr−1), Djougou (+2.24 % yr−1), and Zoétélé (+3.42 % yr−1). From the outcome of our investigation, we conclude that air temperature, leaf area index, and rainfall combined with biomass burning, agricultural, and residential activities are the key drivers of atmospheric NH3 in the INDAAF stations. The results also show that the drivers of trends are (1) agriculture in the dry savanna of Katibougou; (2) air temperature and agriculture in the wet savanna of Djougou and Lamto; and (3) leaf area index, air temperature, residential, and agriculture in the forest of Bomassa.</p

Erasmus Language students in a British University – a case study

Students’ assessment of their academic experience is actively sought by Higher Education institutions, as evidenced in the National Student Survey introduced in 2005. Erasmus students, despite their growing numbers, tend to be excluded from these satisfaction surveys, even though they, too, are primary customers of a University. This study aims to present results from bespoke questionnaires and semi-structured interviews with a sample of Erasmus students studying languages in a British University. These methods allow us insight into the experience of these students and their assessment as a primary customer, with a focus on language learning and teaching, university facilities and student support. It investigates to what extent these factors influence their levels of satisfaction and what costs of adaptation if any, they encounter. Although excellent levels of satisfaction were found, some costs affect their experience. They relate to difficulties in adapting to a learning methodology based on a low number of hours and independent learning and to a guidance and support system seen as too stifling. The results portray this cohort’s British University as a well-equipped and well-meaning but ultimately overbearing institution, which may indicate that minimising costs can eliminate some sources of dissatisfaction

Rectal Transmission of Transmitted/Founder HIV-1 Is Efficiently Prevented by Topical 1% Tenofovir in BLT Humanized Mice

Rectal microbicides are being developed to prevent new HIV infections in both men and women. We focused our in vivo preclinical efficacy study on rectally-applied tenofovir. BLT humanized mice (n = 43) were rectally inoculated with either the primary isolate HIV-1(JRCSF) or the MSM-derived transmitted/founder (T/F) virus HIV-1(THRO) within 30 minutes following treatment with topical 1% tenofovir or vehicle. Under our experimental conditions, in the absence of drug treatment we observed 50% and 60% rectal transmission by HIV-1(JRCSF) and HIV-1(THRO), respectively. Topical tenofovir reduced rectal transmission to 8% (1/12; log rank p = 0.03) for HIV-1(JRCSF) and 0% (0/6; log rank p = 0.02) for HIV-1(THRO). This is the first demonstration that any human T/F HIV-1 rectally infects humanized mice and that transmission of the T/F virus can be efficiently blocked by rectally applied 1% tenofovir. These results obtained in BLT mice, along with recent ex vivo, Phase 1 trial and non-human primate reports, provide a critically important step forward in the development of tenofovir-based rectal microbicides