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

Distraction from pain and executive functioning: an experimental investigation of the role of inhibition, task switching and working memory

Although many studies have investigated the effectiveness of distraction as a method of pain control, the cognitive processes by which attentional re-direction is achieved, remain unclear. In this study the role of executive functioning abilities (inhibition, task switching and working memory) in the effectiveness of distraction is investigated. We hypothesized that the effectiveness of distraction in terms of pain reduction would be larger in participants with better executive functioning abilities. Ninety-one undergraduate students first performed executive functioning tasks, and subsequently participated in a cold pressor task (CPT). Participants were randomly assigned to (1) a distraction group, in which an attention-demanding tone-detection task was performed during the CPT, or (2) a control group, in which no distraction task was performed. Participants in the distraction group reported significantly less pain during the CPT, but the pain experience was not influenced by executive functioning abilities. However, the performance on the distraction task improved with better inhibition abilities, indicating that inhibition abilities might be important in focussing on a task despite the pain

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

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

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

Diversity studies in the interaction between the anthracnose fungus Colletotrichum gloeosporioides and its host plant Stylosanthes spp. in Mexico

Pests and diseases are important constraints to production in both traditional and modern agricultural systems. It is widely accepted that crop diversity, mainly through use of resistance and tolerance genes, is an important asset in reducing the risk of crop losses related to pests and diseases. However, little is known about the effect of the natural pathogen diversity on the occurrence and severity of phytopathological infestations. This publication summarizes the results of the multidisciplinary project ‘Genetic diversity studies in the interaction between the anthracnose fungus Colletotrichum gloeosporioides and its host plant Stylosanthes spp.’ The legume Stylosanthes is an important forage crop worldwide and Colletotrichum gloeosporioides is its most important pathogen. This project was a multidisciplinary bi-national effort centred in Mexico, a centre of origin of the host plant, which focused on characterizing both the host plant and the pathogen using different characterization techniques, from macro-morphological through molecular. As anthracnosis is reducing Stylosanthes yields from Africa to Australia, an increased knowledge and understanding of the co-existence of crop and pathogen diversity will benefit stakeholders outside the study area as well. A team of international researchers undertook a coordinated effort to increase the inclusion of information on host and pathogen diversity in areas where the crop and its pathogen are native. The Unité de Phytopathologie de l’Université catholique de Louvain, Louvain-la-Neuve, Belgium (UCL) focused on the characterization of C. gloeosporioides and other Colletotrichum species associated with wild Stylosanthes species in Mexico, while Stylosanthes diversity and taxonomy were studied by the Laboratorio de Recursos Naturales, Unidad de Biología, Tecnología y Prototipos, Facultad de Estudios Superiores Iztacala de la Universidad Nacional Autónoma de México (UNAM) at the morphological level and by the Laboratory of Gene Technology, Katholieke Universiteit Leuven, Belgium (KUL) that studied the material at the molecular level. The Mexican partner, UNAM, was responsible for the collection of materials, both host plant and pathogen, while the Belgian partners, UCL and KUL, carried out the molecular analysis. This study is a clear example of how a collaborative, multidisciplinary effort, including the exchange of plant material, allows for the optimal use of existing synergies between different research centres, leading to a better understanding of a complex theme such as host-pathogen diversity. This will permit a better use of the crop’s genetic diversity, and the corresponding resistance genes available, as well as the application of better screening methods for pest or disease resistance, based on a more extensive pathogen diversity. Bioversity International, formerly known as IPGRI, and its Regional Office for the Americas in Cali, Colombia is honoured that it was allowed to coordinate this project

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