Ranger perceptions of the role of local communities in providing actionable information on wildlife crime

Wildlife crime in protected areas remains a major challenge to conservation. However, little is known about the role of local communities in providing information on illegal activities to help improve law enforcement efforts in protected areas. As an initial exploration of this complex topic, we aimed to understand the perceptions of law enforcement authorities working directly with local communities on the conditions under which local people provide information to park rangers, using Murchison Falls Protected Area in Uganda as a case study. We used semi‐structured interviews and questionnaires to understand the perceptions of staff from the Uganda Wildlife Authority and nongovernmental organizations. There was consensus among participants that people who provide information are those who have trusted relationships with ranger

The Influence of N-Linked Glycans on the MolecularDynamics of the HIV-1 gp120 V3 Loop

N-linked glycans attached to specific amino acids of the gp120 envelope trimer of a HIV virion can modulate the binding affinity of gp120 to CD4, influence coreceptor tropism, and play an important role in neutralising antibody responses. Because of the challenges associated with crystallising fully glycosylated proteins, most structural investigations have focused on describing the features of a non-glycosylated HIV-1 gp120 protein. Here, we use a computational approach to determine the influence of N-linked glycans on the dynamics of the HIV-1 gp120 protein and, in particular, the V3 loop. We compare the conformational dynamics of a non-glycosylated gp120 structure to that of two glycosylated gp120 structures, one with a single, and a second with five, covalently linked high-mannose glycans. Our findings provide a clear illustration of the significant effect that N-linked glycosylation has on the temporal and spatial properties of the underlying protein structure. We find that glycans surrounding the V3 loop modulate its dynamics, conferring to the loop a marked propensity towards a more narrow conformation relative to its non-glycosylated counterpart. The conformational effect on the V3 loop provides further support for the suggestion that N-linked glycosylation plays a role in determining HIV-1 coreceptor tropism.Scopu

Perceptual Inference in Chronic Pain:An Investigation into the Economy of Action Hypothesis

Objective: The experience of chronic pain critically alters one's ability to interact with their environment. One fundamental issue that has received little attention, however, is whether chronic pain disrupts how one perceives their environment in the first place. The Economy of Action hypothesis purports that the environment is spatially scaled according to the ability of the observer. Under this hypothesis it has been proposed that the perception of the world is different between those with and without chronic pain. Such a possibility has profound implications for the investigation and treatment of pain. The present investigation tested the application of this hypothesis to a heterogenous chronic pain population. Methods: Individuals with chronic pain (36; 27F) and matched pain-free controls were recruited. Each participant was required to judge the distance to a series of target cones, to which they were to subsequently walk. In addition, at each distance, participants used Numerical Rating Scales to indicate their perceived effort and perceived pain associated with the distance presented. Results: Our findings do not support the Economy of Action hypothesis: there were no significant differences in distance estimates between the chronic pain and pain-free groups (F 1,60 =0.927; P=0.340). In addition, we found no predictive relationship in the chronic pain group between anticipated pain and estimated distance (F 1,154 =0.122, P=0.727), nor anticipated effort (1.171, P=0.281) and estimated distance (F 1,154 =1.171, P=0.281). Discussion: The application of the Economy of Action hypothesis and the notion of spatial perceptual scaling as a means to assess and treat the experience of chronic pain are not supported by the results of this study

Identification of Functional Platelet-Activating Factor Receptors on Human Keratinocytes

Platelet-activating factor (PAP) is a potent inflammatory mediator that has been shown to be produced by human keratinocytes and is thought to play a role in cutaneous inflammation, Immunofluorescence and radioligand binding studies were used to characterize PAP receptors (PAF-R) on human keratinocytes and the human epidermoid cell lines A-431 and HaCaT. Indirect immunofluorescence studies demonstrated anti-PAF-R staining of primary cultures of human keratinocytes, A-431 cells, and HaCaT cells, Primary cultures of human fibroblasts and the melanoma cell line SK-30 failed to show immunostaining above that seen with control antiserum. With indirect immunofluorescence studies of sections of normal human skin, a granular anti-PAF-R staining pattern was noted on the keratinocyte cell membranes. A-431 cells readily metabolized PAF by deacetylationreacylation at 37°C, but not at 4°C. Binding studies on crude membrane preparations of A-431 cells conducted at 4°C demonstrated specific binding that reached saturation by 120 min. Scatchard analysis of PAF binding data revealed a single class of high-affinity (KD = 6.3 ± 0.3 nM) PAP binding sites, The immunofluorescence and radioligand binding sites were shown to be functional PAF-Rs, as 10 pM to 1 μM PAF increased intracellular calcium in primary cultures of human keratinocytes, A-.431 cells, and HaCaT cells, whereas PAF treatment of primary cultures of human fibroblasts or the melanoma cell line SK-30 did not result in changes in the intracellular calcium concentration. The structurally dissimilar PAF-R antagonists CV-6209, Ro19-3704, and alprazolam all inhibited the PAF-induced calcium changes in A-431 cells, The CV-6209 inhibition was seen at doses that competed with the PAF binding to these cells. These studies provide the first evidence for the presence of a functional PAF-R expressed on human keratinocytes, suggesting that this lipid mediator may play an important role in normal keratinocytes or in inflammatory dermatology

Trends in genotypic HIV-1 antiretroviral resistance between 2006 and 2012 in South African patients receiving first- and second-line antiretroviral treatment regimens

The original publication is available at http://www.plosone.org/Publication of this article was funded by the Stellenbosch University Open Access Fund.BibliographyObjectives: South Africa’s national antiretroviral (ARV) treatment program expanded in 2010 to include the nucleoside reverse transcriptase (RT) inhibitors (NRTI) tenofovir (TDF) for adults and abacavir (ABC) for children. We investigated the associated changes in genotypic drug resistance patterns in patients with first-line ARV treatment failure since the introduction of these drugs, and protease inhibitor (PI) resistance patterns in patients who received ritonavir-boosted lopinavir (LPV/r)-containing therapy. Methods: We analysed ARV treatment histories and HIV-1 RT and protease mutations in plasma samples submitted to the Tygerberg Academic Hospital National Health Service Laboratory. Results: Between 2006 and 2012, 1,667 plasma samples from 1,416 ARV-treated patients, including 588 children and infants, were submitted for genotypic resistance testing. Compared with 720 recipients of a d4T or AZT-containing first-line regimen, the 153 recipients of a TDF-containing first-line regimen were more likely to have the RT mutations K65R (46% vs 4.0%; p<0.001), Y115F (10% vs. 0.6%; p<0.001), L74VI (8.5% vs. 1.8%; p<0.001), and K70EGQ (7.8% vs. 0.4%) and recipients of an ABC-containing first-line regimen were more likely to have K65R (17% vs 4.0%; p<0.001), Y115F (30% vs 0.6%; p<0.001), and L74VI (56% vs 1.8%; p<0.001). Among the 490 LPV/r recipients, 55 (11%) had ≥1 LPV-resistance mutations including 45 (9.6%) with intermediate or high-level LPV resistance. Low (20 patients) and intermediate (3 patients) darunavir (DRV) cross resistance was present in 23 (4.6%) patients. Conclusions: Among patients experiencing virological failure on a first-line regimen containing two NRTI plus one NNRTI, the use of TDF in adults and ABC in children was associated with an increase in four major non- thymidine analogue mutations. In a minority of patients, LPV/r-use was associated with intermediate or high-level LPV resistance with predominantly low-level DRV cross-resistance.Stellenbosch University Open Access FundPublishers' Versio

Accurate detection of sepsis at ED triage using machine learning with clinical natural language processing

Sepsis is a life-threatening condition with organ dysfunction and is a leading cause of death and critical illness worldwide. Accurate detection of sepsis during emergency department triage would allow early initiation of lab analysis, antibiotic administration, and other sepsis treatment protocols. The purpose of this study was to determine whether EHR data can be extracted and synthesized with the latest machine learning algorithms (KATE Sepsis) and clinical natural language processing to produce accurate sepsis models, and compare KATE Sepsis performance with existing sepsis screening protocols, such as SIRS and qSOFA. A machine learning model (KATE Sepsis) was developed using patient encounters with triage data from 16 participating hospitals. KATE Sepsis, SIRS, standard screening (SIRS with source of infection) and qSOFA were tested in three settings. Cohort-A was a retrospective analysis on medical records from a single Site 1. Cohort-B was a prospective analysis of Site 1. Cohort-C was a retrospective analysis on Site 1 with 15 additional sites. Across all cohorts, KATE Sepsis demonstrates an AUC of 0.94-0.963 with 73-74.87% TPR and 3.76-7.17% FPR. Standard screening demonstrates an AUC of 0.682-0.726 with 39.39-51.19% TPR and 2.9-6.02% FPR. The qSOFA protocol demonstrates an AUC of 0.544-0.56, with 10.52-13.18% TPR and 1.22-1.68% FPR. For severe sepsis, across all cohorts, KATE Sepsis demonstrates an AUC of 0.935-0.972 with 70-82.26% TPR and 4.64-8.62% FPR. For septic shock, across all cohorts, KATE Sepsis demonstrates an AUC of 0.96-0.981 with 85.71-89.66% TPR and 4.85-8.8% FPR. SIRS, standard screening, and qSOFA demonstrate low AUC and TPR for severe sepsis and septic shock detection. KATE Sepsis provided substantially better sepsis detection performance in triage than commonly used screening protocols.Comment: 35 pages, 1 figure, 6 tables, 7 supplementary table

EcoCyc: fusing model organism databases with systems biology.

EcoCyc (http://EcoCyc.org) is a model organism database built on the genome sequence of Escherichia coli K-12 MG1655. Expert manual curation of the functions of individual E. coli gene products in EcoCyc has been based on information found in the experimental literature for E. coli K-12-derived strains. Updates to EcoCyc content continue to improve the comprehensive picture of E. coli biology. The utility of EcoCyc is enhanced by new tools available on the EcoCyc web site, and the development of EcoCyc as a teaching tool is increasing the impact of the knowledge collected in EcoCyc

Putting the brakes on the unfolded protein response

The unfolded protein response is an ancient cellular pathway for rapidly responding to endoplasmic reticulum stress. Two studies in this issue (Rubio et al. 2011. J. Cell. Biol. doi:10.1083/jcb.201007077 and Chawla et al. 2011. J. Cell. Biol. doi:10.1083/jcb.201008071) provide insight into how the unfolded protein response is tamped down to restore normal endoplasmic reticulum function. Although both papers implicate the Ire1 kinase domain as the key effector of the off-switch mechanism, alternate models for how this is achieved are proposed

Tectonic collision and uplift of Wallacea triggered the global songbird radiation

Songbirds (oscine passerines) are the most species-rich and cosmopolitan bird group, comprising almost half of global avian diversity. Songbirds originated in Australia, but the evolutionary trajectory from a single species in an isolated continent to worldwide proliferation is poorly understood. Here, we combine the first comprehensive genome-scale DNA sequence data set for songbirds, fossil-based time calibrations, and geologically informed biogeographic reconstructions to provide a well-supported evolutionary hypothesis for the group. We show that songbird diversification began in the Oligocene, but accelerated in the early Miocene, at approximately half the age of most previous estimates. This burst of diversification occurred coincident with extensive island formation in Wallacea, which provided the first dispersal corridor out of Australia, and resulted in independent waves of songbird expansion through Asia to the rest of the globe. Our results reconcile songbird evolution with Earth history and link a major radiation of terrestrial biodiversity to early diversification within an isolated Australian continent