Power line risk to Cape (Gyps coprotheres) and white-backed (G. africanus) vultures in Southern Africa

A dissertation submitted to the Faculty of Science, University of Witwatersrand, in fulfilment of the requirements for the degree of Master of Science Johannesburg, South Africa March 2016This study examined the movements of white-backed (Gyps africanus) and Cape vultures (G. coprotheres) to assess their habitat preferences, measure seasonal changes in foraging behaviour, and examine where vultures are at risk of electrocution by and collision with power lines. White-backed and Cape vultures are two Old World vulture species found in southern Africa. They are listed as Critically Endangered and Endangered respectively, with massive population declines over the past three decades. These declines are due to poisoning, habitat loss, lack of food, use in traditional medicine, and electrical infrastructure mortality. Vultures provide key ecosystem services such as reducing disease transmission, cycling nutrients, and attracting tourists and therefore, a loss of vultures could cost the continent millions of US dollars. Thirteen vultures (five white-backed and eight Cape vultures) were tracked using either DUCK-4A or BUBO-4A GPS-GSM trackers (Ecotone Telemetry, Sopot, Poland). Birds were tracked between April 2013 and October 2014. These data were used to examine the habitat suitability of both species using MaxEnt habitat suitability modelling. Key drivers of country-wide habitat suitability for white-backed vultures were mean temperature (30.9% contribution), precipitation seasonality (22.0% contribution), and biome (19.5% contribution), while key drivers for Cape vultures were distance to artificial feeding station (24.8% contribution), and precipitation seasonality (50.5% contribution). Anthropological variables (land use, cattle density, and population density) contributed very little to the models. Using the same tracking data, seasonal changes in foraging movements were examined, particularly in relation to hypothetical food availability. Data were categorised by seasons (winter, spring, summer, and autumn) using weather data over the past decade. There was little evidence for seasonal movement in white-backed or Cape vultures which may be because food availability is not the limiting factor regardless of time of year. Lastly, a model was constructed in MaxEnt using the Endangered Wildlife Trust’s Wildlife and Energy Programme dataset of white-backed and Cape vulture electrocutions by and collisions with power lines. Voltage was a major contributor to risk in every model for both collision and electrocution. This is likely to be related to the type and height of the power line structures rather than actual voltage. Either land use or population density also contributed to all four models. Slope contributed to white-backed vulture models while feeding station and elevation contributed to Cape vulture models. Each of these variables probably relates not only to the likelihood of vulture presence but also how vultures behave in the area (e.g. flying lower in natural or low population areas to forage more effectively therefore putting them at higher risk of collision). This study suggests that management initiatives should include carefully placing vulture feeding stations to change foraging patterns and provide safe, uncontaminated carrion, and proactive retrofitting of high risk power lines to reduce the high unnatural mortality in white-backed and Cape vultures in South Africa. It is important to continue to improve these models using more tracking data from more populations of white-backed and Cape vultures, and more electrocution and collision data gathered from regular, randomly selected power line surveys.M T 201

Myosin IIA-mediated forces regulate multicellular integrity during vascular sprouting

Angiogenic sprouting is a critical process involved in vascular network formation within tissues. During sprouting, tip cells and ensuing stalk cells migrate collectively into the extracellular matrix while preserving cell-cell junctions, forming patent structures that support blood flow. Although several signaling pathways have been identified as controlling sprouting, it remains unclear to what extent this process is mechanoregulated. To address this question, we investigated the role of cellular contractility in sprout morphogenesis, using a biomimetic model of angiogenesis. Three-dimensional maps of mechanical deformations generated by sprouts revealed that mainly leader cells, not stalk cells, exert contractile forces on the surrounding matrix. Surprisingly, inhibiting cellular contractility with blebbistatin did not affect the extent of cellular invasion but resulted in cell-cell dissociation primarily between tip and stalk cells. Closer examination of cell-cell junctions revealed that blebbistatin impaired adherens-junction organization, particularly between tip and stalk cells. Using CRISPR/Cas9-mediated gene editing, we further identified NMIIA as the major isoform responsible for regulating multicellularity and cell contractility during sprouting. Together, these studies reveal a critical role for NMIIA-mediated contractile forces in maintaining multicellularity during sprouting and highlight the central role of forces in regulating cell-cell adhesions during collective motility.R01 EB000262 - NIBIB NIH HHS; R01 HL115553 - NHLBI NIH HHSPublished versio

Deweyan tools for inquiry and the epistemological context of critical pedagogy

This article develops the notion of resistance as articulated in the literature of critical pedagogy as being both culturally sponsored and cognitively manifested. To do so, the authors draw upon John Dewey\u27s conception of tools for inquiry. Dewey provides a way to conceptualize student resistance not as a form of willful disputation, but instead as a function of socialization into cultural models of thought that actively truncate inquiry. In other words, resistance can be construed as the cognitive and emotive dimensions of the ongoing failure of institutions to provide ideas that help individuals both recognize social problems and imagine possible solutions. Focusing on Dewey\u27s epistemological framework, specifically tools for inquiry, provides a way to grasp this problem. It also affords some innovative solutions; for instance, it helps conceive of possible links between the regular curriculum and the study of specific social justice issues, a relationship that is often under-examined. The aims of critical pedagogy depend upon students developing dexterity with the conceptual tools they use to make meaning of the evidence they confront; these are background skills that the regular curriculum can be made to serve even outside social justice-focused curricula. Furthermore, the article concludes that because such inquiry involves the exploration and potential revision of students\u27 world-ordering beliefs, developing flexibility in how one thinks may be better achieved within academic subjects and topics that are not so intimately connected to students\u27 current social lives, especially where students may be directly implicated

Exome-wide Rare Variant Analysis Identifies TUBA4A Mutations Associated with Familial ALS

Exome sequencing is an effective strategy for identifying human disease genes. However, this methodology is difficult in late-onset diseases where limited availability of DNA from informative family members prohibits comprehensive segregation analysis. To overcome this limitation, we performed an exome-wide rare variant burden analysis of 363 index cases with familial ALS (FALS). The results revealed an excess of patient variants within TUBA4A, the gene encoding the Tubulin, Alpha 4A protein. Analysis of a further 272 FALS cases and 5,510 internal controls confirmed the overrepresentation as statistically significant and replicable. Functional analyses revealed that TUBA4A mutants destabilize the microtubule network, diminishing its repolymerization capability. These results further emphasize the role of cytoskeletal defects in ALS and demonstrate the power of gene-based rare variant analyses in situations where causal genes cannot be identified through traditional segregation analysis

The International Limits and Population at Risk of Plasmodium vivax Transmission in 2009

Growing evidence shows that Plasmodium vivax malaria is clinically less benign than has been commonly believed. In addition, it is the most widely distributed species of human malaria and is likely to cause more illness in certain regions than the more extensively studied P. falciparum malaria. Understanding where P. vivax transmission exists and measuring the number of people who live at risk of infection is a fundamental first step to estimating the global disease toll. The aim of this paper is to generate a reliable map of the worldwide distribution of this parasite and to provide an estimate of how many people are exposed to probable infection. A geographical information system was used to map data on the presence of P. vivax infection and spatial information on climatic conditions that impede transmission (low ambient temperature and extremely arid environments) in order to delineate areas where transmission was unlikely to take place. This map was combined with population distribution data to estimate how many people live in these areas and are, therefore, exposed to risk of infection by P. vivax malaria. The results show that 2.85 billion people were exposed to some level of risk of transmission in 2009

Histone Deacetylase 3 indirectly modulates tubulin acetylation

Histone Deacetylase 3 (HDAC3), a member of the Class I subfamily of histone deacetylases, is found in both the nucleus and the cytoplasm. Its roles in the nucleus have been well characterised, but its cytoplasmic roles are still not elucidated fully. We found that blocking HDAC3 activity using MI192, a compound specific for HDAC3, modulated tubulin acetylation in the human prostate cancer cell line PC3. A brief 1 hour treatment of PC3 cells with MI192 significantly increased levels of tubulin acetylation and ablated the dynamic behaviour of microtubules in live cells. siRNA mediated knockdown of HDAC3 in PC3 cells, significantly increased levels of tubulin acetylation, and overexpression reduced it. However, the active HDAC3:SMRT-DAD complex did not directly deacetylate tubulin in vitro. These data suggest that HDAC3 indirectly modulates tubulin acetylation

Dopamine signaling enriched striatal gene set predicts striatal dopamine synthesis and physiological activity in vivo

The polygenic architecture of schizophrenia implicates several molecular pathways involved in synaptic function. However, it is unclear how polygenic risk funnels through these pathways to translate into syndromic illness. Using tensor decomposition, we analyze gene co-expression in the caudate nucleus, hippocampus, and dorsolateral prefrontal cortex of post-mortem brain samples from 358 individuals. We identify a set of genes predominantly expressed in the caudate nucleus and associated with both clinical state and genetic risk for schizophrenia that shows dopaminergic selectivity. A higher polygenic risk score for schizophrenia parsed by this set of genes predicts greater dopamine synthesis in the striatum and greater striatal activation during reward anticipation. These results translate dopamine-linked genetic risk variation into in vivo neurochemical and hemodynamic phenotypes in the striatum that have long been implicated in the pathophysiology of schizophrenia

Developing Global Maps of the Dominant Anopheles Vectors of Human Malaria

Simon Hay and colleagues describe how the Malaria Atlas Project has collated anopheline occurrence data to map the geographic distributions of the dominant mosquito vectors of human malaria

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients

Single-dose BNT162b2 vaccine protects against asymptomatic SARS-CoV-2 infection

The BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech) is being utilised internationally for mass COVID-19 vaccination. Evidence of single-dose protection against symptomatic disease has encouraged some countries to opt for delayed booster doses of BNT162b2, but the effect of this strategy on rates of asymptomatic SARS-CoV-2 infection remains unknown. We previously demonstrated frequent pauci- and asymptomatic SARS-CoV-2 infection amongst healthcare workers (HCWs) during the UK’s first wave of the COVID-19 pandemic, using a comprehensive PCR-based HCW screening programme (Rivett et al., 2020; Jones et al., 2020). Here, we evaluate the effect of first-dose BNT162b2 vaccination on test positivity rates and find a fourfold reduction in asymptomatic infection amongst HCWs ≥12 days post-vaccination. These data provide real-world evidence of short-term protection against asymptomatic SARS-CoV-2 infection following a single dose of BNT162b2 vaccine, suggesting that mass first-dose vaccination will reduce SARS-CoV-2 transmission, as well as the burden of COVID-19 disease