221 research outputs found

    Visual Narratives: Exploring the Impacts of Tourism Development in Placencia, Belize

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156219/2/napa12135_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156219/1/napa12135.pd

    Drivers of plankton community structure in intermittent and continuous coastal upwelling systems–from microbes and microscale in-situ imaging to large scale patterns

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    Eastern Boundary Systems support major fisheries whose early life stages depend on upwelling production. Upwelling can be highly variable at the regional scale, with substantial repercussions for new productivity and microbial loop activity. Studies that integrate the classic trophic web based on new production with the microbial loop are rare due to the range in body forms and sizes of the taxa. Underwater imaging can overcome this limitation, and with machine learning, enables fine resolution studies spanning large spatial scales. We used the In-situ Ichthyoplankton Imaging System (ISIIS) to investigate the drivers of plankton community structure in the northern California Current, sampled along the Newport Hydrographic (NH) and Trinidad Head (TR) lines, in OR and CA, respectively. The non-invasive imaging of particles and plankton over 1644km in the winters and summers of 2018 and 2019 yielded 1.194 billion classified plankton images. Combining nutrient analysis, flow cytometry, and 16S rRNA gene sequencing of the microbial community with mesoplankton underwater imaging enabled us to study taxa from 0.2µm to 15cm, including prokaryotes, copepods, ichthyoplankton, and gelatinous forms. To assess community structure, >2000 single-taxon distribution profiles were analyzed using high resolution spatial correlations. Co-occurrences on the NH line were consistently significantly higher off-shelf while those at TR were highest on-shelf. Random Forests models identified the concentrations of microbial loop associated taxa such as protists, Oithona copepods, and appendicularians as important drivers of co-occurrences at NH line, while at TR, cumulative upwelling and chlorophyll a were of the highest importance. Our results indicate that the microbial loop is driving plankton community structure in intermittent upwelling systems such as the NH line and supports temporal stability, and further, that taxa such as protists, Oithona copepods, and appendicularians connect a diverse and functionally redundant microbial community to stable plankton community structure. Where upwelling is more continuous such as at TR, primary production may dominate patterns of community structure, obscuring the underlying role of the microbial loop. Future changes in upwelling strength are likely to disproportionately affect plankton community structure in continuous upwelling regions, while high microbial loop activity enhances community structure resilience

    RBM5 Is a Male Germ Cell Splicing Factor and Is Required for Spermatid Differentiation and Male Fertility

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    Alternative splicing of precursor messenger RNA (pre-mRNA) is common in mammalian cells and enables the production of multiple gene products from a single gene, thus increasing transcriptome and proteome diversity. Disturbance of splicing regulation is associated with many human diseases; however, key splicing factors that control tissue-specific alternative splicing remain largely undefined. In an unbiased genetic screen for essential male fertility genes in the mouse, we identified the RNA binding protein RBM5 (RNA binding motif 5) as an essential regulator of haploid male germ cell pre-mRNA splicing and fertility. Mice carrying a missense mutation (R263P) in the second RNA recognition motif (RRM) of RBM5 exhibited spermatid differentiation arrest, germ cell sloughing and apoptosis, which ultimately led to azoospermia (no sperm in the ejaculate) and male sterility. Molecular modelling suggested that the R263P mutation resulted in compromised mRNA binding. Within the adult mouse testis, RBM5 localises to somatic and germ cells including spermatogonia, spermatocytes and round spermatids. Through the use of RNA pull down coupled with microarrays, we identified 11 round spermatid-expressed mRNAs as putative RBM5 targets. Importantly, the R263P mutation affected pre-mRNA splicing and resulted in a shift in the isoform ratios, or the production of novel spliced transcripts, of most targets. Microarray analysis of isolated round spermatids suggests that altered splicing of RBM5 target pre-mRNAs affected expression of genes in several pathways, including those implicated in germ cell adhesion, spermatid head shaping, and acrosome and tail formation. In summary, our findings reveal a critical role for RBM5 as a pre-mRNA splicing regulator in round spermatids and male fertility. Our findings also suggest that the second RRM of RBM5 is pivotal for appropriate pre-mRNA splicing.This work was supported by grants from the National Health and Medical Research Council (NHMRC) to DJ (#606503); the Australian Research Council (ARC) to MKO and CJO; the New South Wales Cancer Council, Cancer Institute New South Wales, Banque Nationale de Paris-Paribas Australia and New Zealand, RT Hall Trust, and the National Breast Cancer Foundation to CJO. DJ was an NHMRC Peter Doherty Postdoctoral Fellow (#384297). MKO and CJO are NHMRC Senior Research Fellows (#545805, #481310). CCG is an NHMRC Australia Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

    Persistence of the immune response induced by BCG vaccination.

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    BACKGROUND: Although BCG vaccination is recommended in most countries of the world, little is known of the persistence of BCG-induced immune responses. As novel TB vaccines may be given to boost the immunity induced by neonatal BCG vaccination, evidence concerning the persistence of the BCG vaccine-induced response would help inform decisions about when such boosting would be most effective. METHODS: A randomised control study of UK adolescents was carried out to investigate persistence of BCG immune responses. Adolescents were tested for interferon-gamma (IFN-gamma) response to Mycobacterium tuberculosis purified protein derivative (M.tb PPD) in a whole blood assay before, 3 months, 12 months (n = 148) and 3 years (n = 19) after receiving teenage BCG vaccination or 14 years after receiving infant BCG vaccination (n = 16). RESULTS: A gradual reduction in magnitude of response was evident from 3 months to 1 year and from 1 year to 3 years following teenage vaccination, but responses 3 years after vaccination were still on average 6 times higher than before vaccination among vaccinees. Some individuals (11/86; 13%) failed to make a detectable antigen-specific response three months after vaccination, or lost the response after 1 (11/86; 13%) or 3 (3/19; 16%) years. IFN-gamma response to Ag85 was measured in a subgroup of adolescents and appeared to be better maintained with no decline from 3 to 12 months. A smaller group of adolescents were tested 14 years after receiving infant BCG vaccination and 13/16 (81%) made a detectable IFN-gamma response to M.tb PPD 14 years after infant vaccination as compared to 6/16 (38%) matched unvaccinated controls (p = 0.012); teenagers vaccinated in infancy were 19 times more likely to make an IFN-gamma response of > 500 pg/ml than unvaccinated teenagers. CONCLUSION: BCG vaccination in infancy and adolescence induces immunological memory to mycobacterial antigens that is still present and measurable for at least 14 years in the majority of vaccinees, although the magnitude of the peripheral blood response wanes from 3 months to 12 months and from 12 months to 3 years post vaccination. The data presented here suggest that because of such waning in the response there may be scope for boosting anti-tuberculous immunity in BCG vaccinated children anytime from 3 months post-vaccination. This supports the prime boost strategies being employed for some new TB vaccines currently under development

    Parkinson's disease biomarkers: perspective from the NINDS Parkinson's Disease Biomarkers Program

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    Biomarkers for Parkinson's disease (PD) diagnosis, prognostication and clinical trial cohort selection are an urgent need. While many promising markers have been discovered through the National Institute of Neurological Disorders and Stroke Parkinson's Disease Biomarker Program (PDBP) and other mechanisms, no single PD marker or set of markers are ready for clinical use. Here we discuss the current state of biomarker discovery for platforms relevant to PDBP. We discuss the role of the PDBP in PD biomarker identification and present guidelines to facilitate their development. These guidelines include: harmonizing procedures for biofluid acquisition and clinical assessments, replication of the most promising biomarkers, support and encouragement of publications that report negative findings, longitudinal follow-up of current cohorts including the PDBP, testing of wearable technologies to capture readouts between study visits and development of recently diagnosed (de novo) cohorts to foster identification of the earliest markers of disease onset

    Evidence for Reduced Drug Susceptibility without Emergence of Major Protease Mutations following Protease Inhibitor Monotherapy Failure in the SARA Trial

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    Background Major protease mutations are rarely observed following failure with protease inhibitors (PI), and other viral determinants of failure to PI are poorly understood. We therefore characterized Gag-Protease phenotypic susceptibility in subtype A and D viruses circulating in East Africa following viral rebound on PIs. Methods Samples from baseline and treatment failure in patients enrolled in the second line LPV/r trial SARA underwent phenotypic susceptibility testing. Data were expressed as fold-change in susceptibility relative to a LPV-susceptible reference strain. Results We cloned 48 Gag-Protease containing sequences from seven individuals and performed drug resistance phenotyping from pre-PI and treatment failure timepoints in seven patients. For the six patients where major protease inhibitor resistance mutations did not emerge, mean fold-change EC50 to LPV was 4.07 fold (95% CI, 2.08–6.07) at the pre-PI timepoint. Following viral failure the mean fold-change in EC50 to LPV was 4.25 fold (95% CI, 1.39–7.11, p = 0.91). All viruses remained susceptible to DRV. In our assay system, the major PI resistance mutation I84V, which emerged in one individual, conferred a 10.5-fold reduction in LPV susceptibility. One of the six patients exhibited a significant reduction in susceptibility between pre-PI and failure timepoints (from 4.7 fold to 9.6 fold) in the absence of known major mutations in protease, but associated with changes in Gag: V7I, G49D, R69Q, A120D, Q127K, N375S and I462S. Phylogenetic analysis provided evidence of the emergence of genetically distinct viruses at the time of treatment failure, indicating ongoing viral evolution in Gag-protease under PI pressure. Conclusions Here we observe in one patient the development of significantly reduced susceptibility conferred by changes in Gag which may have contributed to treatment failure on a protease inhibitor containing regimen. Further phenotype-genotype studies are required to elucidate genetic determinants of protease inhibitor failure in those who fail without traditional resistance mutations whilst PI use is being scaled up globally

    Reducing publication delay to improve the efficiency and impact of conservation science.

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    Evidence-based decision-making is most effective with comprehensive access to scientific studies. If studies face significant publication delays or barriers, the useful information they contain may not reach decision-makers in a timely manner. This represents a potential problem for mission-oriented disciplines where access to the latest data is required to ensure effective actions are undertaken. We sought to analyse the severity of publication delay in conservation science-a field that requires urgent action to prevent the loss of biodiversity. We used the Conservation Evidence database to assess the length of publication delay (time from finishing data collection to publication) in the literature that tests the effectiveness of conservation interventions. From 7,447 peer-reviewed and non-peer-reviewed studies of conservation interventions published over eleven decades, we find that the raw mean publication delay was 3.2 years (±2SD = 0.1) and varied by conservation subject. A significantly shorter delay was observed for studies focused on Bee Conservation, Sustainable Aquaculture, Management of Captive Animals, Amphibian Conservation, and Control of Freshwater Invasive Species (Estimated Marginal Mean range from 1.4-1.9 years). Publication delay was significantly shorter for the non-peer-reviewed literature (Estimated Marginal Mean delay of 1.9 years ± 0.2) compared to the peer-reviewed literature (i.e., scientific journals; Estimated Marginal Mean delay of 3.0 years ± 0.1). We found publication delay has significantly increased over time (an increase of ~1.2 years from 1912 (1.4 years ± 0.2) to 2020 (2.6 years ± 0.1)), but this change was much weaker and non-significant post-2000s; we found no evidence for any decline. There was also no evidence that studies on more threatened species were subject to a shorter delay-indeed, the contrary was true for mammals, and to a lesser extent for birds. We suggest a range of possible ways in which scientists, funders, publishers, and practitioners can work together to reduce delays at each stage of the publication process

    Galaxy and Mass Assembly (GAMA): Variation in galaxy structure across the green valley

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    Using a sample of 472 local Universe (z \u3c 0.06) galaxies in the stellar mass range 10.25 \u3c logM*/M⊙ \u3c 10.75, we explore the variation in galaxy structure as a function of morphology and galaxy colour. Our sample of galaxies is subdivided into red, green, and blue colour groups and into elliptical and non-elliptical (disk-type) morphologies. Using Kilo- Degree Survey (KiDS) and Visible and Infrared Survey Telescope for Astronomy (VISTA) Kilo-Degree Infrared Galaxy Survey (VIKING) derived postage stamp images, a group of eight volunteers visually classified bars, rings, morphological lenses, tidal streams, shells, and signs of merger activity for all systems. We find a significant surplus of rings (2.3s) and lenses (2.9s) in disk-type galaxies as they transition across the green valley. Combined, this implies a joint ring/lens green valley surplus significance of 3.3s relative to equivalent disk-types within either the blue cloud or the red sequence. We recover a bar fraction of ~44 per cent which remains flat with colour, however, we find that the presence of a bar acts to modulate the incidence of rings and (to a lesser extent) lenses, with rings in barred disk-type galaxies more common by ~20-30 percentage points relative to their unbarred counterparts, regardless of colour. Additionally, green valley disk-type galaxies with a bar exhibit a significant 3.0s surplus of lenses relative to their blue/red analogues. The existence of such structures rules out violent transformative events as the primary end-of-life evolutionary mechanism, with a more passive scenario the favoured candidate for the majority of galaxies rapidly transitioning across the green valley
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