230 research outputs found

    Temperature-dependent phenology of Plutella xylostella (Lepidoptera: Plutellidae): Simulation and visualization of current and future distributions along the Eastern Afromontane

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    There is a scarcity of laboratory and field-based results showing the movement of the diamondback moth (DBM) Plutella xylostella (L.) across a spatial scale. We studied the population growth of the diamondback moth (DBM) Plutella xylostella (L.) under six constant temperatures, to understand and predict population changes along altitudinal gradients and under climate change scenarios. Non-linear functions were fitted to continuously model DBM development, mortality, longevity and oviposition. We compiled the best-fitted functions for each life stage to yield a phenology model, which we stochastically simulated to estimate the life table parameters. Three temperature-dependent indices (establishment, generation and activity) were derived from a logistic population growth model and then coupled to collected current (2013) and downscaled temperature data from AFRICLIM (2055) for geospatial mapping. To measure and predict the impacts of temperature change on the pest's biology, we mapped the indices along the altitudinal gradients of Mt. Kilimanjaro (Tanzania) and Taita Hills (Kenya) and assessed the differences between 2013 and 2055 climate scenarios. The optimal temperatures for development of DBM were 32.5, 33.5 and 33ÊC for eggs, larvae and pupae, respectively. Mortality rates increased due to extreme temperatures to 53.3, 70.0 and 52.4% for egg, larvae and pupae, respectively. The net reproduction rate reached a peak of 87.4 female offspring/female/generation at 20ÊC. Spatial simulations indicated that survival and establishment of DBM increased with a decrease in temperature, from low to high altitude. However, we observed a higher number of DBM generations at low altitude. The model predicted DBM population growth reduction in the low and medium altitudes by 2055. At higher altitude, it predicted an increase in the level of suitability for establishment with a decrease in the number of generations per year. If climate change occurs as per the selected scenario, DBM infestation may reduce in the selected region. The study highlights the need to validate these predictions with other interacting factors such as cropping practices, host plants and natural enemies.Peer reviewe

    A novel strategy for the identification of antigens that are recognised by bovine MHC class I restricted cytotoxic T cells in a protozoan infection using reverse vaccinology

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    BACKGROUND: Immunity against the bovine protozoan parasite Theileria parva has previously been shown to be mediated through lysis of parasite-infected cells by MHC class I restricted CD8(+ )cytotoxic T lymphocytes. It is hypothesized that identification of CTL target schizont antigens will aid the development of a sub-unit vaccine. We exploited the availability of the complete genome sequence data and bioinformatics tools to identify genes encoding secreted or membrane anchored proteins that may be processed and presented by the MHC class I molecules of infected cells to CTL. RESULTS: Of the 986 predicted open reading frames (ORFs) encoded by chromosome 1 of the T. parva genome, 55 were selected based on the presence of a signal peptide and/or a transmembrane helix domain. Thirty six selected ORFs were successfully cloned into a eukaryotic expression vector, transiently transfected into immortalized bovine skin fibroblasts and screened in vitro using T. parva-specific CTL. Recognition of gene products by CTL was assessed using an IFN-γ ELISpot assay. A 525 base pair ORF encoding a 174 amino acid protein, designated Tp2, was identified by T. parva-specific CTL from 4 animals. These CTL recognized and lysed Tp2 transfected skin fibroblasts and recognized 4 distinct epitopes. Significantly, Tp2 specific CD8(+ )T cell responses were observed during the protective immune response against sporozoite challenge. CONCLUSION: The identification of an antigen containing multiple CTL epitopes and its apparent immunodominance during a protective anti-parasite response makes Tp2 an attractive candidate for evaluation of its vaccine potential

    Grand Challenges in global eye health: a global prioritisation process using Delphi method

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    Background: We undertook a Grand Challenges in Global Eye Health prioritisation exercise to identify the key issues that must be addressed to improve eye health in the context of an ageing population, to eliminate persistent inequities in health-care access, and to mitigate widespread resource limitations. Methods: Drawing on methods used in previous Grand Challenges studies, we used a multi-step recruitment strategy to assemble a diverse panel of individuals from a range of disciplines relevant to global eye health from all regions globally to participate in a three-round, online, Delphi-like, prioritisation process to nominate and rank challenges in global eye health. Through this process, we developed both global and regional priority lists. Findings: Between Sept 1 and Dec 12, 2019, 470 individuals complete round 1 of the process, of whom 336 completed all three rounds (round 2 between Feb 26 and March 18, 2020, and round 3 between April 2 and April 25, 2020) 156 (46%) of 336 were women, 180 (54%) were men. The proportion of participants who worked in each region ranged from 104 (31%) in sub-Saharan Africa to 21 (6%) in central Europe, eastern Europe, and in central Asia. Of 85 unique challenges identified after round 1, 16 challenges were prioritised at the global level; six focused on detection and treatment of conditions (cataract, refractive error, glaucoma, diabetic retinopathy, services for children and screening for early detection), two focused on addressing shortages in human resource capacity, five on other health service and policy factors (including strengthening policies, integration, health information systems, and budget allocation), and three on improving access to care and promoting equity. Interpretation: This list of Grand Challenges serves as a starting point for immediate action by funders to guide investment in research and innovation in eye health. It challenges researchers, clinicians, and policy makers to build collaborations to address specific challenges. Funding: The Queen Elizabeth Diamond Jubilee Trust, Moorfields Eye Charity, National Institute for Health Research Moorfields Biomedical Research Centre, Wellcome Trust, Sightsavers, The Fred Hollows Foundation, The Seva Foundation, British Council for the Prevention of Blindness, and Christian Blind Mission. Translations: For the French, Spanish, Chinese, Portuguese, Arabic and Persian translations of the abstract see Supplementary Materials section

    Comprehensive transcriptome of the maize stalk borer, Busseola fusca, from multiple tissue types, developmental stages, and parasitoid wasp exposures

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    Advancing the Sustainable Development Goals through improving eye health: a scoping review.

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    UN member states have committed to achieving the Sustainable Development Goals (SDGs) by 2030. This Review examines the published evidence on how improving eye health can contribute to advancing the SDGs (beyond SDG 3). We identified 29 studies that showed direct benefits from providing eye health services on SDGs related to one or more of poverty (SDGs 1, 2, and 8), education (SDG 4), equality (SDGs 5 and 10), and sustainable cities (SDG 11). The eye health services included cataract surgery, free cataract screening, provision of spectacles, trichiasis surgery, rehabilitation services, and rural community eye health volunteers. These findings provide a comprehensive perspective on the direct links between eye health services and advancing the SDGs. In addition, eye health services likely have indirect effects on multiple SDGs, mediated through one of the direct effects. Finally, there are additional plausible links to other SDGs, for which evidence has not yet been established

    Multi-site benchmark classification of major depressive disorder using machine learning on cortical and subcortical measures

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    Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, we overcome these limitations with the largest multi-site sample size to date (N = 5365) to provide a generalizable ML classification benchmark of major depressive disorder (MDD) using shallow linear and non-linear models. Leveraging brain measures from standardized ENIGMA analysis pipelines in FreeSurfer, we were able to classify MDD versus healthy controls (HC) with a balanced accuracy of around 62%. But after harmonizing the data, e.g., using ComBat, the balanced accuracy dropped to approximately 52%. Accuracy results close to random chance levels were also observed in stratified groups according to age of onset, antidepressant use, number of episodes and sex. Future studies incorporating higher dimensional brain imaging/phenotype features, and/or using more advanced machine and deep learning methods may yield more encouraging prospects

    Delivery Practices and Associated Factors among Mothers Seeking Child Welfare Services in Selected Health Facilities in Nyandarua South District, Kenya

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    <p>Abstract</p> <p>Background</p> <p>A measure of the proportion of deliveries assisted by skilled attendants is one of the indicators of progress towards achieving Millennium Development Goal (MDG) 5, which aims at improving maternal health. This study aimed at establishing delivery practices and associated factors among mothers seeking child welfare services at selected health facilities in Nyandarua South district, Kenya to determine whether mothers were receiving appropriate delivery care.</p> <p>Methods</p> <p>A hospital-based cross-sectional survey among women who had recently delivered while in the study area was carried out between August and October 2009. Binary Logistic regression was used to identify factors that predicted mothers' delivery practice.</p> <p>Results</p> <p>Among the 409 mothers who participated in the study, 1170 deliveries were reported. Of all the deliveries reported, 51.8% were attended by unskilled birth attendants. Among the deliveries attended by unskilled birth attendants, 38.6% (452/1170) were by neighbors and/or relatives. Traditional Birth Attendants attended 1.5% (17/1170) of the deliveries while in 11.7% (137/1170) of the deliveries were self administered. Mothers who had unskilled birth attendance were more likely to have <3 years of education (Adjusted Odds ratio [AOR] 19.2, 95% confidence interval [CI] 1.7 - 212.8) and with more than three deliveries in a life time (AOR 3.8, 95% CI 2.3 - 6.4). Mothers with perceived similarity in delivery attendance among skilled and unskilled delivery attendants were associated with unsafe delivery practice (AOR 1.9, 95% CI 1.1 - 3.4). Mother's with lower knowledge score on safe delivery (%) were more likely to have unskilled delivery attendance (AOR 36.5, 95% CI 4.3 - 309.3).</p> <p>Conclusion</p> <p>Among the mothers interviewed, utilization of skilled delivery attendance services was still low with a high number of deliveries being attended by unqualified lay persons. There is need to implement cost effective and sustainable measures to improve the quality of maternal health services with an aim of promoting safe delivery and hence reducing maternal mortality.</p

    Two Theileria parva CD8 T Cell Antigen Genes Are More Variable in Buffalo than Cattle Parasites, but Differ in Pattern of Sequence Diversity

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    &lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Theileria parva causes an acute fatal disease in cattle, but infections are asymptomatic in the African buffalo (Syncerus caffer). Cattle can be immunized against the parasite by infection and treatment, but immunity is partially strain specific. Available data indicate that CD8(+) T lymphocyte responses mediate protection and, recently, several parasite antigens recognised by CD8(+) T cells have been identified. This study set out to determine the nature and extent of polymorphism in two of these antigens, Tp1 and Tp2, which contain defined CD8(+) T-cell epitopes, and to analyse the sequences for evidence of selection.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methodology/Principal Findings:&lt;/b&gt; Partial sequencing of the Tp1 gene and the full-length Tp2 gene from 82 T. parva isolates revealed extensive polymorphism in both antigens, including the epitope-containing regions. Single nucleotide polymorphisms were detected at 51 positions (similar to 12%) in Tp1 and in 320 positions (similar to 61%) in Tp2. Together with two short indels in Tp1, these resulted in 30 and 42 protein variants of Tp1 and Tp2, respectively. Although evidence of positive selection was found for multiple amino acid residues, there was no preferential involvement of T cell epitope residues. Overall, the extent of diversity was much greater in T. parva isolates originating from buffalo than in isolates known to be transmissible among cattle.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions/Significance:&lt;/b&gt; The results indicate that T. parva parasites maintained in cattle represent a subset of the overall T. parva population, which has become adapted for tick transmission between cattle. The absence of obvious enrichment for positively selected amino acid residues within defined epitopes indicates either that diversity is not predominantly driven by selection exerted by host T cells, or that such selection is not detectable by the methods employed due to unidentified epitopes elsewhere in the antigens. Further functional studies are required to address this latter point.&lt;/p&gt

    Two Theileria parva CD8 T Cell Antigen Genes Are More Variable in Buffalo than Cattle Parasites, but Differ in Pattern of Sequence Diversity

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    &lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Theileria parva causes an acute fatal disease in cattle, but infections are asymptomatic in the African buffalo (Syncerus caffer). Cattle can be immunized against the parasite by infection and treatment, but immunity is partially strain specific. Available data indicate that CD8(+) T lymphocyte responses mediate protection and, recently, several parasite antigens recognised by CD8(+) T cells have been identified. This study set out to determine the nature and extent of polymorphism in two of these antigens, Tp1 and Tp2, which contain defined CD8(+) T-cell epitopes, and to analyse the sequences for evidence of selection.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methodology/Principal Findings:&lt;/b&gt; Partial sequencing of the Tp1 gene and the full-length Tp2 gene from 82 T. parva isolates revealed extensive polymorphism in both antigens, including the epitope-containing regions. Single nucleotide polymorphisms were detected at 51 positions (similar to 12%) in Tp1 and in 320 positions (similar to 61%) in Tp2. Together with two short indels in Tp1, these resulted in 30 and 42 protein variants of Tp1 and Tp2, respectively. Although evidence of positive selection was found for multiple amino acid residues, there was no preferential involvement of T cell epitope residues. Overall, the extent of diversity was much greater in T. parva isolates originating from buffalo than in isolates known to be transmissible among cattle.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions/Significance:&lt;/b&gt; The results indicate that T. parva parasites maintained in cattle represent a subset of the overall T. parva population, which has become adapted for tick transmission between cattle. The absence of obvious enrichment for positively selected amino acid residues within defined epitopes indicates either that diversity is not predominantly driven by selection exerted by host T cells, or that such selection is not detectable by the methods employed due to unidentified epitopes elsewhere in the antigens. Further functional studies are required to address this latter point.&lt;/p&gt

    14-3-3σ Regulates β-Catenin-Mediated Mouse Embryonic Stem Cell Proliferation by Sequestering GSK-3β

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    [[abstract]]Background: Pluripotent embryonic stem cells are considered to be an unlimited cell source for tissue regeneration and cell-based therapy. Investigating the molecular mechanism underlying the regulation of embryonic stem cell expansion is thus important. 14-3-3 proteins are implicated in controlling cell division, signaling transduction and survival by interacting with various regulatory proteins. However, the function of 14-3-3 in embryonic stem cell proliferation remains unclear. Methodology and Principal Findings: In this study, we show that all seven 14-3-3 isoforms were detected in mouse embryonic stem cells. Retinoid acid suppressed selectively the expression of 14-3-3σ isoform. Knockdown of 14-3-3σ with siRNA reduced embryonic stem cell proliferation, while only 14-3-3σ transfection increased cell growth and partially rescued retinoid acid-induced growth arrest. Since the growth-enhancing action of 14-3-3σ was abrogated by β-catenin knockdown, we investigated the influence of 14-3-3σ overexpression on β-catenin/GSK-3β. 14-3-3σ bound GSK-3β and increased GSK-3β phosphorylation in a PI-3K/Akt-dependent manner. It disrupted β-catenin binding by the multiprotein destruction complex. 14-3-3σ overexpression attenuated β-catenin phosphorylation and rescued the decline of β-catenin induced by retinoid acid. Furthermore, 14-3-3σ enhanced Wnt3a-induced β-catenin level and GSK-3β phosphorylation. DKK, an inhibitor of Wnt signaling, abolished Wnt3a-induced effect but did not interfere GSK-3β/14-3-3σ binding. Significance:Our findings show for the first time that 14-3-3σ plays an important role in regulating mouse embryonic stem cell proliferation by binding and sequestering phosphorylated GSK-3β and enhancing Wnt-signaled GSK-3β inactivation. 14-3-3σ is a novel target for embryonic stem cell expansion
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