35 research outputs found

    South African research in the Southern Ocean: New opportunities but serious challenges

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    South Africa has a long track record in Southern Ocean and Antarctic research and has recently invested considerable funds in acquiring new infrastructure for ongoing support of this research. This infrastructure includes a new base at Marion Island and a purpose-built ice capable research vessel, which greatly expand research opportunities. Despite this investment, South Africa's standing as a participant in this critical field is threatened by confusion, lack of funding, lack of consultation and lack of transparency. The research endeavour is presently bedevilled by political manoeuvring among groups with divergent interests that too often have little to do with science, while past and present contributors of research are excluded from discussions that aim to formulate research strategy. This state of affairs is detrimental to the country's aims of developing a leadership role in climate change and Antarctic research and squanders both financial and human capital

    Long-Term Impact of Malaria Chemoprophylaxis on Cognitive Abilities and Educational Attainment: Follow-Up of a Controlled Trial

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    OBJECTIVES: We investigated the long-term impact of early childhood malaria prophylaxis on cognitive and educational outcomes. DESIGN: This was a household-based cluster-controlled intervention trial. SETTING: The study was conducted in 15 villages situated between 32 km to the east and 22 km to the west of the town of Farafenni, the Gambia, on the north bank of the River Gambia. PARTICIPANTS: A total of 1,190 children aged 3–59 mo took part in the trial. We traced 579 trial participants (291 in the prophylaxis group and 288 in the placebo group) in 2001, when their median age was 17 y 1 mo (range 14 y 9 mo to 19 y 6 mo). INTERVENTIONS: Participants received malaria chemoprophylaxis (dapsone/pyrimethamine) or placebo for between one and three malaria transmission seasons from 1985 to 1987 during the controlled trial. At the end of the trial, prophylaxis was provided for all children under 5 y of age living in the study villages. OUTCOME MEASURES: The outcome measures were cognitive abilities, school enrolment, and educational attainment (highest grade reached at school). RESULTS: There was no significant overall intervention effect on cognitive abilities, but there was a significant interaction between intervention group and the duration of post-trial prophylaxis (p = 0.034), with cognitive ability somewhat higher in the intervention group among children who received no post-trial prophylaxis (treatment effect = 0.2 standard deviations [SD], 95% confidence interval [CI] βˆ’0.03 to 0.5) and among children who received less than 1 y of post-trial prophylaxis (treatment effect = 0.4 SD, 95% CI 0.1 to 0.8). The intervention group had higher educational attainment by 0.52 grades (95% CI = βˆ’0.041 to 1.089; p = 0.069). School enrolment was similar in the two groups. CONCLUSIONS: The results are suggestive of a long-term effect of malaria prophylaxis on cognitive function and educational attainment, but confirmatory studies are needed

    On the β€œDuel” Nature of History: Revisiting Contingency versus Determinism

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    Are we β€œhistorical accidents” of an undirected evolutionary history? In his recent book, Islands in the Cosmos, Dale Russell addresses this question, and Brian Swartz reviews his synthesis of this β€œcosmic” evolutionary debate

    Evaluation of unclassified variants in the breast cancer susceptibility genes BRCA1 and BRCA2 using five methods: results from a population-based study of young breast cancer patients

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    Introduction Efforts are ongoing to determine the significance of unclassified variants (UVs) in the breast cancer susceptibility genes BRCA1/BRCA2, but no study has systematically assessed whether women carrying the suspected deleterious UVs have characteristics commonly seen among women carrying known deleterious or disease-causing mutations in BRCA1/BRCA2. Methods We sequenced BRCA1/BRCA2 in 1,469 population-based female breast cancer patients diagnosed between the ages of 20 and 49 years. We used existing literature to classify variants into known deleterious mutations, polymorphic variants, and UVs. The UVs were further classified as high risk or low risk based on five methods: allele frequency, Polyphen algorithm, sequence conservation, Grantham matrix scores, and a combination of the Grantham matrix score and sequence conservation. Furthermore, we examined whether patients who carry the variants classified as high risk using these methods have risk characteristics similar to patients with known deleterious BRCA1/BRCA2 mutations (early age at diagnosis, family history of breast cancer or ovarian cancer, and negative estrogen receptor/progesterone receptor). Results We identified 262 distinct BRCA1/BRCA2 variants, including 147 UVs, in our study population. The BRCA1 UV carriers, but not the BRCA2 UV carriers, who were classified as high risk using each classification method were more similar to the deleterious mutation carriers with respect to family history than those carriers classified as low risk. For example, the odds ratio of having a first-degree family history for the high-risk women classified using Polyphen was 3.39 (95% confidence interval = 1.16 to 9.94) compared with normal/polymorphic BRCA1 carriers. The corresponding odds ratio of low-risk women was 1.53 (95% confidence interval = 1.07 to 2.18). The odds ratio for high-risk women defined by allele frequency was 2.00 (95% confidence interval = 1.14 to 3.51), and that of low-risk women was 1.30 (95% confidence interval = 0.87 to 1.93). Conclusion The results suggest that the five classification methods yielded similar results. Polyphen was particularly better at isolating BRCA1 UV carriers likely to have a family history of breast cancer or ovarian cancer, and may therefore help to classify BRCA1 UVs. Our study suggests that these methods may not be as successful in classifying BRCA2 UVs

    Loss of apical monocilia on collecting duct principal cells impairs ATP secretion across the apical cell surface and ATP-dependent and flow-induced calcium signals

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    Renal epithelial cells release ATP constitutively under basal conditions and release higher quantities of purine nucleotide in response to stimuli. ATP filtered at the glomerulus, secreted by epithelial cells along the nephron, and released serosally by macula densa cells for feedback signaling to afferent arterioles within the glomerulus has important physiological signaling roles within kidneys. In autosomal recessive polycystic kidney disease (ARPKD) mice and humans, collecting duct epithelial cells lack an apical central cilium or express dysfunctional proteins within that monocilium. Collecting duct principal cells derived from an Oak Ridge polycystic kidney (orpkTg737) mouse model of ARPKD lack a well-formed apical central cilium, thought to be a sensory organelle. We compared these cells grown as polarized cell monolayers on permeable supports to the same cells where the apical monocilium was genetically rescued with the wild-type Tg737 gene that encodes Polaris, a protein essential to cilia formation. Constitutive ATP release under basal conditions was low and not different in mutant versus rescued monolayers. However, genetically rescued principal cell monolayers released ATP three- to fivefold more robustly in response to ionomycin. Principal cell monolayers with fully formed apical monocilia responded three- to fivefold greater to hypotonicity than mutant monolayers lacking monocilia. In support of the idea that monocilia are sensory organelles, intentionally harsh pipetting of medium directly onto the center of the monolayer induced ATP release in genetically rescued monolayers that possessed apical monocilia. Mechanical stimulation was much less effective, however, on mutant orpk collecting duct principal cell monolayers that lacked apical central monocilia. Our data also show that an increase in cytosolic free Ca2+ primes the ATP pool that is released in response to mechanical stimuli. It also appears that hypotonic cell swelling and mechanical pipetting stimuli trigger release of a common ATP pool. Cilium-competent monolayers responded to flow with an increase in cell Ca2+ derived from both extracellular and intracellular stores. This flow-induced Ca2+ signal was less robust in cilium-deficient monolayers. Flow-induced Ca2+ signals in both preparations were attenuated by extracellular gadolinium and by extracellular apyrase, an ATPase/ADPase. Taken together, these data suggest that apical monocilia are sensory organelles and that their presence in the apical membrane facilitates the formation of a mature ATP secretion apparatus responsive to chemical, osmotic, and mechanical stimuli. The cilium and autocrine ATP signaling appear to work in concert to control cell Ca2+. Loss of a cilium-dedicated autocrine purinergic signaling system may be a critical underlying etiology for ARPKD and may lead to disinhibition and/or upregulation of multiple sodium (Na+) absorptive mechanisms and a resultant severe hypertensive phenotype in ARPKD and, possibly, other diseases

    Appendix A. Life-history characteristics of marine invertebrates found in species lists at the 91 sites analyzed for this study.

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    Life-history characteristics of marine invertebrates found in species lists at the 91 sites analyzed for this study

    Data from: A case for a joint strategy of diversified bet hedging and plasticity in the pea aphid wing polyphenism

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    Phenotypic plasticity and diversified bet hedging are strategies for coping with variable environments. Plasticity is favoured when an organism can predict future conditions using environmental cues, while bet hedging is favoured when predictive cues are not available. Theoretical analyses suggest that many organisms should use a mixture of both strategies, because environments often present both scenarios. Here, we examine if the pea aphid wing polyphenism, a well-known case of plasticity, is potentially a mixture of plasticity and bet hedging. In this polyphenism, asexual females produce more winged offspring in crowded conditions, and wingless offspring in uncrowded conditions. We find that pea aphids use plasticity to respond to crowding and we find considerable genetic variation for this response. We further show that individual aphids produce both winged and wingless offspring, consistent with the variability expected in a bet hedging trait. We conclude that the pea aphid wing polyphenism system is probably a mixture of plasticity and bet hedging. Our study adds to a limited list of empirical studies examining mixed strategy usage, and suggests that mixed strategies may be common in dispersal traits

    Impaired everyday memory associated with encephalopathy of severe malaria: the role of seizures and hippocampal damage.

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    BACKGROUND: Seizures are common in children admitted with severe falciparum malaria and are associated with neuro-cognitive impairments. Prolonged febrile seizures are associated with hippocampal damage and impaired memory. It was hypothesized that severe malaria causes impaired everyday memory which may be associated with hippocampal damage. METHODS: An everyday memory battery was administered on 152 children with cerebral malaria (CM) (mean age, 7 y 4 months [SD 13 months]; 77 males) 156 children (mean age, 7 y 4 months [SD, 14 months]; 72 males) with malaria plus complex seizures (MS) and 179 children (mean age, 7 y 6 months [SD, 13 months]; 93 males) unexposed to either condition. RESULTS: CM was associated with poorer everyday memory [95% CI, -2.46 to -0.36, p = 0.004] but not MS [95% CI, -0.91 to 1.16, p = 1.00] compared to unexposed children. Children with exposure to CM performed more poorly in recall [95% CI, -0.79 to -0.04, p = 0.024] and recognition subtests [95% CI, -0.90 to -0.17, p = 0.001] but not in prospective memory tests compared to controls. The health factors that predicted impaired everyday memory outcome in children with exposure to CM was profound coma [95% CI, 0.02 to 0.88, p = 0.037] and multiple episodes of hypoglycaemia [95% CI, 0.05 to 0.78, p = 0.020], but not seizures. DISCUSSION: The findings show that exposure to CM was associated with a specific impairment of everyday memory. Seizures commonly observed in severe malaria may not have a causal relationship with poor outcome, but rather be associated with profound coma and repeated metabolic insults (multi-hypoglycaemia) that are strongly associated with impaired everyday memory
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