516 research outputs found

    Competitive assembly of South Pacific invasive ant communities

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    <p>Abstract</p> <p>Background</p> <p>The relative importance of chance and determinism in structuring ecological communities has been debated for nearly a century. Evidence for determinism or assembly rules is often evaluated with null models that randomize the occurrence of species in particular locales. However, analyses of the presence or absence of species ignores the potential influence of species abundances, which have long been considered of major importance on community structure. Here, we test for community assembly rules in ant communities on small islands of the Tokelau archipelago using both presence-absence and abundance data. We conducted three sets of analyses on two spatial scales using three years of sampling data from 39 plots on 11 islands.</p> <p>Results</p> <p>First, traditional null model tests showed support for negative species co-occurrence patterns among plots within islands, but not among islands. A plausible explanation for this result is that analyses at larger spatial scales merge heterogeneous habitats that have considerable effects on species occurrences. Second, analyses of ant abundances showed that samples with high ant abundances had fewer species than expected by chance, both within and among islands. One ant species, the invasive yellow crazy ant <it>Anoplolepis gracilipes</it>, appeared to have a particularly strong effect on community structure correlated with its abundance. Third, abundances of most ant species were inversely correlated with the abundances of all other ants at both spatial scales. This result is consistent with competition theory, which predicts species distributions are affected by diffuse competition with suites of co-occurring species.</p> <p>Conclusion</p> <p>Our results support a pluralistic explanation for ant species abundances and assembly. Both stochastic and deterministic processes interact to determine ant community assembly, though abundance patterns clearly drive the deterministic patterns in this community. These deterministic patterns were observed at two spatial scales. Results indicate that abundance-based null models may be more sensitive in detecting non-random patterns in community assembly than species co-occurrences analyses.</p

    Biallelic JAK1 mutations in immunodeficient patient with mycobacterial infection

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    Mutations in genes encoding components of the immune system cause primary immunodeficiencies. Here, we study a patient with recurrent atypical mycobacterial infection and early-onset metastatic bladder carcinoma. Exome sequencing identified two homozygous missense germline mutations, P733L and P832S, in the JAK1 protein that mediates signalling from multiple cytokine receptors. Cells from this patient exhibit reduced JAK1 and STAT phosphorylation following cytokine stimulations, reduced induction of expression of interferon-regulated genes and dysregulated cytokine production; which are indicative of signalling defects in multiple immune response pathways including Interferon-γ production. Reconstitution experiments in the JAK1-deficient cells demonstrate that the impaired JAK1 function is mainly attributable to the effect of the P733L mutation. Further analyses of the mutant protein reveal a phosphorylation-independent role of JAK1 in signal transduction. These findings clarify JAK1 signalling mechanisms and demonstrate a critical function of JAK1 in protection against mycobacterial infection and possibly the immunological surveillance of cancer.Wellcome Trust (095198/Z/10/Z and 090233/Z/09/Z); Higher Education Funding Council for England; Great Ormond Street Hospital Children’s Charity; National Institute for Health Research (NIHR); Great Ormond Street Hospital Biomedical Research Centre; NIHR Cambridge Biomedical Research Centre; Alfonso Martin Escudero Foundatio

    Long-term outcomes for adults with chronic granulomatous disease in the United Kingdom

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    Uncorrected CGD is associated with significant morbidity and mortality in adulthood, in particular due to inflammatory complications including life-limiting interstitial lung disease

    Atropselective syntheses of (-) and (+) rugulotrosin A utilizing point-to-axial chirality transfer

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    Chiral, dimeric natural products containing complex structures and interesting biological properties have inspired chemists and biologists for decades. A seven-step total synthesis of the axially chiral, dimeric tetrahydroxanthone natural product rugulotrosin A is described. The synthesis employs a one-pot Suzuki coupling/dimerization to generate the requisite 2,2'-biaryl linkage. Highly selective point-to-axial chirality transfer was achieved using palladium catalysis with achiral phosphine ligands. Single X-ray crystal diffraction data were obtained to confirm both the atropisomeric configuration and absolute stereochemistry of rugulotrosin A. Computational studies are described to rationalize the atropselectivity observed in the key dimerization step. Comparison of the crude fungal extract with synthetic rugulotrosin A and its atropisomer verified that nature generates a single atropisomer of the natural product.P50 GM067041 - NIGMS NIH HHS; R01 GM099920 - NIGMS NIH HHS; GM-067041 - NIGMS NIH HHS; GM-099920 - NIGMS NIH HH

    HIVAN and medication use in chronic dialysis patients in the United States: analysis of the USRDS DMMS Wave 2 study

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    BACKGROUND: The use and possible effects of factors known to improve outcomes in patients with human immunodeficiency virus associated nephropathy (HIVAN), namely of angiotensin converting enzyme inhibitors (ACE) and antiretroviral therapy, has not been reported for a national sample of dialysis patients. METHODS: We conducted a historical cohort study of the United States Renal Data System (USRDS) Dialysis Morbidity and Mortality Study (DMMS) Wave 2 to identify risk factors associated with increased mortality in these patients. Data were available for 3374 patients who started dialysis and were followed until March 2000. Cox Regression analysis was used to model adjusted hazard ratios (AHR) with HIVAN as a cause of end stage renal disease (ESRD) and its impact on mortality during the study period, adjusted for potential confounders. RESULTS: Of the 3374 patients who started dialysis, 36 (1.1%) had ESRD as a result of HIVAN. Only 22 (61%) of patients with HIVAN received antiretroviral agents, and only nine patients (25%) received combination antiretroviral therapy, and only 14% received ACE inhibitors. Neither the use of multiple antiretroviral drugs (AHR, 0.62, 95% CI, 0.10, 3.86, p = 0.60), or ACE inhibitors were associated with a survival advantage. Patients with HIVAN had an increased risk of mortality (adjusted hazard ratio, 4.74, 95% Confidence Interval, 3.12, 7.32, p < 0.01) compared to patients with other causes of ESRD. CONCLUSIONS: Medications known to improve outcomes in HIV infected patients were underutilized in patients with HIVAN. Adjusted for other factors, a primary diagnosis of HIVAN was associated with increased mortality compared with other causes of ESRD

    Use of low-dose oral theophylline as an adjunct to inhaled corticosteroids in preventing exacerbations of chronic obstructive pulmonary disease: study protocol for a randomised controlled trial.

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    BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with high morbidity, mortality, and health-care costs. An incomplete response to the anti-inflammatory effects of inhaled corticosteroids is present in COPD. Preclinical work indicates that 'low dose' theophylline improves steroid responsiveness. The Theophylline With Inhaled Corticosteroids (TWICS) trial investigates whether the addition of 'low dose' theophylline to inhaled corticosteroids has clinical and cost-effective benefits in COPD. METHOD/DESIGN: TWICS is a randomised double-blind placebo-controlled trial conducted in primary and secondary care sites in the UK. The inclusion criteria are the following: an established predominant respiratory diagnosis of COPD (post-bronchodilator forced expiratory volume in first second/forced vital capacity [FEV1/FVC] of less than 0.7), age of at least 40 years, smoking history of at least 10 pack-years, current inhaled corticosteroid use, and history of at least two exacerbations requiring treatment with antibiotics or oral corticosteroids in the previous year. A computerised randomisation system will stratify 1424 participants by region and recruitment setting (primary and secondary) and then randomly assign with equal probability to intervention or control arms. Participants will receive either 'low dose' theophylline (Uniphyllin MR 200 mg tablets) or placebo for 52 weeks. Dosing is based on pharmacokinetic modelling to achieve a steady-state serum theophylline of 1-5 mg/l. A dose of theophylline MR 200 mg once daily (or placebo once daily) will be taken by participants who do not smoke or participants who smoke but have an ideal body weight (IBW) of not more than 60 kg. A dose of theophylline MR 200 mg twice daily (or placebo twice daily) will be taken by participants who smoke and have an IBW of more than 60 kg. Participants will be reviewed at recruitment and after 6 and 12 months. The primary outcome is the total number of participant-reported COPD exacerbations requiring oral corticosteroids or antibiotics during the 52-week treatment period. DISCUSSION: The demonstration that 'low dose' theophylline increases the efficacy of inhaled corticosteroids in COPD by reducing the incidence of exacerbations is relevant not only to patients and clinicians but also to health-care providers, both in the UK and globally. TRIAL REGISTRATION: Current Controlled Trials ISRCTN27066620 was registered on Sept. 19, 2013, and the first subject was randomly assigned on Feb. 6, 2014

    Pulse wave velocity is associated with increased plasma oxLDL in ageing but not with FGF21 and habitual exercise

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    Fibroblast growth factor 21 (FGF21) and adiponectin increase expression of genes involved in antioxidant pathways, but their roles in mediating oxidative stress and arterial stiffness with ageing and habitual exercise remain unknown. We explored the role of the FGF21–adiponectin axis in mediating oxidative stress and arterial stiffness with ageing and habitual exercise. Eighty age- and sex-matched healthy individuals were assigned to younger sedentary or active (18–36 years old,n=20 each) and older sedentary or active (45–80 years old,n=20 each) groups. Arterial stiffness was measured indirectly using pulse wave velocity (PWV). Fasted plasma concentrations of FGF21, adiponectin and oxidized low-density lipoprotein (oxLDL) were measured. PWV was 0.2-fold higher and oxLDL concentration was 25.6% higher (both p<0.001) in older than younger adults, despite no difference in FGF21 concentration (p=0.097) between age groups. PWV (p=0.09) and oxLDL concentration (p=0.275) did not differ between activity groups but FGF21 concentration was 9% lower in active than sedentary individuals (p=0.011). Adiponectin concentration did not differ by age (p=0.642) or exercise habits (p=0.821). In conclusion, age, but not habitual exercise, was associated with higher oxidative stress and arterial stiffness. FGF21 and adiponectin did not differ between younger and older adults, unlikely mediating oxidative stress and arterial stiffness in healthy adults. <br

    Association of CCR2-CCR5 Haplotypes and CCL3L1 Copy Number with Kawasaki Disease, Coronary Artery Lesions, and IVIG Responses in Japanese Children

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    BACKGROUND: The etiology of Kawasaki Disease (KD) is enigmatic, although an infectious cause is suspected. Polymorphisms in CC chemokine receptor 5 (CCR5) and/or its potent ligand CCL3L1 influence KD susceptibility in US, European and Korean populations. However, the influence of these variations on KD susceptibility, coronary artery lesions (CAL) and response to intravenous immunoglobulin (IVIG) in Japanese children, who have the highest incidence of KD, is unknown. METHODOLOGY/PRINCIPAL FINDINGS: We used unconditional logistic regression analyses to determine the associations of the copy number of the CCL3L1 gene-containing duplication and CCR2-CCR5 haplotypes in 133 Japanese KD cases [33 with CAL and 25 with resistance to IVIG] and 312 Japanese controls without a history of KD. We observed that the deviation from the population average of four CCL3L1 copies (i.e., <or>four copies) was associated with an increased risk of KD and IVIG resistance (adjusted odds ratio (OR)=2.25, p=0.004 and OR=6.26, p=0.089, respectively). Heterozygosity for the CCR5 HHF*2 haplotype was associated with a reduced risk of both IVIG resistance (OR=0.21, p=0.026) and CAL development (OR=0.44, p=0.071). CONCLUSIONS/SIGNIFICANCE: The CCL3L1-CCR5 axis may play an important role in KD pathogenesis. In addition to clinical and laboratory parameters, genetic markers may also predict risk of CAL and resistance to IVIG

    Are Nested Networks More Robust to Disturbance? A Test Using Epiphyte-Tree, Comensalistic Networks

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    Recent research on ecological networks suggests that mutualistic networks are more nested than antagonistic ones and, as a result, they are more robust against chains of extinctions caused by disturbances. We evaluate whether mutualistic networks are more nested than comensalistic and antagonistic networks, and whether highly nested, host-epiphyte comensalistic networks fit the prediction of high robustness against disturbance. A review of 59 networks including mutualistic, antagonistic and comensalistic relationships showed that comensalistic networks are significantly more nested than antagonistic and mutualistic networks, which did not differ between themselves. Epiphyte-host networks from old-growth forests differed from those from disturbed forest in several topological parameters based on both qualitative and quantitative matrices. Network robustness increased with network size, but the slope of this relationship varied with nestedness and connectance. Our results indicate that interaction networks show complex responses to disturbances, which influence their topology and indirectly affect their robustness against species extinctions
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