168 research outputs found

    The Impacat of Personality Type on Blog Participation

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    The objective of this study is to explore the impact of individual personality type on blog participation. Results indicate that blog participants are more likely to be introverts and perceptives

    Original Research Effects of Iron Intake on Iron Stores in Elderly Men and Women: Longitudinal and Cross-Sectional Results

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    Key words: iron intake, ferritin, iron stores, elderly men and women Objective: For middle aged and elderly subjects there is a concern that increased iron intake, especially heme iron associated with consumption of red meat, leads to increased iron stores resulting in disturbed glucose homeostasis and risk for cardiovascular disease and certain types of cancer. The aim of this study was to investigate the influence of heme, non-heme and iron supplementation on iron stores in healthy elderly men and women. Method: We conducted a 10 year longitudinal study (48 men and 77 women) and a one year cross-sectional study (165 men and 226 women) in healthy elderly men and women enrolled in the New Mexico Aging Process Study. Iron stores were estimated by serum ferritin concentrations and iron intake was determined by three-day food records in the longitudinal study and by a food frequency questionnaire in the cross-sectional study. Results: We found no association between heme iron intake and iron stores in either the longitudinal or cross sectional study. In the cross-sectional study we found in women, but not in men, that age and supplemental iron intake were significantly and positively associated with increased iron stores. Conclusion: Iron stores in elderly men are thought to reach steady state levels where iron absorption is adjusted to a level just sufficient to cover basal iron losses. In elderly women, we speculate that not enough time has elapsed for postmenopausal women to reach steady state levels of iron stores resulting in increases in iron absorption with age. Another factor is that use of hormone replacement therapy could further delay some women in reaching steady state iron levels due to continued menstrual blood losses

    Cytomegalovirus-mediated T cell receptor repertoire perturbation is present in early life

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    Human cytomegalovirus (CMV) is a highly prevalent herpesvirus, particularly in sub-Saharan Africa, where it is endemic from infancy. The T cell response against CMV is important in keeping the virus in check, with CD8 T cells playing a major role in the control of CMV viraemia. Human leukocyte antigen (HLA) B*44:03-positive individuals raise a robust response against the NEGVKAAW (NW8) epitope, derived from the immediate-early-2 (IE-2) protein. We previously showed that the T cell receptor (TCR) repertoire raised against the NW8-HLA-B*44:03 complex was oligoclonal and characterised by superdominant clones, which were shared amongst unrelated individuals (i.e., “public”). Here, we address the question of how stable the CMV-specific TCR repertoire is over the course of infection, and whether substantial differences are evident in TCR repertoires in children, compared with adults. We present a longitudinal study of four HIV/CMV co-infected mother-child pairs, who in each case express HLA-B*44:03 and make responses to the NW8 epitope, and analyse their TCR repertoire over a period spanning more than 10 years. Using high-throughput sequencing, the paediatric CMV-specific repertoire was found to be highly diverse. In addition, paediatric repertoires were remarkably similar to adults, with public TCR responses being shared amongst children and adults alike. The CMV-specific repertoire in both adults and children displayed strong fluctuations in TCR clonality and repertoire architecture over time. Previously characterised superdominant clonotypes were readily identifiable in the children at high frequency, suggesting that the distortion of the CMV-specific repertoire is incurred as a direct result of CMV infection rather than a product of age-related “memory inflation.” Early distortion of the TCR repertoire was particularly apparent in the case of the TCR-β chain, where oligoclonality was low in children and positively correlated with age, a feature we did not observe for TCR-α. This discrepancy between TCR-α and -β chain repertoire may reflect differential contribution to NW8 recognition. Altogether, the results of the present study provide insight into the formation of the TCR repertoire in early life and pave the way to better understanding of CD8 T cell responses to CMV at the molecular level

    New OH Zeeman measurements of magnetic field strengths in molecular clouds

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    We present the results of a new survey of 23 molecular clouds for the Zeeman effect in OH undertaken with the ATNF Parkes 64-m radio telescope and the NRAO Green Bank 43-m radio telescope. The Zeeman effect was clearly detected in the cloud associated with the HII region RCW 38, with a field strength of 38+/-3 micro-Gauss, and possibly detected in a cloud associated with the HII region RCW 57, with a field strength of -203+/-24 micro-Gauss. The remaining 21 measurements give formal upper limits to the magnetic field strength, with typical 1-sigma sensitivities <20 micro-Gauss. For 22 of the molecular clouds we are also able to determine thecolumn density of the gas in which we have made a sensitive search for the Zeeman effect. We combine these results with previous Zeeman studies of 29 molecular clouds, most of which were compiled by Crutcher (1999), for a comparsion of theoretical models with the data. This comparison implies that if the clouds can be modeled as initially spherical with uniform magnetic fields and densities that evolve to their final equilibrium state assuming flux-freezing then the typical cloud is magnetically supercritical, as was found by Crutcher (1999). If the clouds can be modeled as highly flattened sheets threaded by uniform perpendicular fields, then the typical cloud is approximately magnetically critical, in agreement with Shu et al. (1999), but only if the true values of the field for the non-detections are close to the 3-sigma upper limits. If instead these values are significantly lower (for example, similar to the 1-sigma limits), then the typical cloud is generally magnetically supercritical.Comment: 39 pages, 7 figures. Accepted for publication in Ap

    Bacterial-based systems for expression and purification of recombinant Lassa virus proteins of immunological relevance

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    <p>Abstract</p> <p>Background</p> <p>There is a significant requirement for the development and acquisition of reagents that will facilitate effective diagnosis, treatment, and prevention of Lassa fever. In this regard, recombinant Lassa virus (LASV) proteins may serve as valuable tools in diverse antiviral applications. Bacterial-based systems were engineered for expression and purification of recombinant LASV nucleoprotein (NP), glycoprotein 1 (GP1), and glycoprotein 2 (GP2).</p> <p>Results</p> <p>Full-length NP and the ectodomains of GP1 and GP2 were generated as maltose-binding protein (MBP) fusions in the Rosetta strains of <it>Escherichia coli </it>(<it>E. coli</it>) using pMAL-c2x vectors. Average fusion protein yields per liter of culture for MBP-NP, MBP-GP1, and MBP-GP2 were 10 mg, 9 mg, and 9 mg, respectively. Each protein was captured from cell lysates using amylose resin, cleaved with Factor Xa, and purified using size-exclusion chromatography (SEC). Fermentation cultures resulted in average yields per liter of 1.6 mg, 1.5 mg, and 0.7 mg of purified NP, GP1 and GP2, respectively. LASV-specific antibodies in human convalescent sera specifically detected each of the purified recombinant LASV proteins, highlighting their utility in diagnostic applications. In addition, mouse hyperimmune ascitic fluids (MHAF) against a panel of Old and New World arenaviruses demonstrated selective cross reactivity with LASV proteins in Western blot and enzyme-linked immunosorbent assay (ELISA).</p> <p>Conclusion</p> <p>These results demonstrate the potential for developing broadly reactive immunological assays that employ all three arenaviral proteins individually and in combination.</p

    The impact of obesity and bariatric surgery on the immune microenvironment of the endometrium

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    BACKGROUND: The incidence of endometrial cancer is rising in parallel with the obesity epidemic. Obesity increases endometrial cancer risk and weight loss is protective, but the underlying mechanisms are incompletely understood. We hypothesise that the immune microenvironment may influence susceptibility to malignant transformation in the endometrium. The aim of this study was to measure the impact of obesity and weight loss on the immunological landscape of the endometrium. METHODS: We conducted a prospective cohort study of women with class III obesity (body mass index, BMI ≥ 40 kg/m(2)) undergoing bariatric surgery or medically-supervised low-calorie diet. We collected blood and endometrial samples at baseline, and two and 12 months after weight loss intervention. Serum was analysed for inflammatory markers CRP, IL-6 and TNF-α. Multiplex immunofluorescence was used to simultaneously identify cells positive for immune markers CD68, CD56, CD3, CD8, FOXP3 and PD-1 in formalin-fixed paraffin-embedded endometrial tissue sections. Kruskal–Wallis tests were used to determine whether changes in inflammatory and immune biomarkers were associated with weight loss. RESULTS: Forty-three women with matched serum and tissue samples at all three time points were included in the analysis. Their median age and BMI were 44 years and 52 kg/m(2), respectively. Weight loss at 12 months was greater in women who received bariatric surgery (n = 37, median 63.3 kg) than low-calorie diet (n = 6, median 12.8 kg). There were significant reductions in serum CRP (p = 3.62 × 10(−6), r = 0.570) and IL-6 (p = 0.0003, r = 0.459), but not TNF-α levels, with weight loss. Tissue immune cell densities were unchanged except for CD8+ cells, which increased significantly with weight loss (p = 0.0097, r = −0.323). Tissue CD3+ cell density correlated negatively with systemic IL-6 levels (p = 0.0376; r = −0.318). CONCLUSION: Weight loss is associated with reduced systemic inflammation and a recruitment of protective immune cell types to the endometrium, supporting the concept that immune surveillance may play a role in endometrial cancer prevention

    Intracellular oligomeric amyloid-beta rapidly regulates GluA1 subunit of AMPA receptor in the hippocampus

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    The acute neurotoxicity of oligomeric forms of amyloid-beta 1-42 (A beta) is implicated in the pathogenesis of Alzheimer&apos;s disease (AD). However, how these oligomers might first impair neuronal function at the onset of pathology is poorly understood. Here we have examined the underlying toxic effects caused by an increase in levels of intracellular A beta, an event that could be important during the early stages of the disease. We show that oligomerised A beta induces a rapid enhancement of AMPA receptor-mediated synaptic transmission (EPSCA) when applied intracellularly. This effect is dependent on postsynaptic Ca2+ and PKA. Knockdown of GluA1, but not GluA2, prevents the effect, as does expression of a S8(45)-phosphomutant of GluA1. Significantly, an inhibitor of Ca2+-permeable AMPARs (CP-AMPARs), IEM 1460, reverses the increase in the amplitude of EPSCA. These results suggest that a primary neuronal response to intracellular A beta oligomers is the rapid synaptic insertion of CP-AMPARs114161sciescopu
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