637 research outputs found

    P08-04. The role of class I HLA-B and HLA-Cw in disease progression and maternal-infant HIV-1 transmission in a South African population

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    Background: Human leukocyte antigens play an integral role in the cytotoxic T-cell pathway and serve as ligands for natural killer cell receptors. We have investigated the role of two HLA class I; genes on disease progression and maternal-infant HIV-1 transmission using 222 South African mother-infant pairs recruited as part of a mother-to-infant HIV-1 transmission study. Methods: High resolution genotyping of HLA class I; B and Cw loci was performed using a sequence-based typing strategy and alleles were collapsed to a four-digit assignment for purpose of analysis. Results: B*5802 and Cw*0602 were significantly associated with high viral load (VL) (P = 0.038 and P = 0.017 respectively) and low CD4 count (P < 0.001 and P = 0.005 respectively). These two alleles are in linkage disequilibrium (D' = 1.00; P < 0.001) and the most prevalent haplotype amongst Black South Africans (f = 9.94%). The B*5802-Cw*0602 haplotype was also significantly associated with low CD4 count (P = 0.001) and showed a trend with high VL (P = 0.073). Furthermore, B*4501 showed a trend with high VL (P = 0.086) and low CD4 count (P = 0.062). B*4201 was significantly associated with low VL (P = 0.045) and another prevalent haplotype, B*4201-Cw*1701 (f = 9.65%), was significantly associated with low VL (P = 0.049). The Cw allotype groups (C1&C2) showed no significant association with markers of disease severity, whereas, contrary to other studies, Bw4/Bw4 homozygosity was significantly associated with high VL (P = 0.038) and low CD4 count (P = 0.015). B*0801 showed a trend (P = 0.064) of lower representation amongst infected infants compared to exposed uninfected infants. Transmitting mothers had significantly higher representation of B*1402 (P = 0.034) and a trend of lower representation of B*4201 (P = 0.082) compared to non-transmitting mothers. No Cw* alleles or allotype groups showed significant association with HIV-1 transmission. Conclusion: This study highlights the different roles played by HLA in disease progression and maternal-infant HIV-1 transmission and also serves as a basis for future work that will study the role of KIR-HLA in the same contexts

    Prediction of peptide and protein propensity for amyloid formation

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    Understanding which peptides and proteins have the potential to undergo amyloid formation and what driving forces are responsible for amyloid-like fiber formation and stabilization remains limited. This is mainly because proteins that can undergo structural changes, which lead to amyloid formation, are quite diverse and share no obvious sequence or structural homology, despite the structural similarity found in the fibrils. To address these issues, a novel approach based on recursive feature selection and feed-forward neural networks was undertaken to identify key features highly correlated with the self-assembly problem. This approach allowed the identification of seven physicochemical and biochemical properties of the amino acids highly associated with the self-assembly of peptides and proteins into amyloid-like fibrils (normalized frequency of β-sheet, normalized frequency of β-sheet from LG, weights for β-sheet at the window position of 1, isoelectric point, atom-based hydrophobic moment, helix termination parameter at position j+1 and ΔGº values for peptides extrapolated in 0 M urea). Moreover, these features enabled the development of a new predictor (available at http://cran.r-project.org/web/packages/appnn/index.html) capable of accurately and reliably predicting the amyloidogenic propensity from the polypeptide sequence alone with a prediction accuracy of 84.9 % against an external validation dataset of sequences with experimental in vitro, evidence of amyloid formation

    Features of mammalian microRNA promoters emerge from polymerase II chromatin immunoprecipitation data

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    Background: MicroRNAs (miRNAs) are short, non-coding RNA regulators of protein coding genes. miRNAs play a very important role in diverse biological processes and various diseases. Many algorithms are able to predict miRNA genes and their targets, but their transcription regulation is still under investigation. It is generally believed that intragenic miRNAs (located in introns or exons of protein coding genes) are co-transcribed with their host genes and most intergenic miRNAs transcribed from their own RNA polymerase II (Pol II) promoter. However, the length of the primary transcripts and promoter organization is currently unknown. Methodology: We performed Pol II chromatin immunoprecipitation (ChIP)-chip using a custom array surrounding regions of known miRNA genes. To identify the true core transcription start sites of the miRNA genes we developed a new tool (CPPP). We showed that miRNA genes can be transcribed from promoters located several kilobases away and that their promoters share the same general features as those of protein coding genes. Finally, we found evidence that as many as 26% of the intragenic miRNAs may be transcribed from their own unique promoters. Conclusion: miRNA promoters have similar features to those of protein coding genes, but miRNA transcript organization is more complex. © 2009 Corcoran et al

    The developmental trajectory of attentional orienting to socio-biological cues.

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    It has been proposed that the orienting of attention in the same direction as another’s point of gaze relies on innate brain mechanisms which are present from birth, but direct evidence relating to the influence of eye gaze cues on attentional orienting in young children is limited. In two experiments, 137 children aged 3–10 years old performed an adapted pro-saccade task with centrally presented uninformative eye gaze, finger pointing and arrow pre-cues which were either congruent or incongruent with the direction of target presentations. When the central cue overlapped with presentation of the peripheral target (Experiment 1), children up to 5 years old had difficulty disengaging fixation from central fixation in order to saccade to the target. This effect was found to be particularly marked for eye gaze cues. When central cues were extinguished simultaneously with peripheral target onset (Experiment 2), this effect was greatly reduced. In both experiments finger pointing cues (image of pointing index finger presented at fixation) exerted a strong influence on saccade reaction time to the peripheral stimulus for the youngest group of children (<5 years). Overall the results suggest that although young children are strongly engaged by centrally presented eye gaze cues, the directional influence of such cues on overt attentional orienting is only present in older children, meaning that the effect is unlikely to be dependent upon an innate brain module. Instead, the results are consistent with the existence of stimulus–response associations which develop with age and environmental experience

    To respond or not to respond - a personal perspective of intestinal tolerance

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    For many years, the intestine was one of the poor relations of the immunology world, being a realm inhabited mostly by specialists and those interested in unusual phenomena. However, this has changed dramatically in recent years with the realization of how important the microbiota is in shaping immune function throughout the body, and almost every major immunology institution now includes the intestine as an area of interest. One of the most important aspects of the intestinal immune system is how it discriminates carefully between harmless and harmful antigens, in particular, its ability to generate active tolerance to materials such as commensal bacteria and food proteins. This phenomenon has been recognized for more than 100 years, and it is essential for preventing inflammatory disease in the intestine, but its basis remains enigmatic. Here, I discuss the progress that has been made in understanding oral tolerance during my 40 years in the field and highlight the topics that will be the focus of future research

    HIV-Specific Antibodies Capable of ADCC Are Common in Breastmilk and Are Associated with Reduced Risk of Transmission in Women with High Viral Loads

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    There are limited data describing the functional characteristics of HIV-1 specific antibodies in breast milk (BM) and their role in breastfeeding transmission. The ability of BM antibodies to bind HIV-1 envelope, neutralize heterologous and autologous viruses and direct antibody-dependent cell cytotoxicity (ADCC) were analyzed in BM and plasma obtained soon after delivery from 10 non-transmitting and 9 transmitting women with high systemic viral loads and plasma neutralizing antibodies (NAbs). Because subtype A is the dominant subtype in this cohort, a subtype A envelope variant that was sensitive to plasma NAbs was used to assess the different antibody activities. We found that NAbs against the subtype A heterologous virus and/or the woman's autologous viruses were rare in IgG and IgA purified from breast milk supernatant (BMS) – only 4 of 19 women had any detectable NAb activity against either virus. Detected NAbs were of low potency (median IC50 value of 10 versus 647 for the corresponding plasma) and were not associated with infant infection (p = 0.58). The low NAb activity in BMS versus plasma was reflected in binding antibody levels: HIV-1 envelope specific IgG titers were 2.2 log10 lower (compared to 0.59 log10 lower for IgA) in BMS versus plasma. In contrast, antibodies capable of ADCC were common and could be detected in the BMS from all 19 women. BMS envelope-specific IgG titers were associated with both detection of IgG NAbs (p = 0.0001)and BMS ADCC activity (p = 0.014). Importantly, BMS ADCC capacity was inversely associated with infant infection risk (p = 0.039). Our findings indicate that BMS has low levels of envelope specific IgG and IgA with limited neutralizing activity. However, this small study of women with high plasma viral loads suggests that breastmilk ADCC activity is a correlate of transmission that may impact infant infection risk

    TRY plant trait database - enhanced coverage and open access

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    Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

    Effective Rheology of Bubbles Moving in a Capillary Tube

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    We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur
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