Acute rejection is associated with antibodies to non-Gal antigens in baboons using Gal-knockout pig kidneys

We transplanted kidneys from α1,3-galactosyltransferase knockout (GalT-KO) pigs into six baboons using two different immunosuppressive regimens, but most of the baboons died from severe acute humoral xenograft rejection. Circulating induced antibodies to non-Gal antigens were markedly elevated at rejection, which mediated strong complement-dependent cytotoxicity against GalT-KO porcine target cells. These data suggest that antibodies to non-Gal antigens will present an additional barrier to transplantation of organs from GalT-KO pigs to humans. © 2005 Nature Publishing Group

The Impact of Imputation on Meta-Analysis of Genome-Wide Association Studies

Genotype imputation is often used in the meta-analysis of genome-wide association studies (GWAS), for combining data from different studies and/or genotyping platforms, in order to improve the ability for detecting disease variants with small to moderate effects. However, how genotype imputation affects the performance of the meta-analysis of GWAS is largely unknown. In this study, we investigated the effects of genotype imputation on the performance of meta-analysis through simulations based on empirical data from the Framingham Heart Study. We found that when fix-effects models were used, considerable between-study heterogeneity was detected when causal variants were typed in only some but not all individual studies, resulting in up to ∼25% reduction of detection power. For certain situations, the power of the meta-analysis can be even less than that of individual studies. Additional analyses showed that the detection power was slightly improved when between-study heterogeneity was partially controlled through the random-effects model, relative to that of the fixed-effects model. Our study may aid in the planning, data analysis, and interpretation of GWAS meta-analysis results when genotype imputation is necessary

African tropical rainforest net carbon dioxide fluxes in the twentieth century

The African humid tropical biome constitutes the second largest rainforest region, significantly impacts global carbon cycling and climate, and has undergone major changes in functioning owing to climate and land-use change over the past century. We assess changes and trends in CO2 fluxes from 1901 to 2010 using nine land surface models forced with common driving data, and depict the inter-model variability as the uncertainty in fluxes. The biome is estimated to be a natural (no disturbance) net carbon sink (−0.02 kg C m−2 yr−1 or −0.04 Pg C yr−1, p < 0.05) with increasing strength fourfold in the second half of the century. The models were in close agreement on net CO2 flux at the beginning of the century (σ1901 = 0.02 kg C m−2 yr−1), but diverged exponentially throughout the century (σ2010 = 0.03 kg C m−2 yr−1). The increasing uncertainty is due to differences in sensitivity to increasing atmospheric CO2, but not increasing water stress, despite a decrease in precipitation and increase in air temperature. However, the largest uncertainties were associated with the most extreme drought events of the century. These results highlight the need to constrain modelled CO2 fluxes with increasing atmospheric CO2 concentrations and extreme climatic events, as the uncertainties will only amplify in the next century

The Choice of the Filtering Method in Microarrays Affects the Inference Regarding Dosage Compensation of the Active X-Chromosome

The hypothesis of dosage compensation of genes of the X chromosome, supported by previous microarray studies, was recently challenged by RNA-sequencing data. It was suggested that microarray studies were biased toward an over-estimation of X-linked expression levels as a consequence of the filtering of genes below the detection threshold of microarrays.To investigate this hypothesis, we used microarray expression data from circulating monocytes in 1,467 individuals. In total, 25,349 and 1,156 probes were unambiguously assigned to autosomes and the X chromosome, respectively. Globally, there was a clear shift of X-linked expressions toward lower levels than autosomes. We compared the ratio of expression levels of X-linked to autosomal transcripts (X∶AA) using two different filtering methods: 1. gene expressions were filtered out using a detection threshold irrespective of gene chromosomal location (the standard method in microarrays); 2. equal proportions of genes were filtered out separately on the X and on autosomes. For a wide range of filtering proportions, the X∶AA ratio estimated with the first method was not significantly different from 1, the value expected if dosage compensation was achieved, whereas it was significantly lower than 1 with the second method, leading to the rejection of the hypothesis of dosage compensation. We further showed in simulated data that the choice of the most appropriate method was dependent on biological assumptions regarding the proportion of actively expressed genes on the X chromosome comparative to the autosomes and the extent of dosage compensation.This study shows that the method used for filtering out lowly expressed genes in microarrays may have a major impact according to the hypothesis investigated. The hypothesis of dosage compensation of X-linked genes cannot be firmly accepted or rejected using microarray-based data

The National Women's Health Study: assembly and description of a population-based reproductive cohort

BACKGROUND: Miscarriage is a common event but is remarkably difficult to measure in epidemiological studies. Few large-scale population-based studies have been conducted in the UK. METHODS: This was a population-based two-stage postal survey of reproductive histories of adult women living in the United Kingdom in 2001, sampled from the electronic electoral roll. In Stage 1 a short "screening" questionnaire was sent to over 60,000 randomly selected women in order to identify those aged 55 and under who had ever been pregnant or ever attempted to achieve a pregnancy, from whom a brief reproductive history was requested. Stage 2 involved a more lengthy questionnaire requesting detailed information on every pregnancy (and fertility problems), and questions relating to socio-demographic, behavioural and other factors for the most recent pregnancy in order to examine risk factors for miscarriage. Data on stillbirth, multiple birth and maternal age are compared to national data in order to assess response bias. RESULTS: The response rate was 49% for Stage 1 and 73% for the more targeted Stage 2. A total of 26,050 questionnaires were returned in Stage 1. Of the 17,748 women who were eligible on the grounds of age, 27% reported that they had never been pregnant and had never attempted to conceive a child. The remaining 13,035 women reported a total of 30,661 pregnancies. Comparison of key reproductive indicators (stillbirth and multiple birth rates and maternal age at first birth) with national statistics showed that the data look remarkably similar to the general population. CONCLUSIONS: This study has enabled the assembly of a large population-based dataset of women's reproductive histories which appears unbiased compared to the general UK population and which will enable investigation of hard-to-measure outcomes such as miscarriage and infertility

HiTSEE KNIME: a visualization tool for hit selection and analysis in high-throughput screening experiments for the KNIME platform

We present HiTSEE (High-Throughput Screening Exploration Environment), a visualization tool for the analysis of large chemical screens used to examine biochemical processes. The tool supports the investigation of structure-activity relationships (SAR analysis) and, through a flexible interaction mechanism, the navigation of large chemical spaces. Our approach is based on the projection of one or a few molecules of interest and the expansion around their neighborhood and allows for the exploration of large chemical libraries without the need to create an all encompassing overview of the whole library. We describe the requirements we collected during our collaboration with biologists and chemists, the design rationale behind the tool, and two case studies on different datasets. The described integration (HiTSEE KNIME) into the KNIME platform allows additional flexibility in adopting our approach to a wide range of different biochemical problems and enables other research groups to use HiTSEE

QGP Theory: Status and Perspectives

The current status of Quark-Gluon-Plasma Theory is reviewed. Special emphasis is placed on QGP signatures, the interpretation of current data and what to expect from RHIC in the near future.Comment: 20 pages, invited overview talk at the 4th International Conference on the Physcis and Astrophysics of the Quark-Gluon-Plasma, November 2001, Jaipur, India, to appear in Praman

Development and Functional Analysis of Novel Genetic Promoters Using DNA Shuffling, Hybridization and a Combination Thereof

BACKGROUND: Development of novel synthetic promoters with enhanced regulatory activity is of great value for a diverse range of plant biotechnology applications. METHODOLOGY: Using the Figwort mosaic virus full-length transcript promoter (F) and the sub-genomic transcript promoter (FS) sequences, we generated two single shuffled promoter libraries (LssF and LssFS), two multiple shuffled promoter libraries (LmsFS-F and LmsF-FS), two hybrid promoters (FuasFScp and FSuasFcp) and two hybrid-shuffled promoter libraries (LhsFuasFScp and LhsFSuasFcp). Transient expression activities of approximately 50 shuffled promoter clones from each of these libraries were assayed in tobacco (Nicotiana tabacum cv. Xanthi) protoplasts. It was observed that most of the shuffled promoters showed reduced activity compared to the two parent promoters (F and FS) and the CaMV35S promoter. In silico studies (computer simulated analyses) revealed that the reduced promoter activities of the shuffled promoters could be due to their higher helical stability. On the contrary, the hybrid promoters FuasFScp and FSuasFcp showed enhanced activities compared to F, FS and CaMV 35S in both transient and transgenic Nicotiana tabacum and Arabidopsis plants. Northern-blot and qRT-PCR data revealed a positive correlation between transcription and enzymatic activity in transgenic tobacco plants expressing hybrid promoters. Histochemical/X-gluc staining of whole transgenic seedlings/tissue-sections and fluorescence images of ImaGene Green™ treated roots and stems expressing the GUS reporter gene under the control of the FuasFScp and FSuasFcp promoters also support the above findings. Furthermore, protein extracts made from protoplasts expressing the human defensin (HNP-1) gene driven by hybrid promoters showed enhanced antibacterial activity compared to the CaMV35S promoter. SIGNIFICANCE/CONCLUSION: Both shuffled and hybrid promoters developed in the present study can be used as molecular tools to study the regulation of ectopic gene expression in plants

Design of a multicentre randomized trial to evaluate CT colonography versus colonoscopy or barium enema for diagnosis of colonic cancer in older symptomatic patients: The SIGGAR study

Background and Aims: The standard whole-colon tests used to investigate patients with symptoms of colorectal cancer are barium enema and colonoscopy. Colonoscopy is the reference test but is technically difficult, resource intensive, and associated with adverse events, especially in the elderly. Barium enema is safer but has reduced sensitivity for cancer. CT colonography ("virtual colonoscopy") is a newer alternative that may combine high sensitivity for cancer with safety and patient acceptability. The SIGGAR trial aims to determine the diagnostic efficacy, acceptability, and economic costs associated with this new technology.Methods: The SIGGAR trial is a multi-centre randomised comparison of CT colonography versus standard investigation ( barium enema or colonoscopy), the latter determined by individual clinician preference. Diagnostic efficacy for colorectal cancer and colonic polyps measuring 1 cm or larger will be determined, as will the physical and psychological morbidity associated with each diagnostic test, the latter via questionnaires developed from qualitative interviews. The economic costs of making or excluding a diagnosis will be determined for each diagnostic test and information from the trial and other data from the literature will be used to populate models framed to summarise the health effects and costs of alternative approaches to detection of significant colonic neoplasia in patients of different ages, prior risks and preferences. This analysis will focus particularly on the frequency, clinical relevance, costs, and psychological and physical morbidity associated with detection of extracolonic lesions by CT colonography.Results: Recruitment commenced in March 2004 and at the time of writing ( July 2007) 5025 patients have been randomised. A lower than expected prevalence of end-points in the barium enema sub-trial has caused an increase in sample size. In addition to the study protocol, we describe our approach to recruitment, notably the benefits of extensive piloting, the use of a sham-randomisation procedure, which was employed to determine whether centres interested in participating were likely to be effective in practice, and the provision of funding for dedicated sessions for a research nurse at each centre to devote specifically to this trial

Status report on emerging photovoltaics

\ua9 2023 Society of Photo-Optical Instrumentation Engineers (SPIE).This report provides a snapshot of emerging photovoltaic (PV) technologies. It consists of concise contributions from experts in a wide range of fields including silicon, thin film, III-V, perovskite, organic, and dye-sensitized PVs. Strategies for exceeding the detailed balance limit and for light managing are presented, followed by a section detailing key applications and commercialization pathways. A section on sustainability then discusses the need for minimization of the environmental footprint in PV manufacturing and recycling. The report concludes with a perspective based on broad survey questions presented to the contributing authors regarding the needs and future evolution of PV