Mapping of citrullinated fibrinogen B-cell epitopes in rheumatoid arthritis by imaging surface plasmon resonance

Introduction  

Rheumatoid arthritis (RA) frequently involves the loss of tolerance to citrullinated antigens, which may play a role in pathogenicity. Citrullinated fibrinogen is commonly found in inflamed synovial tissue and is a frequent target of autoantibodies in RA patients. To obtain insight into the B-cell response to citrullinated fibrinogen in RA, its autoepitopes were systematically mapped using a new methodology.     

Quantification of global transcription patterns in prokaryotes using spotted microarrays

We describe an analysis, applicable to any spotted microarray dataset produced using genomic DNA as a reference, that quantifies prokaryotic levels of mRNA on a genome-wide scale. Applying this to Mycobacterium tuberculosis, we validate the technique, show a correlation between level of expression and biological importance, define the complement of invariant genes and analyze absolute levels of expression by functional class to develop ways of understanding an organism's biology without comparison to another growth condition.     

An annotated catalogue of salivary gland transcripts in the adult female mosquito, Ædes ægypti*

Background

The number of completely sequenced plastid genomes available is growing rapidly. This array of sequences presents new opportunities to perform comParative analyses. In comParative studies, it is often useful to compare across wide phylogenetic spans and, within angiosperms, to include representatives from basally diverging lineages such as the genomes reported here: Nuphar advena (from a basal-most lineage) and Ranunculus macranthus (a basal eudicot). We report these two new plastid genome sequences and make comparisons (within angiosperms, seed plants, or all photosynthetic lineages) to evaluate features such as the status of ycf15 and ycf68 as protein coding genes, the distribution of simple sequence repeats (SSRs) and longer dispersed repeats (SDR), and patterns of nucleotide composition.

Results

The Nuphar [GenBank:NC_008788] and Ranunculus [GenBank:NC_008796] plastid genomes share characteristics of gene content and organization with many other chloroplast genomes. Like other plastid genomes, these genomes are A+T-rich, except for rRNA and tRNA genes. Detailed comparisons of Nuphar with Nymphaea, another Nymphaeaceae, show that more than two-thirds of these genomes exhibit at least 95% sequence identity and that most SSRs are shared. In broader comparisons, SSRs vary among genomes in s of abundance and length and most contain repeat motifs based on A and T nucleotides.

Conclusion

SSR and SDR abundance varies by genome and, for SSRs, is proportional to genome size. Long SDRs are rare in the genomes assessed. SSRs occur less frequently than predicted and, although the majority of the repeat motifs do include A and T nucleotides, the A+T bias in SSRs is less than that predicted from the underlying genomic nucleotide composition. In codon usage third positions show an A+T bias, however variation in codon usage does not correlate with differences in A+T-richness. Thus, although plastome nucleotide composition shows "A+T richness", an A+T bias is not apparent upon more in-depth analysis, at least in these aspects. The pattern of evolution in the sequences identified as ycf15 and ycf68 is not consistent with them being protein-coding genes. In fact, these regions show no evidence of sequence conservation beyond what is normal for non-coding regions of the IR.     

Minimum information about a marker gene sequence (MIMARKS) and minimum information about any (x) sequence (MIxS) specifications

Here we present a standard developed by the Genomic Standards Consortium (GSC) for reporting marker gene sequences--the minimum information about a marker gene sequence (MIMARKS). We also introduce a system for describing the environment from which a biological sample originates. The 'environmental packages' apply to any genome sequence of known origin and can be used in combination with MIMARKS and other GSC checklists. Finally, to establish a unified standard for describing sequence data and to provide a single point of entry for the scientific community to access and learn about GSC checklists, we present the minimum information about any (x) sequence (MIxS). Adoption of MIxS will enhance our ability to analyze natural genetic diversity documented by massive DNA sequencing efforts from myriad ecosystems in our ever-changing biosphere.     

Rapid quantification and taxonomic classification of environmental DNA from both prokaryotic and eukaryotic origins using a microarray

A microarray has been designed using 62,358 probes matched to both prokaryotic and eukaryotic small-subunit ribosomal RNA genes. The array categorized environmental DNA to specific phylogenetic clusters in under 9 h. To a background of DNA generated from natural outdoor aerosols, known quantities of rRNA gene copies from distinct organisms were added producing corresponding hybridization intensity scores that correlated well with their concentrations (r=0.917). Reproducible differences in microbial community composition were observed by altering the genomic DNA extraction method. Notably, gentle extractions produced peak intensities for Mycoplasmatales and Burkholderiales, whereas a vigorous disruption produced peak intensities for Vibrionales, Clostridiales, and Bacillales.     

Canonical Wnt signaling: high-throughput RNAi widens the path

The canonical Wnt signaling pathway is highly conserved in evolution, widely used throughout animal development, and frequently hyperactive in cancer. Although Wnt signaling has been the subject of extensive genetic analysis in the past, some 200 genes have now been identified as candidate modulators of this pathway by a recent study using high-throughput RNAi screening.     

Metabolic effect of telmisartan and losartan in hypertensive patients with metabolic syndrome

Background

Metabolic syndrome is a cluster of common cardiovascular risk factors that includes hypertension and insulin resistance. Hypertension and diabetes mellitus are frequent comorbidities and, like metabolic syndrome, increase the risk of cardiovascular events. Telmisartan, an antihypertensive agent with evidence of partial peroxisome proliferator-activated receptor activity-gamma (PPARγ) activity, may improve insulin sensitivity and lipid profile in patients with metabolic syndrome.

Methods

In a double-blind, parallel-group, randomized study, patients with World Health Organization criteria for metabolic syndrome received once-daily doses of telmisartan (80 mg, n = 20) or losartan (50 mg, n = 20) for 3 months. At baseline and end of treatment, fasting and postprandial plasma glucose, insulin sensitivity, glycosylated haemoglobin (HBA_1c) and 24-hour mean systolic and diastolic blood pressures were determined.

Results

Telmisartan, but not losartan, significantly (p < 0.05) reduced free plasma glucose, free plasma insulin, homeostasis model assessment of insulin resistance and HbA_ic. Following treatment, plasma glucose and insulin were reduced during the oral glucose tolerance test by telmisartan, but not by losartan. Telmisartan also significantly reduced 24-hour mean systolic blood pressure (p < 0.05) and diastolic blood pressure (p < 0.05) compared with losartan.

Conclusion

As well as providing superior 24-hour blood pressure control, telmisartan, unlike losartan, displayed insulin-sensitizing activity, which may be explained by its partial PPARγ activity.     

Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB

A 16S rRNA gene database (http://greengenes.lbl.gov) addresses limitations of public repositories by providing chimera screening, standard alignment, and taxonomic classification using multiple published taxonomies. It was found that there is incongruent taxonomic nomenclature among curators even at the phylum level. Putative chimeras were identified in 3% of environmental sequences and in 0.2% of records derived from isolates. Environmental sequences were classified into 100 phylum-level lineages in the Archaea and Bacteria.