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Rate control is fundamental in the treatment of patients with atrial fibrillation (AF). The independent association of heart rate with outcomes and range of heart rate associated with best outcomes remains uncertain. We assessed the relationship between heart rate and clinical outcomes in patients with persistent or permanent AF enrolled in the randomized, double-blind ARISTOTLE trial. In patients with persistent or permanent AF, a faster heart rate is associated with a modest, but statistically significant increase in death and heart failure hospitalizations. ClinicalTrials.gov (NCT00412984).

Controlled‐source electromagnetics (CSEM) has been used as a de‐risking tool in the hydrocarbon exploration industry. Although there have been successful applications of CSEM, this technique is still not widely used in the industry because the limited types of hydrocarbon reservoirs CSEM can detect. In this paper, we apply the concept of synthetic aperture to CSEM data. Synthetic aperture allows us to design sources with specific radiation patterns for different purposes. The ability to detect reservoirs is dramatically increased after forming an appropriate synthetic aperture antenna. Consequently, the types of hydrocarbon reservoirs that CSEM can detect are significantly extended. Because synthetic apertures are constructed as a data processing step, there is no additional cost for the CSEM acquisition. Synthetic aperture has potential for simplifying and reducing the cost of CSEM acquisition. We show a data example that illustrates the increased sensitivity obtained by applying synthetic aperture CSEM source.

In plants, 14-3-3 proteins are key regulators of primary metabolism and membrane transport. Although the current dogma states that 14-3-3 isoforms are not very specific with regard to target proteins, recent data suggest that the specificity may be high. Therefore, identification and characterization of all 14-3-3 (GF14) isoforms in the model plant Arabidopsis are important. Using the information now available from The Arabidopsis Information Resource, we found three new GF14 genes. The potential expression of these three genes, and of two additional novel GF14 genes (Rosenquist et al., 2000), in leaves, roots, and flowers was examined using reverse transcriptase-polymerase chain reaction and cDNA library polymerase chain reaction screening. Under normal growth conditions, two of these genes were found to be transcribed. These genes were named grf11 and grf12, and the corresponding new 14-3-3 isoforms were named GF14omicron and GF14iota, respectively. The gene coding for GF14omicron was expressed in leaves, roots, and flowers, whereas the gene coding for GF14iota was only expressed in flowers. Gene structures and relationships between all members of the GF14 gene family were deduced from data available through The Arabidopsis Information Resource. The data clearly support the theory that two 14-3-3 genes were present when eudicotyledons diverged from monocotyledons. In total, there are 15 14-3-3 genes (grfs 1-15) in Arabidopsis, of which 12 (grfs 1-12) now have been shown to be expressed.

The human gut contains a dense, complex and diverse microbial community, comprising the gut microbiome. Metagenomics has recently revealed the composition of genes in the gut microbiome, but provides no direct information about which genes are expressed or functioning. Therefore, our goal was to develop a novel approach to directly identify microbial proteins in fecal samples to gain information about the genes expressed and about key microbial functions in the human gut. We used a non-targeted, shotgun mass spectrometry-based whole community proteomics, or metaproteomics, approach for the first deep proteome measurements of thousands of proteins in human fecal samples, thus demonstrating this approach on the most complex sample type to date. The resulting metaproteomes had a skewed distribution relative to the metagenome, with more proteins for translation, energy production and carbohydrate metabolism when compared to what was earlier predicted from metagenomics. Human proteins, including antimicrobial peptides, were also identified, providing a non-targeted glimpse of the host response to the microbiota. Several unknown proteins represented previously undescribed microbial pathways or host immune responses, revealing a novel complex interplay between the human host and its associated microbes.

Background: Large interindividual variation in the composition of the intestinal microbiota between unrelated individuals has made it challenging to identify specific aspects of dysbiosis that lead to Crohn's disease (CD). Methods: To reduce variations in exposure during establishment of the gut flora and the influence of genotype, we studied the mucosa‐associated microbiota of monozygotic twin pairs that were discordant (n = 6) or concordant (n = 4) for CD. DNA was extracted from biopsies collected from 5 locations between the ileum and rectum. Bacterial 16S ribosomal RNA genes were amplified and community composition assessed by terminal‐restriction fragment length polymorphism, cloning and sequencing, and quantitative real‐time polymerase chain reaction (PCR). Results: The microbial compositions at all biopsy locations for each individual were similar, regardless of disease state, but there were differences between individuals. In particular, individuals with predominantly ileal CD had a dramatically lower abundance (P < 0.001) of Faecalibacterium prausnitzii and increased abundance (P < 0.03) of Escherichia coli compared to healthy co‐twins and those with CD localized in the colon. This dysbiosis was significantly correlated to the disease phenotype rather than genotype. Conclusions: The reduced abundance of F. prausnitzii and increased abundance of E. coli are indicative of an ileal CD phenotype, distinct from colonic CD, and the relative abundances of these specific bacterial populations are promising biomarker candidates for differential diagnosis of CD and eventually customized treatment. (Inflamm Bowel Dis 2009)

Increasing evidence suggests that a combination of host genetics and the composition of the gut microbiota are important for development of Crohn's disease (CD). Our aim was to study identical twins with CD to determine microbial factors independent of host genetics. Fecal samples were studied from 10 monozygotic twin pairs with CD (discordant n =6 and concordant n =4) and 8 healthy twin pairs. DNA was extracted, 16S rRNA genes were PCR amplified and T-RFLP fingerprints generated using general bacterial and Bacteroides group-specific primers. The microbial communities were also profiled based on their percentage G+C contents. Bacteroides 16S rRNA genes were cloned and sequenced from a subset of the samples. The bacterial diversity in each sample and similarity indices between samples were estimated based on the T-RFLP data using a combination of statistical approaches. Healthy individuals had a significantly higher bacterial diversity compared to individuals with CD. The fecal microbial communities were more similar between healthy twins than between twins with CD, especially when these were discordant for the disease. The microbial community profiles of individuals with ileal CD were significantly different from healthy individuals and those with colonic CD. Also, CD individuals had a lower relative abundance of B. uniformis and higher relative abundances of B. ovatus and B. vulgatus . Our results suggest that genetics and/or environmental exposure during childhood, in part, determine the gut microbial composition. However, CD is associated with dramatic changes in the gut microbiota and this was particularly evident for individuals with ileal CD.

As information on the economic, environmental and social benefits of cocoa has grown, so has the understanding that only a coordinated effort by all stakeholders can ensure cocoa sustainability. This chapter describes how challenges to cocoa supplies brought seemingly disparate - if not competitive - groups together in unique public/private partnerships. While it is not meant to be an exhaustive listing of every initiative that has been developed, it provides an overview of how working across sectors has benefited all of those involved in the cocoa industry - corporations, governments, nongovernment organizations and individual farmers. The progress they have made and the lessons learned from these partnerships will help frame policies and practices aimed at ensuring a healthy future for all involved in the cocoa industry, and be a model for such initiatives for the development of other shaded perennial crops in agroforestry systems.

The use of silver ions in industry to prevent microbial growth is increasing and silver is a new and an overlooked heavy-metal contaminant in sewage sludge-amended soil. The denitrifying community was the model used to assess the dose-dependent effects of silver ions on microorganisms overtime in soil microcosms. Silver caused a sigmoid dose-dependent reduction in denitrification activity, and no recovery was observed during 90 days. Dentrifiers with nirK, which encodes the copper nitrite reductase, were targeted to estimate abundance and community composition for some of the concentrations. The nirK copy number decreased by the highest addition (100 mg Ag kg⁻¹ soil), but the nirK diversity increased. Treatment-specific sequences not clustering with any deposited nirK sequences were found, indicating that silver induces enrichment of novel nirK denitrifiers.

The plant plasma membrane H+- ATPase is activated by the binding of 14-3-3 protein to the C-terminal region of the enzyme, thus forming an ${\\rm H}^{+}\\text{-}{\\rm ATPase}-14\\text{-}3\\text{-}3$ complex that can be stabilized by the fungal toxin fusicoccin. A novel 14-3-3 binding motif, ${\\rm QQXYpT}_{948}{\\rm V}$, at the C terminus of the H+- ATPase is identified and characterized, and the protein kinase activity in the plasma membrane fraction that phosphorylates this threonine residue in the H+- ATPase is identified. A synthetic peptide that corresponds to the C-terminal 16 amino acids of the H+- ATPase and that is phosphorylated on Thr-948 prevents the in vitro activation of the H+- ATPase that is obtained in the presence of recombinant 14-3-3 and fusicoccin. Furthermore, binding of 14-3-3 to the H+- ATPase in the absence of fusicoccin is absolutely dependent on the phosphorylation of Thr-948, whereas binding of 14-3-3 in the presence of fusicoccin occurs independently of phosphorylation but still involves the C-terminal motif YTV. Finally, by complementing yeast that lacks its endogenous H+- ATPase with wild-type and mutant forms of the Nicotiana plumbaginifolia H+- ATPase isoform PMA2, we provide physiological evidence for the importance of the phosphothreonine motif in 14-3-3 binding and, hence, in the activation of the H+- ATPase in vivo. Indeed, replacing Thr-948 in the plant H+- ATPase with alanine is lethal because this mutant fails to functionally replace the yeast H+- ATPase. Considering the importance of the motif QQXYpTV for 14-3-3 binding and yeast growth, this motif should be of vital importance for regulating H+- ATPase activity in the plant and thus for plant growth.

14-3-3 proteins constitute a family of eukaryotic proteins that are key regulators of a large number of processes ranging from mitosis to apoptosis. 14-3-3s function as dimers and bind to particular motifs in their target proteins. To date, 14-3-3s have been implicated in regulation or stabilization of more than 35 different proteins. This number is probably only a fraction of the number of proteins that 14-3-3s bind to, as reports of new target proteins have become more frequent. An examination of 14-3-3 entries in the public databases reveals 153 isoforms, including alleloforms, reported in 48 different species. The number of isoforms range from 2, in the unicellular organism Saccharomyces cerevisiae, to 12 in the multicellular organism Arabidopsis thaliana. A phylogenetic analysis reveals that there are four major evolutionary lineages: Viridiplantae (plants), Fungi, Alveolata, and Metazoa (animals). A close examination of the aligned amino acid sequences identifies conserved amino acid residues and regions of importance for monomer stabilization, dimer formation, target protein binding, and the nuclear export function. Given the fact that 53% of the protein is conserved, including all amino acid residues in the target binding groove of the 14-3-3 monomer, one might expect little to no isoform specificity for target protein binding. However, using surface plasmon resonance we show that there are large differences in affinity between nine 14-3-3 isoforms of A. thaliana and a target peptide representing a novel binding motif present in the C terminus of the plant plasma membrane H(+)ATPase. Thus, our data suggest that one reason for the large number of isoforms found in multicellular organisms is isoform-specific functions.