Heat-shock responsive genes identified and validated in Atlantic cod (Gadus morhua) liver, head kidney and skeletal muscle using genomic techniques

Background

The Mongolian gerbils are a good model to mimic the Helicobacter pylori -associated pathogenesis of the human stomach. In the current study the gerbil-adapted strain B8 was completely sequenced, annotated and compared to previous genomes, including the 73 supercontigs of the parental strain B128.

Results

The complete genome of H. pylori B8 was manually curated gene by gene, to assign as much function as possible. It consists of a circular chromosome of 1,673,997 bp and of a small plasmid of 6,032 bp carrying nine putative genes. The chromosome contains 1,711 coding sequences, 293 of which are strain-specific, coding mainly for hypothetical proteins, and a large plasticity zone containing a putative type-IV-secretion system and coding sequences with unknown function. The cag -pathogenicity island is rearranged such that the cag A-gene is located 13,730 bp downstream of the inverted gene cluster cag B- cag 1. Directly adjacent to the cag A-gene, there are four hypothetical genes and one variable gene with a different codon usage compared to the rest of the H. pylori B8-genome. This indicates that these coding sequences might be acquired via horizontal gene transfer. The genome comparison of strain B8 to its parental strain B128 delivers 425 unique B8-proteins. Due to the fact that strain B128 was not fully sequenced and only automatically annotated, only 12 of these proteins are definitive singletons that might have been acquired during the gerbil-adaptation process of strain B128.

Conclusion

Our sequence data and its analysis provide new insight into the high genetic diversity of H. pylori -strains. We have shown that the gerbil-adapted strain B8 has the potential to build, possibly by a high rate of mutation and recombination, a dynamic pool of genetic variants (e.g. fragmented genes and repetitive regions) required for the adaptation-processes. We hypothesize that these variants are essential for the colonization and persistence of strain B8 in the gerbil stomach during inflammation.     

Interleukin-17A upregulates receptor activator of NF-κB on osteoclast precursors

Introduction  

The interaction between the immune and skeletal systems is evidenced by the bone loss observed in autoimmune diseases such as rheumatoid arthritis. In this paper we describe a new mechanism by which the immune cytokine IL-17A directly affects osteoclastogenesis.     

Thermal Properties of Tree Cavities During Winter in a Northern Hardwood Forest

ABSTRACT Tree cavities likely vary in their thermal quality for cavity-nesting animals, which could be especially important during winter. We conducted a winter field experiment to test whether cavities vary either in their buffering capacity or in their mean temperature according to predictable characteristics. We found that cavities buffered temperature and that there was a lag effect in temperature that appeared to be related to heating and cooling. Diameter at breast height was the most important variable influencing cavity temperature during the day, with smaller trees warming up more. During the night, diameter at breast height and tree decay class were important, such that larger, live trees cooled down less. Maintaining live trees with cavities in managed forests should be considered in addition to snag retention, because live trees appear to provide warmer structures during winter.     

Modeling the Spatial and Temporal Dependence in fMRI Data

Summary Functional magnetic resonance imaging (fMRI) data sets are large and characterized by complex dependence structures driven by highly sophisticated neurophysiology and aspects of the experimental designs. Typical analyses investigating task‐related changes in measured brain activity use a two‐stage procedure in which the first stage involves subject‐specific models and the second‐stage specifies group (or population) level parameters. Customarily, the first‐level accounts for temporal correlations between the serial scans acquired during one scanning session. Despite accounting for these correlations, fMRI studies often include multiple sessions and temporal dependencies may persist between the corresponding estimates of mean neural activity. Further, spatial correlations between brain activity measurements in different locations are often unaccounted for in statistical modeling and estimation. We propose a two‐stage, spatio‐temporal, autoregressive model that simultaneously accounts for spatial dependencies between voxels within the same anatomical region and for temporal dependencies between a subject's estimates from multiple sessions. We develop an algorithm that leverages the special structure of our covariance model, enabling relatively fast and efficient estimation. Using our proposed method, we analyze fMRI data from a study of inhibitory control in cocaine addicts.     

Alpine plants show species-level differences in the uptake of organic and inorganic nitrogen

As an estimate of species-level differences in the capacity to take up different forms of N, we measured plant uptake of ¹⁵N-NH₄ ⁺, ¹⁵N-NO₃ ^– and ¹⁵N, [1]-¹³C glycine within a set of herbaceous species collected from three alpine community types. Plants grown from cuttings in the greenhouse showed similar growth responses to the three forms of N but varied in the capacity to take up NH₄ ⁺, NO₃ ^– and glycine. Glycine uptake ranged from approximately 42% to greater than 100% of NH₄ ⁺ uptake; however, four out of nine species showed significantly greater uptake of either NH₄ ⁺ or NO₃ ^– than of glycine. Relative concentrations of exchangeable N at the sites of plant collection did not correspond with patterns of N uptake among species; instead, species from the same community varied widely in the capacity to take up NH₄ ⁺, NO₃ ^–, and glycine, suggesting the potential for differentiation among species in resource (N) use.     

The rho-guanine nucleotide exchange factor domain of obscurin regulates assembly of titin at the Z-disk through interactions with Ran binding protein 9

Obscurin is an approximately 800-kDa protein composed of structural and signaling domains that organizes contractile structures in striated muscle. We have studied the Rho-GEF domain of obscurin to understand its roles in morphogenesis and signaling. We used adenoviral overexpression of this domain, together with ultrastructural and immunofluorescence methods, to examine its effect on maturing myofibrils. We report that overexpression of the Rho-GEF domain specifically inhibits the incorporation of titin into developing Z-disks and disrupts the structure of the Z-disk and Z/I junction, and alters features of the A/I junction. The organization of other sarcomeric markers, including alpha-actinin, was not affected. We identified Ran binding protein 9 (RanBP9) as a novel ligand of the Rho-GEF domain and showed that binding is specific, with an apparent binding affinity of 1.9 muM. Overexpression of the binding region of RanBP9 also disrupted the incorporation of titin into developing Z-disks. Immunofluorescence localization during myofibrillogenesis indicated that the Rho-GEF domain assembles into sarcomeres before RanBP9, which first occurs in myonuclei and later in development translocates to the myoplasm, where it colocalizes with obscurin. Both the Rho-GEF domain and its binding region on RanBP9 bind directly to the N-terminal Ig domains of titin, which flank the Z-disk. Our results suggest that the Rho-GEF domain interacts with RanBP9 and that both can interact with the N-terminal region of titin to influence the formation of the Z-disk and A/I junction.     

Measuring persistence of implementation: QUERI Series

Background

We describe how we used the framework of the U.S. Department of Veterans Affairs (VA) Quality Enhancement Research Initiative (QUERI) to develop a program to improve rates of diagnostic testing for the Human Immunodeficiency Virus (HIV). This venture was prompted by the observation by the CDC that 25% of HIV-infected patients do not know their diagnosis – a point of substantial importance to the VA, which is the largest provider of HIV care in the United States.

Methods

Following the QUERI steps (or process), we evaluated: 1) whether undiagnosed HIV infection is a high-risk, high-volume clinical issue within the VA, 2) whether there are evidence-based recommendations for HIV testing, 3) whether there are gaps in the performance of VA HIV testing, and 4) the barriers and facilitators to improving current practice in the VA. Based on our findings, we developed and initiated a QUERI step 4/phase 1 pilot project using the precepts of the Chronic Care Model. Our improvement strategy relies upon electronic clinical reminders to provide decision support; audit/feedback as a clinical information system, and appropriate changes in delivery system design. These activities are complemented by academic detailing and social marketing interventions to achieve provider activation.

Results

Our preliminary formative evaluation indicates the need to ensure leadership and team buy-in, address facility-specific barriers, refine the reminder, and address factors that contribute to inter-clinic variances in HIV testing rates. Preliminary unadjusted data from the first seven months of our program show 3–5 fold increases in the proportion of at-risk patients who are offered HIV testing at the VA sites (stations) where the pilot project has been undertaken; no change was seen at control stations.

Discussion

This project demonstrates the early success of the application of the QUERI process to the development of a program to improve HIV testing rates. Preliminary unadjusted results show that the coordinated use of audit/feedback, provider activation, and organizational change can increase HIV testing rates for at-risk patients. We are refining our program prior to extending our work to a small-scale, multi-site evaluation (QUERI step 4/phase 2). We also plan to evaluate the durability/sustainability of the intervention effect, the costs of HIV testing, and the number of newly identified HIV-infected patients. Ultimately, we will evaluate this program in other geographically dispersed stations (QUERI step 4/phases 3 and 4).     

The political gender gap: gender bias in facial inferences that predict voting behavior

Background

Throughout human history, a disproportionate degree of political power around the world has been held by men. Even in democracies where the opportunity to serve in top political positions is available to any individual elected by the majority of their constituents, most of the highest political offices are occupied by male leaders. What psychological factors underlie this political gender gap? Contrary to the notion that people use deliberate, rational strategies when deciding whom to vote for in major political elections, research indicates that people use shallow decision heuristics, such as impressions of competence solely from a candidate''s facial appearance, when deciding whom to vote for. Because gender has previously been shown to affect a number of inferences made from the face, here we investigated the hypothesis that gender of both voter and candidate affects the kinds of facial impressions that predict voting behavior.

Methodology/Principal Finding

Male and female voters judged a series of male and female political candidates on how competent, dominant, attractive and approachable they seemed based on their facial appearance. Then they saw a series of pairs of political candidates and decided which politician they would vote for in a hypothetical election for President of the United States. Results indicate that both gender of voter and candidate affect the kinds of facial impressions that predict voting behavior. All voters are likely to vote for candidates who appear more competent. However, male candidates that appear more approachable and female candidates who appear more attractive are more likely to win votes. In particular, men are more likely to vote for attractive female candidates whereas women are more likely to vote for approachable male candidates.

Conclusions/Significance

Here we reveal gender biases in the intuitive heuristics that voters use when deciding whom to vote for in major political elections. Our findings underscore the impact of gender and physical appearance on shaping voter decision-making and provide novel insight into the psychological foundations underlying the political gender gap.     

BMP and Wnt specify hematopoietic fate by activation of the Cdx-Hox pathway

The formation of blood in the embryo is dependent on bone morphogenetic protein (BMP), but how BMP signaling intersects with other regulators of hematopoietic development is unclear. Using embryonic stem (ES) cells, we show that BMP4 first induces ventral-posterior (V-P) mesoderm and subsequently directs mesodermal cells toward blood fate by activating Wnt3a and upregulating Cdx and Hox genes. When BMP signaling is blocked during this latter phase, enforced expression of either Cdx1 or Cdx4 rescues hematopoietic development, thereby placing BMP4 signaling upstream of the Cdx-Hox pathway. Wnt signaling cooperates in BMP-induced hemogenesis, and the Wnt effector LEF1 mediates BMP4 activation of Cdx genes. Our data suggest that BMP signaling plays two distinct and sequential roles during blood formation, initially as an inducer of mesoderm, and later to specify blood via activation of Wnt signaling and the Cdx-Hox pathway.