Expression of VjbR under Nutrient Limitation Conditions Is Regulated at the Post-Transcriptional Level by Specific Acidic pH Values and Urocanic Acid

VjbR is a LuxR homolog that regulates transcription of many genes including important virulence determinants of the facultative intracellular pathogen Brucella abortus. This transcription factor belongs to a family of regulators that participate in a cell-cell communication process called quorum sensing, which enables bacteria to respond to changes in cell population density by monitoring concentration of self produced autoinducer molecules. Unlike almost all other LuxR-type proteins, VjbR binds to DNA and activates transcription in the absence of any autoinducer signal. To investigate the mechanisms by which Brucella induces VjbR-mediated transcriptional activation, and to determine how inappropriate spatio-temporal expression of the VjbR target genes is prevented, we focused on the study of expression of vjbR itself. By assaying different parameters related to the intracellular lifestyle of Brucella, we identified a restricted set of conditions that triggers VjbR protein expression. Such conditions required the convergence of two signals of different nature: a specific pH value of 5.5 and the presence of urocanic acid, a metabolite involved in the connection between virulence and metabolism of Brucella. In addition, we also observed an urocanic acid, pH-dependent expression of RibH2 and VirB7, two additional intracellular survival-related proteins of Brucella. Analysis of promoter activities and determination of mRNA levels demonstrated that the urocanic acid-dependent mechanisms that induced expression of VjbR, RibH2, and VirB7 act at the post-transcriptional level. Taken together, our findings support a model whereby Brucella induces VjbR-mediated transcription by modulating expression of VjbR in response to specific signals related to the changing environment encountered within the host

Time warping of evolutionary distant temporal gene expression data based on noise suppression

<p>Abstract</p> <p>Background</p> <p>Comparative analysis of genome wide temporal gene expression data has a broad potential area of application, including evolutionary biology, developmental biology, and medicine. However, at large evolutionary distances, the construction of global alignments and the consequent comparison of the time-series data are difficult. The main reason is the accumulation of variability in expression profiles of orthologous genes, in the course of evolution.</p> <p>Results</p> <p>We applied Pearson distance matrices, in combination with other noise-suppression techniques and data filtering to improve alignments. This novel framework enhanced the capacity to capture the similarities between the temporal gene expression datasets separated by large evolutionary distances. We aligned and compared the temporal gene expression data in budding (<it>Saccharomyces cerevisiae</it>) and fission (<it>Schizosaccharomyces pombe</it>) yeast, which are separated by more then ~400 myr of evolution. We found that the global alignment (time warping) properly matched the duration of cell cycle phases in these distant organisms, which was measured in prior studies. At the same time, when applied to individual ortholog pairs, this alignment procedure revealed groups of genes with distinct alignments, different from the global alignment.</p> <p>Conclusion</p> <p>Our alignment-based predictions of differences in the cell cycle phases between the two yeast species were in a good agreement with the existing data, thus supporting the computational strategy adopted in this study. We propose that the existence of the alternative alignments, specific to distinct groups of genes, suggests presence of different synchronization modes between the two organisms and possible functional decoupling of particular physiological gene networks in the course of evolution.</p

Mirizzi syndrome type IV associated with cholecystocolic fistula: a very rare condition- report of a case

<p>Abstract</p> <p>Background</p> <p>Mirizzi syndrome is a rare complication of prolonged cholelithiasis with presence of large, impacted gallstone into the Hartman's pouch, causing chronic extrinsic compression of common bile duct (CBD). Fistula formation between the CBD and the gallbladder may represent an outcome of that condition. According to Mirizzi's classification and Csendes's subclassification, Mirizzi syndrome type IV represents the most uncommon type (4%).</p> <p>Spontaneous biliary-enteric fistulas have also been rarely reported (1.2–5%) in a large series of cholecystectomies. Cholecystocolic fistula is the most infrequent biliary enteric fistula, causing significant morbidity and representing a diagnostic challenge.</p> <p>Case presentation</p> <p>We describe a very rare, to our knowledge, combination of Mirizzi syndrome type IV and cholecystocolic fistula. A 52 year old male, presented to our clinic complaining of episodic diarrhea (monthly episodes lasting 16 days), high temperature (38°C–39°C), right upper quadrant pain without jaundice. The definitive diagnosis was made intraoperatively. Magnetic Resonance Imaging (MRI) and Endoscopic Retrograde Cholangiopancreatography (ERCP) demonstrated the presence of Mirizzi syndrome with cholecystocolic fistula formation. The patient was operated upon, and cholecystectomy, cholecystocolic fistula excision and Roux-en-Y biliary-enteric anastomosis were undertaken with excellent post-operative course.</p> <p>Conclusion</p> <p>Appropriate biliary tree imaging with ERCP and MRI/MRCP is essential for the diagnosis of Mirizzi syndrome and its complications. Cholecystectomy, fistula excision and biliary-enteric anastomosis with Roux-en-Y loop appears to be the most appropriate surgical intervention in order to avoid damage to Calot's triangle anatomic elements. Particularly in our case, ERCP was a valuable diagnostic tool that Mirizzi syndrome type IV and cholecystocolic fistula.</p

Particulate air pollution and chronic ischemic heart disease in the eastern United States: a county level ecological study using satellite aerosol data

<p>Abstract</p> <p>Background</p> <p>There are several known factors that cause ischemic heart disease. However, the part played by air pollution still remains something of a mystery. Recent attention has focused on the chronic effect of particulate matter on heart disease. Satellite-derived aerosol optical depth (AOD) was found to be correlated with <it>PM</it>_2.5in the eastern US. The objective of this study was to examine if there is an association between aerosol air pollution as indicated by AOD and chronic ischemic heart disease (CIHD) in the eastern US.</p> <p>Methods</p> <p>An ecological geographic study method was employed. Race and age standardized mortality rate (SMR) of CIHD was computed for each of the 2306 counties for the time period 2003–2004. A mean AOD raster grid for the same period was derived from Moderate Resolution Imaging Spectrometer (MODIS) aerosol data and the average AOD was calculated for each county. A bivariate Moran's I scatter plot, a map of local indicator of spatial association (LISA) clusters, and three regression models (ordinary least square, spatial lag, and spatial error) were used to analyze the relationship between AOD and CIHD SMR.</p> <p>Results</p> <p>The global Moran's I value is 0.2673 (<it>p </it>= 0.001), indicating an overall positive spatial correlation of CIHD SMR and AOD. The entire study area is dominated by spatial clusters of AOD against SMR (high AOD and high SMR in the east, and low AOD and low SMR in the west) (permutations = 999, <it>p </it>= 0.05). Of the three regression models, the spatial error model achieved the best fit (R²= 0.28). The effect of AOD is positive and significant (beta = 0.7774, p = 0.01).</p> <p>Conclusion</p> <p>Aerosol particle pollution has adverse effect on CIHD mortality risk in the eastern US. High risk of CIHD mortality was found in areas with elevated levels of outdoor aerosol air pollution as indicated by satellite derived AOD. The evidence of the association would support targeting of policy interventions on such areas to reduce air pollution levels. Remote sensing AOD data could be used as an alternative health-related indictor of air quality.</p

X-ray emission from the Sombrero galaxy: discrete sources

We present a study of discrete X-ray sources in and around the bulge-dominated, massive Sa galaxy, Sombrero (M104), based on new and archival Chandra observations with a total exposure of ~200 ks. With a detection limit of L_X = 1E37 erg/s and a field of view covering a galactocentric radius of ~30 kpc (11.5 arcminute), 383 sources are detected. Cross-correlation with Spitler et al.'s catalogue of Sombrero globular clusters (GCs) identified from HST/ACS observations reveals 41 X-rays sources in GCs, presumably low-mass X-ray binaries (LMXBs). We quantify the differential luminosity functions (LFs) for both the detected GC and field LMXBs, whose power-low indices (~1.1 for the GC-LF and ~1.6 for field-LF) are consistent with previous studies for elliptical galaxies. With precise sky positions of the GCs without a detected X-ray source, we further quantify, through a fluctuation analysis, the GC LF at fainter luminosities down to 1E35 erg/s. The derived index rules out a faint-end slope flatter than 1.1 at a 2 sigma significance, contrary to recent findings in several elliptical galaxies and the bulge of M31. On the other hand, the 2-6 keV unresolved emission places a tight constraint on the field LF, implying a flattened index of ~1.0 below 1E37 erg/s. We also detect 101 sources in the halo of Sombrero. The presence of these sources cannot be interpreted as galactic LMXBs whose spatial distribution empirically follows the starlight. Their number is also higher than the expected number of cosmic AGNs (52+/-11 [1 sigma]) whose surface density is constrained by deep X-ray surveys. We suggest that either the cosmic X-ray background is unusually high in the direction of Sombrero, or a distinct population of X-ray sources is present in the halo of Sombrero.Comment: 11 figures, 5 tables, ApJ in pres

Genetic background determines response to hemostasis and thrombosis

BACKGROUND: Thrombosis is the fatal and disabling consequence of cardiovascular diseases, the leading cause of mortality and morbidity in Western countries. Two inbred mouse strains, C57BL/6J and A/J, have marked differences in susceptibility to obesity, atherosclerosis, and vessel remodeling. However, it is unclear how these diverse genetic backgrounds influence pathways known to regulate thrombosis and hemostasis. The objective of this study was to evaluate thrombosis and hemostasis in these two inbred strains and determine the phenotypic response of A/J chromosomes in the C57BL/6J background. METHODS: A/J and C57Bl/6J mice were evaluated for differences in thrombosis and hemostasis. A thrombus was induced in the carotid artery by application of the exposed carotid to ferric chloride and blood flow measured until the vessel occluded. Bleeding and rebleeding times, as surrogate markers for thrombosis and hemostasis, were determined after clipping the tail and placing in warm saline. Twenty-one chromosome substitution strains, A/J chromosomes in a C57BL/6J background, were screened for response to the tail bleeding assay. RESULTS: Thrombus occlusion time was markedly decreased in the A/J mice compared to C57BL/6J mice. Tail bleeding time was similar in the two strains, but rebleeding time was markedly increased in the A/J mice compared to C57BL/6J mice. Coagulation times and tail morphology were similar, but tail collagen content was higher in A/J than C57BL/6J mice. Three chromosome substitution strains, B6-Chr5(A/J), B6-Chr11(A/J), and B6-Chr17(A/J), were identified with increased rebleeding time, a phenotype similar to A/J mice. Mice heterosomic for chromosomes 5 or 17 had rebleeding times similar to C57BL/6J mice, but when these two chromosome substitution strains, B6-Chr5(A/J )and B6-Chr17(A/J), were crossed, the A/J phenotype was restored in these doubly heterosomic progeny. CONCLUSION: These results indicate that susceptibility to arterial thrombosis and haemostasis is remarkably different in C57BL/and A/J mice. Three A/J chromosome substitution strains were identified that expressed a phenotype similar to A/J for rebleeding, the C57Bl/6J background could modify the A/J phenotype, and the combination of two A/J QTL could restore the phenotype. The diverse genetic backgrounds and differences in response to vascular injury induced thrombosis and the tail bleeding assay, suggest the potential for identifying novel genetic determinants of thrombotic risk

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Trans Fat Consumption and Aggression

Background: Dietary trans fatty acids (dTFA) are primarily synthetic compounds that have been introduced only recently; little is known about their behavioral effects. dTFA inhibit production of omega-3 fatty acids, which experimentally have been shown to reduce aggression. Potential behavioral effects of dTFA merit investigation. We sought to determine whether dTFA are associated with aggression/irritability. Methodolgy/Prinicpal Findings: We capitalized on baseline dietary and behavioral assessments in an existing clinical trial to analyze the relationship of dTFA to aggression. Of 1,018 broadly sampled baseline subjects, the 945 adult men and women who brought a completed dietary survey to their baseline visit are the target of this analysis. Subjects (seen 1999– 2004) were not on lipid medications, and were without LDL-cholesterol extremes, diabetes, HIV, cancer or heart disease. Outcomes assessed adverse behaviors with impact on others: Overt Aggression Scale Modified-aggression subscale (primary behavioral endpoint); Life History of Aggression; Conflict Tactics Scale; and self-rated impatience and irritability. The association of dTFA to aggression was analyzed via regression and ordinal logit, unadjusted and adjusted for potential confounders (sex, age, education, alcohol, and smoking). Additional analyses stratified on sex, age, and ethnicity, and examined the prospective association. Greater dTFA were strongly significantly associated with greater aggression, with dTFA more consistently predictive than other assessed aggression predictors. The relationship was upheld wit