Role of modifying genes on the severity of rare mutation of MYH7 gene in hypertrophic obstructive cardiomyopathy

Hypertrophic Cardiomyopathy (HCM) is an autosomal dominant disorder due to mutations in sacromeric genes with variable penetrance. Hypertrophic Obstructive Cardiomyopathy (HOCM) is a major complication of Hypertrophic Cardiomyopathy. Unexplained hypertrophy in the Left Ventricle (LV) or Intraventricular Septum (IVS) had been the diagnostic criterion for HCM which is more often confirmed by the echocardiography. The frequency of HCM in general population is 1:500 and about 60-70% genetic predisposition is known. It has been observed that mutations in the Cardiac myosin binding proteinC (MYBPC3) gene causes late onset of disease with mild symptoms while mutations in the Beta Myosin Heavy chain (MYH7) gene leads to early onset with severe symptoms. Apart from Epigenetic and Environmental factors, modifier genes further complicate the situation leading to altered clinical outcome even among the same family members having identical mutation

Complex relationships between greenness, air pollution, and mortality in a population-based Canadian cohort

Background: Epidemiological studies have consistently demonstrated that exposure to fine particulate matter (PM 2.5 )is associated with increased risks of mortality. To a lesser extent, a series of studies suggest that living in greener areas is associated with reduced risks of mortality. Only a handful of studies have examined the interplay between PM 2.5 , greenness, and mortality. Methods: We investigated the role of residential greenness in modifying associations between long-term exposures to PM 2.5 and non-accidental and cardiovascular mortality in a national cohort of non-immigrant Canadian adults (i.e., the 2001 Canadian Census Health and Environment Cohort). Specifically, we examined associations between satellite-derived estimates of PM 2.5 exposure and mortality across quintiles of greenness measured within 500 m of individual's place of residence during 11 years of follow-up. We adjusted our survival models for many personal and contextual measures of socioeconomic position, and residential mobility data allowed us to characterize annual changes in exposures. Results: Our cohort included approximately 2.4 million individuals at baseline, 194,270 of whom died from non-accidental causes during follow-up. Adjustment for greenness attenuated the association between PM 2.5 and mortality (e.g., hazard ratios (HRs)and 95% confidence intervals (CIs)per interquartile range increase in PM 2.5 in models for non-accidental mortality decreased from 1.065 (95% CI: 1.056–1.075)to 1.041 (95% CI: 1.031–1.050)). The strength of observed associations between PM 2.5 and mortality decreased as greenness increased. This pattern persisted in models restricted to urban residents, in models that considered the combined oxidant capacity of ozone and nitrogen dioxide, and within neighbourhoods characterised by high or low deprivation. We found no increased risk of mortality associated with PM 2.5 among those living in the greenest areas. For example, the HR for cardiovascular mortality among individuals in the least green areas was 1.17 (95% CI: 1.12–1.23)compared to 1.01 (95% CI: 0.97–1.06)among those in the greenest areas. Conclusions: Studies that do not account for greenness may overstate the air pollution impacts on mortality. Residents in deprived neighbourhoods with high greenness benefitted by having more attenuated associations between PM 2.5 and mortality than those living in deprived areas with less greenness. The findings from this study extend our understanding of how living in greener areas may lead to improved health outcomes

Metabolic profiling of HepG2 cells incubated with S(−) and R(+) enantiomers of anti-coagulating drug warfarin

Warfarin is a commonly prescribed oral anticoagulant with narrow therapeutic index. It achieves anti-coagulating effects by interfering with the vitamin K cycle. Warfarin has two enantiomers, S(−) and R(+) and undergoes stereoselective metabolism, with the S(−) enantiomer being more effective. We reported the intracellular metabolic profile in HepG2 cells incubated with S(−) and R(+) warfarin by GCMS. Chemometric method PCA was applied to analyze the individual samples. A total of 80 metabolites which belong to different categories were identified. Two batches of experiments (with and without the presence of vitamin K) were designed. In samples incubated with S(−) and R(+) warfarin, glucuronic acid showed significantly decreased in cells incubated with R(+) warfarin but not in those incubated with S(−) warfarin. It may partially explain the lower bio-activity of R(+) warfarin. And arachidonic acid showed increased in cells incubated with S(−) warfarin but not in those incubated with R(+) warfarin. In addition, a number of small molecules involved in γ-glutamyl cycle displayed ratio variations. Intracellular glutathione detection further validated the results. Taken together, our findings provided molecular evidence on a comprehensive metabolic profile on warfarin-cell interaction which may shed new lights on future improvement of warfarin therapy

An image classification approach to analyze the suppression of plant immunity by the human pathogen <it>Salmonella</it> Typhimurium

<p>Abstract</p> <p>Background</p> <p>The enteric pathogen <it>Salmonella</it> is the causative agent of the majority of food-borne bacterial poisonings. Resent research revealed that colonization of plants by <it>Salmonella</it> is an active infection process. <it>Salmonella</it> changes the metabolism and adjust the plant host by suppressing the defense mechanisms. In this report we developed an automatic algorithm to quantify the symptoms caused by <it>Salmonella</it> infection on <it>Arabidopsis</it>.</p> <p>Results</p> <p>The algorithm is designed to attribute image pixels into one of the two classes: healthy and unhealthy. The task is solved in three steps. First, we perform segmentation to divide the image into foreground and background. In the second step, a support vector machine (SVM) is applied to predict the class of each pixel belonging to the foreground. And finally, we do refinement by a neighborhood-check in order to omit all falsely classified pixels from the second step. The developed algorithm was tested on infection with the non-pathogenic <it>E. coli</it> and the plant pathogen <it>Pseudomonas syringae</it> and used to study the interaction between plants and <it>Salmonella</it> wild type and T3SS mutants. We proved that T3SS mutants of <it>Salmonella</it> are unable to suppress the plant defenses. Results obtained through the automatic analyses were further verified on biochemical and transcriptome levels.</p> <p>Conclusion</p> <p>This report presents an automatic pixel-based classification method for detecting “unhealthy” regions in leaf images. The proposed method was compared to existing method and showed a higher accuracy. We used this algorithm to study the impact of the human pathogenic bacterium <it>Salmonella</it> Typhimurium on plants immune system. The comparison between wild type bacteria and T3SS mutants showed similarity in the infection process in animals and in plants. Plant epidemiology is only one possible application of the proposed algorithm, it can be easily extended to other detection tasks, which also rely on color information, or even extended to other features.</p

The dynamic geophysical environment of (101955) Bennu based on OSIRIS-REx measurements

The top-shaped morphology characteristic of asteroid (101955) Bennu, often found among fast-spinning asteroids and binary asteroid primaries, may have contributed substantially to binary asteroid formation. Yet a detailed geophysical analysis of this morphology for a fast-spinning asteroid has not been possible prior to the Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) mission. Combining the measured Bennu mass and shape obtained during the Preliminary Survey phase of the OSIRIS-REx mission, we find a notable transition in Bennu’s surface slopes within its rotational Roche lobe, defined as the region where material is energetically trapped to the surface. As the intersection of the rotational Roche lobe with Bennu’s surface has been most recently migrating towards its equator (given Bennu’s increasing spin rate), we infer that Bennu’s surface slopes have been changing across its surface within the last million years. We also find evidence for substantial density heterogeneity within this body, suggesting that its interior is a mixture of voids and boulders. The presence of such heterogeneity and Bennu’s top shape are consistent with spin-induced failure at some point in its past, although the manner of its failure cannot yet be determined. Future measurements by the OSIRIS-REx spacecraft will provide insight into and may resolve questions regarding the formation and evolution of Bennu’s top-shape morphology and its link to the formation of binary asteroids

Evidence for widespread hydrated minerals on asteroid (101955) Bennu

Early spectral data from the Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) mission reveal evidence for abundant hydrated minerals on the surface of near-Earth asteroid (101955) Bennu in the form of a near-infrared absorption near 2.7 µm and thermal infrared spectral features that are most similar to those of aqueously altered CM-type carbonaceous chondrites. We observe these spectral features across the surface of Bennu, and there is no evidence of substantial rotational variability at the spatial scales of tens to hundreds of metres observed to date. In the visible and near-infrared (0.4 to 2.4 µm) Bennu’s spectrum appears featureless and with a blue (negative) slope, confirming previous ground-based observations. Bennu may represent a class of objects that could have brought volatiles and organic chemistry to Earth

Double aortic arch as a source of airway obstruction in a child

Double aortic arch (DAA) is a congenital vascular anomaly. The diagnosis was difficult till the child was symptomatic, and other causes were ruled out. We present the interesting images of a child of respiratory distress because of tracheal compression from DAA

Synthesis and antimicrobial activity of 3-methoxy-4-[4-chloro phenyl thioethoxy]-5-cyanophenyl benzaldehyde and its intermediates

627-630Synthesis of 3-methoxy-4-[4-chlorophenyl thioethoxy]-5-cyanophenyl benzaldehyde, as an important intermediate in the synthesis of 2,5-trans-diaryl tetrahydrofuran, is reported

Cholesteryl cytofectin-oligodeoxyribonucleotide lipoplexes: Protection against serum nuclease digestion and interaction with mammalian cells in vitro

Submicron unilamellar cationic liposomes constructed from equimolar amounts of a cholesteryl cytofectin 3  [N-(N’,N’-dimethylaminopropane)-carbamoyl] cholesterol (Chol-T) and dioleoylphosphatidylethanolamine (DOPE) were shown to bind a model antisense oligodeoxyribonucleotide (ODN) dT18 in a saturable manner to afford electropositive lipoplexes. Liposomes imparted to the ODN [3H]dT18A7 full protection against nuclease catalyzed degradation in 10% foetal calf serum at 37oC for 3 h, while under the same conditions the naked ODN underwent approximately 50% degradation. Liposomes also promoted association of ODNs to Chinese hamster ovary (CHO) cells while at a liposome (+ve) : ODN (- ve) charge ratio of 1.3:1 lipoplexes were well tolerated by the human hepatoma cell line HepG2 at levels of ODN ordinarily employed in antisense ODN-mediated gene knockdown experiments. The findings of this study suggest that cationic liposomes based on the cationic cholesterol derivative Chol-T and the neutral co-lipid DOPE may be used in antisense ODN applications in mammalian cell lines grown in culture