Quantitative MR measurements of regional and global left ventricular function and strain after intramyocardial transfer of VM202 into infarcted swine myocardium

Previous studies have shown the beneficial effects of the hepatocyte growth factor (HGF) gene on myocardial perfusion and infarction size but not on the regional strain in relationship to global left ventricular function. A noninvasive magnetic resonance (MR) study was performed to determine the effect of a new HGF gene, VM202, expressing two isoforms of HGF, on regional and global left ventricular function. Pigs (8/group) were divided into three groups: 1) controls without infarction; 2) reperfused, infarcted controls; and 3) infarcted, treated (1 h after reperfusion) with VM202 injected at eight sites. Cine, tagging, and delayed enhancement MR images were acquired at 3 and 50 +/- 3 days after infarction. At 50 days, ejection fraction in infarcted, treated animals increased (38 +/- 1% to 47 +/- 2%, P < 0.01) to the level of controls without infarction (52 +/- 1%, P = 0.16) but decreased in infarcted controls (41 +/- 1% to 37 +/- 1%, P < 0.05). Two-dimensional strain improved in remote, peri-infarcted, and infarcted myocardium. Furthermore, the infarction size was smaller in infarcted, treated animals (7.0 +/- 0.5%) compared with infarcted controls (13.2 +/- 1.6%, P < 0.05). Histopathology showed a lack of hypertrophy in myocytes in peri-infarcted and remote myocardium and the formation of islands/peninsulas of myocytes in infarcted, treated animals but not in infarcted controls. In conclusion, the plasmid HGF gene caused a near complete recovery of ejection fraction and improved the radial and circumferential strain of remote, peri-infarcted, and infarcted regions within 50 days. These beneficial effects may be explained by the combined effects of a speedy and significant infarct resorption and island/peninsulas of hypertrophied myocytes within the infarcted territory but not by compensatory hypertrophy. The combined use of cine and tagging MR imaging provides valuable information on the efficacy of gene therapy.     

Whole tissue hydrogen sulfide concentrations are orders of magnitude lower than presently accepted values

Hydrogen sulfide is gaining acceptance as an endogenously produced modulator of tissue function. The present paradigm of H(2)S (diprotonated, gaseous form of hydrogen sulfide) as a tissue messenger consists of H(2)S being released from the desulfhydration of l-cysteine at a rate sufficient to maintain whole tissue hydrogen sulfide concentrations of 30 microM to >100 microM, and these tissue concentrations serve a messenger function. Utilizing physiological concentrations of l-cysteine and aerobic conditions, we found that catabolism of hydrogen sulfide by mouse liver and brain homogenates exceeded the rate of enzymatic release of this compound such that measureable hydrogen sulfide release was less with tissue-containing vs. tissue-free buffers. Analyses of the gas space over rapidly homogenized mouse brain and liver indicated that in situ tissue hydrogen sulfide concentrations were only about 15 nM. Human alveolar air measurements indicated negligible free H(2)S concentrations in blood. We conclude rapid tissue catabolism of hydrogen sulfide maintains whole tissue brain and liver concentrations of free hydrogen sulfide that are three orders of magnitude less than conventionally accepted values and only 1/5,000 of the hydrogen sulfide concentration (100 microM) required to alter cellular function in vitro. For hydrogen sulfide to serve as an endogenously produced messenger, tissue production and catabolism must result in intracellular microenvironments with a sufficiently high hydrogen sulfide concentration to activate a local signaling mechanism, while whole tissue concentrations remain very low.     

Fast and systematic genome-wide discovery of conserved regulatory elements using a non-alignment based approach

We describe a powerful new approach for discovering globally conserved regulatory elements between two genomes. The method is fast, simple and comprehensive, without requiring alignments. Its application to pairs of yeasts, worms, flies and mammals yields a large number of known and novel putative regulatory elements. Many of these are validated by independent biological observations, have spatial and/or orientation biases, are co-conserved with other elements and show surprising conservation across large phylogenetic distances.     

Mutations in C2orf37, Encoding a Nucleolar Protein, Cause Hypogonadism, Alopecia, Diabetes Mellitus, Mental Retardation, and Extrapyramidal Syndrome

Hypogonadism, alopecia, diabetes mellitus, mental retardation, and extrapyramidal syndrome (also referenced as Woodhouse-Sakati syndrome) is a rare autosomal recessive multisystemic disorder. We have identified a founder mutation consisting of a single base-pair deletion in C2orf37 in eight families of Saudi origin. Three other loss-of-function mutations were subsequently discovered in patients of different ethnicities. The gene encodes a nucleolar protein of unknown function, and the cellular phenotype observed in patient lymphoblasts implicates a role for the nucleolus in the pathogenesis of this disease. Our findings expand the list of human disorders linked to the nucleolus and further highlight the developmental and/or maintenance functions of this organelle.     

Osteoblastic cells: differentiation and trans-differentiation

The osteoblast is the bone forming cell and is derived from mesenchymal stem cells (MSC) present among the bone marrow stroma. MSC are capable of multi-lineage differentiation into mesoderm-type cells such as osteoblasts and adipocytes. Understanding the mechanisms underlying osteoblast differentiation from MSC is a central topic in bone biology that can provide insight into mechanisms of bone maintenance and also novel pharmacological targets to increase osteoblast differentiation and consequently bone formation.     

An Evidence-Based Combining Classifier for Brain Signal Analysis

Nowadays, brain signals are employed in various scientific and practical fields such as Medical Science, Cognitive Science, Neuroscience, and Brain Computer Interfaces. Hence, the need for robust signal analysis methods with adequate accuracy and generalizability is inevitable. The brain signal analysis is faced with complex challenges including small sample size, high dimensionality and noisy signals. Moreover, because of the non-stationarity of brain signals and the impacts of mental states on brain function, the brain signals are associated with an inherent uncertainty. In this paper, an evidence-based combining classifiers method is proposed for brain signal analysis. This method exploits the power of combining classifiers for solving complex problems and the ability of evidence theory to model as well as to reduce the existing uncertainty. The proposed method models the uncertainty in the labels of training samples in each feature space by assigning soft and crisp labels to them. Then, some classifiers are employed to approximate the belief function corresponding to each feature space. By combining the evidence raised from each classifier through the evidence theory, more confident decisions about testing samples can be made. The obtained results by the proposed method compared to some other evidence-based and fixed rule combining methods on artificial and real datasets exhibit the ability of the proposed method in dealing with complex and uncertain classification problems.