Ultrasound Imaging Versus Morphopathology in Cardiovascular Diseases: The Heart Failure

This review article summarizes the results of histopathological studies to assess heart failure in humans. Different histopathological features underlying the clinical manifestations of heart failure are reviewed. In addition, the present role of echocardiographic techniques in assessing the failing heart is briefly summarized

The role of left and right hemispheres in the comprehension of idiomatic language: an electrical neuroimaging study

<p>Abstract</p> <p>Background</p> <p>The specific role of the two cerebral hemispheres in processing idiomatic language is highly debated. While some studies show the involvement of the left inferior frontal gyrus (LIFG), other data support the crucial role of right-hemispheric regions, and particularly of the middle/superior temporal area. Time-course and neural bases of literal vs. idiomatic language processing were compared. Fifteen volunteers silently read 360 idiomatic and literal Italian sentences and decided whether they were semantically related or unrelated to a following target word, while their EEGs were recorded from 128 electrodes. Word length, abstractness and frequency of use, sentence comprehensibility, familiarity and cloze probability were matched across classes.</p> <p>Results</p> <p>Participants responded more quickly to literal than to idiomatic sentences, probably indicating a difference in task difficulty. Occipito/temporal N2 component had a greater amplitude in response to idioms between 250-300 ms. Related swLORETA source reconstruction revealed a difference in the activation of the left fusiform gyrus (FG, BA19) and medial frontal gyri for the contrast idiomatic-minus-literal. Centroparietal N400 was much larger to idiomatic than to literal phrases (360-550 ms). The intra-cortical generators of this effect included the left and right FG, the left cingulate gyrus, the right limbic area, the right MTG (BA21) and the left middle frontal gyrus (BA46). Finally, an anterior late positivity (600-800 ms) was larger to idiomatic than literal phrases. ERPs also showed a larger right centro-parietal N400 to associated than non-associated targets (not differing as a function of sentence type), and a greater right frontal P600 to idiomatic than literal associated targets.</p> <p>Conclusion</p> <p>The data indicate bilateral involvement of both hemispheres in idiom comprehension, including the right MTG after 350 ms and the right medial frontal gyrus in the time windows 270-300 and 500-780 ms. In addition, the activation of left and right limbic regions (400-450 ms) suggests that they have a role in the emotional connotation of colourful idiomatic language. The data support the view that there is direct access to the idiomatic meaning of figurative language, not dependent on the suppression of its literal meaning, for which the LIFG was previously thought to be responsible.</p

Divergent functional isoforms drive niche specialisation for nutrient acquisition and use in rumen microbiome

Many microbes in complex competitive environments share genes for acquiring and utilising nutrients, questioning whether niche specialisation exists and if so, how it is maintained. We investigated the genomic signatures of niche specialisation in the rumen microbiome, a highly competitive, anaerobic environment, with limited nutrient availability determined by the biomass consumed by the host. We generated individual metagenomic libraries from 14 cows fed an ad libitum diet of grass silage and calculated functional isoform diversity for each microbial gene identified. The animal replicates were used to calculate confidence intervals to test for differences in diversity of functional isoforms between microbes that may drive niche specialisation. We identified 153 genes with significant differences in functional isoform diversity between the two most abundant bacterial genera in the rumen (Prevotella and Clostridium). We found Prevotella possesses a more diverse range of isoforms capable of degrading hemicellulose, whereas Clostridium for cellulose. Furthermore, significant differences were observed in key metabolic processes indicating that isoform diversity plays an important role in maintaining their niche specialisation. The methods presented represent a novel approach for untangling complex interactions between microorganisms in natural environments and have resulted in an expanded catalogue of gene targets central to rumen cellulosic biomass degradation

A metagenomic assessment of winter and summer bacterioplankton from Antarctica Peninsula coastal surface waters

© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in The ISME Journal 6 (2012): 1901-1915, doi:10.1038/ismej.2012.31.Antarctic surface oceans are well-studied during summer when irradiance levels are high, sea ice is melting and primary productivity is at a maximum. Coincident with this timing, the bacterioplankton respond with significant increases in secondary productivity. Little is known about bacterioplankton in winter when darkness and sea-ice cover inhibit photoautotrophic primary production. We report here an environmental genomic and small subunit ribosomal RNA (SSU rRNA) analysis of winter and summer Antarctic Peninsula coastal seawater bacterioplankton. Intense inter-seasonal differences were reflected through shifts in community composition and functional capacities encoded in winter and summer environmental genomes with significantly higher phylogenetic and functional diversity in winter. In general, inferred metabolisms of summer bacterioplankton were characterized by chemoheterotrophy, photoheterotrophy and aerobic anoxygenic photosynthesis while the winter community included the capacity for bacterial and archaeal chemolithoautotrophy. Chemolithoautotrophic pathways were dominant in winter and were similar to those recently reported in global ‘dark ocean’ mesopelagic waters. If chemolithoautotrophy is widespread in the Southern Ocean in winter, this process may be a previously unaccounted carbon sink and may help account for the unexplained anomalies in surface inorganic nitrogen content.CSR was supported by an NSF Postdoctoral Fellowship in Biological Informatics (DBI-0532893). The research was supported by National Science Foundation awards: ANT 0632389 (to AEM and JJG), and ANT 0632278 and 0217282 (to HWD), all from the Antarctic Organisms and Ecosystems Program

Expression of G protein-coupled receptors and related proteins in HEK293, AtT20, BV2, and N18 cell lines as revealed by microarray analysis

<p>Abstract</p> <p>Background</p> <p>G protein coupled receptors (GPCRs) are one of the most widely studied gene superfamilies. Thousands of GPCR research studies have utilized heterologous expression systems such as human embryonic kidney cells (HEK293). Though often treated as 'blank slates', these cell lines nevertheless endogenously express GPCRs and related signaling proteins. The outcome of a given GPCR study can be profoundly influenced by this largely unknown complement of receptors and/or signaling proteins. Little easily accessible information exists that describes the expression profiles of the GPCRs in cell lines. What is accessible is often limited in scope - of the hundreds of GPCRs and related proteins, one is unlikely to find information on expression of more than a dozen proteins in a given cell line. Microarray technology has allowed rapid analysis of mRNA levels of thousands of candidate genes, but though often publicly available, the results can be difficult to efficiently access or even to interpret.</p> <p>Results</p> <p>To bridge this gap, we have used microarrays to measure the mRNA levels of a comprehensive profile of non-chemosensory GPCRs and over a hundred GPCR signaling related gene products in four cell lines frequently used for GPCR research: HEK293, AtT20, BV2, and N18.</p> <p>Conclusions</p> <p>This study provides researchers an easily accessible mRNA profile of the endogenous signaling repertoire that these four cell lines possess. This will assist in choosing the most appropriate cell line for studying GPCRs and related signaling proteins. It also provides a better understanding of the potential interactions between GPCRs and those signaling proteins.</p

Metagenomics of the Deep Mediterranean, a Warm Bathypelagic Habitat

BACKGROUND: Metagenomics is emerging as a powerful method to study the function and physiology of the unexplored microbial biosphere, and is causing us to re-evaluate basic precepts of microbial ecology and evolution. Most marine metagenomic analyses have been nearly exclusively devoted to photic waters. METHODOLOGY/PRINCIPAL FINDINGS: We constructed a metagenomic fosmid library from 3,000 m-deep Mediterranean plankton, which is much warmer (approximately 14 degrees C) than waters of similar depth in open oceans (approximately 2 degrees C). We analyzed the library both by phylogenetic screening based on 16S rRNA gene amplification from clone pools and by sequencing both insert extremities of ca. 5,000 fosmids. Genome recruitment strategies showed that the majority of high scoring pairs corresponded to genomes from Rhizobiales within the Alphaproteobacteria, Cenarchaeum symbiosum, Planctomycetes, Acidobacteria, Chloroflexi and Gammaproteobacteria. We have found a community structure similar to that found in the aphotic zone of the Pacific. However, the similarities were significantly higher to the mesopelagic (500-700 m deep) in the Pacific than to the single 4000 m deep sample studied at this location. Metabolic genes were mostly related to catabolism, transport and degradation of complex organic molecules, in agreement with a prevalent heterotrophic lifestyle for deep-sea microbes. However, we observed a high percentage of genes encoding dehydrogenases and, among them, cox genes, suggesting that aerobic carbon monoxide oxidation may be important in the deep ocean as an additional energy source. CONCLUSIONS/SIGNIFICANCE: The comparison of metagenomic libraries from the deep Mediterranean and the Pacific ALOHA water column showed that bathypelagic Mediterranean communities resemble more mesopelagic communities in the Pacific, and suggests that, in the absence of light, temperature is a major stratifying factor in the oceanic water column, overriding pressure at least over 4000 m deep. Several chemolithotrophic metabolic pathways could supplement organic matter degradation in this most depleted habitat

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events