Establishment of a canine model of cardiac memory using endocardial pacing via internal jugular vein

<p>Abstract</p> <p>Background</p> <p>Development of experimental animal models has played an important role in understanding the mechanisms of cardiac memory. The purpose of this study was to evaluate a new canine model of cardiac memory using endocardial ventricular pacing via internal jugular vein.</p> <p>Methods</p> <p>Twelve Beagle dogs underwent placement of a permanent ventricular pacemaker mimicking the use of pacemakers in humans and induction of cardiac memory by endocardial ventricular pacing.</p> <p>Results</p> <p>Cardiac memory was achieved in 11 of 12 attempts overall. Procedural mortality due to cardiac tamponade (n = 1) occurred in the first attempt. The T-wave memory persisted for 96 ± 17 minutes and 31 ± 6 days in the short-term and long-term cardiac memory groups, respectively. There were no significant differences in the heart rate, blood pressure and echocardiographic parameters in the animals between before and after ventricular pacing in the short-term and long-term cardiac memory groups. No significant pathologic changes with the light microscopy were found in the present study in all dogs.</p> <p>Conclusion</p> <p>The model does require surgery but is not as invasive as an open-chest model. This canine model can serve as a useful tool for studying mechanisms of cardiac memory.</p

Cultivation of Human Corneal Endothelial Cells Isolated from Paired Donor Corneas

Consistent expansion of human corneal endothelial cells (hCECs) is critical in the development of tissue engineered endothelial constructs. However, a wide range of complex culture media, developed from different basal media have been reported in the propagation of hCECs, some with more success than others. These results are further confounded by donor-to-donor variability. The aim of this study is to evaluate four culture media in the isolation and propagation of hCECs isolated from a series of paired donor corneas in order to negate donor variability

Monsoon versus Uplift in Southwestern China–Late Pliocene Climate in Yuanmou Basin, Yunnan

Yuanmou Basin of Yunnan, SW China, is a famous locality with hominids, hominoids, mammals and plant fossils. Based on the published megaflora and palynoflora data from Yuanmou Basin, the climate of Late Pliocene is reconstructed using the Coexistence Approach. The results indicate a warm and humid subtropical climate with a mean annual temperature of ca. 16–17°C and a mean annual precipitation of ca. 1500–1600 mm in the Late Pliocene rather than a dry, hot climate today, which may be due to the local tectonic change and gradual intensification of India monsoon. The comparison of Late Pliocene climate in Eryuan, Yangyi, Longling, and Yuanmou Basin of Yunnan Province suggests that the mean annual temperatures generally show a latitudinal gradient and fit well with their geographic position, while the mean annual precipitations seem to be related to the different geometries of the valleys under the same monsoon system

Lubiprostone ameliorates the cystic fibrosis mouse intestinal phenotype

<p>Abstract</p> <p>Background</p> <p>Cystic fibrosis (CF) is caused by mutations in the <it>CFTR </it>gene that impair the function of CFTR, a cAMP-regulated anion channel. In the small intestine loss of CFTR function creates a dehydrated, acidic luminal environment which is believed to cause an accumulation of mucus, a phenotype characteristic of CF. CF mice have small intestinal bacterial overgrowth, an altered innate immune response, and impaired intestinal transit. We investigated whether lubiprostone, which can activate the CLC2 Cl^-channel, would improve the intestinal phenotype in CF mice.</p> <p>Methods</p> <p><it>Cftr^tm1UNC</it>(CF) and wildtype (WT) littermate mice on the C57BL/6J background were used. Lubiprostone (10 μg/kg-day) was administered by gavage for two weeks. Mucus accumulation was estimated from crypt lumen widths in periodic acid-Schiff base, Alcian blue stained sections. Luminal bacterial load was measured by qPCR for the bacterial 16<it>S </it>gene. Gastric emptying and small intestinal transit in fasted mice were assessed using gavaged rhodamine dextran. Gene expression was evaluated by Affymetrix Mouse430 2.0 microarray and qRT-PCR.</p> <p>Results</p> <p>Crypt width in control CF mice was 700% that of WT mice (<it>P </it>< 0.001). Lubiprostone did not affect WT crypt width but, unexpectedly, increased CF crypt width 22% (<it>P </it>= 0.001). Lubiprostone increased bacterial load in WT mice to 490% of WT control levels (<it>P </it>= 0.008). Conversely, lubiprostone decreased bacterial overgrowth in CF mice by 60% (<it>P </it>= 0.005). Lubiprostone increased gastric emptying at 20 min postgavage in both WT (<it>P </it>< 0.001) and CF mice (<it>P </it>< 0.001). Lubiprostone enhanced small intestinal transit in WT mice (<it>P </it>= 0.024) but not in CF mice (<it>P </it>= 0.377). Among other innate immune markers, expression of mast cell genes was elevated 4-to 40-fold in the CF intestine as compared to WT, and lubiprostone treatment of CF mice decreased expression to WT control levels.</p> <p>Conclusions</p> <p>These results indicate that lubiprostone has some benefits for the CF intestinal phenotype, especially on bacterial overgrowth and the innate immune response. The unexpected observation of increased mucus accumulation in the crypts of lubiprostone-treated CF mice suggests the possibility that lubiprostone increases mucus secretion.</p

Impact of ENSO longitudinal position on teleconnections to the NAO

While significant improvements have been made in understanding how the El Niño–Southern Oscillation (ENSO) impacts both North American and Asian climate, its relationship with the North Atlantic Oscillation (NAO) remains less clear. Observations indicate that ENSO exhibits a highly complex relationship with the NAO-associated atmospheric circulation. One critical contribution to this ambiguous ENSO/NAO relationship originates from ENSO’s diversity in its spatial structure. In general, both eastern (EP) and central Pacific (CP) El Niño events tend to be accompanied by a negative NAO-like atmospheric response. However, for two different types of La Niña the NAO response is almost opposite. Thus, the NAO responses for the CP ENSO are mostly linear, while nonlinear NAO responses dominate for the EP ENSO. These contrasting extra-tropical atmospheric responses are mainly attributed to nonlinear air-sea interactions in the tropical eastern Pacific. The local atmospheric response to the CP ENSO sea surface temperature (SST) anomalies is highly linear since the air-sea action center is located within the Pacific warm pool, characterized by relatively high climatological SSTs. In contrast, the EP ENSO SST anomalies are located in an area of relatively low climatological SSTs in the eastern equatorial Pacific. Here only sufficiently high positive SST anomalies during EP El Niño events are able to overcome the SST threshold for deep convection, while hardly any anomalous convection is associated with EP La Niña SSTs that are below this threshold. This ENSO/NAO relationship has important implications for NAO seasonal prediction and places a higher requirement on models in reproducing the full diversity of ENSO

Burial Depth and Stolon Internode Length Independently Affect Survival of Small Clonal Fragments

Disturbance can fragment plant clones into different sizes and unstabilize soils to different degrees, so that clonal fragments of different sizes can be buried in soils at different depths. As a short-term storage organ, solon internode may help fragmented clones of stoloniferous plants to withstand deeper burial in soils. We address (1) whether burial in soils decreases survival and growth of small clonal fragments, and (2) whether increasing internode length increases survival and growth of small fragments under burial. We conducted an experiment with the stoloniferous, invasive herb Alternanthera philoxeroides, in which single-node fragments with stolon internode of 0, 2, 4 and 8 cm were buried in soils at 0, 2, 4 and 8 cm depth, respectively. Increasing burial depth significantly reduced survival of the A. philoxeroides plants and increased root to shoot ratio and total stolon length, but did not change growth measures. Increasing internode length significantly increased survival and growth measures, but there was no interaction effect with burial depth on any traits measured. These results indicate that reserves stored in stolon internodes can contribute to the fitness of the A. philoxeroides plants subject to disturbance. Although burial reduced the regeneration capacity of the A. philoxeroides plants, the species may maintain the fitness by changing biomass allocation and stolon length once it survived the burial. Such responses may play an important role for A. philoxeroides in establishment and invasiveness in frequently disturbed habitats

A New Fluorescence-Based Method Identifies Protein Phosphatases Regulating Lipid Droplet Metabolism

In virtually every cell, neutral lipids are stored in cytoplasmic structures called lipid droplets (LDs) and also referred to as lipid bodies or lipid particles. We developed a rapid high-throughput assay based on the recovery of quenched BODIPY-fluorescence that allows to quantify lipid droplets. The method was validated by monitoring lipid droplet turnover during growth of a yeast culture and by screening a group of strains deleted in genes known to be involved in lipid metabolism. In both tests, the fluorimetric assay showed high sensitivity and good agreement with previously reported data using microscopy. We used this method for high-throughput identification of protein phosphatases involved in lipid droplet metabolism. From 65 yeast knockout strains encoding protein phosphatases and its regulatory subunits, 13 strains revealed to have abnormal levels of lipid droplets, 10 of them having high lipid droplet content. Strains deleted for type I protein phosphatases and related regulators (ppz2, gac1, bni4), type 2A phosphatase and its related regulator (pph21 and sap185), type 2C protein phosphatases (ptc1, ptc4, ptc7) and dual phosphatases (pps1, msg5) were catalogued as high-lipid droplet content strains. Only reg1, a targeting subunit of the type 1 phosphatase Glc7p, and members of the nutrient-sensitive TOR pathway (sit4 and the regulatory subunit sap190) were catalogued as low-lipid droplet content strains, which were studied further. We show that Snf1, the homologue of the mammalian AMP-activated kinase, is constitutively phosphorylated (hyperactive) in sit4 and sap190 strains leading to a reduction of acetyl-CoA carboxylase activity. In conclusion, our fast and highly sensitive method permitted us to catalogue protein phosphatases involved in the regulation of LD metabolism and present evidence indicating that the TOR pathway and the SNF1/AMPK pathway are connected through the Sit4p-Sap190p pair in the control of lipid droplet biogenesis

The Bifidobacterium dentium Bd1 Genome Sequence Reflects Its Genetic Adaptation to the Human Oral Cavity

Bifidobacteria, one of the relatively dominant components of the human intestinal microbiota, are considered one of the key groups of beneficial intestinal bacteria (probiotic bacteria). However, in addition to health-promoting taxa, the genus Bifidobacterium also includes Bifidobacterium dentium, an opportunistic cariogenic pathogen. The genetic basis for the ability of B. dentium to survive in the oral cavity and contribute to caries development is not understood. The genome of B. dentium Bd1, a strain isolated from dental caries, was sequenced to completion to uncover a single circular 2,636,368 base pair chromosome with 2,143 predicted open reading frames. Annotation of the genome sequence revealed multiple ways in which B. dentium has adapted to the oral environment through specialized nutrient acquisition, defences against antimicrobials, and gene products that increase fitness and competitiveness within the oral niche. B. dentium Bd1 was shown to metabolize a wide variety of carbohydrates, consistent with genome-based predictions, while colonization and persistence factors implicated in tissue adhesion, acid tolerance, and the metabolism of human saliva-derived compounds were also identified. Global transcriptome analysis demonstrated that many of the genes encoding these predicted traits are highly expressed under relevant physiological conditions. This is the first report to identify, through various genomic approaches, specific genetic adaptations of a Bifidobacterium taxon, Bifidobacterium dentium Bd1, to a lifestyle as a cariogenic microorganism in the oral cavity. In silico analysis and comparative genomic hybridization experiments clearly reveal a high level of genome conservation among various B. dentium strains. The data indicate that the genome of this opportunistic cariogen has evolved through a very limited number of horizontal gene acquisition events, highlighting the narrow boundaries that separate commensals from opportunistic pathogens