Stress-induced mitogen-activated protein kinase (MAP) p38 is activated in various forms of heart failure, yet its effects on the intact heart remain to be established. Targeted activation of p38 MAP ...kinase in ventricular myocytes was achieved in vivo by using a gene-switch transgenic strategy with activated mutants of upstream kinases MKK3bE and MKK6bE. Transgene expression resulted in significant induction of p38 kinase activity and premature death at 7-9 weeks. Both groups of transgenic hearts exhibited marked interstitial fibrosis and expression of fetal marker genes characteristic of cardiac failure, but no significant hypertrophy at the organ level. Echocardiographic and pressure-volume analyses revealed a similar extent of systolic contractile depression and restrictive diastolic abnormalities related to markedly increased passive chamber stiffness. However, MKK3bE-expressing hearts had increased end-systolic chamber volumes and a thinned ventricular wall, associated with heterogeneous myocyte atrophy, whereas MKK6bE hearts had reduced end-diastolic ventricular cavity size, a modest increase in myocyte size, and no significant myocyte atrophy. These data provide in vivo evidence for a negative inotropic and restrictive diastolic effect from p38 MAP kinase activation in ventricular myocytes and reveal specific roles of p38 pathway in the development of ventricular end-systolic remodeling.
Functional coupling between the sarcolemmal membrane and the sarcoplasmic reticulum is based on distinct structures called junctional membrane complexes (JMCs). Recently, junctophilins are found to ...be responsible for normal formation of JMCs. In the present study, we found that junctophilin type 2 (JP-2), a unique isoform in the heart, was localized in caveolin-rich membranes, and that the expression of JP-2 was up-regulated during normal development and down-regulated in a hypertrophic or a dilated cardiomyopathic mouse model. The expression levels of JP-2 may be associated with the development of T-tubules and impaired Ca
2+-induced Ca
2+ release in the heart.
In the centres of stars where the temperature is high enough, three alpha-particles (helium nuclei) are able to combine to form C-12 because of a resonant reaction leading to a nuclear excited ...state(1). (Stars with masses greater than similar to0.5 times that of the Sun will at some point in their lives have a central temperature high enough for this reaction to proceed.) Although the reaction rate is of critical significance for determining elemental abundances in the Universe(1), and for determining the size of the iron core of a star just before it goes supernova(2), it has hitherto been insufficiently determined(2). Here we report a measurement of the inverse process, where a C-12 nucleus decays to three alpha-particles. We find a dominant resonance at an energy of similar to11 MeV, but do not confirm the presence of a resonance at 9.1 MeV (ref. 3). We show that interference between two resonances has important effects on our measured spectrum. Using these data, we calculate the triple-a rate for temperatures from 10(7) K to 10(10) K and find significant deviations from the standard rates(3). Our rate below similar to5 x 10(7) K is higher than the previous standard, implying that the critical amounts of carbon that catalysed hydrogen burning in the first stars are produced twice as fast as previously believed(4). At temperatures above 10(9) K, our rate is much less, which modifies predicted nucleosynthesis in supernovae(5,6).
Activation of stress-activated mitogen-activated protein kinases (SAPKs), mainly c-Jun N-terminal kinase (JNK) and p38, have long been associated with different forms of cardiac pathology across a ...wide spectrum of species. However, their specific roles in the development of heart failure are still unclear. Previous studies in neonatal myocytes in culture suggest a critical role for both JNK and p38 in hypertrophy and apoptosis. A far more complex picture has been provided by recent observations from both cellular and transgenic models that have not only challenged their role in hypertrophy and cell death but have also pointed out novel functions of SAPKs in different aspects of cardiac pathology, including contractile function, extracellular matrix remodeling, intercellular communication, and metabolic regulation.
The effectiveness on water quality, population density of bacteria, and shrimp production in ponds treated with commercial probiotics was tested in Penaeus vannamei ponds in Hai‐yan, China. Six ponds ...with replicates for treatment and control were used. Results showed that the probiotics could improve the population density of beneficial bacterial flora, reduce concentrations of nitrogen and phosphorus, and increase yields of shrimp. The average counts of Bacillus sp., ammonifying bacteria, and protein mineralizing bacteria were found to be significantly higher in treated ponds compared to control ponds (P < 0.05). In control ponds, an increase in presumptive vibrios was observed and the average density was up to 2.09 × 103 cfu/mL, whereas that was only 4.37 × 102 cfu/mL in treated ponds (P < 0.05). The use of probiotics also significantly increased dissolved oxygen (P < 0.05) and reduced dissolved reactive‐phosphorus, total inorganic nitrogen and chemical oxygen demand (P < 0.05). An average of 8215 ± 265 kg shrimp/ha was obtained in treated ponds with a feed conversion ratio (FCR) of 1.13 ± 0.05 and survival rate of 81.00 ± 6.25% compared with 4985 ± 503 kg shrimp/ha, 1.35 ± 0.12 and 48.67 ± 3.51%, respectively, in control ponds. This indicates that the addition of the commercial probiotics had a noticeable influence on water quality of shrimp ponds and shrimp production.
The oral administration of Enterococcus faecium EF1 to new-born suckling and weaning piglets along with their growth performances and intestinal microbiota was investigated in this study. Twenty-four ...new-born piglets were initially divided into 2 groups. The probiotics group received 2 ml of 10% sterilised skimmed milk by oral gavage supplemented with 6×108 cfu/ml viable E. faecium EF1 at the first, the third and the fifth day after birth, while the control group received 2 ml of 10% sterilised skimmed milk without probiotics at the same time. Results showed that oral administration of E. faecium EF1 was associated with a remarkable increase on the body weight of piglets for both suckling and weaning periods, by 30.73% (P<0.01) and 320.84% (P<0.01), and also decreased the diarrhoea rate, by 43.21% (P<0.05) and 71.42% (P<0.05), respectively. In addition, 454-pyrosequencing analysis revealed that there was no significant difference in the intestinal microbial diversity of the suckling piglets between the two groups; nevertheless, when compared to the control group, the relative abundance of Firmicutes in the probiotics group was substantially augmented, while the relative abundance of Proteobacteria, Bacteroidetes and Fusobacteria diminished. However, results indicated that oral administration of E. faecium EF1 did not have any influence on the relative abundance of Firmicutes in weaning piglets rather than increasing the relative abundance of Bacteroidetes and decreasing the relative abundance of Proteobacteria. Furthermore, at the level of the Firmicutes phylum, the relative abundance of Lactobacillales in the probiotic group increased significantly. These findings suggest that oral administration of E. faecium EF1 to new-born piglets could improve the growth performance and intestinal microbiota of piglets for both suckling and weaning periods.
Calcimicrobialites, which could be correlated to the layer 27 in Meishan section according to the Hindeodus parvus, occur abruptly on the end-Permian mass extinction boundary in South China. ...Microbialites mainly distribute on the top of reef facies or shallow carbonate platforms, thinning into deep facies. All the microbialites discovered are composed of micrite and coarse crystal digitate carbonate or patch carbonate. Microfossils usually dominate in the microbialites, and small gastropods, bivalves and ostracodes can also be found. This fossil assemblage represents a simple but particular remanent biota after the end-Permian mass extinction on the top of reefs or shallow carbonate platforms. Abrupt occurrence of microbialites above the mass extinction boundary is the ecological response to the end-Permian global event in reef or shallow carbonate facies. Many studies have been done on the Permian-Triassic boundary and event in deep water facies sections or middle to lower shelf facies sections. However, the calcimicrobialites in South China are mainly located above reef facies or shallow carbonate platform facies. It will surely be helpful for people to know more about the different responses in different depths of ancient marine environment during the transition between Permian and Triassic by the study of petrology, palaeontology and palaeoecology of the calcimicrobialites.
p38 mitogen-activated protein (MAP) kinase activities were significantly increased in mouse hearts after chronic transverse aortic constriction, coincident with the onset of ventricular hypertrophy. ...Infection of cardiomyocytes with adenoviral vectors expressing upstream activators for the p38 kinases, activated mutants of MAP kinase kinase 3b(E) (MKK3bE) and MAP kinase kinase 6b(E) (MKK6bE), elicited characteristic hypertrophic responses, including an increase in cell size, enhanced sarcomeric organization, and elevated atrial natriuretic factor expression. Overexpression of the activated MKK3bE in cardiomyocytes also led to an increase in apoptosis. The hypertrophic response was enhanced by co-infection of an adenoviral vector expressing wild type p38β, and was suppressed by the p38β dominant negative mutant. In contrast, the MKK3bE-induced cell death was increased by co-infection of an adenovirus expressing wild type p38α, and was suppressed by the dominant negative p38α mutant. This provides the first evidence in any cell system for divergent physiological functions for different members of the p38 MAP kinase family. The direct involvement of p38 pathways in cardiac hypertrophy and apoptosis suggests a significant role for p38 signaling in the pathophysiology of heart failure.
A technique is described for assembly of multiple batches of micro components onto a single substrate. The substrate is prepared with hydrophobic alkanethiol-coated gold binding sites. To perform ...assembly, a hydrocarbon oil, which is applied to the substrate, wets exclusively the hydrophobic binding sites in water. Micro components are then added to the water, and assembled on the oil-wetted binding sites. Moreover, assembly can be controlled to take place on desired binding sites by using an electrochemical method to deactivate specific substrate binding sites. By repeatedly applying this technique, different batches of micro components can be sequentially assembled to a single substrate. As a post assembly procedure, electroplating is incorporated into the technique to establish electrical connections for assembled components. Important issues presented are: substrate fabrication techniques, electrochemical modulation by using a suitable alkanethiol (dodecanethiol), electroplating of tin and lead alloy and binding site design simulations. Finally, we demonstrate a two-batch assembly of silicon square parts, and establishing electrical connectivity for assembled surface-mount light emitting diodes (LEDs) by electroplating.
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