Multiple Ca2+ signaling pathways regulate intracellular Ca 2+ activity in human cardiac fibroblasts

Ca2+ signaling pathways are well studied in cardiac myocytes, but not in cardiac fibroblasts. The aim of the present study is to characterize Ca2+ signaling pathways in cultured human cardiac fibroblasts using confocal scanning microscope and RT-PCR techniques. It was found that spontaneous intracellular Ca2+ (Cai 2+) oscillations were present in about 29% of human cardiac fibroblasts, and the number of cells with Cai 2+ oscillations was increased to 57.3% by application of 3% fetal bovine serum. Cai 2+ oscillations were dependent on Ca2+ entry. Cai2+ oscillations were abolished by the store-operated Ca2+ (SOC) entry channel blocker La3+, the phospholipase C inhibitor U-73122, and the inositol trisphosphate receptors (IP3Rs) inhibitor 2-aminoethoxydiphenyl borate, but not by ryanodine. The IP3R agonist thimerosal enhanced Ca2+ i oscillations. Inhibition of plasma membrane Ca2+ pump (PMCA) and Na+-Ca2+ exchanger (NCX) also suppressed Ca i 2+ oscillations. In addition, the frequency of Ca i 2+ oscillations was reduced by nifedipine, and increased by Bay K8644 in cells with spontaneous Cai 2+ oscillations. RT-PCR revealed that mRNAs for IP3R1-3, SERCA1-3, CaV1.2, NCX3, PMCA1,3,4, TRPC1,3,4,6, STIM1, and Orai1-3, were readily detectable, but not RyRs. Our results demonstrate for the first time that spontaneous Cai 2+ oscillations are present in cultured human cardiac fibroblasts and are regulated by multiple Ca2+ pathways, which are not identical to those of the well-studied contractile cardiomyocytes. This study provides a base for future investigations into how Ca2+ signals regulate biological activity in human cardiac fibroblasts and cardiac remodeling under pathological conditions. © 2009 Wiley-Liss, Inc.postprin

C-Reactive Protein Promotes Diabetic Kidney Disease in db/db Mice via the CD32b-Smad3-mTOR signaling Pathway

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Two maternal origins of Chinese domestic light-body type goose

China is particularly rich in goose genetic resources. The systemic study of genetic diversity and origin of Chinese indigenous geese will provide important scientific basis for the conservation, utilization of resources and human history. The 521 bp control region (D-loop) of mitochondrial DNA from 13 lightbody type breeds was sequenced. The results showed that in the D-loop region of the 13 gray goose breeds, the content of T, C, A and G nucleotides was 23.8, 29.0, 32.2 and 15.1%, respectively. The average haplotype diversity (Hd) and nucleotide diversity (Pi) of domestic geese were 0.2153 and 0.00046, respectively. The 13 light-body type breeds had bigger nucleotide variance value among populations than the value within populations and all the breeds did not exist population expansion.Shared haplotype analysis and systemic systematic evolution analysis revealed that Chinese lightbody type domestic goose owned two maternal origins. YL goose breed originated from greylag goose (anser anser), and the other 12 light- body type goose breeds originated from swan goose (anser cygnoides)

An invisibility cloak using silver nanowires

In this paper, we use the parameter retrieval method together with an analytical effective medium approach to design a well-performed invisible cloak, which is based on an empirical revised version of the reduced cloak. The designed cloak can be implemented by silver nanowires with elliptical cross-sections embedded in a polymethyl methacrylate host. This cloak is numerically proved to be robust for both the inner hidden object as well as incoming detecting waves, and is much simpler thus easier to manufacture when compared with the earlier proposed one [Nat. Photon. 1, 224 (2007)].Comment: 7 pages, 4 figures, 2 table

Improvement of Myocardial Function Following Catheter-Based Renal Denervation in Heart Failure

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CDAL: A Scalable Scheme for Digital Resource Reorganization

In many circumstances, including e-learning, there is a need to reorganize digital resources, scattered in many places, into a coherently accessible repository. This paper introduces a methodology to do the job efficiently. Specifically, the resources that the scheme needs to handle presents the following challenges, 1) mass, 2) various data types, 3) coming out continuously, i.e., the scheme must support incremental reorganization. 4) usually existing with its own directory structures. We describe the scheme in detail, together with considerations for trade-offs. The following features are highlighted: 1) the reorganization of scattered resources is modeled as a tree-merging process., which results in a good trade-off between efficiency and quality. 2) hierarchical storage arrangement with a uniform index at each level ensures scalability. As an application of the scheme, CDAL (Chinese Digital Assets Library) is briefed, which is a TB-scale archive of digital resources on the Web.Computer Science, Artificial IntelligenceComputer Science, Interdisciplinary ApplicationsComputer Science, Theory & MethodsSCI(E)CPCI-S(ISTP)

Incremental prognostic value of global longitudinal strain in patients with type 2 diabetes mellitus

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Differential-phase-shift quantum key distribution using heralded narrow-band single photons

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Intra-breath arterial oxygen oscillations detected by a fast oxygen sensor in an animal model of acute respiratory distress syndrome

Background There is considerable interest in oxygen partial pressure (Po2) monitoring in physiology, and in tracking PO2 changes dynamically when it varies rapidly. For example, arterial PO2 (PaO2) can vary within the respiratory cycle in cyclical atelectasis (CA), where PaO2 is thought to increase and decrease during inspiration and expiration, respectively. A sensor that detects these PaO2 oscillations could become a useful diagnostic tool of CA during acute respiratory distress syndrome (ARDS). Methods We developed a fibreoptic PO2 sensor (<200 µm diameter), suitable for human use, that has a fast response time, and can measure PO2 continuously in blood. By altering the inspired fraction of oxygen (FIO2) from 21 to 100% in four healthy animal models, we determined the linearity of the sensor's signal over a wide range of PaO2 values in vivo. We also hypothesized that the sensor could measure rapid intra-breath PaO2 oscillations in a large animal model of ARDS. Results In the healthy animal models, PaO2 responses to changes in FIO2 were in agreement with conventional intermittent blood-gas analysis (n=39) for a wide range of PaO2 values, from 10 to 73 kPa. In the animal lavage model of CA, the sensor detected PaO2 oscillations, also at clinically relevant PaO2 levels close to 9 kPa. Conclusions We conclude that these fibreoptic PaO2 sensors have the potential to become a diagnostic tool for CA in ARDS

Predictive value of high-sensitivity troponin-I for future adverse cardiovascular outcome in stable patients with type 2 diabetes mellitus

INTRODUCTION: High-sensitivity cardiac troponin I(hs-TnI) and T levels(hs-TnT) are sensitive biomarkers of cardiomyocyte turnover or necrosis. Prior studies of the predictive role of hs-TnT in type 2 diabetes mellitus(T2DM) patients have yielded conflicting results. This study aimed to determine whether hs-TnI, which is detectable in a higher proportion of normal subjects than hsTnT, is associated with a major adverse cardiovascular event(MACE) in T2DM patients. METHODS AND RESULTS: We compared hs-TnI level in stored serum samples from 276 consecutive patients (mean age 65 +/- 10 years; 57% male) with T2DM with that of 115 age-and sex-matched controls. All T2DM patients were prospectively followed up for at least 4 years for incidence of MACE including heart failure(HF), myocardial infarction(MI) and cardiovascular mortality. At baseline, 274(99%) patients with T2DM had detectable hs-TnI, and 57(21%) had elevated hs-TnI (male: 8.5 ng/L, female: 7.6 ng/L, above the 99th percentile in healthy controls). A total of 43 MACE occurred: HF(n = 18), MI(n = 11) and cardiovascular mortality(n = 14). Kaplan-Meier analysis showed that an elevated hs-TnI was associated with MACE, HF, MI and cardiovascular mortality. Although multivariate analysis revealed that an elevated hs-TnI independently predicted MACE, it had limited sensitivity(62.7%) and positive predictive value(38.5%). Contrary to this, a normal hs-TnI level had an excellent negative predictive value(92.2%) for future MACE in patients with T2DM. CONCLUSION: The present study demonstrates that elevated hs-TnI in patients with T2DM is associated with increased MACE, HF, MI and cardiovascular mortality. Importantly, a normal hs-TnI level has an excellent negative predictive value for future adverse cardiovascular events during long-term follow-up.published_or_final_versio