Search

The aim of the study was to investigate the association of left ventricular diastolic dysfunction (LVDD) with central and peripheral hemodynamics. A total of 1599 community-based senior residents (aged ≥ 65 years) in northern Shanghai, China, were recruited as of August 2015. Echocardiography was performed for each participant using the MyLab30 Gold CV system. According to the recommendations from the American Society of Echocardiography, the ratio of E (peak early diastolic transmitral flow velocity) to E′ (early diastolic lateral mitral annulus velocity) was assessed for the evaluation of LVDD. Central blood pressure (BP) components were measured using the SphygmoCor system. In community older population (72.7 ± 6.01 years), brachial systolic BP (mm Hg) was higher than central systolic BP (141.9 ± 19.5 vs. 130.3 ± 20.1 mm Hg). A total of 214 subjects (13.4%) showed LVDD, and female showed higher prevalence of diastolic dysfunction than male (17.3% vs. 8.4%, P < .01). After adjustment for confounding variables, only central systolic BP, not brachial systolic BP, was significantly associated with E/E′ in the total population. Similar result was found in the subgroup analysis (participants without antihypertensive agents treatment, man, woman). Similar findings were obtained for the pulse pressure (PP) analysis. Within central hemodynamics, only central PP, but not central systolic BP or augmentation pressure, was significantly associated with E/E′ after adjustment. When LVDD was defined by E/E′ and other echocardiographic parameters, our findings remained unaltered in the multivariate logistic regression with similar adjustment in the total population and subgroup analysis. In the Chinese elderly cohort, central hemodynamics, especially central PP, is superior to other BP components in identifying LVDD (NCT02368938). [ABSTRACT FROM AUTHOR]

Abstract: Background: Framingham Study data indicate an incremental risk of cardiovascular death in relation to low exercise capacity in women. The reason for death is still not clear. Methods: QT restitution properties in 80 middle-aged women were investigated to confirm whether the cardiac restitution property was affected by the exercise capacity. Exercise tests were performed according to the Bruce protocol. Seventy cases were divided into the low–exercise capacity group (LEC group) and high–exercise capacity group (HEC group) by median exercise capacities. Sequential QT intervals and their preceding TQ intervals were measured, and the QT restitution curve (QTRC) was constructed. Two exponential equations were used to match the data and calculate the maximum slope (Smax) of QTRC, respectively. Results: With elevation in the exercise level, the women in the LEC group had a higher change rate of QT intervals (41 ± 10 vs 29 ± 3 ms/Met, P = .001) and TQ intervals (46 ± 12 vs 41 ± 7 ms/Met, P = .046); and the ratio of QT interval alterations to TQ interval alterations increased (0.41 ± 0.09 vs 0.36 ± 0.07, P = .003). The Smax of the QTRC in the LEC group was higher than that in the HEC group (1.43 ± 0.44 vs 1.13 ± 0.34, P = .002). There was an inverse relationship between Smax and exercise capacity (r = −0.43, P = .001). Conclusion: Middle-aged women with low exercise capacity have steeper QTRCs than those with high exercise capacity, denoting a more unstable alternation of QT interval with elevation in exercise level. [Copyright &y& Elsevier]

Abstract: Two different complex maps were obtained by generalizing 3x +1 function to the complex plane, and fractal images for these two complex maps were constructed by using escape time, stopping time and total stopping time arithmetic. The dynamics of the generalized 3x +1 function based on the structural characteristics of the fractal images was studied. We found that: (1) the size and structure of the stable regions, stopping regions, total stopping regions, and divergent regions for the three types of fractal images depend on convergence rate of the map on the x and y axes. (2) The black stable regions constructed, respectively, by escape time and total stopping time are almost overlapped, demonstrating that 3x +1 function converged steadily. (3) All of the three fractal images are symmetric to the real axis. The structures on the neighborhood of positive integer number are symmetric to a perpendicular line, which is corresponding to the point or its nearby points on the x axis. And the structures have complicated fractal structure characteristics. These findings indicate that the generalized 3x +1 function on integer number and its neighborhood contains plentiful information in the complex plane. [Copyright &y& Elsevier]

Abstract: We analyze the Julia sets theory for the standard Newton’s method, Halley’s method, and Schröder’s method, study structural characteristics of Julia sets, show the properties and conditions of fixed points for the standard Newton’s method, Halley’s method, and Schröder’s method. We observe the relation between roots of polynomial and Julia sets structure, namely if keeping the relative position of the roots of a polynomial invariable, then the topological structure is also invariable. If there is an extraneous fixed point, then the extraneous fixed point is also invariable. Otherwise, the structures of Julia sets and fixed points would be changed. [Copyright &y& Elsevier]

The metabolic rewiring of cardiomyocytes is a widely accepted hallmark of heart failure (HF). These metabolic changes include a decrease in mitochondrial pyruvate oxidation and an increased export of lactate. We identify the mitochondrial pyruvate carrier (MPC) and the cellular lactate exporter monocarboxylate transporter 4 (MCT4) as pivotal nodes in this metabolic axis. We observed that cardiac assist device-induced myocardial recovery in chronic HF patients was coincident with increased myocardial expression of the MPC. Moreover, the genetic ablation of the MPC in cultured cardiomyocytes and in adult murine hearts was sufficient to induce hypertrophy and HF. Conversely, MPC overexpression attenuated drug-induced hypertrophy in a cell-autonomous manner. We also introduced a novel, highly potent MCT4 inhibitor that mitigated hypertrophy in cultured cardiomyocytes and in mice. Together, we find that alteration of the pyruvate-lactate axis is a fundamental and early feature of cardiac hypertrophy and failure. • Myocardial MPC expression coincides with LVAD-mediated recovery in chronic HF patients • Loss of the MPC in cells or mouse hearts is sufficient to induce hypertrophy and HF • MPC overexpression attenuates drug-induced hypertrophy in a cell-autonomous manner • Inhibition of MCT4 can mitigate hypertrophy in cultured cardiomyocytes and in mice Cluntun et al. identify the pyruvate-lactate axis as a critical node in cardiac homeostasis and health. This axis is maintained by a careful regulation of the disposition of pyruvate, including mitochondrial import and cellular export as lactate. During hypertrophy and heart failure, this balance is disrupted. Regaining this balance by inhibiting MCT4 ameliorated the hypertrophic phenotype. [ABSTRACT FROM AUTHOR]

The massive accumulation of polyethylene terephthalate (PET) in the global ecosystem is a growing environmental crisis. Development of environmental friendly strategies to achieve enzyme–catalyzed PET degradation has attracted tremendous attention. In this study, we demonstrated the synergistic effects of combining a specific PET–degrading enzyme Is PETaseEHA variant from PET–assimilating bacterium Ideonella sakaiensis and a lytic polysaccharide monooxygenase from a white–rot fungus Pycnoporus coccineus (Pc AA14A) in PET degradation. We found that the presence of Pc AA14A alone did not result in PET hydrolysis, but its presence could stimulate Is PETaseEHA–mediated hydrolytic efficiency by up to 1.3-fold. Notably, the stimulatory effects of Pc AA14A on Is PETaseEHA–catalyzed PET hydrolysis were found to be independent of monooxygenase activity. Dose–effects of Is PETaseEHA and Pc AA14A on PET hydrolysis were observed, with the optimal concentrations being determined to 25 μg/mL and 0.25 μg/mL, respectively. In the 5-day PET hydrolysis experiment, 1097 μM hydrolysis products were produced by adding the optimized concentrations of Is PETaseEHA and Pc AA14A, which was 27.7% higher than those were produced by Is PETaseEHA alone. Our study reports the first time that Pc AA14A could stimulate the Is PETaseEHA–mediated PET hydrolysis through a monooxygenase activity independent manner. [ABSTRACT FROM AUTHOR]

Alanine and proline-rich protein (Apa) is a secreted antigen of Mycobacterium spp. which involves in stimulating immune responses and adhering to host cells by binding to fibronectin (Fn). Here, we report the crystal structure of Apa from Mycobacterium tuberculosis (Mtb) and its Fn-binding characteristics. The crystal structure of Mtb Apa was determined at resolutions of 1.54 Å. The dissociation constants (K D) of Apa and individual modules of Fn were determined by surface plasmon resonance and enzyme-linked immunosorbent assay. Site-directed mutagenesis was performed to investigate the putative Fn-binding motif of Apa. Mtb Apa folds into a large seven-stranded anti-parallel β-sheet which is flanked by three α-helices. The binding affinity of Mtb Apa to individual Fn modules was assessed and the results indicated that the Mtb Apa binds to FnIII-4 and FnIII-5 of Fn CBD segment. Notably, structure analysis suggested that the previously proposed Fn-binding motif 258RWFV261 is buried within the protein and may not be accessible to the binding counterpart. The structural and Fn-binding characteristics we reported here provide molecular insights into the multifunctional protein Mtb Apa. FnIII-4 and FnIII-5 of CBD are the only two modules contributing to Apa-Fn interaction. This is the first study to report the structure and Fn-binding characteristics of mycobacterial Apa. Since Apa plays a central role in stimulating immune responses and host cells adhesion, these results are of great importance in understanding the pathogenesis of mycobacterium. This information shall provide a guidance for the development of anti-mycobacteria regimen. Unlabelled Image • Apa folds into a seven-stranded anti-parallel β-sheet flanked by three α-helices. • Apa binds to fibronectin with a dissociation constant (K D) of 0.58 ± 0.06 μM. • FnIII-4 and FnIII-5 of cell-binding domain contribute to Apa-Fn interaction. • RWFV motif of Apa did not involve in Apa-Fn binding. [ABSTRACT FROM AUTHOR]

Pseudomonas syringae pv. syringae van Hall CFCC 1336 ( Pss 1336) is the causal agent of bacterial disease of stone fruit trees, and also able to elicit hypersensitive response (HR) in non-host tobacco. It is known that this pathogen uses PCS-pathway to synthesize phosphatidylcholine (PC), and mutation of the pcs gene abolishes bacterial PC synthesis. Previous study also found that the 1336 pcs − mutant lacking PC in its membrane phospholipids was unable to secrete HrpZ harpin and elicit HR in non-host plants. In this study, we further analyzed virulence of lipodepsipeptide phytoxins of Pss 1336 wild type ( pcs + ), the 1336RM ( pcs −/+) and the 1336 pcs − mutant, and found that the 1336 pcs− mutant was unable to cause necrosis of Chinese date fruits and inhibit fungal growth. HPLC analysis also showed that the 1336 pcs− mutant markedly reduced its secretion of lipodepsipeptide phytoxins. Analysis of semi-quantitative RT-PCR revealed that PC presence or absence did not affect gene expressions of SyrD, PseABC and PseEF efflux systems at transcriptional level. However, western blotting assays found that PseE and PseF present only in the cytoplasmic fractions but undetectable in the membrane extract of the 1336 pcs− mutant. PC absence obviously interrupted the translocation of two membrane-associated proteins PseE and PseF from cytoplasm to cell membranes to form an intact PseEF efflux system in bacterial membranes. Failure to form PseEF efflux system could be a major factor for less lipopeptide-phytoxin secretion. Our results demonstrate that PC in bacterial membrane phospholipids plays an important role in maintaining physiological functions of PseEF efflux system. [ABSTRACT FROM AUTHOR]