Deletion of CXCR4 in cardiomyocytes exacerbates cardiac dysfunction following isoproterenol administration.

Altered alpha- and beta-adrenergic receptor signaling is associated with cardiac hypertrophy and failure. Stromal cell-derived factor-1α (SDF-1α) and its cognate receptor CXCR4 have been reported to mediate cardioprotection after injury through the mobilization of stem cells into injured tissue. However, little is known regarding whether SDF-1/CXCR4 induces acute protection following pathological hypertrophy and if so, by what molecular mechanism. We have previously reported that CXCR4 physically interacts with the beta-2 adrenergic receptor and modulates its downstream signaling. Here we have shown that CXCR4 expression prevents beta-adrenergic receptor-induced hypertrophy. Cardiac beta-adrenergic receptors were stimulated with the implantation of a subcutaneous osmotic pump administrating isoproterenol and CXCR4 expression was selectively abrogated in cardiomyocytes using Cre-loxP-mediated gene recombination. CXCR4 knockout mice showed worsened fractional shortening and ejection fraction. CXCR4 ablation increased susceptibility to isoproterenol-induced heart failure, by upregulating apoptotic markers and reducing mitochondrial function; cardiac function decreases whereas fibrosis increases. In addition, CXCR4 expression was rescued with the use of cardiotropic adeno-associated viral-9 vectors. CXCR4 gene transfer reduced cardiac apoptotic signaling, improved mitochondrial function and resulted in a recovered cardiac function. Our results represent the first evidence that SDF-1/CXCR4 signaling mediates acute cardioprotection through modulating beta-adrenergic receptor signaling in vivo.

Pilot study of a fluidized-pellet-bed technique for simultaneous solid/liquid separation and sludge thickening in a sewage treatment plant.

A fluidized-pellet-bed separator with movable sludge hoppers was applied in pilot scale for the separation and thickening of activated sludge mixture liquid. Under the condition of suspension SS around 4,000 mg/L, polymer (CJX103, cationic, MW 5 x 10(6)) dose at a dry solid ratio of 0.003 and upward flow rate at 5.4 m/hr, the fluidized pellet bed performed solid/liquid separation and sludge thickening well. The SS concentration of the treated water was about 5 mg/L on average and the moisture content of the sludge after screening for 5 min was less than 94%, which is much lower than that after conventional settling and thickening and easy to be finally disposed. At a higher upward flow rate of 7.2 m/hr, similar results could also be obtained but higher polymer dose (solid ratio of 0.004) was required. The morphological characteristics and density-size relationship of the granular particles formed in the fluidized pellet bed were also investigated by image analysis and settling velocity measurement of individual particles. The two-dimensional fractal dimension was evaluated to be 1.6-1.8, showing a good quasi-spherical morphology of the granular particles with their density much higher than the conventional flocs. The results of the pilot study indicate a possible way to innovate the conventional secondary settling and gravitational thickening processes for solid/liquid separation and sludge handling, especially for small scale wastewater treatment plants to reach the goal of space saving and higher treatment efficiency.

[Comparative studies on the repetitive DNA sequences of diploid and triploid forms of Paragonimus westermani by restriction endonuclease and Southern blotting].

Restriction enzyme digestion of total genomic DNA of two chromosomes forms of Paragonimus westermani showed the presence of homologous highly repeated DNA in both diploid and triploid forms. Southern blotting analysis provided further evidence that the distribution of restriction enzyme sites (with 3 enzymes) on repetitive sequence of DNA of both forms were similar. However, with Pstl, Ddel, HaeIII and HpaII, their polymorphism revealed differences which were also found in each form tested separately with the hybridization technique. The present study, at the molecular level, supports the previously reported biological and biochemical results that they might be considered as different isolates or forms. It is suggested that PstI, DdeI, HaeIII and HpaII digestion pattern might be useful to distinguish the diploid from the triploid forms of Paragonimus westermani.