Loss of function of hNav1.5 by a ZASP1 mutation associated with intraventricular conduction disturbances in left ventricular noncompaction

BACKGROUND: Defects of cytoarchitectural proteins can cause left ventricular noncompaction, which is often associated with conduction system diseases. We have previously identified a p.D117N mutation in the LIM domain-binding protein 3-encoding Z-band alternatively spliced PDZ motif gene (ZASP) in a patient with left ventricular noncompaction and conduction disturbances. We sought to investigate the role of p.D117N mutation in the LBD3 NM_001080114.1 isoform (ZASP1-D117N) for the regulation of cardiac sodium channel (Na(v)1.5) that plays an important role in the cardiac conduction system. METHODS AND RESULTS: Effects of ZASP1-wild-type and ZASP1-D117N on Na(v)1.5 were studied in human embryonic kidney-293 cells and neonatal rat cardiomyocytes. Patch-clamp study demonstrated that ZASP1-D117N significantly attenuated I(Na) by 27% in human embryonic kidney-293 cells and by 32% in neonatal rat cardiomyocytes. In addition, ZASP1-D117N rightward shifted the voltage-dependent activation and inactivation in both systems. In silico simulation using Luo-Rudy phase 1 model demonstrated that altered Na(v)1.5 function can reduce cardiac conduction velocity by 28% compared with control. Pull-down assays showed that both wild-type and ZASP1-D117N can complex with Na(v)1.5 and telethonin/T-Cap, which required intact PDZ domains. Immunohistochemical staining in neonatal rat cardiomyocytes demonstrates that ZASP1-D117N did not significantly disturb the Z-line structure. Disruption of cytoskeletal networks with 5-iodonaphthalene-1-sulfonyl homopiperazine and cytochalasin D abolished the effects of ZASP1-D117N on Na(v)1.5. CONCLUSIONS: ZASP1 can form protein complex with telethonin/T-Cap and Na(v)1.5. The left ventricular noncompaction-specific ZASP1 mutation can cause loss of function of Na(v)1.5, without significant alteration of the cytoskeletal protein complex. Our study suggests that electric remodeling can occur in left ventricular noncompaction subject because of a direct effect of mutant ZASP on Na(v)1.5

Parazite fauna of carp (Cyprinus carpio) from the lake Dojran, Macedonia

During the parasitological investigations of fishes from the Lake Dojran (Macedonia), in carp (Cyprinus carpio L. 1758) are found 4 parasite species monogenean trematods Dactylogyrus extensus (on gills) and Eudiplozoon nipponicum (on gills), cestod Bothriocephalus opsariichthydis (in guts) and acantocephalan Acanthocephalus anguillae (in guts). Prevalence of infestation with Dactylogyrus extensus is 31,25%, with Eudiplozoon nipponicum is 30,0% with Bothriocephalus opsariichthydis is 13,33%, and with Acanthocephalus anguillae is the lowest and amounts 6,67%. All monogenean species have expressed pathological influence. During that, Dactylogyrus extensus and Eudiplozoon nipponicum are new species for the parasite fauna of fishes in Macedo nia.U toku parazitoloških istraživanja na ribama iz Dojranskog jezera (Makedonija), kod šarana (Cyprinus carpio L. 1758) su pronađene 4 vrste parazita: monogene trematode Dactylogyrus extensus (na škrgama) i Eudiplozoon nipponicum (na škrgama), cestoda Bothriocephalus opsariichthydis (u crevima) i akantocefala Acanthocephalus anguillae (u crevima). Ekstenzitet infestacije sa Dactylogyrus extensus iznosi 31,25%, sa Eudiplozoon nipponicum iznosi 30,0%, sa Bothriocephalus opsariichthydis iznosi 13,33%, a sa Acanthocephalus anguillae je najniži i iznosi 6,67%. Sve pronađene vrste parazita imaju izraženo patogeno delovanje. Pritom, Dactylogyrus extensus i Eudiplozoon nipponicum su nove vrste za parazitofaunu riba Makedonije.nul

Parazite fauna of carp (Cyprinus carpio) from the lake Dojran, Macedonia

During the parasitological investigations of fishes from the Lake Dojran (Macedonia), in carp (Cyprinus carpio L. 1758) are found 4 parasite species monogenean trematods Dactylogyrus extensus (on gills) and Eudiplozoon nipponicum (on gills), cestod Bothriocephalus opsariichthydis (in guts) and acantocephalan Acanthocephalus anguillae (in guts). Prevalence of infestation with Dactylogyrus extensus is 31,25%, with Eudiplozoon nipponicum is 30,0% with Bothriocephalus opsariichthydis is 13,33%, and with Acanthocephalus anguillae is the lowest and amounts 6,67%. All monogenean species have expressed pathological influence. During that, Dactylogyrus extensus and Eudiplozoon nipponicum are new species for the parasite fauna of fishes in Macedo nia.U toku parazitoloških istraživanja na ribama iz Dojranskog jezera (Makedonija), kod šarana (Cyprinus carpio L. 1758) su pronađene 4 vrste parazita: monogene trematode Dactylogyrus extensus (na škrgama) i Eudiplozoon nipponicum (na škrgama), cestoda Bothriocephalus opsariichthydis (u crevima) i akantocefala Acanthocephalus anguillae (u crevima). Ekstenzitet infestacije sa Dactylogyrus extensus iznosi 31,25%, sa Eudiplozoon nipponicum iznosi 30,0%, sa Bothriocephalus opsariichthydis iznosi 13,33%, a sa Acanthocephalus anguillae je najniži i iznosi 6,67%. Sve pronađene vrste parazita imaju izraženo patogeno delovanje. Pritom, Dactylogyrus extensus i Eudiplozoon nipponicum su nove vrste za parazitofaunu riba Makedonije.nul

Research regarding the replacement of high-nickel heat-treatable alloy steels with boron titanium or boron and titanium microalloyed steels

22.00; Translated from Romanian (Metalurgia (Bucharest) 1985 (9) p. 462-466)SIGLEAvailable from British Library Document Supply Centre- DSC:9022.06(BISI--25722)T / BLDSC - British Library Document Supply CentreGBUnited Kingdo