The role of cardiac troponin T quantity and function in cardiac development and dilated cardiomyopathy

Background: Hypertrophic (HCM) and dilated (DCM) cardiomyopathies results from sarcomeric protein mutations, including cardiac troponin T (cTnT, TNNT2). We determined whether TNNT2 mutations cause cardiomyopathies by altering cTnT function or quantity; whether the severity of DCM is related to the ratio of mutant to wildtype cTnT; whether Ca2+ desensitization occurs in DCM; and whether absence of cTnT impairs early embryonic cardiogenesis. Methods and Findings: We ablated Tnnt2 to produce heterozygous Tnnt2+/ mice, and crossbreeding produced homozygous null Tnnt2-/-embryos. We also generated transgenic mice overexpressing wildtype (TGWT) or DCM mutant (TGK210Δ) Tnnt2. Crossbreeding produced mice lacking one allele of Tnnt2, but carrying wildtype (Tnnt2+/-/TGWT) or mutant (Tnnt2+/-/TGK210Δ) transgenes. Tnnt2+/-mice relative to wildtype had significantly reduced transcript (0.82 ± 0.06 [SD] vs. 1.00 ± 0.12 arbitrary units; p = 0.025), but not protein (1.01 ± 0.20 vs. 1.00 ± 0.13 arbitrary units; p = 0.44). Tnnt2+/-mice had normal hearts (histology, mass, left ventricular end diastolic diameter [LVEDD], fractional shortening [FS]). Moreover, whereas Tnnt2+/-/ TGK210Δ mice had severe DCM, TGK210Δ mice had only mild DCM (FS 18 ± 4 vs. 29 ± 7%; p < 0.01). The difference in severity of DCM may be attributable to a greater ratio of mutant to wildtype Tnnt2 transcript in Tnnt2+/-/TGK210Δ relative to TGK210Δ mice (2.42±0.08, p = 0.03). Tnnt2+/-/TGK210Δ muscle showed Ca2+ desensitization (pCa50 = 5.34 ± 0.08 vs. 5.58 ± 0.03 at sarcomere length 1.9 μm. p<0.01), but no difference in maximum force generation. Day 9.5 Tnnt2-/-embryos had normally looped hearts, but thin ventricular walls, large pericardial effusions, noncontractile hearts, and severely disorganized sarcomeres. Conclusions: Absence of one Tnnt2 allele leads to a mild deficit in transcript but not protein, leading to a normal cardiac phenotype. DCM results from abnormal function of a mutant protein, which is associated with myocyte Ca2+ desensitization. The severity of DCM depends on the ratio of mutant to wildtype Tnnt2 transcript. cTnT is essential for sarcomere formation, but normal embryonic heart looping occurs without contractile activity. © 2008 Ahmad et al

One-step synthesis of high purity silicon carbide powder

Silicon carbide (Sic) powder was synthesized from liquid silicon in one step at the presence of a catalyst bar consisting of silica and carbon. The silicon carbide powders were formed by the carbothermal reaction between liquid silicon and gaseous CO, and the average particle size (D-50) of the as-prepared silicon carbide powder was 0.41 mu m. The powder was characterized by XRD, SEM, particle size analysis and elemental analysis. The mechanism for the formation of the silicon carbide powder was discussed

Compensatory density feedback of Oncomelania hupensis populations in two different environmental settings in China

BACKGROUND: The most recent strategy for schistosomiasis control in the People's Republic of China aims to reduce the likelihood of environmental contamination of schistosome eggs. Despite considerable progress, it is believed that achievements would be further consolidated with additional intermediate host snail control measures. We provide an empirical framework for discerning the relative contribution of intrinsic effects (density feedback) from other extrinsic drivers of snail population dynamics. METHODS: We set up experiments in two study locations to collect reproduction data of Oncomelania hupensis, the intermediate host snail of Schistosoma japonicum. We applied a set of four population dynamic models that have been widely used to study phenomenological time-series data to examine the properties of demographic density feedback patterns from abundance data. We also contrasted the obtained results with the component feedback of density on survival rate to determine whether adult survival was the principal driver of the demographic feedback observed. RESULTS: Demographic density feedback models (Ricker- and Gompertz-logistic) accounted for <99% of Akaike's information criterion model weight, with the Gompertz ranking highest in all O. hupensis population groups. We found some evidence for stronger compensatory feedback in the O. hupensis population from Sichuan compared to a Jiangsu population. Survival rates revealed strong component feedback, but the log-linear relationships (i.e. Gompertz) had less support in the demographic feedback analysis. CONCLUSIONS: Our findings indicate that integrated schistosomiasis control measures must continue to reduce parasite abundance further because intermediate host snail populations tend to grow exponentially at low densities, especially O. hupensis populations in mountainous regions. We conclude that density feedback in adult survival is the principal component contribution to the demographic phenomenon observed in the population fitness (r)-abundance relationship

Overexpression of CDC2/CyclinB1 in gliomas, and CDC2 depletion inhibits proliferation of human glioma cells in vitro and in vivo

<p>Abstract</p> <p>Background</p> <p>Gliomas are the most common and aggressive primary brain tumors for which unfortunately no effective treatment modalities exist despite advances in molecular biology as the knowledge base to unravel the extremely complex molecular mechanisms of tumorigenesis is limited. In this study an attempt has been made to understand the molecular pathological basis of tumorigenesis which led to an identification of an oncogene, CDC2, and an epigenetic strategy has been evaluated to control the tumorigensis by downregulating this oncogene.</p> <p>Methods</p> <p>Tissue microarrays were utilized to investigate the expression of genes in a large number of tumor samples and to identify overexpressed genes which could be potentially causing tumorigenesis. Retroviral vectors expressing short hairpin RNAs (shRNAs) targeted against CDC2 were designed and transducted into human glioma cell line ex vivo in order to downregulate the expression of CDC2. Real-Time PCR was used to determine the level of CDC2 mRNA. Western Blotting was used to determine the level of expression of CDC2 protein as measure to quantify down regulation of CDC2 expression along with use of flow cytometry to investigate effect of shRNAs on cell cycles and detection of apoptosis. Following ex vivo study, viral particles containing small interfering RNA for CDC2 were subsequently injected into xenogeneic graft tumor of nude mice and the weight of human glioma xenografts, survival and resulting phenotypic changes of target gene were investigated.</p> <p>Results</p> <p>Human glioma tissue microarrays indicated the positive expression rates of CDC2/CyclinB1 with a positive correlation with pathologic grades (r = 0.982, r = 0.959, respectively). Retroviral vectors expressing short hairpin RNAs (shRNAs) against CDC2 caused efficient deletion of CDC2, cellular G2/M arrest concluding in apoptosis and inhibition of proliferation in human glioma cells U251 and SHG-44 cell lines ex vivo. And the viral particles containing small interfering RNA for CDC2 were subsequently injected into subcutaneous and intracranial xenogeneic graft tuomrs of nude mice. For subcutaneous tumors, injection of CDC2-shRNA retroviruses significantly decreased tumor weight and volume compared with control. Immunohistochemistry indicated that CDC2 are negative and TUNEL are positive in tumors treated with recombinant retrovirus. For mice implanted with intracranial gliomas, treatment of CDC2-shRNA retroviruses increased survival times compared with control.</p> <p>Conclusion</p> <p>CDC2 gene plays an important role in the proliferation of human gliomas. Downregulation of CDC2 could potentialy inhibit human gliomas cells growth ex vivo and in vivo. From these results, it was suggested that CDC2 might be a potential target on gene therapy of human gliomas.</p

Anchoring ultrafine metallic and oxidized Pt nanoclusters on yolk-shell TiO2 for unprecedentedly high photocatalytic hydrogen production

We demonstrate an alkali modification process to produce highly dispersed ultrafine Pt nanoclusters with metallic Pt$^0$ and oxidized Pt$^{2+}$ species as co-catalyst anchored on nanosheet-constructed yolk-shell TiO$_2$ (NYTiO$_2$-Pt) acting as light harvesting reactor for highly efficient photocatalytic H$_2$ production. Benefiting from the high surface area, highly dispersed ultrafine Pt nanoclusters (~0.6 nm) with Pt$^0$ and Pt$^{2+}$ species and special nanosheet-constructed yolk-shell structure, this novel light harvesting reactor exhibits excellent performance for photocatalytic H$_2$ production. The NYTiO$_2$-Pt-0.5 (0.188 wt% Pt) demonstrates an unprecedentedly high H$_2$ evolution rate of 20.88 mmol h$^{−1}$ g$^{−1}$ with excellent photocatalytic stability, which is 87 times than that of NYTiO$_2$-Pt-3.0 (0.24 mmol h$^{−1}$ g$^{−1}$, 1.88 wt% Pt), and also much higher than those of other TiO$_2$ nanostructures with the same Pt content. Such H$_2$ evolution rate is the highest reported for photocatalytic H$_2$ production with such a low Pt content under simulated solar light. Our strategy here suggests that via alkali modifying the photocatalysts, we can not only enhance the H$_2$ production for solar energy conversion but also significantly decrease the noble metal content for cost saving.B. L. Su acknowledges the Chinese Central Government for an “Expert of the State” position in the Program of the “Thousand Talents” and a Life Membership at the Clare Hall, Cambridge and the financial support of the Department of Chemistry, University of Cambridge. Y. Li acknowledges Hubei Provincial Department of Education for the “Chutian Scholar” program. T. H. acknowledges support from the Royal Academy of Engineering through a Research Fellowship and an EPSRC Impact acceleration grant. This work is supported by the National Key Research and Development Program of China (2016YFA0202602), Program for Changjiang Scholars and Innovative Research Team in University (IRT_15R52), International Science & Technology Cooperation Program of China (2015DFE52870), National Natural Science Foundation of China (51302204 and 51502225) and the Fundamental Research Funds for the Central Universities (WUT: 2016 029)

A strategy for emergency treatment of Schistosoma japonicum-infested water

<p>Abstract</p> <p>Background</p> <p>Schistosomiasis japonica, caused by contact with <it>Schistosoma japonicum </it>cercaria-infested water when washing, bathing or production, remains a major public-health concern in China. The purpose of the present study was to investigate the effect of a suspension concentrate of niclosamide (SCN) on killing cercaria of <it>S. japonicum </it>that float on the water surface, and its toxicity to fish, so as to establish an emergency-treatment intervention for rapidly killing cercaria and eliminating water infectivity.</p> <p>Results</p> <p>At 30 min after spraying 100 mg/L SCN, with niclosamide dosages of 0.01, 0.02, 0.03, 0.04 g/m², the water infectivity reduced significantly and no infectivity was found at 60 min after spraying SCN. The surface of static water was sprayed with 100 mg/L SCN, the peak concentration was found at 0 min, and the solution diffused to site with a water depth of 10 cm after 10 min. 30 min later, SCN diffused to the whole water body, and distributed evenly. After spraying 100 mg/L SCN onto the surface of the water with a volume of(3.14 × 20²×50)cm³, with niclosamide dosages of 0.02 g/m², 96 h later, no death of zebra fish was observed.</p> <p>Conclusions</p> <p>By spraying 100 mg/L SCN, with a niclosamide dosage of 0.02 g/m²onto the surface of <it>S. japonicum</it>-infested water, infectivity of the water can be eliminated after 30-60 min, and there is no evident toxicity to fish. This cercaria-killing method, as an emergency-treatment intervention for infested water, can be applied in those forecasting and early warning systems for schistosomiasis.</p

Structure of hadron resonances with a nearby zero of the amplitude

We discuss the relation between the analytic structure of the scattering amplitude and the origin of an eigenstate represented by a pole of the amplitude.If the eigenstate is not dynamically generated by the interaction in the channel of interest, the residue of the pole vanishes in the zero coupling limit. Based on the topological nature of the phase of the scattering amplitude, we show that the pole must encounter with the Castillejo-Dalitz-Dyson (CDD) zero in this limit. It is concluded that the dynamical component of the eigenstate is small if a CDD zero exists near the eigenstate pole. We show that the line shape of the resonance is distorted from the Breit-Wigner form as an observable consequence of the nearby CDD zero. Finally, studying the positions of poles and CDD zeros of the KbarN-piSigma amplitude, we discuss the origin of the eigenstates in the Lambda(1405) region.Comment: 7 pages, 3 figures, v2: published versio

Toward Sustainable and Comprehensive Control of Schistosomiasis in China: Lessons from Sichuan

Triggered by a fascinating publication in the New England Journal of Medicine detailing China's new multi-pronged strategy to control and eventually interrupt the transmission of Schistosoma japonicum, this PLoS Neglected Tropical Diseases Debate critically examines the generalizability and financial costs of the studies presented from the marshlands of the lake region. Edmund Seto from the University of California and colleagues emphasize that the epidemiology and control of schistosomiasis varies according to the social-ecological context. They conjecture that the successful intervention packages piloted in the lake region is not fully fit for the hilly and mountainous environments in Sichuan and Yunnan provinces, and hence call for more flexible, setting-specific, and less expensive control strategies. In response, Xiao-Nong Zhou from the National Institute of Parasitic Diseases at the Chinese Center of Disease Control and Prevention and colleagues explain the steps from designing pilot studies to the articulation and implementation of a new national control strategy through a careful process of scaling-up and adaptations. Finally, the two opponents converge. The need for integrated, intersectoral, and setting-specific control measures is stressed, supported by rigorous surveillance and continuous research. Experiences and lessons from China are important for shaping the schistosomiasis elimination agenda

Surveillance of Schistosoma japonicum Infection in Domestic Ruminants in the Dongting Lake Region, Hunan Province, China

Background: Schistosomiasis japonica is prevalent in Asian countries and it remains a major public health problem in China. The major endemic foci are the marsh and lake regions of southern China, particularly the Dongting Lake region bordering Hunan and Hubei provinces, and the Poyang Lake region in Jiangxi province. Domestic ruminants, especially bovines, have long been considered to play a major role in the transmission of Schistosoma japonicum to humans. Methods and Findings: A miracidial hatching technique was used to investigate the prevalence of S. japonicum infections in domestic ruminants and field feces collected from two towns located to the south and east of Dongting Lake, Hunan province, between 2005 and 2010. The overall prevalence of infection was not significantly reduced from 4.93 % in 2005 to 3.64 % in 2008, after which it was maintained at this level. Bovines comprised 23.5–58.2 % of the total infected ruminants, while goats comprised 41.8–76.5%. Infection rates in cattle and goats were significantly higher than those found in buffalo in most study years. The prevalence in buffalo younger than three years was significantly higher than that in those aged over three years. All the positive field samples of feces were derived from bovines in Nandashan. In Matang Town, 61.22 % of the positive field feces were from bovines, while the rest were from goats. The positive rates for field feces were approximately the same in April and November/October. Conclusions: The present study found that bovines and goats are major sources of S. japonicum infection in the Dongtin