Glycogen synthase kinase 3α and 3β have distinct functions during cardiogenesis of zebrafish embryo

<p>Abstract</p> <p>Background</p> <p>Glycogen synthase kinase 3 (GSK3) encodes a serine/threonine protein kinase, is known to play roles in many biological processes. Two closely related GSK3 isoforms encoded by distinct genes: GSK3α (51 kDa) and GSK3β (47 kDa). In previously studies, most GSK3 inhibitors are not only inhibiting GSK3, but are also affecting many other kinases. In addition, because of highly similarity in amino acid sequence between GSK3α and GSK3β, making it difficult to identify an inhibitor that can be selective against GSK3α or GSK3β. Thus, it is relatively difficult to address the functions of GSK3 isoforms during embryogenesis. At this study, we attempt to specifically inhibit either GSK3α or GSK3β and uncover the isoform-specific roles that GSK3 plays during cardiogenesis.</p> <p>Results</p> <p>We blocked <it>gsk3α </it>and <it>gsk3β </it>translations by injection of morpholino antisense oligonucleotides (MO). Both <it>gsk3α</it>- and <it>gsk3β</it>-MO-injected embryos displayed similar morphological defects, with a thin, string-like shaped heart and pericardial edema at 72 hours post-fertilization. However, when detailed analysis of the <it>gsk3α</it>- and <it>gsk3β</it>-MO-induced heart defects, we found that the reduced number of cardiomyocytes in <it>gsk3α </it>morphants during the heart-ring stage was due to apoptosis. On the contrary, <it>gsk3β </it>morphants did not exhibit significant apoptosis in the cardiomyocytes, and the heart developed normally during the heart-ring stage. Later, however, the heart positioning was severely disrupted in <it>gsk3β </it>morphants. <it>bmp4 </it>expression in <it>gsk3β </it>morphants was up-regulated and disrupted the asymmetry pattern in the heart. The cardiac valve defects in <it>gsk3β </it>morphants were similar to those observed in <it>axin1 </it>and <it>apc</it>^{<it>mcr </it>}mutants, suggesting that GSK3β might play a role in cardiac valve development through the Wnt/β-catenin pathway. Finally, the phenotypes of <it>gsk3α </it>mutant embryos cannot be rescued by <it>gsk3β </it>mRNA, and vice versa, demonstrating that GSK3α and GSK3β are not functionally redundant.</p> <p>Conclusion</p> <p>We conclude that (1) GSK3α, but not GSK3β, is necessary in cardiomyocyte survival; (2) the GSK3β plays important roles in modulating the left-right asymmetry and affecting heart positioning; and (3) GSK3α and GSK3β play distinct roles during zebrafish cardiogenesis.</p

Elderly People\u27s Social Support and Walking Space by Space-time Path：A Case Study of Taipei Xinyi District

Due to the trend of global aging, issues of the elderly should be paid attention to. In January 2014, the elderly accounted for 11.57% of the population in Taiwan. By around 2017 Taiwan will become an Aged society. In order to provide seniors with a healthy and better life, the living environment and space arrangements will be important factors in the urban city. This study statistically assesses the walking space and the living path of elders by out-door activity type, walking range time and walking environment to understand the activity conditions and types of elders in Xin-Yu district, referencing the World Health Organisation’s recommendations on “Global Age-friendly Cities: Outdoor Spaces and Buildings”. This study investigates 22 seniors in the Xin-Yi district using the Global Positioning System, observations and deep interviews to explore the influencing factors, such as activity type, activity item, space equipment and walking environment of elders, to propose the requirements of walking spaces and suggestions for improvement in Xin-Yi district. The result found that the condition of elders’ activity and societal support demanded the utilisation of activity environments and walking spaces for social-type elders, including public social spaces, safe road crossings, bus stops and bus information support; for selection-type elders, demand was identified for communication chairs at shopping arcades and diverse sports facilities; and for essential-type elders, demands were on participatory open space and cooperative group facilities. Through the setting and improving of the urban resources above, social support for elders can be improved through the provision of friendly and healthy urban city activity spaces

Association of Chinese Herbal Medicines Use with Development of Chronic Obstructive Pulmonary Disease Among Patients with Rheumatoid Arthritis: A Population-Based Cohort Study

Purpose: Rheumatoid arthritis (RA) patients appear to report a higher risk of chronic obstructive pulmonary disease (COPD). While Chinese herbal medicine (CHMs) is proven to lower COPD risk, the scientific evidence regarding its effect in relation to COPD onset among them is limited. This longitudinal cohort study aimed to determine the relationship between CHMs use and the COPD risk in RA patients. Methods: Using the nationwide claim data, 8349 patients newly diagnosed with RA and simultaneously free of COPD between 1998 and 2010 were eligible for enrollment. From this sample, we enrolled 3360 CHMs users and 3360 non-CHMs users, randomly selected using propensity scores matching from the remaining cases. They were followed until the end of 2012 to record COPD incidence. The hazard ratio (HR) of COPD with regard to CHMs use was estimated by the Cox proportional hazards regression model. Results: In the follow-up period, 136 CHMs users and 202 non-CHMs users developed COPD, representing incidence rates of 5.16 and 7.66, respectively, per 1000 person-years. CHMs use was associated with a 32% lower subsequent risk of COPD (adjusted HR: 0.68, 95% Confidence Interval: 0.54–0.84). Eight commonly prescribed CHMs were discovered to be associated with lower COPD risk: Yan Hu Suo, Sānɡ Zhī, Dang Shen, Huang Qin, Jia-Wei-Xiao-Yao-San, Shu-Jing-Huo-Xue-Tang, Du-Huo-Ji-Sheng-Tang and Ge-Gen-Tang. Conclusion: A significant association of CHMs use with a lower risk of COPD onset in RA patients was found, suggesting that CHMs could be integrated into conventional therapy to reduce COPD risk

De novo duplication of Xq22.1→q24 with a disruption of the NXF gene cluster in a mentally retarded woman with short stature and premature ovarian failure

AbstractObjectiveTo present molecular cytogenetic characterization of a de novo duplication of Xq22.1→q24 in a mentally retarded woman with short stature and premature ovarian failure.Materials and MethodsA 19-year-old woman presented with psychomotor retardation, developmental delay, mental retardation, short stature, low body weight, general muscle hypotonia, distal muscle hypotrophy of the lower extremities, elongated digits, scanty pubic and axillary hair, hypoplastic external female genitalia, and secondary amenorrhea but no clinical features of Pelizaeus-Merzbacher disease. Conventional cytogenetic analysis revealed a karyotype of 46,X,dup(X)(q22.1q24). Fluorescence in situ hybridization determined a direct duplication with a linear tandem orientation. Array comparative genomic hybridization demonstrated partial trisomy Xq [arr cgh Xq22.1q24 (101,490,234–119,070,188 bp)×3] with a 17.6-Mb duplication.ResultsThe duplicated region contained NXF2B, NXF4, NXF3, PLP1, and PGRMC1 genes. There was a disruption of the NXF gene cluster of Xcen-NXF5-NXF2-NXF2B-NXF4-NXF3-Xqter.ConclusionA duplication of Xq22.1→q24 with a disruption of the NXF gene cluster in female patients can be associated with clinical manifestations of mental retardation in addition to short stature and premature ovarian failure

Prenatal Diagnosis and Molecular Cytogenetic Characterization of a Small Supernumerary Marker Chromosome Derived from Chromosome 18 and Associated With a Reciprocal Translocation Involving Chromosomes 17 And 18

SummaryObjectivePrenatal diagnosis of small supernumerary marker chromosomes (sSMC) gives rise to difficulties in genetic counseling, and requires molecular cytogenetic technologies such as spectral karyotyping, fluorescence in situ hybridization, multicolor-fluorescence in situ hybridization, or array-comparative genomic hybridization to identify the nature of the aberrant chromosome. We report such a case associated with a reciprocal translocation.Materials, Methods and ResultsA 36-year-old woman, gravida 7, para 1, abortus 5, was referred for amniocentesis at 18 weeks of gestation because of advanced maternal age. Amniocentesis revealed a reciprocal translocation between chromosomes 17q and 18q and an sSMC. The karyotype was 47,XY,t(17;18)(q11.1;q11.2), +mar. Chromosome preparations from blood lymphocytes revealed that she had the same reciprocal translocation and sSMC. Spectral karyotyping showed that the sSMC was derived from the centromeric region of chromosome 18, and there was a reciprocal translocation between chromosomes 17 and 18. The derivative chromosome 17 had positive 17p terminal (17pTEL) and chromosome 17 centromeric (cep17) signals but did not have a positive chromosome 18 centromeric signal (cep18). The derivative chromosome 18 had positive 18p terminal (18pTEL), chromosome 18 centromeric (cep18) and cep17 signals. The sSMC had only a positive cep18 signal. These findings suggested that a breakpoint occurred at 17q11.1 and another at 18q11.2 during translocation, and the sSMC originated from chromosome 18. The karyotype of the fetus was thus 47,XY,t(17;18)(q11.1;q11.2), +mar.ish der(17)t(17;18)(q11.1;q11.2)(17pTEL+,D17Z1+),der(18)t(17;18)(q11.1;q11.2)(18pTEL+,D18Z1+,D17Z1+), + der(18)(D18Z1+). Oligonucleotide-based array comparative genomic hybridization demonstrated no gain or loss of the gene dosage on chromosomes 17 and 18.ConclusionOur case adds to the reported cases of sSMCs derived from the centromeric region of chromosome 18 without phenotypic consequences

Zebrafish Cyclin-Dependent Protein Kinase–Like 1 (zcdkl1): Identification and Functional Characterization

The cyclin-dependent protein kinase family regulates a wide range of cellular functions such as cell cycle progression, differentiation, and apoptosis. In this study, we identified a zebrafish cyclin-dependent protein kinase-like 1 protein called zebrafish cdkl1 (zcdkl1), which shared a high degree of homology and conserved synteny with mammalian orthologs. zcdkl1 exhibited abilities for phosphorylation of myelin basic protein and histone H1. RT-PCR analysis revealed that zcdkl1 was expressed starting from fertilization and continuing thereafter. In adult tissues, zcdkl1 was predominantly detected in brain, ovary, and testis, and was expressed at low levels in other tissues. At 50% epiboly stage, zcdkl1 was widely expressed. At 12 to 48 h post-fertilization, zcdkl1 was predominantly expressed in the hypochord, the medial and lateral floor plate, and the pronephric duct. Interference of zcdkl1 expression resulted in abnormalities, such as brain and eye malformation, pericardial edema, and body axis curvature. Disruption of zcdkl1 reduced neurogenin-1 in the brain and sonic hedgehog expression in the floor plate region. These deformities were apparently rescued by co-injection of zcdkl1 mRNA. Findings of this study indicate that zcdkl1 plays an essential role in zebrafish development

Pro-angiogenic effects of chalcone derivatives in zebrafish embryos in vivo

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