Nonsyndromic cleft lip with or without a cleft palate (NSCL/P) is among the most common human congenital birth defects and imposes a substantial physical and financial burden on affected individuals. Here, we conduct a case-control-based GWAS followed by two rounds of replication; we include six independent cohorts from China to elucidate the genetic architecture of NSCL/P in Chinese populations. Using this combined analysis, we identify a new locus at 16p13.3 associated with NSCL/P: rs8049367 between CREBBP and ADCY9 (odds ratio ¼ 0.74, P ¼ 8.98 Â 10 À 12 ). We confirm that the reported loci at 1q32.2, 10q25.3, 17p13.1 and 20q12 are also involved in NSCL/P development in Chinese populations. Our results provide additional evidence that the rs2235371-related haplotype at 1q32.2 could play a more important role than the previously identified causal variant rs642961 in Chinese populations. These findings provide information on the genetic basis and mechanisms of NSCL/P.

Purpose This paper aims to examine the mediating role of brand relationship quality in the relationship between brand experience and customer citizenship behavior. Design/methodology/approach Two studies were conducted in China. Data were collected via questionnaire surveys. Structural equation modeling and bootstrapping methods were used for data analyses. Findings Results show that brand relationship quality mediates the effects of the four dimensions of brand experience (i.e. sensory, affective, behavioral and intellectual) on the two aspects of customer citizenship behavior (i.e. toward other customers and toward the organization). In addition, service provider ratings can moderate the effect of brand relationship quality on customer citizenship behavior. Practical implications The findings suggest that marketing or service managers should build high quality of customer–brand relationship to enhance customer citizenship behaviors by providing memorable and pleasurable brand experiences. Brands with high ratings can facilitate the effect of brand relationship quality on customer citizenship behavior. Originality/value This research sheds light on the mediating role of brand relationship quality in the relationship between brand experience and customer citizenship behavior.

BackgroundThe cynomolgus monkey (Macaca fascicularis) has been increasingly used in biomedical research, making knowledge of its blood-based parameters essential to support the selection of healthy subjects and its use in preclinical research. As age and sex affect these blood-based parameters, it is important to establish baseline indices for these parameters on an age and sex basis and determine the effects of age and sex on these indices.MethodsA total of 917 cynomolgus monkeys (374 males and 543 females) were selected and segregated by age (five groups) and sex. A total of 30 hematological and 22 biochemical parameters were measured, and the effects of age and sex were analyzed.ResultsBaseline indices for hematological and biochemical parameters were separately established by age and sex. Significant effects by age, sex, and age-sex interaction were observed in a number of blood parameters. In the 49–60 months and 61–72 months age groups, red blood cell count, hemoglobulin, and hematocrit showed significantly lower values (P<0.01) in females than males. Serum alkaline phosphatase varied with age in both sexes (P<0.01) and was significantly higher in females than males (P<0.05) in the groups aged 13–24 months and 25–36 months; however, in the three groups aged over 25–36 months, serum alkaline phosphatase was significantly lower in females than males (P<0.01). Creatinine concentration increased with age (P<0.01) in all age groups; specifically in the groups aged 49–60 months and 61–72 months, creatinine was significantly higher (P<0.01) in males than females. Total protein and globulin both increased with age (P<0.01).ConclusionThe baseline values of hematological and biochemical parameters reported herein establish reference indices of blood-based parameters in the cynomolgus monkey by age and sex, thereby aiding researchers in selecting healthy subjects and evaluating preclinical studies using this species.

Early in pregnancy, trophoblast invasion into the decidua and inner myometrium is essential for establishment of proper implantation, maternal-fetal exchange, and immunological tolerance of the feto-placental allograft. Unlike villous trophoblasts (VTs), extravillous trophoblasts (EVTs) are unique in their capacity to invade the maternal decidua and myometrium. The largest human microRNA (miRNA) gene cluster, the chromosome 19 miRNA cluster (C19MC), is expressed almost exclusively in the placenta and, rarely, in certain tumors and undifferentiated cells. In the work reported here, we found that the expression of C19MC miRNAs is higher in VTs than in EVTs. Using a bacterial artificial chromosome (BAC)-mediated overexpression of C19MC miRNAs in an EVT-derived cell line, which does not naturally express these miRNAs, we found that C19MC miRNAs selectively attenuate cell migration without affecting cell proliferation or apoptosis. A microarray analysis revealed that C19MC miRNAs regulate target transcripts related to cellular movement. Our data also implicated a specific C19MC member, miR-519d, indirectly regulating the EVT invasive phenotype by targeting CXCL6, NR4A2 and FOXL2 transcripts through a 3'UTR miRNA-responsive element. Together, our data suggest a role for C19MC miRNAs in modulating the migration of EVTs.

MicroRNAs (miRNAs), a class of endogenous small noncoding RNAs in eukaryotes, have been recognized as significant regulators of gene expression through post-transcriptional mechanisms. To date, >2000 miRNAs have been identified in the human genome, and they orchestrate a variety of biological and pathological processes. Disruption of miRNA levels correlates with many diseases, including diabetes mellitus, a complex multifactorial metabolic disorder affecting >400 million people worldwide. miRNAs are involved in the pathogenesis of diabetes mellitus by affecting pancreatic β-cell functions, insulin resistance, or both. In this review, we summarize the investigations of the regulatory roles of important miRNAs in diabetes, as well as the potential of circulating miRNAs as diagnostic markers for diabetes mellitus.

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In vitro fertilization (IVF) therapy is an important treatment for human infertility. However, the methods for clinical IVF have only changed slightly over decades: culture medium is held in oil-covered drops in Petri dishes and manipulation occurs by manual pipetting. Here we report a novel microwell-structured microfluidic device that integrates single oocyte trapping, fertilization and subsequent embryo culture. A microwell array was used to capture and hold individual oocytes during the flow-through process of oocyte and sperm loading, medium substitution and debris cleaning. Different microwell depths were compared by computational modeling and flow washing experiments for their effectiveness in oocyte trapping and debris removal. Fertilization was achieved in the microfluidic devices with similar fertilization rates to standard oil-covered drops in Petri dishes. Embryos could be cultured to blastocyst stages in our devices with developmental status individually monitored and tracked. The results suggest that the microfluidic device may bring several advantages to IVF practices by simplifying oocyte handling and manipulation, allowing rapid and convenient medium changing, and enabling automated tracking of any single embryo development.

MicroRNAs (miRNAs) play important roles in the posttranscriptional regulation of gene expression. Recent evidence has indicated the pathological relevance of miRNA dysregulation in hepatitis virus infection; however, the roles of microRNAs in the regulation of hepatitis B virus (HBV) expression are still largely unknown. In this study we identified that miR-373 was up-regulated in HBV-infected liver tissues and that the members of the miRs-371-372-373 (miRs-371-3) gene cluster were also significantly co-up-regulated in HBV-producing HepG2.2.15 cells. A positive in vivo association was identified between hepatic HBV DNA levels and the copy number variation of the miRs-371-3 gene cluster. The enhanced expression of miRs-372/373 stimulated the production of HBV proteins and HBV core-associated DNA in HepG2 cells transfected with 1.33HBV. Further, nuclear factor I/B (NFIB) was identified to be a direct functional target of miRs-372/373 by in silico algorithms and this was subsequently confirmed by western blotting and luciferase reporter assays. Knockdown of NFIB by small interfering RNA (siRNA) promoted HBV expression, whereas rescue of NFIB attenuated the stimulation in the 1.33HBV-transfected HepG2 cells. Conclusion: Our study revealed that miRNA (miRs-372/373) can promote HBV expression through a pathway involving the transcription factor (NFIB). This novel model provides new insights into the molecular basis in HBV and host interaction. (HEPATOLOGY 2011;54:808-819) H epatitis B virus (HBV) is a 3.2 kb circular hepadnavirus that transcribes four major RNA molecules that encode a viral X protein, surface proteins, core proteins, and a reverse transcriptase. The longest 3.5 kb RNA also acts as a pregenomic RNA (pgRNA) intermediate for the reverse replication. Four promoters and two enhancers have been found to regulate the viral gene transcription.1 After HBV infection, most adults produce a self-limited infection with a quick viral clearance; however, others become carriers or develop Abbreviations: CNV, copy number variation; ENI-Cp, enhancer I and core promoter of hepatitis B virus; FFPE, formalin-fixed, paraffin embedded; HBeAg, hepatitis B virus e antigen; HBsAg, hepatitis B virus surface antigen; HBV, hepatitis B virus; miRNA, microRNA; miRs-371-3, miRs-371-372-373; NFIB, nuclear factor I/B; qPCR, quantitative real-time polymerase chain reaction; SAM, significance analysis of microarrays; UTR, untranslated region.From the