Slc39a7/zip7 Plays a Critical Role in Development and Zinc Homeostasis in Zebrafish

Background: Slc39a7/Zip7, also known as Ke4, is a member of solute carrier family 39 (Slc39a) and plays a critical role in regulating cell growth and death. Because the function of Zip7 in vivo was unclear, the present study investigated the function of zip7 in vertebrate development and zinc metabolism using zebrafish as a model organism. Principal Finding: Using real-time PCR to determine the gene expression pattern of zip7 during zebrafish development, we found that zip7 mRNA is expressed throughout embryonic development and into maturity. Interestingly, whole mount in situ hybridization revealed that while zip7 mRNA is ubiquitously expressed until 12 hours post-fertilization (hpf); at 24 hpf and beyond, zip7 mRNA was specifically detected only in eyes. Morpholino-antisense (MO) gene knockdown assay revealed that downregulation of zip7 expression resulted in several morphological defects in zebrafish including decreased head size, smaller eyes, shorter palates, and shorter and curved spinal cords. Analysis by synchrotron radiation X-ray fluorescence (SR-XRF) showed reduced concentrations of zinc in brain, eyes, and gills of zip7-MO-injected embryos. Furthermore, incubation of the zip7 knockdown embryos in a zinc-supplemented solution was able to rescue the MO-induced morphological defects. Significance: Our data suggest that zip7 is required for eye, brain, and skeleton formation during early embryonic development in zebrafish. Moreover, zinc supplementation can partially rescue defects resulting from zip7 gene knockdown. Taken together, our data provide critical insight into a novel function of zip7 in development and zinc homeostasis in vivo in zebrafish

Analysis on protein structures using statistical and bioinformatical methods

This PhD dissertation mainly focuses on the statistical analysis for the protein structure data. The first research project focuses on data mining and prediction for side chain orientation in protein structure. Through this study, we find that the general side chain orientation can be viewed as a manifestation of hydrophobic force. Along with this study, we also developed the software for visualizing the general side chain vector and applied statistical machine learning methods to fit several models for predicting general side chain orientation. In the second project, we studied the motion of partially assembled ribosome 30S subunit using the coarse-grained elastic network model. Besides our studies on ribosome motion, using 176 NMR structure ensembles, we applied principal component analysis to analyze the essential conformational changes to validate the motion generated by the elastic network model. Furthermore, we also studied the effects of different superposition methods on the correspondence between the conformational changes and the simulated motion. Principal component shaving method is often used to cluster gene with the similar gene expression pattern in micro-array data analysis. In the third research project, we applied this method to cluster the structures within a NMR structure ensemble and demonstrated that this method could be used to find the similar structure cluster

High glucose represses β-klotho expression and impairs fibroblast growth factor 21 action in mouse pancreatic islets: involvement of peroxisome proliferator-activated receptor γ signaling

Circulating fibroblast growth factor 21 (FGF21) levels are elevated in diabetic subjects and correlate directly with abnormal glucose metabolism, while pharmacologically administered FGF21 can ameliorate hyperglycemia. The pancreatic islet is an FGF21 target, yet the actions of FGF21 in the islet under normal and diabetic conditions are not fully understood. This study investigated the effects of high glucose on islet FGF21 actions in a diabetic mouse model by investigating db/db mouse islet responses to exogenous FGF21, the direct effects of glucose on FGF21 signaling, and the involvement of peroxisome proliferator-activated receptor γ (PPARγ) in FGF21 pathway activation. Results showed that both adult db/db mouse islets and normal islets treated with high glucose ex vivo displayed reduced β-klotho expression, resistance to FGF21, and decreased PPARγ expression. Rosiglitazone, an antidiabetic PPARγ ligand, ameliorated these effects. Our data indicate that hyperglycemia in type 2 diabetes mellitus may lead to FGF21 resistance in pancreatic islets, probably through reduction of PPARγ expression, which provides a novel mechanism for glucose-mediated islet dysfunction

Development of College English Teaching in China under Needs Analysis

In China, College English is not only a language course that provides basic knowledge about English, but also a capacity enhancement course that helps students to broaden their horizons and learn about different cultures in the world. The development of College English Teaching is a complex systematic program in which several elements must be considered, i.e. needs analysis, teaching objectives, language testing, material development, language teaching, program evaluation and follow-up courses consisting of ESP and Bilingual education. Among all the elements, “needs analysis” is the logical first step and the important base of a sound College English curriculum design. That is to say, needs analysis is the foundation of the development of College English Teaching.Key words: College English Teaching; Needs analysis; Curriculum desig

Servant leadership and employee voice behavior: a cross-level investigation in China

This study tested the influence and mechanisms of servant leadership on voice behavior, including the mediating role of psychological safety, and the moderating role of supervisor-subordinate Guanxi. Data were collected from 430 civil servants and their immediate supervisors in Changsha, China. Cross-Level investigation revealed that servant leadership had a significant influence on voice behavior, psychological safety mediated the relationship between servant leadership and voice behavior, while supervisor-subordinate Guanxi negatively moderated the relationship between servant leadership and voice behavior

BP Neural Network Algorithms for Fault Diagnosis of Microwave Components

Intelligent diagnosis is the main trend of modern fault diagnosis technology. The emergence of artificial neural network technology provides a new way for this kind of intellectualization. Aiming at the problem of microwave module fault diagnosis, an intelligent fault diagnosis method based on BP(Back Propagation) neural network is proposed in this paper. In this paper, the process of determining the neural network model and the operation flow of BP algorithm are introduced, and the network is trained with training samples. By applying the neural network model to an AQ module for testing, the feasibility, accuracy and efficiency of the fault diagnosis of the microwave module are verified, which provides a new method for intelligent fault diagnosis of this kind of microwave module