Genetic Deficiency of CD40 in Mice Exacerbates Metabolic Manifestations of Diet-induced Obesity: A Dissertation

The past two decades have seen an explosive increase of obesity rates worldwide, with more than one billion adults overweight and 300 million of them obese. Obesity and its associated complications have become leading causes of morbidity and mortality in the United States and major contributing factors to the rising costs of national health care. The pathophysiology of obesity and type 2 diabetes in rodents and humans is characterized by low-grade inflammation and chronic activation of immune pathways in adipose tissue and liver. The CD40 receptor and its ligand, CD40L, initiate immune cell signaling promoting inflammation, but conflicting data on CD40L-null mice confound its role in obesity-associated insulin resistance. A clear understanding of how CD40 and its ligand communicate to regulate and sustain the inflammatory environment of obesity is lacking. Here we demonstrate that CD40 receptor deficient mice on a high-fat diet display the expected decrease in hepatic cytokine levels, but paradoxically exhibit liver steatosis, insulin resistance and glucose intolerance compared with their age-matched wild-type controls. Hyperinsulinemic-euglycemic clamp studies also demonstrated insulin resistance in glucose utilization by the CD40-null mice compared with wild-type mice. In contrast to liver, visceral adipose tissue in CD40 deficient animals harbors elevated cytokine levels and infiltration of inflammatory cells, particularly macrophages and CD8+ effector T cells. In addition, ex vivo explants of epididymal adipose tissue from CD40-null mice display elevated basal and isoproterenol-stimulated lipolysis, suggesting a potential increase of lipid efflux from visceral fat to the liver. These findings reveal that 1) CD40-null mice represent an unusual model of hepatic steatosis with reduced hepatic inflammation, and 2) CD40 unexpectedly functions in adipose tissue to attenuate the chronic inflammation associated with obesity, thereby protecting against hepatic steatosis

Overexpression of soybean ubiquitin-conjugating enzyme gene GmUBC2 confers enhanced drought and salt tolerance through modulating abiotic stress-responsive gene expression in Arabidopsis

Previous studies have shown that ubiquitination plays important roles in plant abiotic stress responses. In the present study, the ubiquitin-conjugating enzyme gene GmUBC2, a homologue of yeast RAD6, was cloned from soybean and functionally characterized. GmUBC2 was expressed in all tissues in soybean and was up-regulated by drought and salt stress. Arabidopsis plants overexpressing GmUBC2 were more tolerant to salinity and drought stresses compared with the control plants. Through expression analyses of putative downstream genes in the transgenic plants, we found that the expression levels of two ion antiporter genes AtNHX1 and AtCLCa, a key gene involved in the biosynthesis of proline, AtP5CS, and the copper chaperone for superoxide dismutase gene AtCCS, were all increased significantly in the transgenic plants. These results suggest that GmUBC2 is involved in the regulation of ion homeostasis, osmolyte synthesis, and oxidative stress responses. Our results also suggest that modulation of the ubiquitination pathway could be an effective means of improving salt and drought tolerance in plants through genetic engineering

Clinical outcomes of osteonecrosis of the femoral head after autologous bone marrow stem cell implantation: a meta-analysis of seven case-control studies

The purpose of this study was to evaluate the clinical outcomes of osteonecrosis of the femoral head after autologous bone marrow stem cell implantation. We searched the PubMed, Embase and Web of Science databases and included all case-control trials that reported on the clinical outcomes of osteonecrosis progression, incidence of total hip arthroplasty and improvement in Harris hip scores. Overall, seven case-control trials were included. Compared with the controls, patients treated with the bone marrow stem cells implantation treatment showed improved clinical outcomes with delayed osteonecrosis progression (odds ratio = 0.17, 95% CI: 0.09 - 0.32;

Klein-bottle quadrupole insulators and Dirac semimetals

The Benalcazar-Bernevig-Hughes (BBH) quadrupole insulator model is a cornerstone model for higher-order topological phases. It requires \pi flux threading through each plaquette of the two-dimensional Su-Schrieffer-Heeger model. Recent studies show that particular \pi-flux patterns can modify the fundamental Brillouin zone from the shape of a torus to a Klein-bottle with emerging topological phases. By designing different \pi-flux patterns, we propose two types of Klein-bottle BBH models. These models show rich topological phases including Klein-bottle quadrupole insulators and Dirac semimetals. The phase with nontrivial Klein-bottle topology shows twined edge modes at open boundaries. These edge modes can further support second-order topology yielding a quadrupole insulator. Remarkably, both models are robust against flux perturbations. Moreover, we show that different \pi-flux patterns dramatically affect the phase diagram of the Klein-bottle BBH models. Going beyond the original BBH model, Dirac semimetal phases emerge in Klein-bottle BBH models featured by the coexistence of twined edge modes and bulk Dirac points.Comment: 11 pages, 11 figure

High-efficient screening method for identification of key genes in breast cancer through microarray and bioinformatics

Background/Aim: The aim of the present study was to identify key pathways and genes in breast cancer and develop a new method for screening key genes with abnormal expression based on bioinformatics. Materials and Methods: Three microarray datasets GSE21422, GSE42568 and GSE45827 were downloaded from the Gene Expression Omnibus (GEO) database and differentially expressed genes (DEGs) were analyzed using GEO2R. The gene ontology (GO) and pathway enrichment analysis were established through DAVID database. The protein–protein interaction (PPI) network was performed through the Search Tool for the Retrieval of Interacting Genes (STRING) database and managed by Cytoscape. The overall survival (OS) analysis of the 4 genes including AURKA, CDH1, CDK1 and PPARG that had higher degrees in this network was uncovered Kaplan-Meier analysis. Results: A total of 811 DEGs were identified in breast cancer, which were enriched in biological processes, including cell cycle, mitosis, vessel development and lipid metabolic. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the up-regulated DEGs were particularly involved in cell cycle, progesterone-mediated oocyte maturation and leukocyte transendothelial migration, while the down-regulated DEGs were mainly involved in regulation of lipolysis, fatty acid degradation and glycerolipid metabolism. Through PPI network analysis, 14 hub genes were identified. Among them, the high expression of AURKA, CDH1 and CDK1 were associated with worse OS of breast cancer patients; while the high expression of PPARG was linked with better OS. Conclusion: The present study identified key pathways and genes involved in breast cancer which are potential molecular targets for breast cancer treatment and diagnosis

Abrupt climatic events recorded by the Ili loess during the last glaciation in Central Asia: Evidence from grain-size and minerals

The loess record of Central Asia provides an important archive of regional climate and environmental changes. In contrast to the widely investigated loess deposits in the Chinese Loess Plateau, Central Asian loess-paleosol sequences remain poorly understood. Here, we present an aeolian loess section in the southern Ili Basin. Based on granularity and mineralogical analyses, we reconstruct climatic changes during the last glaciation. The results indicated that most of the abrupt climatic events (such as Dansgaard-Oeschger events and Heinrich events) were imprinted in this loess section, although their amplitudes and ages showed some differences. Compared with the millennial oscillations recoded in loess and stalagmites in East Asia, the arid Central Asia responded more sensitively to the warming events than to the cooling events. The shifting trajectory of westerlies across Central Asia played an important role in dust deposition during the stadials. The North Atlantic climatic signals may have been transmitted from Central Asia to the East Asian monsoon regions via the westerlies

Three Kinds of Special Relativity via Inverse Wick Rotation

Since the special relativity can be viewed as the physics in an inverse Wick rotation of 4-d Euclid space, which is at almost equal footing with the 4-d Riemann/Lobachevski space, there should be important physics in the inverse Wick rotation of 4-d Riemann/Lobachevski space. Thus, there are three kinds of special relativity in de Sitter/Minkowski/anti-de Sitter space at almost equal footing, respectively. There is an instanton tunnelling scenario in the Riemann-de Sitter case that may explain why \La be positive and link with the multiverse.Comment: 3 pages, no figures, to appear in Chin. Phys. Let

Listen to genes : dealing with microarray data in the frequency domain

Background: We present a novel and systematic approach to analyze temporal microarray data. The approach includes normalization, clustering and network analysis of genes. Methodology: Genes are normalized using an error model based uniform normalization method aimed at identifying and estimating the sources of variations. The model minimizes the correlation among error terms across replicates. The normalized gene expressions are then clustered in terms of their power spectrum density. The method of complex Granger causality is introduced to reveal interactions between sets of genes. Complex Granger causality along with partial Granger causality is applied in both time and frequency domains to selected as well as all the genes to reveal the interesting networks of interactions. The approach is successfully applied to Arabidopsis leaf microarray data generated from 31,000 genes observed over 22 time points over 22 days. Three circuits: a circadian gene circuit, an ethylene circuit and a new global circuit showing a hierarchical structure to determine the initiators of leaf senescence are analyzed in detail. Conclusions: We use a totally data-driven approach to form biological hypothesis. Clustering using the power-spectrum analysis helps us identify genes of potential interest. Their dynamics can be captured accurately in the time and frequency domain using the methods of complex and partial Granger causality. With the rise in availability of temporal microarray data, such methods can be useful tools in uncovering the hidden biological interactions. We show our method in a step by step manner with help of toy models as well as a real biological dataset. We also analyse three distinct gene circuits of potential interest to Arabidopsis researchers

DrugBank: a comprehensive resource for in silico drug discovery and exploration

DrugBank is a unique bioinformatics/cheminformatics resource that combines detailed drug (i.e. chemical) data with comprehensive drug target (i.e. protein) information. The database contains >4100 drug entries including >800 FDA approved small molecule and biotech drugs as well as >3200 experimental drugs. Additionally, >14 000 protein or drug target sequences are linked to these drug entries. Each DrugCard entry contains >80 data fields with half of the information being devoted to drug/chemical data and the other half devoted to drug target or protein data. Many data fields are hyperlinked to other databases (KEGG, PubChem, ChEBI, PDB, Swiss-Prot and GenBank) and a variety of structure viewing applets. The database is fully searchable supporting extensive text, sequence, chemical structure and relational query searches. Potential applications of DrugBank include in silico drug target discovery, drug design, drug docking or screening, drug metabolism prediction, drug interaction prediction and general pharmaceutical education. DrugBank is available at