The role of bile salt export pump gene repression in drug-induced cholestatic liver toxicity.

The bile salt export pump (BSEP, ABCB11) is predominantly responsible for the efflux of bile salts, and disruption of BSEP function is often associated with altered hepatic homeostasis of bile acids and cholestatic liver injury. Accumulating evidence suggests that many drugs can cause cholestasis through interaction with hepatic transporters. To date, a relatively strong association between drug-induced cholestasis and attenuated BSEP activity has been proposed.

Metformin represses drug-induced expression of CYP2B6 by modulating the constitutive androstane receptor signaling.

Metformin is currently the most widely used drug for the treatment of type 2 diabetes. Mechanistically, metformin interacts with many protein kinases and transcription factors that alter the expression of numerous downstream target genes governing lipid metabolism, cell proliferation, and drug metabolism. The constitutive androstane receptor (CAR, NR1i3), a known xenobiotic sensor, has recently been recognized as a novel signaling molecule, in that its activation could be regulated by protein kinases in addition to the traditional ligand binding.

Essential role of CD11a in CD8+ T-cell accumulation and activation in adipose tissue.

Objective: T cells, particularly CD8(+) T cells, are major participants in obesity-linked adipose tissue (AT) inflammation. We examined the mechanisms of CD8(+) T-cell accumulation and activation in AT and the role of CD11a, a β2 integrin.

Approach And Results: CD8(+) T cells in AT of obese mice showed activated phenotypes with increased proliferation and interferon-γ expression.

Knockdown of β-catenin with dicer-substrate siRNAs reduces liver tumor burden in vivo.

Despite progress in identifying molecular drivers of cancer, it has been difficult to translate this knowledge into new therapies, because many of the causal proteins cannot be inhibited by conventional small molecule therapeutics. RNA interference (RNAi), which uses small RNAs to inhibit gene expression, provides a promising alternative to reach traditionally undruggable protein targets by shutting off their expression at the messenger RNA (mRNA) level. Challenges for realizing the potential of RNAi have included identifying the appropriate genes to target and achieving sufficient knockdown in tumors.

Predictors of survival and neurologic outcomes in children with traumatic out-of-hospital cardiac arrest during the early postresuscitative period.

Background: The outcome of children with traumatic out-of-hospital cardiac arrest (OHCA) is poor, and the information regarding survival in the postresuscitative period is limited. The aim of this study was to determine the clinical features during the early postresuscitative period that may predict survival or neurologic outcomes in children with traumatic OHCA.

Methods: Information on 362 children (<19 years) who presented to the emergency departments of three medical centers and experienced traumatic OHCA during the study period (January 2003 to December 2010) were retrospectively included.

CT angiography findings in carotid blowout syndrome and its role as a predictor of 1-year survival.

Background And Purpose: Carotid blowout is a serious late complication of prior treatment of advanced head and neck cancer. We evaluate the efficacy of CTA in the diagnosis of impending carotid blowout syndrome in patients with head and neck cancer, and its capability to predict clinical outcome.

Materials And Methods: The clinical data of 29 patients with impending carotid blowout who underwent CTA were collected and analyzed.

Phylogenetic relationships and Y genome origin in Elymus L. sensu lato (Triticeae; Poaceae) based on single-copy nuclear Acc1 and Pgk1 gene sequences.

To estimate the origin and genomic relationships of the polyploid species within Elymus L. sensu lato, two unlinked single-copy nuclear gene (Acc1 and Pgk1) sequences of eighteen tetraploids (StH and StY genomes) and fourteen hexaploids (StStH, StYP, StYH, and StYW genomes) were analyzed with those of 35 diploid taxa representing 18 basic genomes in Triticeae. Sequence and phylogenetic analysis suggested that: (1) the St, H, W, and P genomes were donated by Pseudoroegneria, Hordeum, Australopyrum, and Agropyron, respectively, while the Y genome is closely related to the Xp genome in Peridictyon sanctum; (2) different hexaploid Elymus s.

Isolation and characterization of cross-amplification microsatellite panels for species of Procapra (Bovidae; Antilopinae).

The three Procapra species, Tibetan gazelle (P. picticaudata), Mongolian gazelle (P. gutturosa) and Przewalski's gazelle (P.

Phage display identifies an Eastern equine encephalitis virus glycoprotein E2-specific B cell epitope.

The present study identified a linear B-cell epitope in the Eastern equine encephalitis virus (EEEV) E2 glycoprotein by screening a phage-displayed random 12-mer peptide library using an EEEV E2 specific monoclonal antibody (mAb) 7C11 and defined L/F-E/R-Y-T-W-G/R-N-H/W-P as the consensus binding motif. A sequence ((321)EGLEYTWGNHPP(332)) encompassing this consensus motif was found in the EEEV E2 glycoprotein and synthesized for further epitope confirmation. Meanwhile, the corresponding epitope peptides in E2 protein of associated alphaviruses were synthesized for specificity identification.

Birds and anthropogenic noise: singing higher may matter.

In a recent theoretical study, Nemeth and Brumm explored the effect of amplitude and frequency variation in birdsongs on signal transmission in forested and noisy urban environments. They argued that "increased song pitch might not be an adaptation" but "an epiphenomenon of urbanization." Here we address the validity of comparing the communication benefits of changes in amplitude and frequency to question the adaptive significance of "urban songs.

Cancer stem-like cells enriched in Panc-1 spheres possess increased migration ability and resistance to gemcitabine.

Pancreatic cancer is one of the most lethal malignancies with poor prognosis. Previously, we found that a subpopulation of cancer stem cells (CSCs) in the Panc-1 pancreatic cancer cell line could propagate to form spheres. Here we characterized the malignant phenotypes of the pancreatic cancer stem CD44+/CD24+ cells, which were enriched under sphere forming conditions as analyzed by flow cytometry.

Generation of murine monoclonal antibodies which cross-neutralize human enterovirus genogroup B isolates.

A live enterovirus 71 (EV71) isolate designated, EV71/E59, with genotype B4 produced in Vero cells and purified over a sucrose gradient was used as the immunogen to generate EV71-specific murine monoclonal antibodies. Four hybridoma clones derived from the fusion of splenocytes of EV71/E59-preimmunized BALB/c (H-2(d)) mice and the NS-1 myeloma cells that exhibit stable growth were selected for detailed characterization. The proof that the hybridomas produced are indeed true independent clones was based on the obervations that they expressed different complementarity-determining regions (CDRs) in their κ light chain genes.

cDNA cloning of a functional water channel from toad urinary bladder epithelium.

A cDNA was cloned from the epithelium of toad (Bufo marinas) urinary bladder, based on homology to the mammalian aquaporins (AQP). The cDNA [947 base pairs (bp), identified as AQP-t1] encoded a 272-amino acid protein with 76% identity to mammalian aquaporin-1 (AQP-1) and 88% identity to frog water channel FA-CHIP. AQP-t1 cDNA was nearly identical to a fragment of a nonfunctional cDNA cloned recently from toad bladder ["AQP-TB"; J.

[Retinoblastoma: cell origin and differentiation].

50 retinoblastoma paraffin blocks were studied immunohistochemically (NSE, GFAP) and histochemically (colloidal-iron, RNA), and 13 cases by EM. The Rb cells demonstrated varying degrees of positive or negative reaction to NSE, most F-W and H-W rosettes being positive and the fleuretes weakly positive or negative. The GFAP positive cells were mainly found in the periphery of the tumor mass and around the blood vessels, and sparsely among the NSE positive cells.

Inhibition of glucosyltransferase activities of Streptococcus mutans by a monoclonal antibody to a subsequence peptide.

Preliminary analysis indicated that a 19-amino-acid peptide sequence (435 to 453 of GtfC) within a highly conserved region of the glucosyltransferases of the cariogenic streptococci might be functionally important (J.-S. Chia, S.

H-Y antigen expression in heterogametic males (XY) and females (ZW): a factor in reproductive strategy?

The cells of heterogametic females with ZW sex chromosomes express H-Y or H-W antigen. A hypothesis is formulated to explain why these animals are capable of 'practicing' amphigonia retardata, i.e.