Evaluating the role of intestinal transporters in fruit juice-drug interactions

Fruit juice-drug interactions (FJDIs) involving non-metabolized oral medications result in decreased drug exposure that may lead to reduced therapeutic efficacy. The effect is thought to be mediated by inhibition of the intestinal drug transporters organic anion transporting polypeptide 1A2 and 2B1 (OATP1A2 and OATP2B1) by fruit juice constituents, however the exact mechanisms remain controversial. We tested the hypothesis that fruit juices limit the absorption of fexofenadine through interactions with specific intestinal transporters. In vitro transport and fruit juice inhibition studies using fexofenadine, a medication involved in FJDIs, revealed that in addition to previously implicated transporters, organic cation transporter 1 (OCT1) and organic solute transporter alpha/beta (OSTα/β) are potential novel targets of fruit juice components. Pharmacokinetic interaction studies in wild-type and mOatp2b1 knockout mice demonstrated that mOatp2b1 is not involved in fexofenadine absorption or FJDIs in vivo. These findings provide new insights into the mechanism of FJDIs

Novel missense mutation of the TP63 gene in a newborn with Hay-Wells/Ankyloblepharon-Ectodermal defects-Cleft lip/palate (AEC) syndrome: clinical report and follow-up

Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome, also known as Hay-Wells syndrome, is a rare genetic syndrome with ectodermal dysplasia. About 100 patients have been reported to date. It is associated to a heterozygous mutation of the tumor protein p63 (TP63) gene, located on chromosome 3q28. Typical clinical manifestations include: filiform ankyloblepharon adnatum (congenital adherence of the eyelids), ectodermal abnormalities (sparse and frizzy hair, skin defects, nail alterations, dental changes and hypohidrosis), and cleft lip/palate. Diagnostic suspicion is based on clinical signs and confirmed by genetic testing

The Caenorhabditis elegans hunchback-like Gene lin-57/hbl-1 Controls Developmental Time and Is Regulated by MicroRNAs

AbstractTemporal control of development is an important aspect of pattern formation that awaits complete molecular analysis. We identified lin-57 as a member of the C. elegans heterochronic gene pathway, which ensures that postembryonic developmental events are appropriately timed. Loss of lin-57 function causes the hypodermis to terminally differentiate and acquire adult character prematurely. lin-57 is hbl-1, revealing a role for the worm hunchback homolog in control of developmental time. Significantly, fly hunchback (hb) temporally specifies cell fates in the nervous system. The hbl-1/lin-57 3′UTR is required for postembryonic downregulation in the hypodermis and nervous system and contains multiple putative binding sites for temporally regulated microRNAs, including let-7. Indeed, we find that hbl-1/lin-57 is regulated by let-7, at least in the nervous system. Examination of the hb 3′UTR reveals potential binding sites for known fly miRNAs. Thus, evolutionary conservation of hunchback genes may include temporal control of cell fate specification and microRNA-mediated regulation

Community-based HIV-1 Early Diagnosis and Risk Behavior Analysis of Men Having Sex with Men in Hong Kong

The increasing prevalence of HIV-1 among men having sex with men (MSM) calls for an investigation of HIV-1 prevalence and incidence in MSM by early diagnosis to assist with early preventive interventions in Hong Kong. The participants were recruited randomly from MSM communities within a one-year period. Rapid HIV Test (RHT) and real-time dried blood spot (DBS)-based quantitative polymerase chain reaction (DBS-qPCR) were used for the early diagnosis of 474 participants. Risk behavior analysis was performed by studying information obtained from the participants during the study period. The HIV-1 prevalence and incident rates in the studied MSM population were 4.01%(19/474) and 1.47% (7/474), respectively. Three infected participants were found at the acute phase of infection by DBS-qPCR. Only 46.4%(220/474) MSM were using condoms regularly for anal sex. HIV infection significantly correlated with unprotected receptive anal sex and syphilis infection. An increased number of infections was found among foreign MSM in Hong Kong. This study is the first to use DBS-qPCR to identify acutely infected individuals in a community setting and to provide both the prevalence and incident rates of HIV-1 infection among MSM in Hong Kong. The risk analysis provided evidence that behavior intervention strengthening is necessary to fight against the increasing HIV-1 epidemic among MSM in Hong Kong and surrounding regions in Asia.published_or_final_versio

Leukocyte transcriptome from chickens infected with avian pathogenic Escherichia coli identifies pathways associated with resistance

Avian pathogenic Escherichia coli (APEC) causes colibacillosis, which is responsible for morbidity and mortality in chickens. Gene expression patterns have previously been demonstrated to differ between chicken populations that are resistant vs. susceptible to bacterial infection, but little is currently known about gene expression response to APEC. Increased understanding of gene expression patterns associated with resistance will facilitate genetic selection to increase resistance to APEC. Male broiler chicks were vaccinated at 2 weeks of age and challenged with APEC at 4 weeks of age. Peripheral blood leukocytes were collected at 1 and 5 day post-infection. Lesions on the liver, pericardium, and air sacs were used to assign a mild or severe pathology status to non-vaccinated, challenged chicks. Ten treatment groups were therefore generated with a priori factors of vaccination, challenge, day post-infection, and the a posteriori factor of pathology status. Global transcriptomic response was evaluated using the Agilent 44K chicken microarray. APEC infection resulted in more up-regulation than down-regulation of differentially expressed genes. Immune response and metabolic processes were enriched with differentially expressed genes. Although vaccination significantly reduced lesions in challenged bird, there was no detectable effect of vaccination on gene expression. This study investigated the transcriptomic differences in host responses associated with mild vs. severe pathology, in addition to the effects of vaccination and challenge, thus revealing genes and networks associated with response to APEC and providing a foundation for future studies on, and genetic selection for, genetic resistance to APEC

Iterative Correction of Reference Nucleotides (iCORN) using second generation sequencing technology

Motivation: The accuracy of reference genomes is important for downstream analysis but a low error rate requires expensive manual interrogation of the sequence. Here, we describe a novel algorithm (Iterative Correction of Reference Nucleotides) that iteratively aligns deep coverage of short sequencing reads to correct errors in reference genome sequences and evaluate their accuracy