Synthesis and Anti‐HIV Activity of [ddN]‐[ddN] Dimers and Benzimidazole Nucleoside Dimers

In an attempt to combine the HIV‐inhibitory capacity of different 2′,3′‐dideoxynucleoside (ddN) analogs, we have designed and synthesized several dimers of [AZT]‐[AZT] and [AZT]‐[d4T]. In addition, we also synthesized the dimers of 1‐(1H‐benzimidazol‐1‐yl)‐1‐deoxy‐β‐D ‐ribofuranose. The in vitro anti‐HIV activity of these compounds on a pseudotype virus, pNL4‐3.Luc.R‐E‐, in the 293T cells has been determined. Among these compounds, 2,2′‐(propane‐1,3‐diyl)bis[1‐(β‐D ‐ribofuranosyl)‐1H‐benzimidazole] ( 3 ) showed the highest anti‐HIV activity with similar effect as AZT.     

AKINβ1 is Involved in the Regulation of Nitrogen Metabolism and Sugar Signaling in Arabidopsis

Sucrose non-fermenting-1-related protein kinase 1 (SnRK1) has been located at the heart of the control of metabolism and development in plants. The active SnRK1 form is usually a heterotrimeric complex. Subcellular localization and specific target of the SnRK1 kinase are regulated by specific beta subunits. In Arabidopsis , there are at least seven genes encoding beta subunits, of which the regulatory functions are not yet clear. Here, we tried to study the function of one beta subunit, AKINβ1. It showed that AKINβ1 expression was dramatically induced by ammonia nitrate but not potassium nitrate, and the investigation of AKINβ1 transgenic Arabidopsis and T-DNA insertion lines showed that AKINβ1 negatively regulated the activity of nitrate ruductase and was positively involved in sugar repression in early seedling development. Meanwhile AKINβ1 expression was reduced upon sugar treatment (including mannitol) and did not affect the activity of sucrose phosphate synthase. The results indicate that AKINβ1 is involved in the regulation of nitrogen metabolism and sugar signaling.     

Progress in miRNA target prediction and identification

Recently, the identification of miRNA targets has received much attention. The strategies to determine miRNA targets include bioinformatic prediction and experimental assays. The bioinformatic prediction methods are mainly based on the confirmed rules of interaction between miRNAs and their targets, and are carried out by programs, such as miRanda, TargetScan, TargetScanS, RNAhybrid, DIANA-microT, PicTar, RNA22 and FindTar, which follow well-known principles. The experimental assays to find miRNA targets employ immunoprecipitation of AGO proteins to identify interacting mRNAs, or the analysis of mRNA or protein levels to identify genes which can be regulated by miRNAs. The improvement of current bioinformatic and experimental assays and the development of novel assays will enable greater efficiency in the identification of miRNA targets and thus facilitate miRNA research. This paper describes progress in the prediction and identification of miRNA targets.     

Automics: an integrated platform for NMR-based metabonomics spectral processing and data analysis

Background  

Spectral processing and post-experimental data analysis are the major tasks in NMR-based metabonomics studies. While there are commercial and free licensed software tools available to assist these tasks, researchers usually have to use multiple software packages for their studies because software packages generally focus on specific tasks. It would be beneficial to have a highly integrated platform, in which these tasks can be completed within one package. Moreover, with open source architecture, newly proposed algorithms or methods for spectral processing and data analysis can be implemented much more easily and accessed freely by the public.     

In vitro drug release behavior from a novel thermosensitive composite hydrogel based on Pluronic f127 and poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) copolymer

Background  

Most conventional methods for delivering chemotherapeutic agents fail to achieve therapeutic concentrations of drugs, despite reaching toxic systemic levels. Novel controlled drug delivery systems are designed to deliver drugs at predetermined rates for predefined periods at the target organ and overcome the shortcomings of conventional drug formulations therefore could diminish the side effects and improve the life quality of the patients. Thus, a suitable controlled drug delivery system is extremely important for chemotherapy.     

Flow‐injection chemiluminescence method for the determination of naphazoline hydrochloride and oxymetazoline hydrochloride

A sensitive and simple flow‐injection chemiluminescence (FI‐CL) method, which was based on the CL intensity generated from the redoxreaction of potassium permanganate (KMnO₄)–formaldehyde in vitriol (H₂SO₄) medium, has been developed, validated and applied for the determination of naphazoline hydrochloride and oxymetazoline hydrochloride. Besides oxidants and sensitizers, the effect of the concentration of H₂SO₄, KMnO₄ and formaldehyde was investigated. Under the optimum conditions, the linear range was 1.0 × 10^?2–7.0 mg/L for naphazoline hydrochloride and 5.0 × 10^?2–10.0 mg/L for oxymetazoline hydrochloride. During seven repeated inter‐day and intra‐day precision tests of 0.1, 1.0 and 10.0 mg/L samples, the relative standard deviations all corresponded to reference values. The detection limit was 8.69 × 10^?3 mg/L for naphazoline hydrochloride and 3.47 × 10^?2 mg/L for oxymetazoline hydrochloride (signal‐to‐noise ratio ≤3). This method has been successfully implemented for the determination of naphazoline hydrochloride and oxymetazoline hydrochloride in pharmaceuticals. Copyright © 2009 John Wiley & Sons, Ltd.     

Integrated Genomic Analysis Implicates Haploinsufficiency of Multiple Chromosome 5q31.2 Genes in De Novo Myelodysplastic Syndromes Pathogenesis

Deletions spanning chromosome 5q31.2 are among the most common recurring cytogenetic abnormalities detectable in myelodysplastic syndromes (MDS). Prior genomic studies have suggested that haploinsufficiency of multiple 5q31.2 genes may contribute to MDS pathogenesis. However, this hypothesis has never been formally tested. Therefore, we designed this study to systematically and comprehensively evaluate all 28 chromosome 5q31.2 genes and directly test whether haploinsufficiency of a single 5q31.2 gene may result from a heterozygous nucleotide mutation or microdeletion. We selected paired tumor (bone marrow) and germline (skin) DNA samples from 46 de novo MDS patients (37 without a cytogenetic 5q31.2 deletion) and performed total exonic gene resequencing (479 amplicons) and array comparative genomic hybridization (CGH). We found no somatic nucleotide changes in the 46 MDS samples, and no cytogenetically silent 5q31.2 deletions in 20/20 samples analyzed by array CGH. Twelve novel single nucleotide polymorphisms were discovered. The mRNA levels of 7 genes in the commonly deleted interval were reduced by 50% in CD34+ cells from del(5q) MDS samples, and no gene showed complete loss of expression. Taken together, these data show that small deletions and/or point mutations in individual 5q31.2 genes are not common events in MDS, and implicate haploinsufficiency of multiple genes as the relevant genetic consequence of this common deletion.     

Isolation and characterization of 12 polymorphic microsatellite markers from ladyfish (Elops saurus Linnaeus)

Ladyfish (Elops saurus Linnaeus) is an economically important marine fish species. 76 microsatellite loci were isolated from an enriched genomic library of Elops saurus. Twelve of these markers were polymorphic in a test population with alleles per locus ranging from three to nine. The number of observed, expected heterozygosity and polymorphism information content (PIC) per locus in 20 individuals ranged from 0.2000 to 1.0000, 0.1897–0.8846, 0.1769–0.8476, respectively. One markers significantly deviated from Hardy-Weinberg equilibrium after Bonferroni correction analysis and there was no significant linkage disequilibrium found between pairs of markers. As a result, 12 microsatellite markers probably should provide sufficient level of genetic diversity to investigate the fine-scale population structure, stock management and enhancement, genetic linkage map construction and molecular marker-assisted breeding in Elops saurus Linnaeus.     

Development of polymorphic microsatellite markers from barfin flounder (Verasper moseri) and their cross-species amplification

Barfin flounder (Verasper moseri) is a rare fish species in the world. Here, we reported 10 polymorphic microsatellite loci isolated from a dinucleotide-enriched genomic library of barfin flounder (Verasper moseri). The number of alleles, observed, and expected heterozygosity per locus in a test population ranged from 2 to 6, from 0.3333 to 1.0000, and from 0.4866 to 0.7774, respectively. One locus significantly deviated from Hardy–Weinberg equilibrium after Bonferroni correction and no significant linkage disequilibrium was found between pairs of loci. Cross-species amplification of these microsatellite loci in additional five fish species was performed. These polymorphic microsatellite loci would be useful for investigating genetic population structure and construction of genetic linkage map in Verasper moseri. Gui-Dong Miao and Chang-Wei Shao Contributed equally to this work.