Application of two-dimensional binary fingerprinting methods for the design of selective Tankyrase I inhibitors.

In the present study, five important binary fingerprinting techniques were used to model novel flavones for the selective inhibition of Tankyrase I. From the fingerprints used: the fingerprint atom pairs resulted in a statistically significant 2D QSAR model using a kernel-based partial least square regression method. This model indicates that the presence of electron-donating groups positively contributes to activity, whereas the presence of electron withdrawing groups negatively contributes to activity.

Protein arginine methylation of Npl3 promotes splicing of the SUS1 intron harboring non-consensus 5' splice site and branch site.

Protein arginine methylation occurs on spliceosomal components and spliceosome-associated proteins, but how this modification contributes to their function in pre-mRNA splicing remains sparse. Here we provide evidence that protein arginine methylation of the yeast SR-/hnRNP-like protein Npl3 plays a role in facilitating efficient splicing of the SUS1 intron that harbors a non-consensus 5' splice site and branch site. In yeast cells lacking the major protein arginine methyltransferase HMT1, we observed a change in the co-transcriptional recruitment of the U1 snRNP subunit Snp1 and Npl3 to pre-mRNAs harboring both consensus (ECM33 and ASC1) and non-consensus (SUS1) 5' splice site and branch site.

Development and validation of reversed-phase high-performance liquid chromatography method for estimation of rizatriptan benzoate in oral strip formulations.

Aim: A simple, accurate, precise, and reproducible reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed and validated for the determination of rizatriptan benzoate in oral strip formulations.

Methodology: Separation was achieved under optimized chromatographic condition on a Hiper C18 column (250 mm × 4.6 mm, 5 m) using Shimadzu HPLC.

Informed consent: Issues and challenges.

Informed consent is an ethical and legal requirement for research involving human participants. It is the process where a participant is informed about all aspects of the trial, which are important for the participant to make a decision and after studying all aspects of the trial the participant voluntarily confirms his or her willingness to participate in a particular clinical trial and significance of the research for advancement of medical knowledge and social welfare. The concept of informed consent is embedded in the principles of Nuremberg Code, The Declaration of Helsinki and The Belmont Report.

Genomic analysis identifies targets of convergent positive selection in drug-resistant Mycobacterium tuberculosis.

M. tuberculosis is evolving antibiotic resistance, threatening attempts at tuberculosis epidemic control. Mechanisms of resistance, including genetic changes favored by selection in resistant isolates, are incompletely understood.

Recruitment of Rpd3 to the telomere depends on the protein arginine methyltransferase Hmt1.

In the yeast Saccharomyces cerevisiae, the establishment and maintenance of silent chromatin at the telomere requires a delicate balance between opposing activities of histone modifying enzymes. Previously, we demonstrated that the protein arginine methyltransferase Hmt1 plays a role in the formation of yeast silent chromatin. To better understand the nature of the Hmt1 interactions that contribute to this phenomenon, we carried out a systematic reverse genetic screen using a null allele of HMT1 and the synthetic genetic array (SGA) methodology.

Development of a sensitive bioanalytical method for the quantification of lacosamide in rat plasma. Application to preclinical pharmacokinetics studies in rats.

A sensitive and selective high performance liquid chromatographic (HPLC) method was developed and validated for quantification of lacosamide in rat plasma. A liquid-liquid extraction procedure was optimized to extract lacosamide from rat plasma. Chromatographic separation was accomplished using a reversed phase C18 Hichrom (250×4.

Next-generation sequencing strategies enable routine detection of balanced chromosome rearrangements for clinical diagnostics and genetic research.

The contribution of balanced chromosomal rearrangements to complex disorders remains unclear because they are not detected routinely by genome-wide microarrays and clinical localization is imprecise. Failure to consider these events bypasses a potentially powerful complement to single nucleotide polymorphism and copy-number association approaches to complex disorders, where much of the heritability remains unexplained. To capitalize on this genetic resource, we have applied optimized sequencing and analysis strategies to test whether these potentially high-impact variants can be mapped at reasonable cost and throughput.