Coordination of metronidazole to Cu(II): Structural characterization of a mononuclear square-planar compound Joshua H.

The reaction between metronidazole [1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole, MET] and CuCl2•2H2O in methanol solution has allowed isolation of blue crystals of composition Cu(MET)2Cl2•MeOH. These crystals have been shown by X-ray diffraction to consist of mononuclear square-planar trans-Cu(MET)2Cl2 molecules in which the metronidazole ligands are trans to each other, as are the Cl ligands. The structure of this compound is very different from other compounds that have been obtained from the reaction between CuCl2•2H2O and metronidazole, namely [Cu(MET)2(μ-Cl)Cl]2 and [Cu(MET)2(μ-Cl)(OH2)]2[Cl]2, which are dimers featuring bridging chloride ligands

Crystal structure of hexa-μ-chlorido-μ4-oxido-tetrakis{[1-(2-hydroxyethyl)-2- methyl-5-nitro-1H-imidazole-κN3]copper(II)} containing short NO2· · ·NO2 contacts

The title tetranuclear copper complex, [Cu4Cl6O(C6H9N3O3)4] or [Cu4Cl6O- (MET)4][MET is 1-(2-hydroxyethyl)-2-methyl-5-nitro-1Η-imidazole or metronidazole], contains a tetrahedral arrangement of copper(II) ions. Each copper atom is also linked to the other three copper atoms in the tetrahedron via bridging chloride ions. A fifth coordination position on each metal atom is occupied by a nitrogen atom of the monodentate MET ligand. The result is a distorted CuCl3NO trigonal–bipyramidal coordination polyhedron with the axial positions occupied by oxygen and nitrogen atoms. The extended structure displays O− H ⋅ ⋅ ⋅O hydrogen bonding, as well as unusual short O⋅ ⋅ ⋅ N interactions [2.775 (4) A ˚ ] between the nitro groups of adjacent clusters that are oriented perpendicular to each other. The scattering contribution of disordered water and methanol solvent molecules was removed using the SQUEEZE procedure [Spek (2015). Acta Cryst. C71, 9–16] in PLATON [Spek (2009). Acta Cryst. D65, 148–155]

Eicosapentaenoic Acid Modulates Trichomonas 1 vaginalis Activity

Trichomonas vaginalis is a sexually transmitted parasite and, while it is often asymptomatic in 50 males, the parasite is associated with disease in both sexes. Metronidazole is an effective 51 treatment for trichomoniasis, but resistant strains have evolved and, thus, it has become 52 necessary to investigate other possible therapies. In this study, we examined the effects of native 53 and oxidized forms of the sodium salts of eicosapentaenoic, docosahexaenoic and arachidonic 54 acids on T. vaginalis activity. Eicosapentaenoic acid was the most toxic with 190 μM and 380 55 μM causing approximately 90% cell death in Casu2 and ATCC 50142 strains, respectively. In 56 contrast, oxidized eicosapentaenoic acid was the least toxic, requiring \u3e3 mM to inhibit activity, 57 while low levels (10μM) were associated with increased parasite density. Mass spectrometric 58 analysis of oxidized eicosapentaenoic acid revealed C20 products containing one to six 59 additional oxygen atoms and various degrees of bond saturation. These results indicate that 60 eicosapentaenoic acid has different effects on T. vaginalis survival, depending on whether it is 61 present in the native or oxidized form. A better understanding of lipid metabolism in T. vaginalis 62 may facilitate the design of synthetic fatty acids that are effective for the treatment of 63 metronidazole-resistant T. vaginalis

Identification of Novel Methylation Markers in Hepatocellular Carcinoma using a Methylation Array

Promoter CpG island hypermethylation has become recognized as an important mechanism for inactivating tumor suppressor genes or tumor-related genes in human cancers of various tissues. Gene inactivation in association with promoter CpG island hypermethylation has been reported to be four times more frequent than genetic changes in human colorectal cancers. Hepatocellular carcinoma is also one of the human cancer types in which aberrant promoter CpG island hypermethylation is frequently found. However, the number of genes identified to date as hypermethylated for hepatocellular carcinoma (HCC) is fewer than that for colorectal cancer or gastric cancer, which can be attributed to fewer attempts to perform genome-wide methylation profiling for HCC. In the present study, we used bead-array technology and coupled methylation-specific PCR to identify new genes showing cancer-specific methylation in HCC. Twenty-four new genes have been identified as hypermethylated at their promoter CpG island loci in a cancer-specific manner. Of these, TNFRSF10C, HOXA9, NPY, and IRF5 were frequently hypermethylated in hepatocellular carcinoma tissue samples and their methylation was found to be closely associated with inactivation of gene expression. Further study will be required to elucidate the clinicopathological implications of these newly found DNA methylation markers in hepatocellular carcinoma

Elevated O-GlcNAc-dependent signaling through inducible mOGT expression selectively triggers apoptosis

O-linked N-acetylglucosamine transferase (OGT) catalyzes O-GlcNAc addition to numerous cellular proteins including transcription and nuclear pore complexes and plays a key role in cellular signaling. One differentially spliced isoform of OGT is normally targeted to mitochondria (mOGT) but is quite cytotoxic when expressed in cells compared with the ncOGT isoform. To understand the basis of this selective cytotoxicity, we constructed a fully functional ecdysone-inducible GFP–OGT. Elevated GFP–OGT expression induced a dramatic increase in intracellular O-GlcNAcylated proteins. Furthermore, enhanced OGT expression efficiently triggered programmed cell death. Apoptosis was dependent upon the unique N-terminus of mOGT, and its catalytic activity. Induction of mOGT expression triggered programmed cell death in every cell type tested including INS-1, an insulin-secreting cell line. These studies suggest that deregulated activity of the mitochondrially targeted mOGT may play a role in triggering the programmed cell death observed with diseases such as diabetes mellitus and neurodegeneration

Internal control genes for quantitative RT-PCR expression analysis in mouse osteoblasts, osteoclasts and macrophages

<p>Abstract</p> <p>Background</p> <p>Real-time quantitative RT-PCR (qPCR) is a powerful technique capable of accurately quantitating mRNA expression levels over a large dynamic range. This makes qPCR the most widely used method for studying quantitative gene expression. An important aspect of qPCR is selecting appropriate controls or normalization factors to account for any differences in starting cDNA quantities between samples during expression studies. Here, we report on the selection of a concise set of housekeeper genes for the accurate normalization of quantitative gene expression data in differentiating osteoblasts, osteoclasts and macrophages. We implemented the use of geNorm, an algorithm that determines the suitability of genes to function as housekeepers by assessing expression stabilities. We evaluated the expression stabilities of 18S, ACTB, B2M, GAPDH, HMBS and HPRT1 genes.</p> <p>Findings</p> <p>Our analyses revealed that 18S and GAPDH were regulated during osteoblast differentiation and are not suitable for use as reference genes. The most stably expressed genes in osteoblasts were ACTB, HMBS and HPRT1 and their geometric average constitutes a suitable normalization factor upon which gene expression data can be normalized. In macrophages, 18S and GAPDH were the most variable genes while HMBS and B2M were the most stably expressed genes. The geometric average of HMBS and B2M expression levels forms a suitable normalization factor to account for potential differences in starting cDNA quantities during gene expression analysis in macrophages. The expression stabilities of the six candidate reference genes in osteoclasts were, on average, more variable than that observed in macrophages but slightly less variable than those seen in osteoblasts. The two most stably expressed genes in osteoclasts were HMBS and B2M and the genes displaying the greatest levels of variability were 18S and GAPDH. Notably, 18S and GAPDH were the two most variably expressed control genes in all three cell types. The geometric average of HMBS, B2M and ACTB creates an appropriate normalization factor for gene expression studies in osteoclasts.</p> <p>Conclusion</p> <p>We have identified concise sets of genes suitable to use as normalization factors for quantitative real-time RT-PCR gene expression studies in osteoblasts, osteoclasts and macrophages.</p

Quadrature Strategies for Constructing Polynomial Approximations

Finding suitable points for multivariate polynomial interpolation and approximation is a challenging task. Yet, despite this challenge, there has been tremendous research dedicated to this singular cause. In this paper, we begin by reviewing classical methods for finding suitable quadrature points for polynomial approximation in both the univariate and multivariate setting. Then, we categorize recent advances into those that propose a new sampling approach and those centered on an optimization strategy. The sampling approaches yield a favorable discretization of the domain, while the optimization methods pick a subset of the discretized samples that minimize certain objectives. While not all strategies follow this two-stage approach, most do. Sampling techniques covered include subsampling quadratures, Christoffel, induced and Monte Carlo methods. Optimization methods discussed range from linear programming ideas and Newton's method to greedy procedures from numerical linear algebra. Our exposition is aided by examples that implement some of the aforementioned strategies

Seasonal changes in patterns of gene expression in avian song control brain regions.

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Photoperiod and hormonal cues drive dramatic seasonal changes in structure and function of the avian song control system. Little is known, however, about the patterns of gene expression associated with seasonal changes. Here we address this issue by altering the hormonal and photoperiodic conditions in seasonally-breeding Gambel's white-crowned sparrows and extracting RNA from the telencephalic song control nuclei HVC and RA across multiple time points that capture different stages of growth and regression. We chose HVC and RA because while both nuclei change in volume across seasons, the cellular mechanisms underlying these changes differ. We thus hypothesized that different genes would be expressed between HVC and RA. We tested this by using the extracted RNA to perform a cDNA microarray hybridization developed by the SoNG initiative. We then validated these results using qRT-PCR. We found that 363 genes varied by more than 1.5 fold (>log(2) 0.585) in expression in HVC and/or RA. Supporting our hypothesis, only 59 of these 363 genes were found to vary in both nuclei, while 132 gene expression changes were HVC specific and 172 were RA specific. We then assigned many of these genes to functional categories relevant to the different mechanisms underlying seasonal change in HVC and RA, including neurogenesis, apoptosis, cell growth, dendrite arborization and axonal growth, angiogenesis, endocrinology, growth factors, and electrophysiology. This revealed categorical differences in the kinds of genes regulated in HVC and RA. These results show that different molecular programs underlie seasonal changes in HVC and RA, and that gene expression is time specific across different reproductive conditions. Our results provide insights into the complex molecular pathways that underlie adult neural plasticity

Prevalence and changes in chronic diseases among South Korean farmers: 1998 to 2005

<p>Abstract</p> <p>Background</p> <p>Epidemiologic studies have suggested a unique pattern of disease among farmers in Western countries, but limited information is available about the magnitude of disease prevalence and their changes over time in Asian farmers. The aim of this study was to compare the prevalence and changes in chronic diseases among farmers with those of other occupational groups in South Korea.</p> <p>Methods</p> <p>Using data from three consecutive cross-sectional national surveys: the Korean National Health and Nutrition Examination Survey 1998 (n = 39,060), 2001 (n = 37,769), and 2005 (n = 34,145), we calculated age and gender-standardized prevalence of chronic diseases by the direct method and compared the prevalence changes from 1998 to 2005.</p> <p>Results</p> <p>Female farmers had significantly higher chronic disease prevalence than other occupational groups in all three surveys. Arthritis was the most prevalent chronic disease among farmers for both men and women. Compared with other populations, farmers demonstrated a higher prevalence of arthritis and intervertebral disc disorders. Farmers showed higher prevalence changes for intervertebral disc disorders than other occupational workers.</p> <p>Conclusion</p> <p>Our findings support that South Korean farmers have a distinct pattern of diseases prevalence from other populations. More detailed studies investigating the risk of musculoskeletal diseases and intensive intervention efforts to reduce the prevalence these diseases, particularly among female farmers, are required.</p

Newborn Genetic Screening for Hearing Impairment: A Preliminary Study at a Tertiary Center

Universal newborn hearing screening (UNHS) is of paramount importance for early identification and management of hearing impairment in children. However, infants with slight/mild, progressive, or late-onset hearing impairment might be missed in conventional UNHS. To investigate whether genetic screening for common deafness-associated mutations could assist in identifying these infants, 1017 consecutive newborns in a tertiary hospital were subjected to both newborn hearing screening using a two-step distortion-product otoacoustic emissions (DPOAE) screening and newborn genetic screening (NGS) for deafness. The NGS targeted 4 deafness-associated mutations commonly found in the Taiwanese population, including p.V37I (c.109G>A) and c.235delC of the GJB2 gene, c.919-2A>G of the SLC26A4 gene, and mitochondrial m.1555A>G of the 12S rRNA gene. The results of the NGS were then correlated to the results of the NHS. Of the 1017 newborns, 16 (1.6%) had unilateral DPOAE screening failure, and 22 (2.2%) had bilateral DPOAE screening failure. A total of 199 (19.6%) babies were found to have at least 1 mutated allele on the NGS for deafness, 11 (1.1%) of whom were homozygous for GJB2 p.V37I, 6 (0.6%) compound heterozygous for GJB2 p.V37I and c.235delC, and 1 (0.1%) homoplasmic for m.1555A>G, who may potentially have hearing loss. Among them, 3 babies, 5 babies, and 1 baby, respectively, passed the NHS at birth. Comprehensive audiological assessments in the 9 babies at 3 months identified 1 with slight hearing loss and 2 with mild hearing loss. NGS for common deafness-associated mutations may identify infants with slight/mild or potentially progressive hearing impairment, thus compensating for the inherent limitations of the conventional UNHS