Int J Inorg Chem. 2011 Jan 1; 2011:
Leblanc MA, Gonzalez-Sarrías A, Beckford FA, Mbarushimana PC, Seeram NP

A novel thiosemicarbazone from 2-acetonaphthone (represented as acnTSC) has been synthesized and its basic coordination chemistry with zinc(II), cobalt(II), and copper(II) explored. The complexes were characterized by elemental analysis and various spectroscopic techniques and are best formulated as [M(acnTSC)(2)Cl(2)] with the metal likely in an octahedral environment. The anticancer activity of the complexes was determined against a panel of human colon cancer cells (HCT-116 and Caco-2). The compounds bind to DNA via an intercalative mode with binding constants of 9.7 × 10(4) M(-1), 1.8 × 10(5) M(-1), and 9.5 × 10(4) M(-1) for the zinc, cobalt, and copper complexes, respectively.

Front Genet. 2012; 3: 2
Zhang L, Liu R, Wang Z, Culver DA, Wu R

Haplotype analysis has been increasingly used to study the genetic basis of human diseases, but models for characterizing genetic interactions between haplotypes from different chromosomal regions have not been well developed in the current literature. In this article, we describe a statistical model for testing haplotype-haplotype interactions for human diseases with a case-control genetic association design. The model is formulated on a contingency table in which cases and controls are typed for the same set of molecular markers. By integrating well-established quantitative genetic principles, the model is equipped with a capacity to characterize physiologically meaningful epistasis arising from interactions between haplotypes from different chromosomal regions. The model allows the partition of epistasis into different components due to additive × additive, additive × dominance, dominance × additive, and dominance × dominance interactions. We derive the EM algorithm to estimate and test the effects of each of these components on differences in the pattern of genetic variation between cases and controls and, therefore, examine their role in the pathogenesis of human diseases. The method was further extended to investigate gene-environment interactions expressed at the haplotype level. The statistical properties of the models were investigated through simulation studies and its usefulness and utilization validated by analyzing the genetic association of sarcoidosis from a human genetics project.

Front Genet. 2011; 2: 44
Imumorin IG, Kim EH, Lee YM, De Koning DJ, van Arendonk JA, De Donato M, Taylor JF, Kim JJ

Parent-of-origin effects (POE) such as genomic imprinting influence growth and body composition in livestock, rodents, and humans. Here, we report the results of a genome scan to detect quantitative trait loci (QTL) with POE on growth and carcass traits in Angus × Brahman cattle crossbreds. We identified 24 POE-QTL on 15 Bos taurus autosomes (BTAs) of which six were significant at 5% genome-wide (GW) level and 18 at the 5% chromosome-wide (CW) significance level. Six QTL were paternally expressed while 15 were maternally expressed. Three QTL influencing post-weaning growth map to the proximal end of BTA2 (linkage region of 0-9 cM; genomic region of 5.0-10.8 Mb), for which only one imprinted ortholog is known so far in the human and mouse genomes, and therefore may potentially represent a novel imprinted region. The detected QTL individually explained 1.4 ∼ 5.1% of each trait's phenotypic variance. Comparative in silico analysis of bovine genomic locations show that 32 out of 1,442 known mammalian imprinted genes from human and mouse homologs map to the identified QTL regions. Although several of the 32 genes have been associated with quantitative traits in cattle, only two (GNAS and PEG3) have experimental proof of being imprinted in cattle. These results lend additional support to recent reports that POE on quantitative traits in mammals may be more common than previously thought, and strengthen the need to identify and experimentally validate cattle orthologs of imprinted genes so as to investigate their effects on quantitative traits.

Front Genet. 2011; 2: 31
Qu C, Schuetz JM, Min JE, Leach S, Daley D, Spinelli JJ, Brooks-Wilson A, Graham J

We describe a statistical approach to predict gender-labeling errors in candidate-gene association studies, when Y-chromosome markers have not been included in the genotyping set. The approach adds value to methods that consider only the heterozygosity of X-chromosome SNPs, by incorporating available information about the intensity of X-chromosome SNPs in candidate genes relative to autosomal SNPs from the same individual. To our knowledge, no published methods formalize a framework in which heterozygosity and relative intensity are simultaneously taken into account. Our method offers the advantage that, in the genotyping set, no additional space is required beyond that already assigned to X-chromosome SNPs in the candidate genes. We also show how the predictions can be used in a two-phase sampling design to estimate the gender-labeling error rates for an entire study, at a fraction of the cost of a conventional design.

Front Genet. 2011; 2: 18
Choi I, Steibel JP, Bates RO, Raney NE, Rumph JM, Ernst CW

A three-generation resource population was constructed by crossing pigs from the Duroc and Pietrain breeds. In this study, 954 F(2) animals were used to identify quantitative trait loci (QTL) affecting carcass and meat quality traits. Based on results of the first scan analyzed with a line-cross (LC) model using 124 microsatellite markers and 510 F(2) animals, 9 chromosomes were selected for genotyping of additional markers. Twenty additional markers were genotyped for 954 F(2) animals and 20 markers used in the first scan were genotyped for 444 additional F(2) animals. Three different Mendelian models using least-squares for QTL analysis were applied for the second scan: a LC model, a half-sib (HS) model, and a combined LC and HS model. Significance thresholds were determined by false discovery rate (FDR). In total, 50 QTL using the LC model, 38 QTL using the HS model, and 3 additional QTL using the combined LC and HS model were identified (q < 0.05). The LC and HS models revealed strong evidence for QTL regions on SSC6 for carcass traits (e.g., 10th-rib backfat; q < 0.0001) and on SSC15 for meat quality traits (e.g., tenderness, color, pH; q < 0.01), respectively. QTL for pH (SSC3), dressing percent (SSC7), marbling score and moisture percent (SSC12), CIE a* (SSC16), and carcass length and spareribs weight (SSC18) were also significant (q < 0.01). Additional marker and animal genotypes increased the statistical power for QTL detection, and applying different analysis models allowed confirmation of QTL and detection of new QTL.

Front Genet. 2011; 2: 16
Zielke LG, Bortfeldt RH, Tetens J, Brockmann GA

The gene encoding the brain-derived neurotrophic factor (BDNF) has been repeatedly associated with human obesity. As such, it could also contribute to the regulation of energy partitioning and the amount of secreted milk fat during lactation, which plays an important role in milk production in dairy cattle. Therefore, we performed an association study using estimated breeding values (EBVs) of bulls and yield deviations of German Holstein dairy cattle to test the effect of BDNF on milk fat yield (FY). A highly significant effect (corrected p-value = 3.362 × 10(-4)) was identified for an SNP 168 kb up-stream of the BDNF transcription start. The association tests provided evidence for an additive allele effect of 5.13 kg of fat per lactation on the EBV for milk FY in bulls and 6.80 kg of fat of the own production performance in cows explaining 1.72 and 0.60% of the phenotypic variance in the analyzed populations, respectively. The analyses of bulls and cows consistently showed three haplotype groups that differed significantly from each other, suggesting at least two different mutations in the BDNF region affecting the milk FY. The FY increasing alleles also had low but significant positive effects on protein and total milk yield which suggests a general role of the BDNF region in energy partitioning, rather than a specific regulation of fat synthesis. The results obtained in dairy cattle suggest similar effects of BDNF on milk composition in other species, including man.

Zookeys. 2011; 85-103
Duy-Jacquemin MN, Uys C, Geoffroy JJ

Two new species of the families Polyxenidae and Synxenidae, are described from Table Mountain National Park, South Africa. Propolyxenus squamatussp. n. (Polyxenidae) has tergites I-X mostly covered by scale-shaped trichomes directed caudally, a character previously known only in Synxenidae. The structure of scale-shaped dorsal trichomes is different to that of the scales in Phryssonotus and Condexenus species. Phryssonotus brevicapensissp. n. (Synxenidae) is the only known species of the genus Phryssonotus having 11 tergites, (including collum and telson) and 15 pairs of legs, as in Condexenus biramipalpus Nguyen Duy-Jacquemin, 2006. These two species therefore appear to occupy an intermediate position between Phryssonotus (12 tergites) and Polyxenoidea (maximum of 11 tergites).

J Chem Crystallogr. 2011 Nov; 41(11): 1712-1716
Rajapakse A, Barnes CL, Gates KS

The helicene, pyrido[3,2-f]quinolino[6,5-c]cinnoline 5-oxide, was prepared by treatment of 6-hydroxylaminoquinoline with xanthine oxidase or treatment of 6-nitroquinoline with glucose in 30% NaOH and the product characterized using NMR, high resolution mass spectrometry, and X-ray crystallography. The hydrogens on carbons 7 and 12 of the terminal aromatic rings are separated by 2.495 Å creating an angle of 25.0° between the planes of the two quinoline ring systems. In the crystal, water molecules serve to link the helicenes into a one dimensional chain structure forming a hydrogen bonded bridge between N2 of one molecule and N4 of another. The molecule (C(18)H(10)N(4)O•H(2)O) crystallized in the monoclinic P2(1)/n space group. Unit cell parameters for pyrido[3,2-f]quinolino[6,5-c]cinnoline 5-oxide monohydrate: a = 7.0829(12), b = 18.559(3), c = 11.0985(19) Å, β = 107.736(2)°, and Z = 4.

Phlebology. 2012 Feb 1;
Eivazi B, Fasunla AJ, Güldner C, Masberg P, Werner JA, Teymoortash A

Objectives/HypothesisPhleboliths in venous malformations (VM) of the head and neck are often observed and may cause significant symptoms. Only a few articles refer to the morphology and composition of the phleboliths in VM. The objective of this study was to analyse and to demonstrate their composition and morphology. METHODS: Patients with VM presenting to a vascular anomalies centre during a three-year period were identified. The incidence of phleboliths was analysed followed by morphological and structural analysis with cone beam tomography and X-ray diffraction. RESULTS: Phleboliths were identified in 28/98 patients with VM of the head and neck. Seven patients underwent conventional surgery to reduce the volume of the VM or to remove the phleboliths, which were localized in the cheek (3 cases), submandibular region (2 cases), infrahyoidal neck or upper eyelid (1 case each). The structural analysis showed that more advanced lamination and an increasing radiopacity of the cortex was observed in larger phleboliths. X-ray powder diffraction analysis revealed that the main constituent in the pulverized phleboliths was carbonate-fluorohydroxylapatite. CONCLUSION: This study shows in a vivid way that phleboliths from VM of the head and neck area show a laminar structure and consist of apatite, without any indication of differences in their chemical composition. Treatment of localized intravascular coagulopathy in VM might be able to prevent the formation and the progression of phleboliths. Hypothetically, another option might be lithotripsy.

Luminescence. 2012 Feb 2;
Hu Y, Yang JP, Liu JS

Mn-doped willemite (Zn(2) SiO(4) :Mn) green phosphor were synthesized by sol-gel technology. The effect of the addition of sodium, as in the composition Zn((1.92 - X)) Na(X) Mn(0.08) SiO(4) , on the emission behavior was studied. FT-IR and EPR results revealed that sodium ion is incorporated into the lattice and results in the formation of isolated Mn(2+) and Mn-Mn pairs. The maximum emission intensity of the sample under ultraviolet (UV) excitation occurred at the sodium concentration of x = ~0.03. The green emission at about 525 nm is assigned to Mn(2+) -Mn(2+) pair centres on nearest neighbour Zn sites. The highest intensity of the green emission for x = ~0.03 is well close to the highest concentration of the Mn(2+) -Mn(2+) pair. Copyright © 2012 John Wiley & Sons, Ltd.

Biol Reprod. 2012 Feb 1;
Halder SK, Sharan C, Al-Hendy A

Uterine leiomyomas (fibroids) are the most common benign tumors in women of reproductive age. These tumors are three to four times more prevalent in African American women, who also have a ten times higher incidence of hypovitaminosis D than white women. Recent studies have demonstrated the anti-tumor effects of 1,25-dihydroxyvitamin D3 on several cancers, but its effects on uterine leiomyomas are still unknown. To determine the anti-tumor and therapeutic effects of 1,25-dihydroxyvitamin D3 on uterine leiomyomas, female Eker rats (14-16 mo old) harboring uterine leiomyomas were randomized into control and experimental groups and were given vehicle versus 1,25-dihydroxyvitamin D3 (0.5 µg/kg/day) subcutaneously for three weeks, respectively. At the end of the experiment, the rats were sacrificed, and the leiomyoma tumors were analyzed. Treatment with 1,25-dihydroxyvitamin D3 significantly reduced leiomyoma tumor size in Eker rats. It also reduced leiomyoma size by suppressing cell growth and proliferation-related genes (Pcna, cyclin D1 [Ccnd1], Myc, Cdk1, Cdk2, and Cdk4), anti-apoptotic genes (Bcl2 and Bcl2l1 [Bcl-x]) and estrogen and progesterone receptors. Additionally, immunohistochemistry revealed decreased expression of PCNA and MKI67 (a marker of proliferation) and increased expression of caspase 3 in 1,25-dihydroxyvitamin D3-treated Eker rat leiomyomas. Toxicity analyses using serum samples showed similar levels of SGOT, SGPT, calcium and total bilirubin in 1,25-dihydroxyvitamin D3-treated and vehicle-treated control Eker rats. These results support that 1,25-dihydroxyvitamin D3 is an antitumor agent that may be a potential safe, non-surgical therapeutic option for the treatment of uterine leiomyomas.

J Antimicrob Chemother. 2012 Feb 1;
Kromdijk W, Mulder JW, Rosing H, Smit PM, Beijnen JH, Huitema AD

OBJECTIVES: Plasma concentrations are frequently used for therapeutic drug monitoring of antiretroviral drugs. Dried blood spot sampling offers a patient-friendly and easy alternative to plasma sampling. However, dried blood spot concentrations are not necessarily equal to plasma concentrations and therefore the objective of this work was to establish the relationship between nevirapine and efavirenz dried blood spot and plasma concentrations to facilitate clinical implementation of dried blood spot sampling. METHODS: Paired dried blood spot and plasma samples were obtained from 40 HIV-infected patients on nevirapine and 40 on efavirenz treatment. All samples were analysed using validated HPLC-tandem mass spectrometry methods for the two matrices. Theoretical plasma concentrations were calculated from dried blood spot concentrations using the formula [dried blood spot concentration/(1 - haematocrit)] × fraction bound to plasma proteins = plasma concentration. Linear regression and Bland-Altman analysis were used to compare the two methods. RESULTS: Dried blood spot and plasma concentrations of nevirapine and efavirenz correlated well (r(2) = 0.867 and 0.972, respectively), although efavirenz dried blood spot concentrations were 39.8% (SD 7.1%) lower than plasma concentrations. Theoretical plasma concentrations (using patient-specific haematocrit) of nevirapine and efavirenz were similar to measured plasma concentrations, with a mean difference between the two methods of 0.29 mg/L (SD 1.35 mg/L) and 0.08 mg/L (SD 0.31 mg/L), respectively. CONCLUSIONS: Dried blood spot concentrations of nevirapine and efavirenz were equal to plasma concentrations after correction for haematocrit and compound-specific plasma protein binding and can therefore be used in clinical practice.