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This study investigated the ractopamine (RAC) distribution and depletion process in goat plasma, urine and various muscle tissues which were associated with a potential risk for consumer health. The experiment was carried out in 21 goats (18 treated and 3 controls). Treated animals were administered orally a dose of 1 mg/kg body mass per day for 28 consecutive days and randomly sacrificed on Days 0.25, 1, 3, 7, 14 and 21 of the withdrawal period. RAC in goat samples was analyzed by using ultra-high performance liquid chromatography-quadrupole-orbitrap high-resolution mass spectrometry. RAC was below the limits of detection (LOD = 0.15 ng/mL) in plasma while which was higher than the LOD in urine on withdrawal day 21. The residues in goat longissimus dorsi muscle, biceps femoris muscle and triceps surae muscle were differed significantly. These findings demonstrated that urine can be used as the target matrix for monitoring RAC abuse in goat. [ABSTRACT FROM AUTHOR]

The taxonomic status of subspecies of Hipposideros pomona (Mammalia: Chiroptera: Hipposideridae) in China is controversial and uncertain. To explore the differences and subspecies differentiation in H. pomona from different regions of China, we conducted a series of bat surveys from 2011 to 2014. We performed multivariate morphometric analyses using 16 external and 21 skull measurements based on 100 samples and compared DNA sequence divergence. The results revealed distinct differences in both the external and skull measurements of H. pomona. The Cytb and COI sequence divergences of H. pomona from 3 regions ranged from 6.0% to 8.5% and 5.2% to 8.0%, respectively, which reached the levels required for subspecies classification. In contrast, the RAG1 gene was not considered to be a good molecular marker for identifying subspecies because the sequence divergence was 0-0.7% within a region and 0-0.8% among regions. Both the morphological and molecular results of this study supported the conclusion that H. pomona from the Min-Guang coastal (SM), South Yunnan (SY), and Hainan Island (SH) subregions in South China belonged to different subspecies. The SM population represents H. p. sinesis, and the SH population may be a unique subspecies. Whether the SY population belongs to H. p. gentilis requires further study. [ABSTRACT FROM AUTHOR]

This study was conducted to investigate the deposition and depletion process of clenbuterol (CL) in goat tissues, plasma and urine after the repeated administration of a growth-promoting dose. The experiment was conducted in 24 goats (21 treated and 3 controls). Treated animals were administered orally in a dose of 16 µg/kg body mass once daily for 21 consecutive days and randomly sacrificed on days 0.25, 1, 3, 7, 14, 21 and 28 of the withdrawal period. CL in goat tissues was extracted with organic solvents and determined using liquid chromatography tandem mass spectrometry. The depletion rates of tissue differed significantly. The highest concentrations of CL in all tissues are detected on day 0.25 of treatment discontinuation. After administration had been discontinued for 28 days, CL still residues in all tissues, especially, in whole eye, where the concentrations reach 363.29 ± 31.60 µg/kg. These findings confirmed that the whole eye, which are rich in pigment, showed a much higher concentration than any other studied tissue during the withdrawal period. [ABSTRACT FROM AUTHOR]

BACKGROUND: Folate metabolism is critical to embryonic development, influencing neural tube defects (NTD) and recurrent early pregnancy loss. Polymorphisms in 5,10-methylenetetrahydrofolate reductase (MTHFR) have been associated with dizygotic (DZ) twinning through pregnancy loss. METHODS: The C677T and A1298C polymorphisms in MTHFR were genotyped in 258 Australasian families (1016 individuals) and 118 Dutch families (462 individuals) of mothers of DZ twins and a population sample of 462 adolescent twin families (1861 individuals). Haplotypes were constructed from the alleles, and transmission of the MTHFR haplotypes to mothers of DZ twins and from parents to twins in the adolescent twin families analysed. RESULTS: The C677T and A1298C were common in all three populations (frequencies > 0.29). There was strong linkage disequilibrium (D′ = 1) between the variants, showing that specific combinations of alleles (haplotypes) were transmitted together. Three haplotypes accounted for nearly all the variation. There was no evidence of any association between MTHFR genotype and twinning in mothers of twins, or of the loss of specific MTHFR genotypes during twin pregnancies. CONCLUSIONS: It is concluded that variation in twinning frequency is not associated with MTHFR genotype. [ABSTRACT FROM AUTHOR]

BACKGROUND Spontaneous dizygotic (DZ) twinning in humans is under genetic control. In sheep, heterozygous loss of function mutations in bone morphogenetic protein 15 (BMP15) increase ovulation and hence twinning rates. METHODS To investigate the role of BMP15 in human twinning, we typed 14 common variants, 4 rare novel variants initially detected by sequencing 279 mothers of DZ twins (MODZT) and 17 variants previously associated with premature ovarian failure (POF) in 933 DZ twinning families. We also typed five additional POF associated GDF9 variants. RESULTS There was some evidence for association between DZ twinning and a common intronic BMP15 variant (rs3897937), but this was not significant after correction for multiple testing. Three of the four novel variants (p.Pro174Ser, p.Ala311Thr and p.Arg392Thr) occurred in 1–5 MODZT but were not detected in 1512 controls. We also detected three POF associated mutations in both BMP15 and GDF9 at low frequencies in MODZT and controls. CONCLUSIONS We conclude that neither rare nor common BMP15 variants play a significant role in the variation in human DZ twinning. [ABSTRACT FROM AUTHOR]

BACKGROUND Endometriosis is a polygenic disease with a complex and multifactorial aetiology that affects 8–10% of women of reproductive age. Epidemiological data support a link between endometriosis and cancers of the reproductive tract. Fibroblast growth factor receptor 2 (FGFR2) has recently been implicated in both endometrial and breast cancer. Our previous studies on endometriosis identified significant linkage to a novel susceptibility locus on chromosome 10q26 and the FGFR2 gene maps within this linkage region. We therefore hypothesized that variation in FGFR2 may contribute to the risk of endometriosis. METHODS We genotyped 13 single nucleotide polymorphisms (SNPs) densely covering a 27 kb region within intron 2 of FGFR2 including two SNPs (rs2981582 and rs1219648) significantly associated with breast cancer and a total 40 tagSNPs across 150 kb of the FGFR2 gene. SNPs were genotyped in 958 endometriosis cases and 959 unrelated controls. RESULTS We found no evidence for association between endometriosis and FGFR2 intron 2 SNPs or SNP haplotypes and no evidence for association between endometriosis and variation across the FGFR2 gene. CONCLUSIONS Common variation in the breast-cancer implicated intron 2 and other highly plausible causative candidate regions of FGFR2 do not appear to be a major contributor to endometriosis susceptibility in our large Australian sample. [ABSTRACT FROM AUTHOR]

BACKGROUND Endometriosis is a polygenic disease with a complex and multifactorial aetiology that affects 8–10% of women of reproductive age. Epidemiological data support a link between endometriosis and cancers of the reproductive tract. Fibroblast growth factor receptor 2 (FGFR2) has recently been implicated in both endometrial and breast cancer. Our previous studies on endometriosis identified significant linkage to a novel susceptibility locus on chromosome 10q26 and the FGFR2 gene maps within this linkage region. We therefore hypothesized that variation in FGFR2 may contribute to the risk of endometriosis. METHODS We genotyped 13 single nucleotide polymorphisms (SNPs) densely covering a 27 kb region within intron 2 of FGFR2 including two SNPs (rs2981582 and rs1219648) significantly associated with breast cancer and a total 40 tagSNPs across 150 kb of the FGFR2 gene. SNPs were genotyped in 958 endometriosis cases and 959 unrelated controls. RESULTS We found no evidence for association between endometriosis and FGFR2 intron 2 SNPs or SNP haplotypes and no evidence for association between endometriosis and variation across the FGFR2 gene. CONCLUSIONS Common variation in the breast-cancer implicated intron 2 and other highly plausible causative candidate regions of FGFR2 do not appear to be a major contributor to endometriosis susceptibility in our large Australian sample. [ABSTRACT FROM AUTHOR]

The tendency to conceive spontaneous dizygotic (DZ) twins is a complex trait with important contributions from both environmental factors and genetic disposition. Twins are relatively common and occur on average 13 times per 1000 maternities, though the twinning frequency varies over time and geographic location. This variation is mostly attributed to the differences in DZ twinning rate, since the monozygotic twinning rate is relatively constant. DZ twinning is in part under genetic control, with mothers of DZ twins reporting significantly more female family members with DZ twins than mothers of monozygotic twins. Maternal factors such as genetic history, advanced age and increased parity are known to increase the risk of DZ twins. Recent research confirmed that taller mothers and mothers with a high body mass index (30>) are at greater risk of DZ twinning. Seasonality, smoking, oral contraceptive use and folic acid show less convincing associations with twinning. Genetic analysis is beginning to identify genes contributing to the variation in twinning. Mutations in one of these genes (growth differentiation factor 9) are significantly more frequent in mothers of DZ twins. However, the mutations are rare and only account for a small part of the genetic contribution for twinning. [ABSTRACT FROM AUTHOR]

Ribosome biogenesis is an orchestrated process that relies on many assembly factors. The AAA-ATPase Midasin 1 (Mdn1) functions as a ribosome assembly factor in yeast (Saccharomyces cerevisiae), but the roles of MDN1 in Arabidopsis (Arabidopsis thaliana) are poorly understood. Here, we showed that the Arabidopsis null mutant of MDN1 is embryo-lethal. Using the weak mutant mdn1-1, which maintains viability, we found that MDN1 is critical for the regular pattern of auxin maxima in the globular embryo and functions in root meristem maintenance. By detecting the subcellular distribution of ribosome proteins, we noted that mdn1-1 impairs nuclear export of the pre-60S ribosomal particle. The processing of ribosomal precusor RNAs, including 35S, 27SB, and 20S, is also affected in this mutant. MDN1 physically interacts with PESCADILLO2 (PES2), an essential assembly factor of the 60S ribosome, and the observed mislocalization of PES2 in mdn1-1 further implied that MDN1 plays an indispensable role in 60S ribosome biogenesis. Therefore, the observed hypersensitivity of mdn1-1 to a eukaryotic translation inhibitor and high-sugar conditions might be associated with the defect in ribosome biogenesis. Overall, this work establishes a role of Arabidopsis MDN1 in ribosome biogenesis, which agrees with its roles in embryogenesis and root development. [ABSTRACT FROM AUTHOR]

In order to monitor salbutamol (SAL) use in goats as a repartitioning, we determined SAL residues in various tissues of goats after repeated oral SAL administration at a dose of 0.15mg/kg daily for 21 days. SAL concentrations were measured by ultra performance liquid chromatography tandem mass spectrometry in extracts of tissues from goats sacrificed 0.25, 1, 3, 7, 14, 21 and 28 days after the last dose. Our results showed that on Day 0.25 of the withdrawal period, the residual proportions of SAL (expressed as percentage) in liver, kidney, lung, hair, stomachs and muscle were 19.5%, 15.3%, 3.3%, 9.6%, 28.2% and 0.8%, respectively. As the withdrawal time increased, the SAL concentrations in most tissues (except hair) decreased rapidly over the first 3 days and more slowly in the following 25 days. After a 28-day withdrawal period, hair, lung, muscle, liver, fat, eyes, rumen, kidney and abomasum still contained ~32.3%, 15.3%, 7.1%, 6.5%, 5.6%, 1.5%, 0.8% and 0.5% compared to the initial residual concentrations determined on Day 0.25, respectively. On withdrawal Day 28, the highest concentrations of SAL were found in hair (16.58 ± 9.48 μg/kg), followed by liver (7.01 ± 0.94 μg/kg), lung (2.81 ± 1.23 μg/kg), kidney (0.64 ± 0.56 μg/kg), whereas the concentrations in other tissues were lower than limit of quantification (0.50 μg/kg). SAL residues were not detected in bile, plasma and brain on Days 7, 7 and 3 after discontinuation of dosing. These findings indicated that the distribution and depletion rates of SAL differed between tissues. It should be noted that SAL residues in stomach were higher than those in muscles during the early withdrawal. We conclude that hair is the preferred tissue to monitor the administration of SAL to living goats, whereas liver can be used to monitor SAL in the carcass for determination of compliance with food safety regulation. [ABSTRACT FROM AUTHOR]

STUDY QUESTIONS: DO DNA variants in the growth regulation by estrogen in breast cancer 1 (GREB1) region regulate endometrial GREB1 expression and increase the risk of developing endometriosis in women? SUMMARY ANSWER: We identified new single nucleotide polymorphisms (SNPs) with strong association with endometriosis at the GREB 1 locus although we did not detect altered GREB 1 expression in endometriosis patients with defined genotypes. WHAT IS ALREADY KNOWN: Genome-wide association studies have identified the GREB 1 region on chromosome 2p25.1 for increasing endometriosis risk. The differential expression of GREB 1 has also been reported by others in association with endometriosis disease phenotype. STUDY DESIGN, SIZE, DURATION: Fine mapping studies comprehensively evaluated SNPs within the GREB 1 region in a large-scale data set (.2500 cases and .4000 controls). Publicly available bioinformatics tools were employed to functionally annotate SNPs showing the strongest association signal with endometriosis risk. Endometrial GREB1 mRNA and protein expression was studied with respect to phases of the menstrual cycle (n = 2-45 per cycle stage) and expression quantitative trait loci (eQTL) analysis for significant SNPs were undertaken for GREB1 [mRNA (n = 94) and protein (n = 44) in endometrium]. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants in this study are females who provided blood and/or endometrial tissue samples in a hospital setting. The key SNPs were genotyped using Sequenom MASS ARRAY. The functional roles and regulatory annotations for identified SNPs are predicted by various publicly available bioinformatics tools. Endometrial GREB1 expression work employed qRT-PCR, western blotting and immunohistochemistry studies. MAIN RESULTS AND THE ROLE OF CHANCE: Fine mapping results identified a number of SNPs showing stronger association (0.004, P, 0.032) with endometriosis risk than the original GWASSNP (rs 13394619) (P = 0.034). Some of these SNPs were predicted to have functional roles, for example, interaction with transcription factor motifs. The haplotype (a combination of alleles) formed by the risk alleles from two common SNPs showed significant association (P = 0.026) with endometriosis and epistasis analysis showed no evidence for interaction between the two SNPs, suggesting an additive effect of SNPs on endometriosis risk. In normal human endometrium, GREB1 protein expression was altered depending on the cycle stage (significantly different in late proliferative versus late secretory, P, 0.05) and cell type (glandular epithelium, not stromal cells). However, GREB 1 expression in endometriosis cases versus controls and eQTL analyses did not reveal any significant changes. LIMITATIONS, REASONS FOR CAUTION: In silico prediction tools are generally based on cell lines different to our tissue and disease of interest. Functional annotations drawn from these analyses should be considered with this limitation in mind. We identified cell-specific and hormone-specific changes in GREB 1 protein expression. The lack of a significant difference observed following our GREB 1 expression studies may be the result of moderate power on mixed cell populations in the endometrial tissue samples. WIDER IMPLICATIONS OF THE FINDINGS: This study further implicates the GREB1 region on chromosome 2p25.1 and the GREB1 gene with involvement in endometriosis risk. More detailed functional studies are required to determine the role of the novel GREB 1 transcripts in endometriosis pathophysiology. [ABSTRACT FROM AUTHOR]

Background. Age and host genetics are important determinants of malaria severity. Lymphotoxin-a (LTa) has been associated with the development of cerebral malaria (CM) and other severe malaria (SM) syndromes. Mutations in genes regulating LTa production contribute to other acute vascular diseases and may contribute to malaria pathogenesis. Methods. We tested the association between rs7291467, a single-nucleotide polymorphism (SNP) in the LTarelated gene encoding galectin-2 (LGALS2), disease severity, and function in a case-control study of ethnic Highland Papuan adults and children with SM (np380) and asymptomatic malaria-exposed controls (np356) originating from a non-malaria-endemic region but residing in a lowland malaria-endemic area of Papua, Indonesia. Results. The LGALS2 SNP showed a significant association with susceptibility to SM (including CM), in children (odds ratio, 2.02 [95% confidence interval, 1.14-3.57]) but not in adults. In SM, the C allele at rs7291467 was associated with enhanced galectin-2 transcript levels. In a separate group of Tanzanian children originating from a malaria-endemic region, we found preservation of the major ancestral LGALS2 allele and no association with susceptibility to CM. Conclusions. Results suggest differences in the inflammatory contribution to the development of SM between children and adults in the same population and potential differences between individuals originating from malariaendemic and non-malaria-endemic areas. [ABSTRACT FROM AUTHOR]

BACKGROUND Genetic variation contributes to the risk of developing endometriosis. This review summarizes gene mapping studies in endometriosis and the prospects of finding gene pathways contributing to disease using the latest genome-wide strategies. METHODS To identify candidate-gene association studies of endometriosis, a systematic literature search was conducted in PubMed of publications up to 1 April 2008, using the search terms ‘endometriosis’ plus ‘allele’ or ‘polymorphism’ or ‘gene’. Papers included were those with information on both case and control selection, showed allelic and/or genotypic results for named germ-line polymorphisms and were published in the English language. RESULTS Genetic variants in 76 genes have been examined for association, but none shows convincing evidence of replication in multiple studies. There is evidence for genetic linkage to chromosomes 7 and 10, but the genes (or variants) in these regions contributing to disease risk have yet to be identified. Genome-wide association is a powerful method that has been successful in locating genetic variants contributing to a range of common diseases. Several groups are planning these studies in endometriosis. For this to be successful, the endometriosis research community must work together to genotype sufficient cases, using clearly defined disease classifications, and conduct the necessary replication studies in several thousands of cases and controls. CONCLUSIONS Genes with convincing evidence for association with endometriosis are likely to be identified in large genome-wide studies. This will provide a starting point for functional and biological studies to develop better diagnosis and treatment for this debilitating disease. [ABSTRACT FROM AUTHOR]