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Sample records for fascicularis dra polymorphism

  1. Polymorphisms of the equine major histocompatibility complex class II DRA locus.

    PubMed

    Brown, J J; Thomson, W; Clegg, P; Eyre, S; Kennedy, L J; Matthews, J; Carter, S; Ollier, W E R

    2004-08-01

    The full extent of the polymorphism of ELA-DRA in Equidae is not yet known. Given the apparent differences in DRA polymorphisms between Equidae and other species, the aims of this study were to more fully characterize ELA-DRA, determine the extent of gene polymorphism and establish the allele-frequency distribution. An allele reference panel for the second exon of ELA-DRA was established by sequence-based typing of 69 equine DNA samples consisting of various breeds of domestic horse (Equus caballus), together with donkeys (Equus asinus), Grant's zebras (Equus boehmi) and one onager (Equus hemionus). Five of the six previously reported alleles detected using single-strand conformation polymorphism were found: ELA-DRA*0101, ELA-DRA*0201, ELA-DRA*0301, ELA-DRA*0501 (Albright-Fraser DG et al. Polymorphism of DRA among equids. Immunogenetics 1996: 43: 315-7) and ELA-DRA*0601 (GenBank accession number AF5419361). In addition to the previously reported alleles, five novel ELA-DRA alleles were detected within the ELA-DRA allele reference panel. One of these was identified in E. caballus (ELA-DRA*JBH11), one in E. boehmi and E. hemionus (ELA-DRA*JBZ185) and three in E. asinus (ELA-DRA*JBD3, ELA-DRA*JBD17 and ELA-DRA*JBH45). A total of 565 equine DNA samples were screened using reference-strand-mediated conformation analysis, a double-stranded conformation-based mutation detection system that can be used to type existing ELA-DRA alleles and identify new variants. Based on our findings, at least 11 ELA-DRA alleles are now known to exist, and this level of polymorphism at the DRA locus appears to be unique to the genus Equus. Both the previously reported alleles and the new alleles displayed a species-specific distribution.

  2. Polymorphism and selection in the major histocompatibility complex DRA and DQA genes in the family Equidae.

    PubMed

    Janova, Eva; Matiasovic, Jan; Vahala, Jiri; Vodicka, Roman; Van Dyk, Enette; Horin, Petr

    2009-07-01

    The major histocompatibility complex genes coding for antigen binding and presenting molecules are the most polymorphic genes in the vertebrate genome. We studied the DRA and DQA gene polymorphism of the family Equidae. In addition to 11 previously reported DRA and 24 DQA alleles, six new DRA sequences and 13 new DQA alleles were identified in the genus Equus. Phylogenetic analysis of both DRA and DQA sequences provided evidence for trans-species polymorphism in the family Equidae. The phylogenetic trees differed from species relationships defined by standard taxonomy of Equidae and from trees based on mitochondrial or neutral gene sequence data. Analysis of selection showed differences between the less variable DRA and more variable DQA genes. DRA alleles were more often shared by more species. The DQA sequences analysed showed strong amongst-species positive selection; the selected amino acid positions mostly corresponded to selected positions in rodent and human DQA genes.

  3. ELA-DRA polymorphisms are not associated with Equine Arteritis Virus infection in horses from Argentina.

    PubMed

    Kalemkerian, P B; Metz, G E; Peral-Garcia, P; Echeverria, M G; Giovambattista, G; Díaz, S

    2012-12-01

    Polymorphisms at Major Histocompatibility Complex (MHC) genes have been associated with resistance/susceptibility to infectious diseases in domestic animals. The aim of this investigation was to evaluate whether polymorphisms of the DRA gene the Equine Lymphocyte Antigen is associated with susceptibility to Equine Arteritis Virus (EAV) infection in horses in Argentina. The equine DRA gene was screened for polymorphisms using Pyrosequencing® Technology which allowed the detection of three ELA-DRA exon 2 alleles. Neither allele frequencies nor genotypic differentiation exhibited any statistically significant (P-values=0.788 and 0.745) differences between the EAV-infected and no-infected horses. Fisher's exact test and OR calculations did not show any significant association. As a consequence, no association could be established between the serological condition and ELA-DRA.

  4. Extensive polymorphism of the major histocompatibility complex DRA gene in Balkan donkeys: perspectives on selection and genealogy.

    PubMed

    Arbanasić, Haidi; Galov, Ana; Ambriović-Ristov, Andreja; Grizelj, Juraj; Arsenos, Georgios; Marković, Božidarka; Dovenski, Toni; Vince, Silvijo; Curik, Ino

    2013-12-01

    The major histocompatibility complex (MHC) contains genes important for immune response in mammals, and these genes exhibit high polymorphism and diversity. The DRA gene, a member of the MHC class II family, is highly conserved across a large number of mammalian species, but it displays exceptionally rich sequence variations in Equidae members. We analyzed allelic polymorphism of the DRA locus in 248 donkeys sampled across the Balkan Peninsula (Albania, Bulgaria, Croatia, Macedonia, Greece and Montenegro). Five known alleles and two new alleles were identified. The new allele Eqas-DRA*0601 was found to carry a synonymous mutation, and new allele Eqas-DRA*0701, a non-synonymous mutation. We further analyzed the historical selection and allele genealogy at the DRA locus in equids. Signals of positive selection obtained by various tests were ambiguous. A conservative conclusion is that DRA polymorphism occurred relatively recently and that positive selection has been acting on the DRA locus for a relatively brief period.

  5. Trans-species polymorphism and selection in the MHC class II DRA genes of domestic sheep.

    PubMed

    Ballingall, Keith T; Rocchi, Mara S; McKeever, Declan J; Wright, Frank

    2010-06-30

    Highly polymorphic genes with central roles in lymphocyte mediated immune surveillance are grouped together in the major histocompatibility complex (MHC) in higher vertebrates. Generally, across vertebrate species the class II MHC DRA gene is highly conserved with only limited allelic variation. Here however, we provide evidence of trans-species polymorphism at the DRA locus in domestic sheep (Ovis aries). We describe variation at the Ovar-DRA locus that is far in excess of anything described in other vertebrate species. The divergent DRA allele (Ovar-DRA*0201) differs from the sheep reference sequences by 20 nucleotides, 12 of which appear non-synonymous. Furthermore, DRA*0201 is paired with an equally divergent DRB1 allele (Ovar-DRB1*0901), which is consistent with an independent evolutionary history for the DR sub-region within this MHC haplotype. No recombination was observed between the divergent DRA and B genes in a range of breeds and typical levels of MHC class II DR protein expression were detected at the surface of leukocyte populations obtained from animals homozygous for the DRA*0201, DRB1*0901 haplotype. Bayesian phylogenetic analysis groups Ovar-DRA*0201 with DRA sequences derived from species within the Oryx and Alcelaphus genera rather than clustering with other ovine and caprine DRA alleles. Tests for Darwinian selection identified 10 positively selected sites on the branch leading to Ovar-DRA*0201, three of which are predicted to be associated with the binding of peptide antigen. As the Ovis, Oryx and Alcelaphus genera have not shared a common ancestor for over 30 million years, the DRA*0201 and DRB1*0901 allelic pair is likely to be of ancient origin and present in the founding population from which all contemporary domestic sheep breeds are derived. The conservation of the integrity of this unusual DR allelic pair suggests some selective advantage which is likely to be associated with the presentation of pathogen antigen to T-cells and the

  6. Trans-Species Polymorphism and Selection in the MHC Class II DRA Genes of Domestic Sheep

    PubMed Central

    Ballingall, Keith T.; Rocchi, Mara S.; McKeever, Declan J.; Wright, Frank

    2010-01-01

    Highly polymorphic genes with central roles in lymphocyte mediated immune surveillance are grouped together in the major histocompatibility complex (MHC) in higher vertebrates. Generally, across vertebrate species the class II MHC DRA gene is highly conserved with only limited allelic variation. Here however, we provide evidence of trans-species polymorphism at the DRA locus in domestic sheep (Ovis aries). We describe variation at the Ovar-DRA locus that is far in excess of anything described in other vertebrate species. The divergent DRA allele (Ovar-DRA*0201) differs from the sheep reference sequences by 20 nucleotides, 12 of which appear non-synonymous. Furthermore, DRA*0201 is paired with an equally divergent DRB1 allele (Ovar-DRB1*0901), which is consistent with an independent evolutionary history for the DR sub-region within this MHC haplotype. No recombination was observed between the divergent DRA and B genes in a range of breeds and typical levels of MHC class II DR protein expression were detected at the surface of leukocyte populations obtained from animals homozygous for the DRA*0201, DRB1*0901 haplotype. Bayesian phylogenetic analysis groups Ovar-DRA*0201 with DRA sequences derived from species within the Oryx and Alcelaphus genera rather than clustering with other ovine and caprine DRA alleles. Tests for Darwinian selection identified 10 positively selected sites on the branch leading to Ovar-DRA*0201, three of which are predicted to be associated with the binding of peptide antigen. As the Ovis, Oryx and Alcelaphus genera have not shared a common ancestor for over 30 million years, the DRA*0201 and DRB1*0901 allelic pair is likely to be of ancient origin and present in the founding population from which all contemporary domestic sheep breeds are derived. The conservation of the integrity of this unusual DR allelic pair suggests some selective advantage which is likely to be associated with the presentation of pathogen antigen to T-cells and the

  7. Dr(a-) polymorphism of decay accelerating factor. Biochemical, functional, and molecular characterization and production of allele-specific transfectants.

    PubMed Central

    Lublin, D M; Thompson, E S; Green, A M; Levene, C; Telen, M J

    1991-01-01

    The Dra antigen belongs to the Cromer-related blood group system, a series of antigens on decay accelerating factor (DAF), a glycosyl-phosphatidylinositol-anchored membrane protein that protects host cells from complement-mediated damage. We studied the rare inherited Dr(a-) phenotype to ascertain the associated biochemical and functional changes in DAF and to characterize the basis for this polymorphism. Radioimmunoassay assay and flow cytometric analysis of Dr(a-) erythrocytes demonstrated 40% of normal surface expression of DAF but normal levels of several other glycosyl-phosphatidylinositol-anchored proteins, distinguishing this phenotype from that of paroxysmal nocturnal hemoglobinuria. Western blots confirmed this reduced DAF expression and indicated a slightly faster mobility of the molecule on SDS-PAGE. Despite the reduced DAF expression, Dr(a-) erythrocytes functioned normally in the complement lysis sensitivity assay. Utilization of the polymerase chain reaction to amplify mononuclear cell genomic DNA from three unrelated Dr(a-) individuals demonstrated that a point mutation underlies the Dr(a-) phenotype: a C to T change in nucleotide 649 resulting in a serine165 to leucine change. This defines the Drb allele of DAF, which can be distinguished from Dra by a Taq I restriction fragment length polymorphism. We created transfected Chinese hamster ovary cell lines expressing either the Dra or the Drb allelic form of DAF. These allele-specific transfectants were tested by inhibition of hemagglutination or flow cytometry and confirmed the specificity of anti-Dra alloantisera. The allele-specific transfectants could form the basis of a new serological approach to immunohematology. Images PMID:1710232

  8. Single nucleotide polymorphisms (SNPs) are highly conserved in rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques

    PubMed Central

    Street, Summer L; Kyes, Randall C; Grant, Richard; Ferguson, Betsy

    2007-01-01

    Background Macaca fascicularis (cynomolgus or longtail macaques) is the most commonly used non-human primate in biomedical research. Little is known about the genomic variation in cynomolgus macaques or how the sequence variants compare to those of the well-studied related species, Macaca mulatta (rhesus macaque). Previously we identified single nucleotide polymorphisms (SNPs) in portions of 94 rhesus macaque genes and reported that Indian and Chinese rhesus had largely different SNPs. Here we identify SNPs from some of the same genomic regions of cynomolgus macaques (from Indochina, Indonesia, Mauritius and the Philippines) and compare them to the SNPs found in rhesus. Results We sequenced a portion of 10 genes in 20 cynomolgus macaques. We identified 69 SNPs in these regions, compared with 71 SNPs found in the same genomic regions of 20 Indian and Chinese rhesus macaques. Thirty six (52%) of the M. fascicularis SNPs were overlapping in both species. The majority (70%) of the SNPs found in both Chinese and Indian rhesus macaque populations were also present in M. fascicularis. Of the SNPs previously found in a single rhesus population, 38% (Indian) and 44% (Chinese) were also identified in cynomolgus macaques. In an alternative approach, we genotyped 100 cynomolgus DNAs using a rhesus macaque SNP array representing 53 genes and found that 51% (29/57) of the rhesus SNPs were present in M. fascicularis. Comparisons of SNP profiles from cynomolgus macaques imported from breeding centers in China (where M. fascicularis are not native) showed they were similar to those from Indochina. Conclusion This study demonstrates a surprisingly high conservation of SNPs between M. fascicularis and M. mulatta, suggesting that the relationship of these two species is closer than that suggested by morphological and mitochondrial DNA analysis alone. These findings indicate that SNP discovery efforts in either species will generate useful resources for both macaque species

  9. RsaI but not DraI polymorphism in CYP2E1 gene increases the risk of gastrointestinal cancer in Malaysians: a case–control study

    PubMed Central

    Chong, Eric Tzyy Jiann; Lee, Chong Cin; Chua, Kek Heng; Chuah, Jitt Aun; Lee, Ping-Chin

    2014-01-01

    Objectives Our study aimed to investigate the association of CYP2E1 C-1019T RsaI and T7678A DraI polymorphisms and factors such as age, gender and ethnicity to the risk of gastrointestinal cancer (GIC) in Malaysians. Design Case–control study. Setting Malaysia. Participants 520 consented healthy blood donors with no previous GIC record and 175 patients with GIC. Measurements C-1019T RsaI and T7678A DraI genotyping of CYP2E1 gene; direct sequencing. Results This study reveals that the variant c2 allele and carrier with at least one c2 allele of C-1019T single nucleotide polymorphism (SNP) significantly increased the risk of GIC but no significant association was found between T7678A SNP and combined analysis of C-1019T and T7678A SNPs to risk of GIC. The Malaysian Chinese had greater risk of GIC compared with the Malays, Indians and KadazanDusun. An increased risk of GIC was observed in individuals aged >40 years and women had a 2.22-fold and 1.58-fold increased risk of stomach and colorectal cancers, respectively, when compared with men. Limitations The future research should be conducted with a larger sample population and including the gene–gene and gene–environmental interactions. Conclusions Our study suggests that the rare c2 allele and carrier with at least one c2 allele of CYP2E1 RsaI polymorphism significantly elevated the risk of GIC and may be used as a genetic biomarker for early screening of GIC in Malaysians. The risk age-group has been shifted to a younger age at 40s and women showed a significant greater risk of stomach and colorectal cancers than men. PMID:24394801

  10. The PstI/RsaI and DraI polymorphisms of CYP2E1 and head and neck cancer risk: a meta-analysis based on 21 case-control studies

    PubMed Central

    2010-01-01

    Background CYP2E1 encodes a member of the cytochrome P450 superfamily of enzymes which play a central role in activating and detoxifying many carcinogens and endogenous compounds thought to be involved in the development of cancer. The PstI/RsaI and DraI polymorphism are two of the most commonly studied polymorphisms of the gene for their association with risk of head and neck cancer, but the results are conflicting. Methods We performed a meta-analysis using 21 eligible case-control studies with a total of 4,951 patients and 6,071 controls to summarize the data on the association between the CYP2E1 PstI/RsaI and DraI polymorphism and head and neck cancer risk, especially by interacting with smoking or alcohol. Results Compared with the wild genotype, the OR was 1.96 (95% CI: 1.33-2.90) for PstI/RsaI and 1.56 (95% CI: 1.06-2.27) for DraI polymorphism respectively. When stratified according to ethnicity, the OR increased in the Asians for both polymorphisms (OR = 2.04, 95% CI: 1.32-3.15 for PstI/RsaI; OR = 2.04, 95% CI: 1.27-3.29 for DraI), suggesting that the risk is more pronounced in Asians. Conclusion Our meta-analysis suggests that individuals with the homozygote genotypes of PstI/RsaI or DraI polymorphism might be associated with an increased risk of head and neck cancer, especially in Asians. PMID:20969746

  11. Swine leukocyte antigen class II genes (SLA-DRA, SLA-DRB1, SLA-DQA, SLA-DQB1) polymorphism and genotyping in Guizhou minipigs.

    PubMed

    Liu, Z Z; Xia, J H; Xin, L L; Wang, Z G; Qian, L; Wu, S G; Yang, S L; Li, K

    2015-11-30

    The swine leukocyte antigen (SLA) complex harbors highly polymorphic gene clusters encoding glycoproteins that are involved in responses to vaccines, infectious disease, and production performance. Pigs with well-defined SLA class II genes are useful for the study of disease, immunology, and vaccines. In this study, we analyzed four SLA class II genes (SLA-DRA, SLA-DRB1, SLA-DQA, SLA-DQB1) in 22 founder Guizhou minipigs using a sequence-based typing method. Twelve alleles were detected, compared with the SLA class II allele sequences in the GenBank, and one of twelve alleles was found to be novel in Guizhou minipigs. There are four SLA II haplotypes, and one of them has been previously reported in Meishan pigs. Furthermore, based on sequence information of these alleles, we developed a simple SLA typing method implemented to SLA-typing for unknown offspring of Guizhou minipigs, relying on designed twelve sequence specific primers that could discriminate between each other. According to the combination of sequence-based typing and PCR-SSP, we were able to rapidly check SLA typing of Guizhou breeding stock and identified four SLA haplotypes in the herd. Therefore, SLA-defined Guizhou minipigs will be useful as animal models for xenotransplantation and immunological research.

  12. Whole-Genome Sequencing of Six Mauritian Cynomolgus Macaques (Macaca fascicularis) Reveals a Genome-Wide Pattern of Polymorphisms under Extreme Population Bottleneck

    PubMed Central

    Osada, Naoki; Hettiarachchi, Nilmini; Adeyemi Babarinde, Isaac; Saitou, Naruya; Blancher, Antoine

    2015-01-01

    Cynomolgus macaques (Macaca fascicularis) were introduced to the island of Mauritius by humans around the 16th century. The unique demographic history of the Mauritian cynomolgus macaques provides the opportunity to not only examine the genetic background of well-established nonhuman primates for biomedical research but also understand the effect of an extreme population bottleneck on the pattern of polymorphisms in genomes. We sequenced the whole genomes of six Mauritian cynomolgus macaques and obtained an average of 20-fold coverage of the genome sequences for each individual. The overall level of nucleotide diversity was 23% smaller than that of the Malaysian cynomolgus macaques, and a reduction of low-frequency polymorphisms was observed. In addition, we also confirmed that the Mauritian cynomolgus macaques were genetically closer to a representative of the Malaysian population than to a representative of the Indochinese population. Excess of nonsynonymous polymorphisms in low frequency, which has been observed in many other species, was not very strong in the Mauritian samples, and the proportion of heterozygous nonsynonymous polymorphisms relative to synonymous polymorphisms is higher within individuals in Mauritian than Malaysian cynomolgus macaques. Those patterns indicate that the extreme population bottleneck made purifying selection overwhelmed by the power of genetic drift in the population. Finally, we estimated the number of founding individuals by using the genome-wide site frequency spectrum of the six samples. Assuming a simple demographic scenario with a single bottleneck followed by exponential growth, the estimated number of founders (∼20 individuals) is largely consistent with previous estimates. PMID:25805843

  13. AG Dra monitoring requested

    NASA Astrophysics Data System (ADS)

    Waagen, Elizabeth O.

    2017-04-01

    Dr. Rudolf Gális (Pavel Jozef Šafárik University) and colleagues have requested AAVSO assistance in observing the symbiotic variable AG Dra. Observations are requested as a follow-up to spectroscopic observations and in order to monitor the system for an anticipated outburst. Gális writes: "AG Dra is one of the best studied symbiotic systems, which undergoes characteristic symbiotic activity with alternating quiescent and active stages. The latter ones consist of several outbursts in intervals of about 1 yr. After seven years of flat quiescence following the 2006-08 major outbursts, in the spring of 2015, AG Dra...[entered the active stage]...with...two minor outbursts (in 2015 and 2016) up to now. Such behaviour is quite unusual in the photometric history of AG Dra, so the further systematic photometric monitoring of this symbiotic binary is highly desirable. We expect the next outburst of AG Dra in the late spring of 2017..." Daily monitoring of AG Dra in UBV(RI) filters is requested beginning at once and continuing until further notice. Visual observations are welcome and are encouraged. When the outburst occurs, revised observing instructions will likely be issued via an AAVSO Special Notice. Finder charts with sequence may be created using the AAVSO Variable Star Plotter (https://www.aavso.org/vsp). Observations should be submitted to the AAVSO International Database. See full Alert Notice for more details.

  14. Cytochrome P450 2E1 RsaI/PstI and DraI Polymorphisms Are Risk Factors for Lung Cancer in Mongolian and Han Population in Inner Mongolia

    PubMed Central

    Su, Xiu-lan; Bin, Ba; Cui, Hong-wei; Ran, Mei-rong

    2011-01-01

    Objective To explore the relationship between cytochrome P450 2E1 (CYP2E1) RsaI/PstI and DraI polymorphism and lung cancer susceptibility in Mongolian and Han population in Inner Mongolia of China. Methods CYP2E1 RsaI/PstI and DraI polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism in 64 lung cancer patients, 150 healthy Mongolian and 150 healthy Han individuals. The distribution of genotype and allele frequencies of CYP2E1 RsaI/PstI and DraI polymorphisms were studied. Results The risk of lung cancer was increased in individuals with CYP2E1 (cl/cl) and CYP2E1 (DD) with OR values of 2.431 (95%CI=1.082-5.460) and 2.778 (95%CI=1.358-5.683) respectively (P<0.05). When CYP2E1 RsaI/PstI and DraI polymorphisms were combined, the risk of lung cancer was reduced in individuals with CYP2E1 (cl/c2+c2/c2 and DD+CC) with OR values of 0.233 (95%CI=0.088-0.615, P<0.05). In smokers, the susceptibility to lung cancer was higher in the individuals with CYP2E1 (c1/c1) and CYP2E1 (DD) than in the individuals with c2 and C allele (P<0.05, OR=2.643 and 4.308 respectively). There was no significant difference in distribution of CYP2E1 genotype frequency between healthy Mongolian, Han population and lung cancer patients, healthy controls in Inner Mongolia. Conclusion CYP2E1 (c1/c1) and CYP2E1 (DD) are predisposing factors of lung cancer in population in Inner Mongolia. CYP2E1 (c2﹢C) co-mutation may decrease the risk of lung cancer. Smoking exerts synergetic effect with CYP2E1 (c1/c1) and CYP2E1 (DD) on the occurrence of lung cancer. PMID:23483202

  15. Mitochondrial DNA sequence phylogeny of 4 populations of the widely distributed cynomolgus macaque (Macaca fascicularis fascicularis).

    PubMed

    Blancher, Antoine; Bonhomme, Maxime; Crouau-Roy, Brigitte; Terao, Keiji; Kitano, Takashi; Saitou, Naruya

    2008-01-01

    We studied the mitochondrial DNA (mtDNA) polymorphism of 304 Macaca fascicularis fascicularis (M. f. fascicularis) individuals, representative of 4 cynomolgus macaque populations (Indochina, Indonesia, Philippines, and Mauritius). By sequencing a 590-bp fragment in the hypervariable II region of the D-loop region, we defined 70 haplotypes. The homologous region was also characterized in 22 Chinese Macaca mulatta and 2 Macaca sylvanus. The phylogenetic analysis confirms the monophyly of M. f. fascicularis and defines 2 haplotype groups inside the M. f. fascicularis clade: one "insular," encompassing 6 Philippines, 2 Mauritius, and 31 Indonesian haplotypes, the other "continental" that contains all Indochinese and 6 Indonesian haplotypes. Continental and insular group divergence time was estimated to be approximately 10(6) years before present (BP). Among Indonesian haplotypes, some have a continental origin. This suggests either direct migration from mainland to Indonesia or that remnant lineages from an ancient population genetically close to the mainland (i.e., in the Sunda Shelf, <550 000 years BP) were subsequently brought southward to Indonesia. The low nucleotide diversity in the Philippines population suggests a bottleneck following colonization by Indonesian individuals, around 110 000 years BP. mtDNA and further observations of nuclear genetic data corroborate the mixed origin (Indonesian/continental) hypothesis of Mauritius individuals and a population bottleneck.

  16. The MedDRA paradox.

    PubMed

    Merrill, Gary H

    2008-11-06

    MedDRA (the Medical Dictionary for Regulatory Activities Terminology) is a controlled vocabulary widely used as a medical coding scheme. However, MedDRA's characterization of its structural hierarchy exhibits some confusing and paradoxical features. The goal of this paper is to examine these features, determine whether there is a coherent view of the MedDRA hierarchy that emerges, and explore what lessons are to be learned from this for using MedDRA and similar terminologies in a broad medical informatics context that includes relations among multiple disparate terminologies, thesauri, and ontologies.

  17. The MedDRA Paradox

    PubMed Central

    Merrill, Gary H.

    2008-01-01

    MedDRA (the Medical Dictionary for Regulatory Activities Terminology) is a controlled vocabulary widely used as a medical coding scheme. However, MedDRA’s characterization of its structural hierarchy exhibits some confusing and paradoxical features. The goal of this paper is to examine these features, determine whether there is a coherent view of the MedDRA hierarchy that emerges, and explore what lessons are to be learned from this for using MedDRA and similar terminologies in a broad medical informatics context that includes relations among multiple disparate terminologies, thesauri, and ontologies. PMID:18998828

  18. Two new restriction endonucleases DraII and DraIII from Deinococcus radiophilus.

    PubMed Central

    Grosskopf, R; Wolf, W; Kessler, C

    1985-01-01

    In addition to recently characterized DraI (1), two new Type II restriction endonucleases, DraII and DraIII, with novel site-specificities were isolated and purified from Deinococcus radiophilus ATCC 27603. DraII and DraIII recognize the hepta- and nonanucleotide sequences (sequence in text) The cleavage sites within both strands are indicated by arrows. The recognition sequences were established by mapping of the cleavage sites on pBR322 (DraII) and fd109 RF DNA (DraIII). The sequence specifities were confirmed by computer-assisted restriction analyses of the generated fragment patterns of the sequenced DNA's of the bacteriophages lambda, phi X174 RF, M13mp8 RF and fd109 RF, the viruses Adeno2 and SV40, and the plasmids pBR322 and pBR328. The cleavage positions within the recognition sequences were determined by sequencing experiments. Images PMID:2987827

  19. Earth observation archive activities at DRA Farnborough

    NASA Technical Reports Server (NTRS)

    Palmer, M. D.; Williams, J. M.

    1993-01-01

    Space Sector, Defence Research Agency (DRA), Farnborough have been actively involved in the acquisition and processing of Earth Observation data for over 15 years. During that time an archive of over 20,000 items has been built up. This paper describes the major archive activities, including: operation and maintenance of the main DRA Archive, the development of a prototype Optical Disc Archive System (ODAS), the catalog systems in use at DRA, the UK Processing and Archive Facility for ERS-1 data, and future plans for archiving activities.

  20. Effect of Genetic Diversity in Swine Leukocyte Antigen-DRA Gene on Piglet Diarrhea

    PubMed Central

    Huang, Xiaoyu; Yang, Qiaoli; Yuan, Junhu; Liu, Lixia; Sun, Wenyang; Jiang, Yingdi; Zhao, Shengguo; Zhang, Shengwei; Huang, Wangzhou; Gun, Shuangbao

    2016-01-01

    The swine leukocyte antigens (SLAs) are the multigene families related to immune responses. Little is known about the effect of the DRA gene on diarrheal disease. This study reported the genetic diversity of the DRA gene in exons 1, 3 and 4 in 290 Chinese Yantai black pigs. No variation was identified in exon 3. In exon 1, three genotypes and two alleles were identified, generated by two single nucleotide polymorphisms (SNPs). In exon 4, there were eight genotypes and five alleles containing seven SNPs were detected with four SNPs being novel SNPs. The low polymorphism found in swine DRA is consistent with the concept that the DRA gene is highly conserved among all mammalian species. Statistical analyses indicated that the genotypes of exon 1 were not significantly associated with piglet diarrhea (p > 0.05); however, genotypes C4C4 (1.80 ± 0.33) and A4E4 (1.66 ± 0.25) of exon 4 were significantly susceptible to diarrhea (p < 0.01). These indicate that the particular genotypes of the DRA gene are susceptible to diarrheal disease, which provides valuable information for disease-resistance breeding in swine. PMID:27429004

  1. DRA 2005: The brave new world.

    PubMed

    Lewis, Richard

    2006-01-01

    The Deficit Reduction Act (DRA) of 2005 was signed into law to achieve 39 billion dollars in reductions from federal spending programs, 11 billion dollars from Medicare and Medicaid alone. Conservative estimates indicate that imaging alone accounts for 2.8 billion dollars of that amount. As of the writing of this article, both houses of Congress were reviewing bills with bipartisan support aimed at defusing, at least temporarily, the negative impact of the DRA; however, these bills do not affect the law in totality. Dealing with the changes that the DRA will force upon outpatient imaging practices will require all parties involved in outpatient imaging--physicians, administrators, and staff alike--to make smart, efficient, but practical changes in operational models to effectively survive in this new legislatively mandated environment.

  2. Genetic diversity of the class II major histocompatibility DRA locus in European, Asiatic and African domestic donkeys.

    PubMed

    Vranova, Marie; Alloggio, Ingrid; Qablan, Moneeb; Vyskocil, Mirko; Baumeisterova, Aneta; Sloboda, Michal; Putnova, Lenka; Vrtkova, Irena; Modry, David; Horin, Petr

    2011-07-01

    The major histocompatibility complex (MHC) genes coding for antigen presenting molecules are the most polymorphic genes in vertebrate genome. The MHC class II DRA gene shows only small variation in many mammalian species, but it exhibits relatively high level of polymorphism in Equidae, especially in donkeys. This extraordinary degree of polymorphism together with signatures of selection in specific amino acids sites makes the donkey DRA gene a suitable model for population diversity studies. The objective of this study was to investigate the DRA gene diversity in three different populations of donkeys under infectious pressure of protozoan parasites, Theileria equi and Babesia caballi. Three populations of domestic donkeys from Italy (N = 68), Jordan (N = 43), and Kenya (N = 78) were studied. A method of the donkey MHC DRA genotyping based on PCR-RFLP and sequencing was designed. In addition to the DRA gene, 12 polymorphic microsatellite loci were genotyped. The presence of Theileria equi and Babesia caballi parasites in peripheral blood was investigated by PCR. Allele and genotype frequencies, observed and expected heterozygosities and F(IS) values were computed as parameters of genetic diversity for all loci genotyped. Genetic distances between the three populations were estimated based on F(ST) values. Statistical associations between parasite infection and genetic polymorphisms were sought. Extensive DRA locus variation characteristic for Equids was found. The results showed differences between populations both in terms of numbers of alleles and their frequencies as well as variation in expected heterozygosity values. Based on comparisons with neutral microsatellite loci, population sub-structure characteristics and association analysis, convincing evidence of pathogen-driven selection at the population level was not provided. It seems that genetic diversity observed in the three populations reflects mostly effects of selective breeding and their different

  3. Brief Note Low diversity of the major histocompatibility complex class II DRA gene in domestic goats (Capra hircus) in Southern China.

    PubMed

    Chen, L P; E, G X; Zhao, Y J; Na, R S; Zhao, Z Q; Zhang, J H; Ma, Y H; Sun, Y W; Zhong, T; Zhang, H P; Huang, Y F

    2015-06-18

    DRA encodes the alpha chain of the DR heterodimer, is closely linked to DRB and is considered almost monomorphic in major histocompatibility complex region. In this study, we identified the exon 2 of DRA to evaluate the immunogenetic diversity of Chinese south indigenous goat. Two single nucleotide polymorphisms in an untranslated region and one synonymous substitution in coding region were identified. These data suggest that high immunodiversity in native Chinese population.

  4. High Data Rate Architecture (HiDRA)

    NASA Technical Reports Server (NTRS)

    Hylton, Alan; Raible, Daniel

    2016-01-01

    high-rate laser terminals. These must interface with the existing, aging data infrastructure. The High Data Rate Architecture (HiDRA) project is designed to provide networked store, carry, and forward capability to optimize data flow through both the existing radio frequency (RF) and new laser communications terminal. The networking capability is realized through the Delay Tolerant Networking (DTN) protocol, and is used for scheduling data movement as well as optimizing the performance of existing RF channels. HiDRA is realized as a distributed FPGA memory and interface controller that is itself controlled by a local computer running DTN software. Thus HiDRA is applicable to other arenas seeking to employ next-generation communications technologies, e.g. deep space. In this paper, we describe HiDRA and its far-reaching research implications.

  5. Continental Monophyly and Molecular Divergence of Peninsular Malaysia's Macaca fascicularis fascicularis

    PubMed Central

    Abdul-Latiff, Muhammad Abu Bakar; Ruslin, Farhani; Faiq, Hamdan; Hairul, Mohd Salleh; Rovie-Ryan, Jeffrine Japning; Abdul-Patah, Pazil; Md-Zain, Badrul Munir

    2014-01-01

    The phylogenetic relationships of long-tailed macaque (Macaca fascicularis fascicularis) populations distributed in Peninsular Malaysia in relation to other regions remain unknown. The aim of this study was to reveal the phylogeography and population genetics of Peninsular Malaysia's M. f. fascicularis based on the D-loop region of mitochondrial DNA. Sixty-five haplotypes were detected in all populations, with only Vietnam and Cambodia sharing four haplotypes. The minimum-spanning network projected a distant relationship between Peninsular Malaysian and insular populations. Genetic differentiation (F ST, Nst) results suggested that the gene flow among Peninsular Malaysian and the other populations is very low. Phylogenetic tree reconstructions indicated a monophyletic clade of Malaysia's population with continental populations (NJ = 97%, MP = 76%, and Bayesian = 1.00 posterior probabilities). The results demonstrate that Peninsular Malaysia's M. f. fascicularis belonged to Indochinese populations as opposed to the previously claimed Sundaic populations. M. f. fascicularis groups are estimated to have colonized Peninsular Malaysia ~0.47 million years ago (MYA) directly from Indochina through seaways, by means of natural sea rafting, or through terrestrial radiation during continental shelf emersion. Here, the Isthmus of Kra played a central part as biogeographical barriers that then separated it from the remaining continental populations. PMID:25143948

  6. Outburst activity of the symbiiotic binary AG Dra

    NASA Astrophysics Data System (ADS)

    Gális, R.; Hric, L.; Leedjärv, L.; Merc, J.

    2016-03-01

    The outburst activity of the symbiotic system AG Dra has been studied using extensive spectroscopic observational material. High luminosity and temperature of the hot component of AG Dra indicate that quasi-steady thermonuclear shell burning takes place on the surface of the white dwarf. The major (cool) outbursts at the beginning of active phases might occur due to enhanced thermonuclear burning triggered by disk instability. Smaller scale hot outbursts might be explained by the accretion disc instability model like in dwarf novae. We discovered significant similarities in photometric and spectroscopic behaviour of AG Dra and prototypical symbiotic star Z And.

  7. Outburst activity of the symbiotic binary AG Dra

    NASA Astrophysics Data System (ADS)

    Gális, R.; Merc, J.; Leedjärv, L.

    2017-04-01

    AG Dra regularly undergoes quiescent and active stages which consist of a series of individual outbursts repeating at about a one-year interval. After seven years of flat quiescence following the 2006-08 major outbursts, in the late spring of 2015, AG Dra begun rising again in brightness toward what appeared to be a new minor outburst. The recent outburst activity of AG Dra was definitely confirmed by a more prominent outburst in April 2016. The photometric and spectroscopic observations suggest that these outbursts are of the hot type. Such behaviour is quite unusual, because the major outbursts in the beginning of active stages are usually cool. Can we expect the major cool or minor hot outburst during the spring of 2017? AG Dra demonstrates the importance of long-term monitoring of symbiotic stars in order to disentangle the nature and mechanisms of their active stages and outbursts.

  8. Outburst Activity of the Symbiotic System AG Dra

    NASA Astrophysics Data System (ADS)

    Gális, R.; Hric, L.; Leedjärv, L.; Kundra, E.

    2015-07-01

    AG Dra is one of the best studied symbiotic systems. A period analysis of new and historical photometric data, as well as radial velocities, confirmed the presence of the two periods — about 550 days, caused by orbital motion, and around 350 days, related to pulsations of the cool component of AG Dra. In addition, the active stages change distinctively, but the outbursts recur with periods from 359 to 375 days.

  9. Mitogenomic phylogeny of the common long-tailed macaque (Macaca fascicularis fascicularis).

    PubMed

    Liedigk, Rasmus; Kolleck, Jakob; Böker, Kai O; Meijaard, Erik; Md-Zain, Badrul Munir; Abdul-Latiff, Muhammad Abu Bakar; Ampeng, Ahmad; Lakim, Maklarin; Abdul-Patah, Pazil; Tosi, Anthony J; Brameier, Markus; Zinner, Dietmar; Roos, Christian

    2015-03-21

    Long-tailed macaques (Macaca fascicularis) are an important model species in biomedical research and reliable knowledge about their evolutionary history is essential for biomedical inferences. Ten subspecies have been recognized, of which most are restricted to small islands of Southeast Asia. In contrast, the common long-tailed macaque (M. f. fascicularis) is distributed over large parts of the Southeast Asian mainland and the Sundaland region. To shed more light on the phylogeny of M. f. fascicularis, we sequenced complete mitochondrial (mtDNA) genomes of 40 individuals from all over the taxon's range, either by classical PCR-amplification and Sanger sequencing or by DNA-capture and high-throughput sequencing. Both laboratory approaches yielded complete mtDNA genomes from M. f. fascicularis with high accuracy and/or coverage. According to our phylogenetic reconstructions, M. f. fascicularis initially diverged into two clades 1.70 million years ago (Ma), with one including haplotypes from mainland Southeast Asia, the Malay Peninsula and North Sumatra (Clade A) and the other, haplotypes from the islands of Bangka, Java, Borneo, Timor, and the Philippines (Clade B). The three geographical populations of Clade A appear as paraphyletic groups, while local populations of Clade B form monophyletic clades with the exception of a Philippine individual which is nested within the Borneo clade. Further, in Clade B the branching pattern among main clades/lineages remains largely unresolved, most likely due to their relatively rapid diversification 0.93-0.84 Ma. Both laboratory methods have proven to be powerful to generate complete mtDNA genome data with similarly high accuracy, with the DNA-capture and high-throughput sequencing approach as the most promising and only practical option to obtain such data from highly degraded DNA, in time and with relatively low costs. The application of complete mtDNA genomes yields new insights into the evolutionary history of M. f

  10. Adaptive molecular evolution of the Major Histocompatibility Complex genes, DRA and DQA, in the genus Equus

    PubMed Central

    2011-01-01

    Background Major Histocompatibility Complex (MHC) genes are central to vertebrate immune response and are believed to be under balancing selection by pathogens. This hypothesis has been supported by observations of extremely high polymorphism, elevated nonsynonymous to synonymous base pair substitution rates and trans-species polymorphisms at these loci. In equids, the organization and variability of this gene family has been described, however the full extent of diversity and selection is unknown. As selection is not expected to act uniformly on a functional gene, maximum likelihood codon-based models of selection that allow heterogeneity in selection across codon positions can be valuable for examining MHC gene evolution and the molecular basis for species adaptations. Results We investigated the evolution of two class II MHC genes of the Equine Lymphocyte Antigen (ELA), DRA and DQA, in the genus Equus with the addition of novel alleles identified in plains zebra (E. quagga, formerly E. burchelli). We found that both genes exhibited a high degree of polymorphism and inter-specific sharing of allele lineages. To our knowledge, DRA allelic diversity was discovered to be higher than has ever been observed in vertebrates. Evidence was also found to support a duplication of the DQA locus. Selection analyses, evaluated in terms of relative rates of nonsynonymous to synonymous mutations (dN/dS) averaged over the gene region, indicated that the majority of codon sites were conserved and under purifying selection (dN polymorphisms supported the conclusion that balancing selection may be acting on these loci. Furthermore, at the DQA, positive selection was occurring at antigen binding

  11. The whole mitochondrial genome of the Cynomolgus macaque (Macaca fascicularis).

    PubMed

    Li, Ruilei; Wang, Huawei; Yang, Liqin; Zhang, Baoming; Li, Yijiang; Hu, Jiansheng; Kong, Qingpeng

    2015-04-01

    Macaca fascicularis, known as the long-tailed macaque, is widely distributed in southern of East Asia and Southeast Asia. It was one of the most commonly used non-human primates in biomedical research. Thus, to illustrate the maternal phylogenetic status of M. fascicularis in primates based on the whole mitochondrial DNA (mtDNA) genome and determine a reference sequence for future population genetic studies by taking mtDNA as molecular marker, in this study, the high quality whole mtDNA genome of M. fascicularis was amplified and sequenced. Our data showed that the whole mtDNA genome of M. fascicularis includes 16,571 base pairs (bps). Further phylogenetic analyses of M. fascicularis were performed by incorporating the 83 available whole mtDNA genomes belonging to 77 primate species with Tupaia belangeri as out-group. Our result supported that M. fascicularis belongs to Macaca. Cercopithecinae. Cercopithecidae. Anthropoidea. Primates, which has the closest genetic affinity with Macaca mulatta. In addition, the ancestral divergence between the tarsier and other primate species was supported with evidence from the whole mtDNA genomes.

  12. Mutations in the draT and draG genes of Rhodospirillum rubrum result in loss of regulation of nitrogenase by reversible ADP-ribosylation.

    PubMed Central

    Liang, J H; Nielsen, G M; Lies, D P; Burris, R H; Roberts, G P; Ludden, P W

    1991-01-01

    Reversible ADP-ribosylation of dinitrogenase reductase forms the basis of posttranslational regulation of nitrogenase activity in Rhodospirillum rubrum. This report describes the physiological effects of mutations in the genes encoding the enzymes that add and remove the ADP-ribosyl moiety. Mutants lacking a functional draT gene had no dinitrogenase reductase ADP-ribosyltransferase (DRAT, the draT gene product) activity in vitro and were incapable of modifying dinitrogenase reductase with ADP-ribose in vivo. Mutants lacking a functional draG gene had no dinitrogenase reductase-activating glycohydrolase (DRAG, the draG gene product) activity in vitro and were unable to remove ADP-ribose from the modified dinitrogenase reductase in vivo. Strains containing polar mutations in draT had no detectable DRAG activity in vitro, suggesting likely cotranscription of draT and draG. In strains containing draT and lacking a functional draG, dinitrogenase reductase accumulated in the active form under derepressing conditions but was rapidly ADP-ribosylated in response to conditions that cause inactivation. Detection of DRAT in these cells in vitro demonstrated that DRAT is itself subject to posttranslational regulation in vivo. Mutants affected in an open reading frame immediately downstream of draTG showed regulation of dinitrogenase reductase by ADP-ribosylation, although differences in the rates of ADP-ribosylation were apparent. Images FIG. 5 FIG. 6 PMID:1938894

  13. The function of the octamer-binding site in the DRA promoter

    SciTech Connect

    Voliva, C.F.; Jabrane-Ferrat, N.; Peterlin, B.M.

    1996-06-01

    The octamer binding site, which is located immediately upstream of the poorly conserved DRA TATA sequence, is important for high levels of expression of this human major histocompatibility class II gene in B cells. In this study, we demonstrate that the substitution of the DRA TATA sequence with the TATA box from the adenovirus Elb promoter removes the requirement for the octamer binding site for high levels of expression from the DRA promoter. Since only the TATA box from the Elb but not the DRA promoters binds the TATA binding protein, we conclude that the octamer binding site helps to recruit TBP to the DRA promoter. 32 refs., 7 figs.

  14. Osseointegration of dental implants in Macaca fascicularis

    NASA Astrophysics Data System (ADS)

    Dewi, R. S.; Odang, R. W.; Odelia, L.

    2017-08-01

    Osseointegration is an important factor in determining the success of a dental implant. It can be assessed from the osseointegration that occurs between the implant and the bone. The implant stability is determined by the osseous support at the implant-bone interface, which is commonly evaluated by histomorphometric analysis. This study aimed to evaluate whether the osseointegration level measured by a Low Resonance Frequency Analyzer (LRFA) gave results as good as those obtained by histomorphometric examination. Six male Macaca fascicularis were used in this study. In each animal, two types of loading were performed: immediate and delayed loading. Clinical examination and LRFA measurement were performed to determine osseointegration at the first and second weeks and at the first, second, third, and fourth months. After four months, histomorphometric examination was performed. The relationship between the histomorphometric examination and LRFA measurement was compared using the Pearson correlation coefficient. There was no significant difference in the osseointegration between immediate loading and delayed loading (p > 0.05) The bone-implant contact percentage in the first group did not differ significantly from that in the second group. Statistical analysis showed that there was a strong correlation between LRFA measurement and histomorphometric examination. Osseointegration could be evaluated through LRFA measurement as well as through histomorphometric examination.

  15. Photometric study of the pulsating, eclipsing binary OO DRA

    SciTech Connect

    Zhang, X. B.; Deng, L. C.; Tian, J. F.; Wang, K.; Yan, Z. Z.; Luo, C. Q.; Sun, J. J.; Liu, Q. L.; Xin, H. Q.; Zhou, Q.; Luo, Z. Q.

    2014-12-01

    We present a comprehensive photometric study of the pulsating, eclipsing binary OO Dra. Simultaneous B- and V-band photometry of the star was carried out on 14 nights. A revised orbital period and a new ephemeris were derived from the data. The first photometric solution of the binary system and the physical parameters of the component stars are determined. They reveal that OO Dra could be a detached system with a less-massive secondary component nearly filling its Roche lobe. By subtracting the eclipsing light changes from the data, we obtained the intrinsic pulsating light curves of the hotter, massive primary component. A frequency analysis of the residual light yields two confident pulsation modes in both B- and V-band data with the dominant frequency detected at 41.865 c/d. A brief discussion concerning the evolutionary status and the pulsation nature of the binary system is finally given.

  16. Chemical abundance analysis of π Dra and HR 7545

    NASA Astrophysics Data System (ADS)

    Elmaslı, Aslı; Nasolo, Yahya

    2017-02-01

    We carried out detailed abundance analysis of two A-type stars; π Dra and HR 7545. High resolution echelle spectra of these stars were obtained at the TÜBİTAK National Observatory. We determined the fundamental parameters of each target star using traditional methods. We also plotted the stars on the H-R diagram and calculated the masses from evolutionary tracks and ages from isochrones.

  17. The medical dictionary for regulatory activities (MedDRA).

    PubMed

    Brown, E G; Wood, L; Wood, S

    1999-02-01

    The International Conference on Harmonisation has agreed upon the structure and content of the Medical Dictionary for Regulatory Activities (MedDRA) version 2.0 which should become available in the early part of 1999. This medical terminology is intended for use in the pre- and postmarketing phases of the medicines regulatory process, covering diagnoses, symptoms and signs, adverse drug reactions and therapeutic indications, the names and qualitative results of investigations, surgical and medical procedures, and medical/social history. It can be used for recording adverse events and medical history in clinical trials, in the analysis and tabulations of data from these trials and in the expedited submission of safety data to government regulatory authorities, as well as in constructing standard product information and documentation for applications for marketing authorisation. After licensing of a medicine, it may be used in pharmacovigilance and is expected to be the preferred terminology for international electronic regulatory communication. MedDRA is a hierarchical terminology with 5 levels and is multiaxial: terms may exist in more than 1 vertical axis, providing specificity of terms for data entry and flexibility in data retrieval. Terms in MedDRA were derived from several sources including the WHO's adverse reaction terminology (WHO-ART), Coding Symbols for a Thesaurus of Adverse Reaction Terms (COSTART), International Classification of Diseases (ICD) 9 and ICD9-CM. It will be maintained, further developed and distributed by a Maintenance Support Services Organisation (MSSO). It is anticipated that using MedDRA will improve the quality of data captured on databases, support effective analysis by providing clinically relevant groupings of terms and facilitate electronic communication of data, although as a new tool, users will need to invest time in gaining expertise in its use.

  18. LUT observations of the mass-transferring binary AI Dra

    NASA Astrophysics Data System (ADS)

    Liao, Wenping; Qian, Shengbang; Li, Linjia; Zhou, Xiao; Zhao, Ergang; Liu, Nianping

    2016-06-01

    Complete UV band light curve of the eclipsing binary AI Dra was observed with the Lunar-based Ultraviolet Telescope (LUT) in October 2014. It is very useful to adopt this continuous and uninterrupted light curve to determine physical and orbital parameters of the binary system. Photometric solutions of the spot model are obtained by using the W-D (Wilson and Devinney) method. It is confirmed that AI Dra is a semi-detached binary with secondary component filling its critical Roche lobe, which indicates that a mass transfer from the secondary component to the primary one should happen. Orbital period analysis based on all available eclipse times suggests a secular period increase and two cyclic variations. The secular period increase was interpreted by mass transfer from the secondary component to the primary one at a rate of 4.12 ×10^{-8}M_{⊙}/yr, which is in agreement with the photometric solutions. Two cyclic oscillations were due to light travel-time effect (LTTE) via the presence of two cool stellar companions in a near 2:1 mean-motion resonance. Both photometric solutions and orbital period analysis confirm that AI Dra is a mass-transferring binary, the massive primary is filling 69 % of its critical Roche lobe. After the primary evolves to fill the critical Roche lobe, the mass transfer will be reversed and the binary will evolve into a contact configuration.

  19. Mechanisms of DRA recycling in intestinal epithelial cells: effect of enteropathogenic E. coli.

    PubMed

    Gujral, Tarunmeet; Kumar, Anoop; Priyamvada, Shubha; Saksena, Seema; Gill, Ravinder K; Hodges, Kim; Alrefai, Waddah A; Hecht, Gail A; Dudeja, Pradeep K

    2015-12-15

    Enteropathogenic Escherichia coli (EPEC) is a food-borne pathogen that causes infantile diarrhea worldwide. EPEC decreases the activity and surface expression of the key intestinal Cl(-)/HCO3(-) exchanger SLC26A3 [downregulated in adenoma (DRA)], contributing to the pathophysiology of early diarrhea. Little is known about the mechanisms governing membrane recycling of DRA. In the current study, Caco-2 cells were used to investigate DRA trafficking under basal conditions and in response to EPEC. Apical Cl(-)/HCO3(-) exchange activity was measured as DIDS-sensitive (125)I(-) uptake. Cell surface biotinylation was performed to assess DRA endocytosis and exocytosis. Inhibition of clathrin-mediated endocytosis by chlorpromazine (60 μM) increased apical Cl(-)/HCO3(-) exchange activity. Dynasore, a dynamin inhibitor, also increased function and surface levels of DRA via decreased endocytosis. Perturbation of microtubules by nocodazole revealed that intact microtubules are essential for basal exocytic (but not endocytic) DRA recycling. Mice treated with colchicine showed a decrease in DRA surface levels as visualized by confocal microscopy. In response to EPEC infection, DRA surface expression was reduced partly via an increase in DRA endocytosis and a decrease in exocytosis. These effects were dependent on the EPEC virulence genes espG1 and espG2. Intriguingly, the EPEC-induced decrease in DRA function was unaltered in the presence of dynasore, suggesting a clathrin-independent internalization of surface DRA. In conclusion, these studies establish the role of clathrin-mediated endocytosis and microtubules in the basal surface expression of DRA and demonstrate that the EPEC-mediated decrease in DRA function and apical expression in Caco-2 cells involves decreased exocytosis.

  20. Keratin 8 knockdown leads to loss of the chloride transporter DRA in the colon.

    PubMed

    Asghar, M Nadeem; Priyamvada, Shubha; Nyström, Joel H; Anbazhagan, Arivarasu Natarajan; Dudeja, Pradeep K; Toivola, Diana M

    2016-06-01

    Keratins (K) are intermediate filament proteins important in protection from stress. The roles of keratins in the intestine are not clear, but K8 knockout (K8(-/-)) mice develop a Th2-type colonic inflammation, epithelial hyperproliferation, and mild diarrhea caused by a keratin level-dependent decrease in short-circuit current and net sodium and chloride absorption in the distal colon. The lack of K8 leads to mistargeting or altered levels of membrane proteins in colonocytes; however, the main transporter responsible for the keratin-related ion transport defect is unknown. We here analyzed protein and mRNA levels of candidate ion transporters CFTR, PAT-1, NHE-3, and DRA in ileum, cecum, and proximal and distal colon. Although no differences were observed for CFTR, PAT-1, or NHE-3, DRA mRNA levels were decreased by three- to fourfold and DRA protein was almost entirely lost in K8(-/-) cecum and proximal and distal colon compared with K8(+/+), whereas the levels in ileum were normal. In K8(+/-) mice, DRA mRNA levels were unaltered, while decreased DRA protein levels were detected in the proximal colon. Immunofluorescence staining confirmed the loss of DRA in K8(-/-) distal colon, while K8(+/-) displayed a similar but more patchy apical DRA distribution compared with K8(+/+) DRA was similarly decreased when K8 was knocked down in Caco-2 cells, confirming that K8 levels modulate DRA levels in an inflammation-independent manner. Taken together, the loss of DRA in the K8(-/-) mouse colon and cecum explains the dramatic chloride transport defect and diarrheal phenotype after K8 inactivation and identifies K8 as a novel regulator of DRA.

  1. Vaginal Stone in a Cynomolgus Macaque (Macaca fascicularis).

    PubMed

    Colagross-Schouten, Angela M; Canfield, Don R

    2015-12-01

    A 20-y-old female cynomolgus macaque (Macaca fascicularis) housed in an indoor primate facility presented for poor appetite and acute weakness after several years of no adverse health events. Physical examination revealed a firm, ovoid mass in the caudal abdomen. Further evaluation revealed the mass to be a vaginal calculus composed of calcium carbonate, apatite, and struvite. To our knowledge, this case is the first reported description of a vaginal stone in an NHP.

  2. Vaginal Stone in a Cynomolgus Macaque (Macaca fascicularis)

    PubMed Central

    Colagross-Schouten, Angela M; Canfield, Don R

    2015-01-01

    A 20-y-old female cynomolgus macaque (Macaca fascicularis) housed in an indoor primate facility presented for poor appetite and acute weakness after several years of no adverse health events. Physical examination revealed a firm, ovoid mass in the caudal abdomen. Further evaluation revealed the mass to be a vaginal calculus composed of calcium carbonate, apatite, and struvite. To our knowledge, this case is the first reported description of a vaginal stone in an NHP. PMID:26678372

  3. First analysis of eight Algol-type binaries: EI Aur, XY Dra, BP Dra, DD Her, VX Lac, WX Lib, RZ Lyn, and TY Tri

    NASA Astrophysics Data System (ADS)

    Zasche, P.

    2016-01-01

    The available photometry from the online databases were used for the first light curve analysis of eight eclipsing binary systems EI Aur, XY Dra, BP Dra, DD Her, VX Lac, WX Lib, RZ Lyn, and TY Tri. All these stars are of Algol-type, having the detached components and the orbital periods from 0.92 to 6.8 days. For the systems EI Aur and BP Dra the large amount of the third light was detected during the light curve solution. Moreover, 468 new times of minima for these binaries were derived, trying to identify the period variations. For the systems XY Dra and VX Lac the third bodies were detected with the periods 17.7, and 49.3 years, respectively.

  4. The functional and physical relationship between the DRA bicarbonate transporter and carbonic anhydrase II.

    PubMed

    Sterling, Deborah; Brown, Nathan J D; Supuran, Claudiu T; Casey, Joseph R

    2002-11-01

    COOH-terminal cytoplasmic tails of chloride/bicarbonate anion exchangers (AE) bind cytosolic carbonic anhydrase II (CAII) to form a bicarbonate transport metabolon, a membrane protein complex that accelerates transmembrane bicarbonate flux. To determine whether interaction with CAII affects the downregulated in adenoma (DRA) chloride/bicarbonate exchanger, anion exchange activity of DRA-transfected HEK-293 cells was monitored by following changes in intracellular pH associated with bicarbonate transport. DRA-mediated bicarbonate transport activity of 18 +/- 1 mM H+ equivalents/min was inhibited 53 +/- 2% by 100 mM of the CAII inhibitor, acetazolamide, but was unaffected by the membrane-impermeant carbonic anhydrase inhibitor, 1-[5-sulfamoyl-1,3,4-thiadiazol-2-yl-(aminosulfonyl-4-phenyl)]-2,6-dimethyl-4-phenyl-pyridinium perchlorate. Compared with AE1, the COOH-terminal tail of DRA interacted weakly with CAII. Overexpression of a functionally inactive CAII mutant, V143Y, reduced AE1 transport activity by 61 +/- 4% without effect on DRA transport activity (105 +/- 7% transport activity relative to DRA alone). We conclude that cytosolic CAII is required for full DRA-mediated bicarbonate transport. However, DRA differs from other bicarbonate transport proteins because its transport activity is not stimulated by direct interaction with CAII.

  5. Formalizing MedDRA to support semantic reasoning on adverse drug reaction terms.

    PubMed

    Bousquet, Cédric; Sadou, Éric; Souvignet, Julien; Jaulent, Marie-Christine; Declerck, Gunnar

    2014-06-01

    Although MedDRA has obvious advantages over previous terminologies for coding adverse drug reactions and discovering potential signals using data mining techniques, its terminological organization constrains users to search terms according to predefined categories. Adding formal definitions to MedDRA would allow retrieval of terms according to a case definition that may correspond to novel categories that are not currently available in the terminology. To achieve semantic reasoning with MedDRA, we have associated formal definitions to MedDRA terms in an OWL file named OntoADR that is the result of our first step for providing an "ontologized" version of MedDRA. MedDRA five-levels original hierarchy was converted into a subsumption tree and formal definitions of MedDRA terms were designed using several methods: mappings to SNOMED-CT, semi-automatic definition algorithms or a fully manual way. This article presents the main steps of OntoADR conception process, its structure and content, and discusses problems and limits raised by this attempt to "ontologize" MedDRA.

  6. The near-contact binary star RZ Dra revisited

    NASA Astrophysics Data System (ADS)

    Erdem, A.; Zola, S.; Winiarski, M.

    2011-01-01

    This paper presents the absolute parameters of RZ Dra. New CCD observations were made at the Mt. Suhora Observatory in 2007. Two photometric data sets (1990 BV and 2007 BVRI) were analysed using modern light-curve synthesis methods. Large asymmetries in the light curves may be explained in terms of a dark starspot on the primary component, an A6 type star. Due to this magnetic activity, the primary component would appear to belong to the class of Ap-stars and would show small amplitude with δ Scuti-type pulsations. With this in mind, a time-series analysis of the residual light curves was made. However, we found no evidence of pulsation behaviour in RZ Dra. Combining the solutions of our light curves and Rucinski et al. (2000)'s radial velocity curves, the following absolute parameters of the components were determined: M1 = 1.63 ± 0.03 M ⊙, M2 = 0.70 ± 0.02 M ⊙, R1 = 1.65 ± 0.02R ⊙, R2 = 1.15 ± 0.02 R ⊙, L1 = 9.72 ± 0.30 L ⊙ and L2 = 0.74 ± 0.10 L ⊙. The distance to RZ Dra was calculated as 400 ± 25 pc, taking into account interstellar extinction. The orbital period of the system was studied using updated O- C information. It was found that the orbital period varied in its long-period sinusoidal form, superimposed on a downward parabola. The parabolic term shows a secular period decrease at a slow rate of 0.06 ± 0.02 s per century and is explained by the mass loss via magnetized wind of the Ap-star primary. The tilted sinusoidal form of the period variation may be considered as an apparent change and may be interpreted in terms of the light-time effect due to the presence of a third body.

  7. Mitochondrial DNA and two Y-chromosome genes of common long-tailed macaques (Macaca fascicularis fascicularis) throughout Thailand and vicinity.

    PubMed

    Bunlungsup, Srichan; Imai, Hiroo; Hamada, Yuzuru; Matsudaira, Kazunari; Malaivijitnond, Suchinda

    2017-02-01

    Macaca fascicularis fascicularis is distributed over a wide area of Southeast Asia. Thailand is located at the center of their distribution range and is the bridge connecting the two biogeographic regions of Indochina and Sunda. However, only a few genetic studies have explored the macaques in this region. To shed some light on the evolutionary history of M. f. fascicularis, including hybridization with M. mulatta, M. f. fascicularis and M. mulatta samples of known origins throughout Thailand and the vicinity were analyzed by molecular phylogenetics using mitochondrial DNA (mtDNA), including the hypervariable region 1, and Y-chromosomal DNA, including SRY and TSPY genes. The mtDNA phylogenetic analysis divided M. f. fascicularis into five subclades (Insular Indonesia, Sundaic Thai Gulf, Vietnam, Sundaic Andaman sea coast, and Indochina) and revealed genetic differentiation between the two sides of the Thai peninsula, which had previously been reported as a single group of Malay peninsular macaques. From the estimated divergence time of the Sundaic Andaman sea coast subclade, it is proposed that after M. f. fascicularis dispersed throughout Southeast Asia, some populations on the south-easternmost Indochina (eastern Thailand, southern Cambodia and southern Vietnam at the present time) migrated south-westwards across the land bridge, which was exposed during the glacial period of the late Pleistocene epoch, to the southernmost Thailand/northern peninsular Malaysia. Then, some of them migrated north and south to colonize the Thai Andaman sea coast and northern Sumatra, respectively. The SRY-TSPY phylogenetic analysis suggested that male-mediated gene flow from M. mulatta southward to M. f. fascicularis was restricted south of, but close to, the Isthmus of Kra. There was a strong impact of the geographical factors in Thailand, such as the Isthmus of Kra, Nakhon Si Thammarat, and Phuket ranges and Sundaland, on M. f. fascicularis biogeography and their hybridization

  8. Geographical, genetic and functional diversity of antiretroviral host factor TRIMCyp in cynomolgus macaque (Macaca fascicularis).

    PubMed

    Saito, Akatsuki; Kono, Ken; Nomaguchi, Masako; Yasutomi, Yasuhiro; Adachi, Akio; Shioda, Tatsuo; Akari, Hirofumi; Nakayama, Emi E

    2012-03-01

    The antiretroviral factor tripartite motif protein 5 (TRIM5) gene-derived isoform (TRIMCyp) has been found in at least three species of Old World monkey: rhesus (Macaca mulatta), pig-tailed (Macaca nemestrina) and cynomolgus (Macaca fascicularis) macaques. Although the frequency of TRIMCyp has been well studied in rhesus and pig-tailed macaques, the frequency and prevalence of TRIMCyp in cynomolgus macaques remain to be definitively elucidated. Here, the geographical and genetic diversity of TRIM5α/TRIMCyp in cynomolgus macaques was studied in comparison with their anti-lentiviral activity. It was found that the frequency of TRIMCyp in a population in the Philippines was significantly higher than those in Indonesian and Malaysian populations. Major and minor haplotypes of cynomolgus macaque TRIMCyp with single nucleotide polymorphisms in the cyclophilin A domain were also found. The functional significance of the polymorphism in TRIMCyp was examined, and it was demonstrated that the major haplotype of TRIMCyp suppressed human immunodeficiency virus type 1 (HIV-1) but not HIV-2, whilst the minor haplotype of TRIMCyp suppressed HIV-2 but not HIV-1. The major haplotype of TRIMCyp did not restrict a monkey-tropic HIV-1 clone, NL-DT5R, which contains a capsid with the simian immunodeficiency virus-derived loop between α-helices 4 and 5 and the entire vif gene. These results indicate that polymorphisms of TRIMCyp affect its anti-lentiviral activity. Overall, the results of this study will help our understanding of the genetic background of cynomolgus macaque TRIMCyp, as well as the host factors composing species barriers of primate lentiviruses.

  9. Geographical, genetic and functional diversity of antiretroviral host factor TRIMCyp in cynomolgus macaque (Macaca fascicularis)

    PubMed Central

    Saito, Akatsuki; Kono, Ken; Nomaguchi, Masako; Yasutomi, Yasuhiro; Shioda, Tatsuo; Akari, Hirofumi

    2012-01-01

    The antiretroviral factor tripartite motif protein 5 (TRIM5) gene-derived isoform (TRIMCyp) has been found in at least three species of Old World monkey: rhesus (Macaca mulatta), pig-tailed (Macaca nemestrina) and cynomolgus (Macaca fascicularis) macaques. Although the frequency of TRIMCyp has been well studied in rhesus and pig-tailed macaques, the frequency and prevalence of TRIMCyp in cynomolgus macaques remain to be definitively elucidated. Here, the geographical and genetic diversity of TRIM5α/TRIMCyp in cynomolgus macaques was studied in comparison with their anti-lentiviral activity. It was found that the frequency of TRIMCyp in a population in the Philippines was significantly higher than those in Indonesian and Malaysian populations. Major and minor haplotypes of cynomolgus macaque TRIMCyp with single nucleotide polymorphisms in the cyclophilin A domain were also found. The functional significance of the polymorphism in TRIMCyp was examined, and it was demonstrated that the major haplotype of TRIMCyp suppressed human immunodeficiency virus type 1 (HIV-1) but not HIV-2, whilst the minor haplotype of TRIMCyp suppressed HIV-2 but not HIV-1. The major haplotype of TRIMCyp did not restrict a monkey-tropic HIV-1 clone, NL-DT5R, which contains a capsid with the simian immunodeficiency virus-derived loop between α-helices 4 and 5 and the entire vif gene. These results indicate that polymorphisms of TRIMCyp affect its anti-lentiviral activity. Overall, the results of this study will help our understanding of the genetic background of cynomolgus macaque TRIMCyp, as well as the host factors composing species barriers of primate lentiviruses. PMID:22113010

  10. ProClaT, a new bioinformatics tool for in silico protein reclassification: case study of DraB, a protein coded from the draTGB operon in Azospirillum brasilense.

    PubMed

    Rubel, Elisa Terumi; Raittz, Roberto Tadeu; Coimbra, Nilson Antonio da Rocha; Gehlen, Michelly Alves Coutinho; Pedrosa, Fábio de Oliveira

    2016-12-15

    Azopirillum brasilense is a plant-growth promoting nitrogen-fixing bacteria that is used as bio-fertilizer in agriculture. Since nitrogen fixation has a high-energy demand, the reduction of N2 to NH4(+) by nitrogenase occurs only under limiting conditions of NH4(+) and O2. Moreover, the synthesis and activity of nitrogenase is highly regulated to prevent energy waste. In A. brasilense nitrogenase activity is regulated by the products of draG and draT. The product of the draB gene, located downstream in the draTGB operon, may be involved in the regulation of nitrogenase activity by an, as yet, unknown mechanism. A deep in silico analysis of the product of draB was undertaken aiming at suggesting its possible function and involvement with DraT and DraG in the regulation of nitrogenase activity in A. brasilense. In this work, we present a new artificial intelligence strategy for protein classification, named ProClaT. The features used by the pattern recognition model were derived from the primary structure of the DraB homologous proteins, calculated by a ProClaT internal algorithm. ProClaT was applied to this case study and the results revealed that the A. brasilense draB gene codes for a protein highly similar to the nitrogenase associated NifO protein of Azotobacter vinelandii. This tool allowed the reclassification of DraB/NifO homologous proteins, hypothetical, conserved hypothetical and those annotated as putative arsenate reductase, ArsC, as NifO-like. An analysis of co-occurrence of draB, draT, draG and of other nif genes was performed, suggesting the involvement of draB (nifO) in nitrogen fixation, however, without the definition of a specific function.

  11. Construction and validation of a systematic ethogram of Macaca fascicularis in a free enclosure.

    PubMed

    Xu, Fan; Xie, Liang; Li, Xin; Li, Qi; Wang, Tao; Ji, Yongjia; Kong, Fei; Zhan, Qunlin; Cheng, Ke; Fang, Liang; Xie, Peng

    2012-01-01

    Behavioral studies in non-human primates have become ideal models for further investigations into advanced cognitive function in humans. To date, there is no systematic ethogram of the cynomolgus monkey (Macaca fascicularis) in a free enclosure. In a field observation of 6012 subjects, 107 distinct behaviors of M. fascicularis were preliminarily described. 83 of these behaviors were then independently validated through a randomized cohort and classified into 12 behavioral categories. 53 of these behaviors were then selected to accurately reflect the daily mundane activity of the species in a free enclosure. These findings systematically document the behavior of M. fascicularis in a free enclosure for use in further investigations.

  12. Construction and Validation of a Systematic Ethogram of Macaca fascicularis in a Free Enclosure

    PubMed Central

    Wang, Tao; Ji, Yongjia; Kong, Fei; Zhan, Qunlin; Cheng, Ke; Fang, Liang; Xie, Peng

    2012-01-01

    Behavioral studies in non-human primates have become ideal models for further investigations into advanced cognitive function in humans. To date, there is no systematic ethogram of the cynomolgus monkey (Macaca fascicularis) in a free enclosure. In a field observation of 6012 subjects, 107 distinct behaviors of M. fascicularis were preliminarily described. 83 of these behaviors were then independently validated through a randomized cohort and classified into 12 behavioral categories. 53 of these behaviors were then selected to accurately reflect the daily mundane activity of the species in a free enclosure. These findings systematically document the behavior of M. fascicularis in a free enclosure for use in further investigations. PMID:22662158

  13. New polymorphic variants of human blood clotting factor IX

    SciTech Connect

    Surin, V.L.; Luk`yanenko, A.V.; Tagiev, A.F.; Smirnova, O.V.; Plutalov, O.V.; Berlin, Yu.A.

    1995-04-01

    The polymorphism of Alu-repeats, which are located in the introns of the human factor IX gene (copies 1-3), was studied. To identify polymorphic variants, direct sequencing of PCR products that contained appropriate repeats was used. In each case, 20 unrelated X chromosomes were studied. A polymorphic Dra I site was found near the 3{prime}-end of Alu copy 3 within the region of the polyA tract. A PCR-based testing system with internal control of restriction hydrolysis was suggested. Testing 81 unrelated X chromosomes revealed that the frequency of the polymorphic Dra I site is 0.23. Taq I polymorphism, which was revealed in Alu copy 4 of factor IX gene in our previous work, was found to be closely linked to Dra I polymorphism. Studies in linkage between different types of polymorphisms of the factor IX gene revealed the presence of a rare polymorphism in intron a that was located within the same minisatellite region as the known polymorphic insertion 50 bp/Dde I. However, the size of the insertion in our case was 26 bp. Only one polymorphic variant was found among over 150 unrelated X chromosomes derived from humans from Moscow and its vicinity. 10 refs., 4 figs., 1 tab.

  14. Automatic annotation of ICD-to-MedDRA mappings with SKOS predicates.

    PubMed

    Declerck, Gunnar; Souvignet, Julien; Rodrigues, Jean-Marie; Jaulent, Marie-Christine

    2014-01-01

    Robust alignments between ICD and MedDRA are essential to enable the secondary use of clinical data for pharmacovigilance research. UMLS makes available ICD-to-MedDRA mappings, but they are only poorly specified, which introduces difficulties when exploited in an automatic way. SKOS vocabulary can help achieve quality and machine-processable mappings. We have developed an algorithm based on several simple rules which annotates automatically ICD-to-MedDRA mappings with SKOS predicates. The method was tested and evaluated on a sample of ICD-10-to MedDRA mappings extracted from UMLS. The algorithm demonstrated satisfying performances, especially for skos:exactMatch properties, which suggests that automatic methods can be used to improve the quality of terminology mappings.

  15. Outburst Activity Driven by Evolved Pulsating Star in the Symbiotic Binary AG Dra

    NASA Astrophysics Data System (ADS)

    Gális, R.; Hric, L.; Leedjärv, L.

    2015-12-01

    The symbiotic system AG Dra regularly undergoes quiescent and active stages which consist of the series of individual outbursts. The period analysis of new and historical photometric data, as well as radial velocities, confirmed the presence of the two periods. The longer one around ≈ 550 d is related to the orbital motion and the shorter one ≈355 d could be due to pulsation of the cool component of AG Dra.

  16. Slc26a3/Dra and Slc26a6 in Murine Ameloblasts

    PubMed Central

    Jalali, R.; Zandieh-Doulabi, B.; DenBesten, P.K.; Seidler, U.; Riederer, B.; Wedenoja, S.; Micha, D.; Bronckers, A.L.J.J.

    2015-01-01

    Formation of apatite crystals during enamel development generates protons. To sustain mineral accretion, maturation ameloblasts need to buffer these protons. The presence of cytosolic carbonic anhydrases, the basolateral Na+ bicarbonate cotransporter Nbce1, and the basolateral anion exchanger Ae2a,b in maturation ameloblasts suggests that these cells secrete bicarbonates into the forming enamel, but it is unknown by which mechanism. Solute carrier (Slc) family 26A encodes different anion exchangers that exchange Cl–/HCO3–, including Slc26a3/Dra, Slc26a6/Pat-1, and Slc26a4/pendrin. Previously, we showed that pendrin is expressed in ameloblasts but is not critical for enamel formation. In this study, we tested the hypothesis that maturation ameloblasts express Dra and Slc26a6 to secrete bicarbonate into the enamel space in exchange for Cl–. Real-time polymerase chain reaction detected mRNA transcripts for Dra and Slc26a6 in mouse incisor enamel organs, and Western blotting confirmed their translation into protein. Both isoforms were immunolocalized in ameloblasts, principally at maturation stage. Mice with null mutation of either Dra or Slc26a6 had a normal dental or skeletal phenotype without changes in mineral density, as measured by micro–computed tomography. In enamel organs of Slc26a6-null mice, Dra and pendrin protein levels were both elevated by 52% and 55%, respectively. The amount of Slc26a6 protein was unchanged in enamel organs of Ae2a,b- and Cftr-null mice but reduced in Dra-null mice by 36%. Our data show that ameloblasts express Dra, pendrin, or Slc26a6 but each of these separately is not critical for formation of dental enamel. The data suggest that in ameloblasts, Slc26a isoforms can functionally compensate for one another. PMID:26394631

  17. Transcellular oxalate and Cl− absorption in mouse intestine is mediated by the DRA anion exchanger Slc26a3, and DRA deletion decreases urinary oxalate

    PubMed Central

    Freel, Robert W.; Whittamore, Jonathan M.

    2013-01-01

    Active transcellular oxalate transport in the mammalian intestine contributes to the homeostasis of this important lithogenic anion. Several members of the Slc26a gene family of anion exchangers have a measurable oxalate affinity and are expressed along the gut, apically and basolaterally. Mouse Slc26a6 (PAT1) targets to the apical membrane of enterocytes in the small intestine, and its deletion results in net oxalate absorption and hyperoxaluria. Apical exchangers of the Slc26a family that mediate oxalate absorption have not been established, yet the Slc26a3 [downregulated in adenoma (DRA)] protein is a candidate mediator of oxalate uptake. We evaluated the role of DRA in intestinal oxalate and Cl− transport by comparing unidirectional and net ion fluxes across short-circuited segments of small (ileum) and large (cecum and distal colon) intestine from wild-type (WT) and DRA knockout (KO) mice. In WT mice, all segments demonstrated net oxalate and Cl− absorption to varying degrees. In KO mice, however, all segments exhibited net anion secretion, which was consistently, and solely, due to a significant reduction in the absorptive unidirectional fluxes. In KO mice, daily urinary oxalate excretion was reduced 66% compared with that in WT mice, while urinary creatinine excretion was unchanged. We conclude that DRA mediates a predominance of the apical uptake of oxalate and Cl− absorbed in the small and large intestine of mice under short-circuit conditions. The large reductions in urinary oxalate excretion underscore the importance of transcellular intestinal oxalate absorption, in general, and, more specifically, the importance of the DRA exchanger in oxalate homeostasis. PMID:23886857

  18. Cycloartane triterpenes from marine green alga Cladophora fascicularis

    NASA Astrophysics Data System (ADS)

    Huang, Xinping; Zhu, Xiaobin; Deng, Liping; Deng, Zhiwei; Lin, Wenhan

    2006-12-01

    Six cycloartanes were isolated from ethanol extract of marine green alga Cladophora fascicularis by column chromatography. Procedure of isolation and description of these compounds are given in this paper. The structures were elucidated as (1). 24-hydroperoxycycloart-25- en-3β-ol; (2). cycloart-25-en-3β 24-diol; (3). 25-hydroperoxycycloart-23-en-3β-ol; (4). cycloart-23-en-3β, 25-diol; (5). cycloart-23, 25-dien-3β-ol; and (6). cycloart-24-en-3β-ol by spectroscopic (MS, ID and 2D NMR) data analysis. Cycloartane derivatives are widely distributed in terrestrial plants, but only few were obtained in the alga. All these compounds that have been isolated from terrestrial plants, were found in the marine alga for the first time.

  19. Estimation of Glomerular Filtration Rate in Cynomolgus Monkeys (Macaca fascicularis)

    PubMed Central

    IWAMA, Ryosuke; SATO, Tsubasa; SAKURAI, Ken; TAKASUNA, Kiyoshi; ICHIJO, Toshihiro; FURUHAMA, Kazuhisa; SATOH, Hiroshi

    2014-01-01

    ABSTRACT To estimate the glomerular filtration rate (GFR) in cynomolgus monkeys (Macaca fascicularis), a three-blood-sample method using iodixanol was assessed in comparison with the conventional multisample strategy using inulin. Iodixanol and inulin were coadministered intravenously 40 mg I/kg and 50 mg/kg, respectively, to male monkeys, followed by blood collection 60, 90 and 120 min later. A close correlation (r=0.96) was noted between the GFR values estimated by both methods. In clinically healthy monkeys, the basal values were determined to be 3.06 ± 0.50 ml/min/kg. This is the first report, suggesting that serum clearance of iodixanol is a ready-to-use tool for a screening the GFR in monkeys, although it is necessary to perform a more longitudinal study using animals with reduced renal function. PMID:24998395

  20. DraGnET: Software for storing, managing and analyzing annotated draft genome sequence data

    PubMed Central

    2010-01-01

    Background New "next generation" DNA sequencing technologies offer individual researchers the ability to rapidly generate large amounts of genome sequence data at dramatically reduced costs. As a result, a need has arisen for new software tools for storage, management and analysis of genome sequence data. Although bioinformatic tools are available for the analysis and management of genome sequences, limitations still remain. For example, restrictions on the submission of data and use of these tools may be imposed, thereby making them unsuitable for sequencing projects that need to remain in-house or proprietary during their initial stages. Furthermore, the availability and use of next generation sequencing in industrial, governmental and academic environments requires biologist to have access to computational support for the curation and analysis of the data generated; however, this type of support is not always immediately available. Results To address these limitations, we have developed DraGnET (Draft Genome Evaluation Tool). DraGnET is an open source web application which allows researchers, with no experience in programming and database management, to setup their own in-house projects for storing, retrieving, organizing and managing annotated draft and complete genome sequence data. The software provides a web interface for the use of BLAST, allowing users to perform preliminary comparative analysis among multiple genomes. We demonstrate the utility of DraGnET for performing comparative genomics on closely related bacterial strains. Furthermore, DraGnET can be further developed to incorporate additional tools for more sophisticated analyses. Conclusions DraGnET is designed for use either by individual researchers or as a collaborative tool available through Internet (or Intranet) deployment. For genome projects that require genome sequencing data to initially remain proprietary, DraGnET provides the means for researchers to keep their data in-house for

  1. Effects of ductile phase additions on the fracture behavior and toughness of DRA composites

    SciTech Connect

    Ellis, L.Y.; Lewandowski, J.J.; Hunt, W.H.

    1996-12-31

    Discontinuously reinforced aluminum (DRA) composites have been processed to contain discrete regions of unreinforced aluminum with the objective of enhancing the damage tolerance. The effects of changes in the ductile phase size, shape and strength as well as the SiC{sub p} reinforcement distribution on the toughness were studied. The incorporation of the ductile phase can increase the crack growth resistance of the DRA composite. In such cases, stable crack propagation (i.e., R curve behavior) is observed in contrast to the behavior of the conventional DRA composite which fails catastrophically under the conditions tested. The level of toughening is affected by the size and mechanical properties of the ductile phase as well as the orientation and shape of the ductile regions with respect to the test geometry (i.e., crack arrestor vs crack divider).

  2. Determining correspondences between high-frequency MedDRA concepts and SNOMED: a case study

    PubMed Central

    2010-01-01

    Background The Systematic Nomenclature of Medicine Clinical Terms (SNOMED CT) is being advocated as the foundation for encoding clinical documentation. While the electronic medical record is likely to play a critical role in pharmacovigilance - the detection of adverse events due to medications - classification and reporting of Adverse Events is currently based on the Medical Dictionary of Regulatory Activities (MedDRA). Complete and high-quality MedDRA-to-SNOMED CT mappings can therefore facilitate pharmacovigilance. The existing mappings, as determined through the Unified Medical Language System (UMLS), are partial, and record only one-to-one correspondences even though SNOMED CT can be used compositionally. Efforts to map previously unmapped MedDRA concepts would be most productive if focused on concepts that occur frequently in actual adverse event data. We aimed to identify aspects of MedDRA that complicate mapping to SNOMED CT, determine pattern in unmapped high-frequency MedDRA concepts, and to identify types of integration errors in the mapping of MedDRA to UMLS. Methods Using one years' data from the US Federal Drug Administrations Adverse Event Reporting System, we identified MedDRA preferred terms that collectively accounted for 95% of both Adverse Events and Therapeutic Indications records. After eliminating those already mapping to SNOMED CT, we attempted to map the remaining 645 Adverse-Event and 141 Therapeutic-Indications preferred terms with software assistance. Results All but 46 Adverse-Event and 7 Therapeutic-Indications preferred terms could be composed using SNOMED CT concepts: none of these required more than 3 SNOMED CT concepts to compose. We describe the common composition patterns in the paper. About 30% of both Adverse-Event and Therapeutic-Indications Preferred Terms corresponded to single SNOMED CT concepts: the correspondence was detectable by human inspection but had been missed during the integration process, which had created

  3. Turritopsis fascicularis Fraser, 1943 (Cnidaria: Hydrozoa): redescription and discussion of its phylogenetic position within the genus.

    PubMed

    Miglietta, Maria Pia

    2016-03-31

    Turritopsis fascicularis Fraser, 1943 was first described off Alligator Reef, Florida, USA, at a depth of 216 m. Presumably a deep-sea species, its validity has often been questioned due to the scarcity of available records. In this paper, T. fascicularis is re-described from some mature colonies from the upper slope of the Gulf of Mexico. Furthermore, new pictures of the colony, polyps, and medusa buds, are provided. A ~600bp sequence of the large ribosomal subunit of the mitochondrial RNA (lsu-rRNA, 16S), also known as the Hydrozoan barcoding molecule, is used for the first time to confirm the validity of T. fascicularis as a species, and analyze its phylogenetic position within the genus Turritopsis.

  4. Mechanical properties of the cement of the stalked barnacle Dosima fascicularis (Cirripedia, Crustacea)

    PubMed Central

    Zheden, Vanessa; Klepal, Waltraud; Gorb, Stanislav N.; Kovalev, Alexander

    2015-01-01

    The stalked barnacle Dosima fascicularis secretes foam-like cement, the amount of which usually exceeds that produced by other barnacles. When Dosima settles on small objects, this adhesive is additionally used as a float which gives buoyancy to the animal. The dual use of the cement by D. fascicularis requires mechanical properties different from those of other barnacle species. In the float, two regions with different morphological structure and mechanical properties can be distinguished. The outer compact zone with small gas-filled bubbles (cells) is harder than the interior one and forms a protective rind presumably against mechanical damage. The inner region with large, gas-filled cells is soft. This study demonstrates that D. fascicularis cement is soft and visco-elastic. We show that the values of the elastic modulus, hardness and tensile stress are considerably lower than in the rigid cement of other barnacles. PMID:25657833

  5. Polyostotic Fibrous Dysplasia in a Cynomolgus Macaque (Macaca fascicularis)

    PubMed Central

    Bauer, Cassondra; Dunn, Betty G; Brothman, Arthur R; Jr, Edward J Dick; Christensen, Chris; Voges, Andra; Moore, Charleen M

    2012-01-01

    A 2.3-y-old female cynomolgus macaque (Macaca fascicularis) presented with a broken right tibia and fibula. Radiographs showed multiple cyst-like defects in all long bones. We suspected that both fractures were pathologic because they occurred through these defects. Ultrasonography, MRI, and dual X-ray absorptiometry revealed that the defects were filled with soft tissue. Grossly, the bones were abnormal in shape, and a gelatinous material filled the defects and the surrounding marrow cavity. Histologically, the gelatinous material was composed of fibrin and cartilage; few normal bone cells were seen. Genetic testing revealed extra material on the short arm of chromosome 8 in all tissues examined, but no copy number alterations of likely clinical significance were observed, and no abnormalities were found that were unique to the lesions. In light of the clinical signs and radiographic and pathologic findings, polyostotic fibrous dysplasia was diagnosed. This report represents the first documented case of fibrous dysplasia in a cynomolgus macaque. PMID:22546922

  6. Cynomolgus macaque (Macaca fascicularis) immunoglobulin heavy chain locus description.

    PubMed

    Yu, Guo-Yun; Mate, Suzanne; Garcia, Karla; Ward, Michael D; Brueggemann, Ernst; Hall, Matthew; Kenny, Tara; Sanchez-Lockhart, Mariano; Lefranc, Marie-Paule; Palacios, Gustavo

    2016-07-01

    Cynomolgus macaques (Macaca fascicularis) have become an important animal model for biomedical research. In particular, it is the animal model of choice for the development of vaccine candidates associated with emerging dangerous pathogens. Despite their increasing importance as animal models, the cynomolgus macaque genome is not fully characterized, hindering molecular studies for this model. More importantly, the lack of knowledge about the immunoglobulin (IG) locus organization directly impacts the analysis of the humoral response in cynomolgus macaques. Recent advances in next generation sequencing (NGS) technologies to analyze IG repertoires open the opportunity to deeply characterize the humoral immune response. However, the IG locus organization for the animal is required to completely dissect IG repertoires. Here, we describe the localization and organization of the rearranging IG heavy (IGH) genes on chromosome 7 of the cynomolgus macaque draft genome. Our annotation comprises 108 functional genes which include 63 variable (IGHV), 38 diversity (IGHD), and 7 joining (IGHJ) genes. For validation, we provide RNA transcript data for most of the IGHV genes and all of the annotated IGHJ genes, as well as proteomic data to validate IGH constant genes. The description and annotation of the rearranging IGH genes for the cynomolgus macaques will significantly facilitate scientific research. This is particularly relevant to dissect the immune response during vaccination or infection with dangerous pathogens such as Ebola, Marburg and other emerging pathogens where non-human primate models play a significant role for countermeasure development.

  7. Polyostotic fibrous dysplasia in a cynomolgus Macaque (Macaca fascicularis).

    PubMed

    Bauer, Cassondra; Dunn, Betty G; Brothman, Arthur R; Dick, Edward J; Christensen, Chris; Voges, Andra; Moore, Charleen M

    2012-04-01

    A 2.3-y-old female cynomolgus macaque (Macaca fascicularis) presented with a broken right tibia and fibula. Radiographs showed multiple cyst-like defects in all long bones. We suspected that both fractures were pathologic because they occurred through these defects. Ultrasonography, MRI, and dual X-ray absorptiometry revealed that the defects were filled with soft tissue. Grossly, the bones were abnormal in shape, and a gelatinous material filled the defects and the surrounding marrow cavity. Histologically, the gelatinous material was composed of fibrin and cartilage; few normal bone cells were seen. Genetic testing revealed extra material on the short arm of chromosome 8 in all tissues examined, but no copy number alterations of likely clinical significance were observed, and no abnormalities were found that were unique to the lesions. In light of the clinical signs and radiographic and pathologic findings, polyostotic fibrous dysplasia was diagnosed. This report represents the first documented case of fibrous dysplasia in a cynomolgus macaque.

  8. Evaluation of Infrared Thermometry in Cynomolgus Macaques (Macaca fascicularis)

    PubMed Central

    Laffins, Michael M; Mellal, Nacera; Almlie, Cynthia L; Regalia, Douglas E

    2017-01-01

    Recording an accurate body temperature is important to assess an animal's health status. We compared temperature data from sedated cynomolgus macaques (Macaca fascicularis) to evaluate differences between rectal, infrared (inguinal and chest), and implanted telemetry techniques with the objective of demonstrating the diagnostic equivalence of the infrared device with other approaches. Infrared thermometer readings are instantaneous and require no contact with the animal. Body temperature data were obtained from 205 (137 male, 68 female) cynomolgus macaques under ketamine (10 mg/kg IM) sedation over a 3-mo period during scheduled physical examinations. Infrared measurements were taken 5 cm from the chest and inguinal areas. We evaluated 10 (9 functional devices) sedated cynomolgus macaques (5 male, 5 female) implanted with telemetry units in a muscular pouch between the internal and external abdominal oblique muscles. We determined that the mean body temperature acquired by using telemetry did not differ from either the mean of inguinal and chest infrared measurements but did differ from the mean of temperature obtained rectally. In addition, the mean rectal temperature differed from the mean of the inguinal reading but not the mean of the chest temperature. The results confirm our hypothesis that the infrared thermometer can be used to replace standard rectal thermometry. PMID:28905720

  9. MN Dra - a SU UMa-type star during its September 2013 superoutburst

    NASA Astrophysics Data System (ADS)

    Bąkowska, Karolina; Olech, Arkadiusz; Pospieszyński, Remigiusz

    2016-06-01

    We report CCD photometry of the cataclysmic variable star MN Draconis. During the season of August-September 2013, one normal outburst and one superoutburst were detected. In the light curves of MN Dra clear superhumps were present during September 2013 superoutburst. That fact confirms that the star is a member of SU UMa class.

  10. VizieR Online Data Catalog: R light curves of MN Dra (Bakowska+, 2017)

    NASA Astrophysics Data System (ADS)

    Bakowska, K.; Olech, A.; Pospieszynski, R.; Swierczynski, E.; Martinelli, F.; Rutkowski, A.; Koff, R.; Drozd, K.; Butkiewicz-Bak, M.; Kankiewicz, P.

    2017-03-01

    The observational data of MN Dra presented here were collected throughout three observation campaigns. The first data were obtained during 6 nights from 2009 October 12 to October 22, in the Skinakas Observatory, Greece. At that time, the star was in a quiescent state. The second campaign was conducted during 15 nights from 2013 July 09 to September 10. On that occasion, data were gathered in Poland, at the Borowiec station of the Poznan Astronomical Observatory, at J. Kochanowski University in Kielce, and at the Ostrowik station of theWarsaw University Observatory. During the 2013 campaign we detected two superoutbursts of MN Dra. The longest campaign was organized in 2015, from June 4 to December 18. Data covering 84 nights of observations were collected at the Borowiec Station, in Pisa in Italy, at Antelope Hills Observatory and at the MDM Observatory in the USA. Once again, two superoutbursts inMN Dra were observed. R broad-band photometry of MN Dra was obtained in three runs organized in 2009 (table 2009.dat), 2013 (table 2013.dat) and 2015 (table 2015.dat). (3 data files).

  11. [Automated grouping of terms associated to cardiac valve fibrosis in MedDRA].

    PubMed

    Asfari, Hadyl; Souvignet, Julien; Lillo-Le Louët, Agnès; Trombert, Béatrice; Jaulent, Marie-Christine; Bousquet, Cédric

    2016-12-01

    To propose an alternative approach for building custom groupings of terms that complements the usual approach based on both hierarchical method (selection of reference groupings in medical dictionary for regulatory activities [MedDRA]) and/or textual method (string search), for case reports extraction from a pharmacovigilance database in response to a safety problem. Here we take cardiac valve fibrosis as an example. The list of terms obtained by an automated approach, based on querying ontology of adverse drug reactions (OntoADR), a knowledge base defining MedDRA terms through relationships with systematized nomenclature of medicine-clinical terms (SNOMED CT) concepts, was compared with the reference list consisting of 53 preferred terms obtained by hierarchical and textual method. Two queries were performed on OntoADR by using a dedicated software: OntoADR query tools. Both queries excluded congenital diseases, and included a procedure or an auscultation method performed on cardiac valve structures. Query 1 also considered MedDRA terms related to fibrosis, narrowing or calcification of heart valves, and query 2 MedDRA terms described according to one of these four SNOMED CT terms: "Insufficiency", "Valvular sclerosis", "Heart valve calcification" or "Heart valve stenosis". The reference grouping consisted of 53 MedDRA preferred terms. Our automated method achieved recall of 79% and precision of 100% for query 1 privileging morphological abnormalities, and recall of 100% and precision of 96% for query 2 privileging functional abnormalities. An alternative approach to MedDRA reference groupings for building custom groupings is feasible for cardiac valve fibrosis. OntoADR is still in development. Its application to other adverse reactions would require significant work for a knowledge engineer to define every MedDRA term, but such definitions could then be queried as many times as necessary by pharmacovigilance professionals. Copyright © 2016 Société fran

  12. False homozygous deletions of SMN1 exon 7 using Dra I PCR-RFLP caused by a novel mutation in spinal muscular atrophy.

    PubMed

    Kang, Seong-Ho; Cho, Sung Im; Chae, Jong-Hee; Chung, Kyu Nam; Ra, Eun Kyung; Kim, So Yeon; Seong, Moon-Woo; Kim, Ji Yeon; Park, Sung Sup

    2009-08-01

    Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder, and about 95% of SMA patients are homozygous for deletions in the SMN1 gene. Herein, classical polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) using DraI yielded false homozygous deletions of SMN1 exon 7 in a patient with SMA, but multiple ligation-dependent probe amplification analysis revealed one remaining copy of SMN1 exon 7. Sequencing showed that this false deletion in the PCR-RFLP resulted from a novel mutation of one SMN1 copy that was not deleted (c.863G > T, p.R288M). This novel sequence variant introduced a mismatch that interfered with primer binding. These findings demonstrate that comprehensive analysis using PCR-RFLP, multiple ligation-dependent probe amplification, and sequencing can reliably and correctly diagnose SMA.

  13. Beneficial Insect Attraction to Milkweeds (Asclepias speciosa, Asclepias fascicularis) in Washington State, USA

    PubMed Central

    James, David G.; Seymour, Lorraine; Lauby, Gerry; Buckley, Katie

    2016-01-01

    Native plant and beneficial insect associations are relatively unstudied yet are important in native habitat restoration programs for improving and sustaining conservation biological control of arthropod pests in agricultural crops. Milkweeds (Asclepias spp.) are currently the focus of restoration programs in the USA aimed at reversing a decline in populations of the milkweed-dependent monarch butterfly (Danaus plexippus); however, little is known of the benefits of these plants to other beneficial insects. Beneficial insects (predators, parasitoids, pollinators) attracted to two milkweed species (Asclepias speciosa, Asclepias fascicularis) in central Washington State, WA, USA were identified and counted on transparent sticky traps attached to blooms over five seasons. Combining all categories of beneficial insects, means of 128 and 126 insects per trap were recorded for A. speciosa and A. fascicularis, respectively. Predatory and parasitic flies dominated trap catches for A. speciosa while parasitic wasps were the most commonly trapped beneficial insects on A. fascicularis. Bees were trapped commonly on both species, especially A. speciosa with native bees trapped in significantly greater numbers than honey bees. Beneficial insect attraction to A. speciosa and A. fascicularis was substantial. Therefore, these plants are ideal candidates for habitat restoration, intended to enhance conservation biological control, and for pollinator conservation. In central Washington, milkweed restoration programs for enhancement of D. plexippus populations should also provide benefits for pest suppression and pollinator conservation. PMID:27367733

  14. Beneficial Insect Attraction to Milkweeds (Asclepias speciosa, Asclepias fascicularis) in Washington State, USA.

    PubMed

    James, David G; Seymour, Lorraine; Lauby, Gerry; Buckley, Katie

    2016-06-29

    Native plant and beneficial insect associations are relatively unstudied yet are important in native habitat restoration programs for improving and sustaining conservation biological control of arthropod pests in agricultural crops. Milkweeds (Asclepias spp.) are currently the focus of restoration programs in the USA aimed at reversing a decline in populations of the milkweed-dependent monarch butterfly (Danaus plexippus); however, little is known of the benefits of these plants to other beneficial insects. Beneficial insects (predators, parasitoids, pollinators) attracted to two milkweed species (Asclepias speciosa, Asclepias fascicularis) in central Washington State, WA, USA were identified and counted on transparent sticky traps attached to blooms over five seasons. Combining all categories of beneficial insects, means of 128 and 126 insects per trap were recorded for A. speciosa and A. fascicularis, respectively. Predatory and parasitic flies dominated trap catches for A. speciosa while parasitic wasps were the most commonly trapped beneficial insects on A. fascicularis. Bees were trapped commonly on both species, especially A. speciosa with native bees trapped in significantly greater numbers than honey bees. Beneficial insect attraction to A. speciosa and A. fascicularis was substantial. Therefore, these plants are ideal candidates for habitat restoration, intended to enhance conservation biological control, and for pollinator conservation. In central Washington, milkweed restoration programs for enhancement of D. plexippus populations should also provide benefits for pest suppression and pollinator conservation.

  15. Effective and basic business strategic tools to overcome the DRA impact in outpatient imaging centers.

    PubMed

    Cerdena, Ernesto A; Corigliano, Barbara A

    2007-01-01

    The implementation of the Deficit Reduction Act (DRA) of 2005 has had adverse impacts with freestanding imaging centers and independent diagnostic testing facilities (IDTF) throughout the nation, including patient's access to quality imaging as well as crippling an organization's bottom line. Basic but effective business strategic tools should be formulated and executed to overcome the negative impact of the DRA. This should include creative and innovative process improvement initiatives while reducing operational costs and optimizing staff, thus improving profitability. Radiology administrators should act as facilitators to articulate and instill the mission, core values, and vision of the organization to the staff. Equally important, leaders in the imaging industry need to manifest a strong commitment in bringing the center into a whole new paradigm shift towards excellence and effective business operations.

  16. Spectral Line Variations of Symbiotic Stars EG And, AG Dra, and BX Mon and Its Interpretation

    NASA Astrophysics Data System (ADS)

    Yoon, Tae Seog; Kim, Soo Hyun; Moon, Hyeonwoo; Kim, Kyu-Seob; Oh, Hyungil

    2013-02-01

    We present some results obtained by high resolution spectroscopic observations for symbiotic stars EG And, AG Dra, and BX Mon in recent years which were performed with 1.8-m reflector and echelle spectrograph BOES at Bohyunsan Optical Astronomy Observatory, Youngcheon, South Korea. The variations of Hα emission line during a night and the variations of H Balmer lines and He I emission lines among several analyzed lines over months and years are shown and discussed.

  17. Korean BAC library construction and characterization of HLA-DRA, HLA-DRB3.

    PubMed

    Park, Mi-Hyun; Lee, Hye-Ja; Bok, Jeong; Kim, Cheol-Hwan; Hong, Seong-Tshool; Park, Chan; Kimm, KuChan; Oh, Bermseok; Lee, Jong-Young

    2006-07-31

    A human bacterial artificial chromosome (BAC) library was constructed with high molecular weight DNA extracted from the blood of a male Korean. This Korean BAC library contains 100,224 clones of insert size ranging from 70 to 150 kb, with an average size of 86 kb, corresponding to a 2.9-fold redundancy of the genome. The average insert size was determined from 288 randomly selected BAC clones that were well distributed among all the chromosomes. We developed a pooling system and three-step PCR screen for the Korean BAC library to isolate desired BAC clones, and we confirmed its utility using primer pairs designed for one of the clones. The Korean BAC library and screening pools will allow PCR-based screening of the Korean genome for any gene of interest. We also determined the allele types of HLA-DRA and HLA-DRB3 of clone KB55453, located in the HLA class II region on chromosome 6p21.3. The HLA-DRA and DRB3 genes in this clone were identified as the DRA*010202 and DRB3*01010201 types, respectively. The haplotype found in this library will provide useful information in future human disease studies.

  18. Isolation and cDNA characteristics of MHC-DRA genes from gayal (Bos frontalis) and gaytle (Bos frontalis × Bos taurus)

    PubMed Central

    Sun, Yongke; Zhang, Xiaomin; Xi, Dongmei; Li, Guozhi; Wang, Liping; Zheng, Huanli; Du, Min; Gu, Zhaobing; Yang, Yulin; Yang, Yuai

    2015-01-01

    The mammalian major histocompatibility complex (MHC) plays important roles in pathogen recognition and disease resistance. In the present study, the coding sequence and the 5′- and 3′-untranslated regions of MHC class II DR alpha chain (the DRA gene) from rare gayal and gaytle were cloned and analyzed to dissect structural and functional variations. The nucleotide and amino acid sequences for the DRA genes in gayal (Bofr-DRA) and gaytle (Bofr × BoLA-DRA) were almost identical to those for cattle and yak (99%). Compared to yak, two amino acids substitutions in the signal peptide (SP) domain for gayal were found within all Bos animals. Except for only one replacement in the amino acid within the α2 domain of the DRA protein in gayal, the additional residues were highly conserved across the species investigated. The 20 peptide-binding sites (PBS) of Bofr-DRA and Bofr × BoLA-DRA were essentially reserved in the α1 domain among all species investigated. The lesser degree of substitution in Bofr-DRA is concordant with the concept that the DRA gene is highly conserved among all mammals. The very high degree of conservativity of the DRA gene among ruminants, including gayal, suggests its recent evolutionary separation. PMID:26019649

  19. Biosorption and desorption of Cd2+ from wastewater by dehydrated shreds of Cladophora fascicularis

    NASA Astrophysics Data System (ADS)

    Deng, Liping; Zhu, Xiaobin; Su, Yingying; Su, Hua; Wang, Xinting

    2008-02-01

    The adsorption and desorption of algae Cladophora fascicularis and their relation with initial Cd2+ concentration, initial pH, and co-existing ions were studied. Adsorption equilibrium and biosorption kinetics were established from batch experiments. The adsorption equilibrium was adequately described by the Langmuir isotherm, and biosorption kinetics was in pseudo-second order model. The experiment on co-existing ions showed that the biosorption capacity of biomass decreased with an increasing concentration of competing ions. Desorption experiments indicated that EDTA was efficient desorbent for recovery from Cd2+. With high capacities of metal biosorption and desorption, the biomass of Cladophora fascicularis is promising as a cost-effective biosorbent for the removal of Cd2+ from wastewater.

  20. Rare Low State of DO Dra, the Magnetic Dwarf Nova=Outbursting Intermediate Polar

    NASA Astrophysics Data System (ADS)

    Breus, Vitalii V.; Andronov, Ivan L.; Yoon, Joh-Na; Dubovský, Pavol

    2017-06-01

    DO Dra is an exotic cataclysmic variable which shows properties either of the intermediate polars, or dwarf novae. It may represent a new subclass of "magnetic Dwarf Nova=outbursting intermediate polar". Very rare low luminosity state (of =16.095±0.007) was detected on June 8/9, 2017. The light curve shows a double-humped shape with a phase of the orbital period, with two unequal maxima, arguing not only for an ellipticity effect, but for a bright spot as well. Totally, we have detected 3 lows states.

  1. The first photometric study of W UMa eclipsing binary OQ Dra

    NASA Astrophysics Data System (ADS)

    Heidarnia, R.; Ebadi, H.; Rooydargard, H.

    2016-11-01

    The present study is an analysis of V-band CCD observations of new W UMa contact binary OQ Dra. To carry out the analysis, Primary and secondary minimum were obtained and new epoch was calculated. The computed period of system was 0.33967 day. Light curve analysis was performed using Binary Maker 3 and PHOEBE that uses the latest Wilson-Devinney code. We obtained photometric mass ratio of qptm = 0.55. O'Connell effect also was seen in the fitted model. Finally, the best model was achieved by introducing 2 spots on each component.

  2. High-Cadence B-Band Search for Optical Flares on BY Dra

    NASA Astrophysics Data System (ADS)

    Vander Haagen, G. A.

    2015-12-01

    The high-cadence search at 50 and 100 samples/sec of BY Dra revealed very short-duration B-band flares. A statistical criterion was used to isolate the short-duration optical flares from random photon events. Three flares, ranging in duration from 60 to 130 ms, with peaks 0.30-0.43 magnitude above the mean, were detected within the 80.2 hours of periodic monitoring from July 2012 through October 2015. This represents a flare rate of 0.04 flares/hour.

  3. Identification and characterization of microRNAs in the crab-eating macaque (Macaca fascicularis) using transcriptome analysis.

    PubMed

    Yang, Hao; Zhang, Rui; Jing, Ying; Zhu, Lin; Zhang, Wen; Liu, Chang; Wang, Jin; Yang, Jie; Zhang, Junfeng; Zen, Ke; Zhang, Chenyu; Li, Donghai

    2014-02-25

    MicroRNAs (miRNAs), with an average length between 16 nt and 26 nt, are small non-coding RNAs that can repress gene expression on the post-transcriptional level. Macaca fascicularis (M. fascicularis), one of the most important nonhuman primate animal models, is widely used in basic and applied preclinical research, especially in studies that involve neuroscience and disease. However, due to the lack of a complete genome sequence, the miRNAs in M. fascicularis have not been completely characterized. In this study, 86 putative M. fascicularis miRNAs were identified using a strategy of our design. The expression of some of these miRNAs in the tissue was confirmed by qRT-PCR. The function and pathway of their targeted genes were analyzed to reveal the potential relevance of miRNA regulation on diseases and physiological processes. The current study provides insight into potential miRNAs and forms a useful knowledge base for the future understanding of the function of miRNAs in M. fascicularis.

  4. New variants near RHOJ and C2, HLA-DRA region and susceptibility to endometriosis in the Polish population-The genome-wide association study.

    PubMed

    Sobalska-Kwapis, Marta; Smolarz, Beata; Słomka, Marcin; Szaflik, Tomasz; Kępka, Ewa; Kulig, Bartosz; Siewierska-Górska, Anna; Polak, Grzegorz; Romanowicz, Hanna; Strapagiel, Dominik; Szyłło, Krzysztof

    2017-09-01

    Endometriosis is a common gynaecological disease, associated with severe pelvic pain and reduced fertility; however, molecular mechanisms remain largely unknown. Genome-wide association studies (GWAS) are able to identify genetic loci, which can play significant role during endometriosis development. The study aimed at localisation of new genes and chromosomal loci, the nucleotide variants of which determine the level of susceptibility to endometriosis. Blood samples from 171 patients with endometriosis were used as material for studies. The patients were recruited to the study at the Department of Operative Gynaecology of the Institute of the Polish Mother's Memorial Hospital in Lodz. A control group (n=2934) came from the POPULOUS collection registered at Biobank Lab, Department of Molecular Biophysics, University of Lodz. DNA of the patients with endometriosis was compared with DNA of women free from that disease, the comparison being supported by GWAS. Genome-wide significant correlation was identified between one new, not previously described, single nucleotide polymorphism (SNP), rs10129516, localised on chromosome 14 in intergenic region between PARP1P2 and RHOJ genes (p=1.44×10(-10), OR=3.104, 95% CI=2.329-4.136) and endometriosis. We have also identified significant association with endometriosis of 18 SNPs localised on chromosome 6 in position range 31883957 - 32681631 (C2 and HLA-DRA genes region) with the lowest observed p value for rs644045 in C2 gene (p=2.04×10(-8), OR=1.955, 95% CI=1.541-2.480). Reported GWAS identified the novel loci associated with endometriosis in Polish women, not previously reported. The most interesting observation shown in our study are regions associated with susceptibility to endometriosis of loci located near C2, HLA-DRA and RHOJ genes. of that study did not correspond to previously published data about polymorphism in that regions and further evaluations are necessary in groups with higher numbers of patients to explain

  5. VizieR Online Data Catalog: BVR photometry of IZ Mon and AR Dra (Yang+, 2016)

    NASA Astrophysics Data System (ADS)

    Yang, Y.-G.; Dai, H.-F.; Zhou, Z.; Li, Q.

    2016-07-01

    CCD Photometry for IZ Mon and AR Dra, was acquired using the 60cm telescope and the 85cm telescope at the Xinglong station (XLs) of National Astronomical Observatories of China (NAOC). Two telescopes are equipped with the standard Johnson-Cousins UBVRcIc. filters. We then obtained the individual observations as heliocentric Julian dates and differential magnitude, which are listed in Table1. The complete light curves for IZ Mon were obtained on 2009 January 20, 22, 24, 25, and 26, and March 1, using the 85cm telescope. The exposure times are fixed to be 20, 15, and 15s for BVR bands, respectively. A total of 961, 960, and 959 effective images in BVR bands are obtained. Another primary eclipse for IZ Mon was monitored on 2011 January 17. AR Dra was observed on 2009 February 20, 25, 26, and 27, with the 65cm telescope. The typical exposure times are 50, 40 and 40s for BVR bands, which depend on the condition of weather. In total, we obtained 733, 728 and 356 images in B, V and R bands, respectively. (6 data files).

  6. Double cyclic variations in orbital period of the eclipsing cataclysmic variable EX Dra

    NASA Astrophysics Data System (ADS)

    Han, Zhong-tao; Qian, Sheng-bang; Voloshina, Irina; Zhu, Li-Ying

    2017-06-01

    EX Dra is a long-period eclipsing dwarf nova with ˜2-3 mag amplitude outbursts. This star has been monitored photometrically from November, 2009 to March, 2016 and 29 new mid-eclipse times were obtained. By using new data together with the published data, the best fit to the O-C curve indicate that the orbital period of EX Dra have an upward parabolic change while undergoing double-cyclic variations with the periods of 21.4 and 3.99 years, respectively. The upward parabolic change reveals a long-term increase at a rate of \\dot{P}= {+7.46}×10^{-11} s s^{-1}. The evolutionary theory of cataclysmic variables (CVs) predicts that, as a CV evolves, the orbital period should be decreasing rather than increasing. Secular increase can be explained as the mass transfer between the secondary and primary or may be just an observed part of a longer cyclic change. Most plausible explanation for the double-cyclic variations is a pair of light travel-time effect via the presence of two companions. Their masses are determined to be MAsin i'A=29.3(±0.6) M_{Jup} and MBsin i'B=50.8(±0.2) M_{Jup}. When the two companions are coplanar to the orbital plane of the central eclipsing pair, their masses would match to brown dwarfs.

  7. Fundamental parameters and origin of the very eccentric binary 41 Dra

    NASA Astrophysics Data System (ADS)

    Tokovinin, A.; Balega, Y. Y.; Pluzhnik, E. A.; Shatsky, N. I.; Gorynya, N. A.; Weigelt, G.

    2003-10-01

    The evolutionary status and origin of the most eccentric known binary in a quadruple system, 41 Dra (e=0.9754, period 3.413 yr), are discussed. New observations include the much improved combined speckle-interferometric orbit, resolved photometry of the components and their spectroscopic analysis. The age of the system is 2.5 +/- 0.2 Gyr; all four components are likely coeval. The high eccentricity of the orbit together with known age and masses provide a constraint on the tidal circularization theory: it seems that the eccentric orbit survived because the convective zones of the F-type dwarfs were very thin. Now as the components of 41 Dra are leaving the Main Sequence, their increased interaction at each periastron passage may result in detectable changes in period and eccentricity. Tables 1, 2, and 3 are only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/cgi-bin/qcat?J/A+A/409/245

  8. Power Requirements for The NASA Mars Design Reference Architecture (DRA) 5.0

    NASA Technical Reports Server (NTRS)

    Cataldo, Robert L.

    2009-01-01

    This paper summarizes the power systems analysis results from NASA s recent Mars DRA 5.0 study which examined three architecture options and resulting mission requirements for a human Mars landing mission in the post-2030 timeframe. DRA 5.0 features a long approximately 500 day surface stay split mission using separate cargo and crewed Mars transfer vehicles. Two cargo flights, utilizing minimum energy trajectories, pre-deploy a cargo lander to the surface and a habitat lander into a 24-hour elliptical Mars parking orbit where it remains until the arrival of the crew during the next mission opportunity approximately 26 months later. The pre-deployment of cargo poses unique challenges for set-up and emplacement of surface assets that results in the need for self or robotically deployed designs. Three surface architecture options were evaluated for breadth of science content, extent of exploration range/capability and variations in system concepts and technology. This paper describes the power requirements for the surface operations of the three mission options, power system analyses including discussion of the nuclear fission, solar photovoltaic and radioisotope concepts for main base power and long range mobility.

  9. The Effect of DRA and SQ3R on the Immediate and Delayed Recall of Seventh-Grade Social Studies Material.

    ERIC Educational Resources Information Center

    Garty, Roberta H.

    The purpose of this study was to examine the effect of the study of organizers, directed reading activity (DRA) and SQ3R, on the immediate and delayed recall of social studies materials. Eighty-four seventh-grade students from an intermediate school participated in this study. The results of the study indicated that the DRA technique was an…

  10. DRA/NASA/ONERA Collaboration on Icing Research. Part 2; Prediction of Airfoil Ice Accretion

    NASA Technical Reports Server (NTRS)

    Wright, William B.; Gent, R. W.; Guffond, Didier

    1997-01-01

    This report presents results from a joint study by DRA, NASA, and ONERA for the purpose of comparing, improving, and validating the aircraft icing computer codes developed by each agency. These codes are of three kinds: (1) water droplet trajectory prediction, (2) ice accretion modeling, and (3) transient electrothermal deicer analysis. In this joint study, the agencies compared their code predictions with each other and with experimental results. These comparison exercises were published in three technical reports, each with joint authorship. DRA published and had first authorship of Part 1 - Droplet Trajectory Calculations, NASA of Part 2 - Ice Accretion Prediction, and ONERA of Part 3 - Electrothermal Deicer Analysis. The results cover work done during the period from August 1986 to late 1991. As a result, all of the information in this report is dated. Where necessary, current information is provided to show the direction of current research. In this present report on ice accretion, each agency predicted ice shapes on two dimensional airfoils under icing conditions for which experimental ice shapes were available. In general, all three codes did a reasonable job of predicting the measured ice shapes. For any given experimental condition, one of the three codes predicted the general ice features (i.e., shape, impingement limits, mass of ice) somewhat better than did the other two. However, no single code consistently did better than the other two over the full range of conditions examined, which included rime, mixed, and glaze ice conditions. In several of the cases, DRA showed that the user's knowledge of icing can significantly improve the accuracy of the code prediction. Rime ice predictions were reasonably accurate and consistent among the codes, because droplets freeze on impact and the freezing model is simple. Glaze ice predictions were less accurate and less consistent among the codes, because the freezing model is more complex and is critically

  11. pH-dependent structural change of the extracellular sensor domain of the DraK histidine kinase from Streptomyces coelicolor

    SciTech Connect

    Yeo, Kwon Joo; Kim, Eun Hye; Hwang, Eunha; Han, Young-Hyun; Eo, Yumi; Kim, Hyun Jung; Kwon, Ohsuk; Hong, Young-Soo; Cheong, Chaejoon; Cheong, Hae-Kap

    2013-02-15

    Highlights: ► We described the biochemical and biophysical properties of the extracellular sensory domain (ESD) of DraK histidine kinase. ► The ESD of DraK showed a reversible pH-dependent conformational change in a wide pH range. ► The E83 is an important residue for the pH-dependent conformational change. -- Abstract: Recently, the DraR/DraK (Sco3063/Sco3062) two-component system (TCS) of Streptomycescoelicolor has been reported to be involved in the differential regulation of antibiotic biosynthesis. However, it has not been shown that under which conditions and how the DraR/DraK TCS is activated to initiate the signal transduction process. Therefore, to understand the sensing mechanism, structural study of the sensory domain of DraK is highly required. Here, we report the biochemical and biophysical properties of the extracellular sensory domain (ESD) of DraK. We observed a reversible pH-dependent conformational change of the ESD in a pH range of 2.5–10. Size-exclusion chromatography and AUC (analytical ultracentrifugation) data indicated that the ESD is predominantly monomeric in solution and exists in equilibrium between monomer and dimer states in acidic condition. Using NMR (nuclear magnetic resonance) and CD (circular dichroism) spectroscopy, our findings suggest that the structure of the ESD at low pH is more structured than that at high pH. In particular, the glutamate at position 83 is an important residue for the pH-dependent conformational change. These results suggest that this pH-dependent conformational change of ESD may be involved in signal transduction process of DraR/DraK TCS.

  12. The Long-Term Spectroscopic Misadventures of AG Dra with a Nod toward V407 Cyg: Degenerates Behaving Badly

    NASA Astrophysics Data System (ADS)

    Shore, S. N.; Genovali, K.; Wahlgren, G. M.

    We present some results of an ongoing study of the long-term spectroscopic variations of AG Dra, a prototypical eruptive symbiotic system. We discuss the effects of the environment and orbital modulation in this system and some of the physical processes revealed by a comparison with the nova outburst of the symbiotic-like recurrent nova V407 Cyg 2010.

  13. High resolution studies of the Afa/Dr adhesin DraE and its interaction with chloramphenicol.

    PubMed

    Pettigrew, David; Anderson, Kirstine L; Billington, Jason; Cota, Ernesto; Simpson, Peter; Urvil, Petri; Rabuzin, Filip; Roversi, Pietro; Nowicki, Bogdan; du Merle, Laurence; Le Bouguénec, Chantal; Matthews, Stephen; Lea, Susan M

    2004-11-05

    Pathogenic Escherichia coli expressing Afa/Dr adhesins are able to cause both urinary tract and diarrheal infections. The Afa/Dr adhesins confer adherence to epithelial cells via interactions with the human complement regulating protein, decay accelerating factor (DAF or CD55). Two of the Afa/Dr adhesions, AfaE-III and DraE, differ from each other by only three residues but are reported to have several different properties. One such difference is disruption of the interaction between DraE and CD55 by chloramphenicol, whereas binding of AfaE-III to CD55 is unaffected. Here we present a crystal structure of a strand-swapped trimer of wild type DraE. We also present a crystal structure of this trimer in complex with chloramphenicol, as well as NMR data supporting the binding position of chloramphenicol within the crystal. The crystal structure reveals the precise atomic basis for the sensitivity of DraE-CD55 binding to chloramphenicol and demonstrates that in contrast to other chloramphenicol-protein complexes, drug binding is mediated via recognition of the chlorine "tail" rather than via intercalation of the benzene rings into a hydrophobic pocket.

  14. The Long-Term Spectroscopic Misadventures of AG Dra with a Nod toward V407 Cyg: Degenerates Behaving Badly

    NASA Technical Reports Server (NTRS)

    Shore, S.N.; Genovali, K.; Wahlgren, G. M.

    2013-01-01

    We present some results of an ongoing study of the long-term spectroscopic variations of AG Dra, a prototypical eruptive symbiotic system. We discuss the effects of the environment and orbital modulation in this system and some of the physical processes revealed by a comparison with the nova outburst of the symbiotic-like recurrent nova V407 Cyg 2010.

  15. Variations in the orbital periods of the Algol-type eclipsing binaries RZ Cas and Z Dra

    NASA Astrophysics Data System (ADS)

    Khaliullina, A. I.

    2016-05-01

    A detailed study of variations of the orbital periods of the Algol-type eclipsing binary systems RZ Cas and Z Dra is presented. The fairly complex variations of the periods of both systems can be represented as a superposition of a secular increase of the period, slow periodic fluctuations, and quasiperiodic oscillations with a small amplitude occurring on timescales of decades. The secular increase of the period can be explained by the steady mass transfer from the less massive to the more massive component with conservation of the total angular momentum. The mass-transfer rate is 5.7 × 10-9 M ⊙/yr for RZ Cas and 3.0×10-8 M ⊙/yr for Z Dra. To explain the long-period cyclic variations of the orbital periods of RZCas and Z Dra, it must be assumed that the eclipsing binaries move in long-period orbits. RZ Cas moves with a period of 133 yr around a third body withmass M 3 > 0.55 M ⊙, while Z Dra moves with a period of 60 yr around a third body with mass M 3 > 0.7 M ⊙. The residual fluctuations of the periods may be due to a superposition of variations due to magnetic cycles and non-stationary ejections of matter.

  16. HyDra: A novel hydrodynamic polishing tool for high quality optical surfaces; Techical Digest

    NASA Astrophysics Data System (ADS)

    Sohn, Erika; Ruiz, Elfego; Luna, Esteban; Salas, Luis; Nunez, Manuel; Valdes, Jorge; Martinez, Benjamin; Cruz-Gonzalez, Irene

    2005-05-01

    A novel hydrodynamic radial polishing tool (HyDRa) is presented. It performs corrective lapping and fine polishing of diverse materials by means of a low-cost abrasive flux and a hydrostatic suspension system that avoids contact of the tool with the working surface. With this tool it is currently possible to polish aspheres and free-form optics of up to 2.5 meters in diameter. It has the advantage of avoiding fallen edges during the polishing process as well as reducing tool wear out and deformation. The functioning principle is based on the generation of a high-velocity, high-pressure abrasive emulsion flux with radial geometry. The polishing process is repeatable and achieves high degrees of precision and accuracy on optical and semiconductor surfaces. An additional advantage of this new tool is the possibility to perform in-process interferometric measurements. Recent results of polished aspheres are discussed.

  17. HyDRA: gene prioritization via hybrid distance-score rank aggregation.

    PubMed

    Kim, Minji; Farnoud, Farzad; Milenkovic, Olgica

    2015-04-01

    Gene prioritization refers to a family of computational techniques for inferring disease genes through a set of training genes and carefully chosen similarity criteria. Test genes are scored based on their average similarity to the training set, and the rankings of genes under various similarity criteria are aggregated via statistical methods. The contributions of our work are threefold: (i) first, based on the realization that there is no unique way to define an optimal aggregate for rankings, we investigate the predictive quality of a number of new aggregation methods and known fusion techniques from machine learning and social choice theory. Within this context, we quantify the influence of the number of training genes and similarity criteria on the diagnostic quality of the aggregate and perform in-depth cross-validation studies; (ii) second, we propose a new approach to genomic data aggregation, termed HyDRA (Hybrid Distance-score Rank Aggregation), which combines the advantages of score-based and combinatorial aggregation techniques. We also propose incorporating a new top-versus-bottom (TvB) weighting feature into the hybrid schemes. The TvB feature ensures that aggregates are more reliable at the top of the list, rather than at the bottom, since only top candidates are tested experimentally; (iii) third, we propose an iterative procedure for gene discovery that operates via successful augmentation of the set of training genes by genes discovered in previous rounds, checked for consistency. Fundamental results from social choice theory, political and computer sciences, and statistics have shown that there exists no consistent, fair and unique way to aggregate rankings. Instead, one has to decide on an aggregation approach using predefined set of desirable properties for the aggregate. The aggregation methods fall into two categories, score- and distance-based approaches, each of which has its own drawbacks and advantages. This work is motivated by the

  18. Urinary cystic calculi in a cynomolgus monkey (Macaca fascicularis): a case report.

    PubMed

    Stephens, E C; Middleton, C C; Thompson, L J

    1979-12-01

    An adult female Macaca fascicularis monkey became acutely anorexic and depressed and was found dead approximately 24 hours later. Necropsy revealed three hard brownish-yellow stones within the urinary bladder and urethra, a moderately shrunken left kidney, hemorrhage of the medulla of the left adrenal gland and a yellow liver. The stones, one of which was lodged in the urethra, were 1-2.5 cm in diameter, and their surfaces were rough and covered with spines. Chemical analysis of the stones revealed oxalates, phosphates, carbonates, ammonium salts, magnesium and calcium. Microscopic examination revealed chronic interstitial and glomerular nephritis and papillary hyperplasia of the transitional epithelium of the bladder.

  19. Finding the factors of reduced genetic diversity on X chromosomes of Macaca fascicularis: male-driven evolution, demography, and natural selection.

    PubMed

    Osada, Naoki; Nakagome, Shigeki; Mano, Shuhei; Kameoka, Yosuke; Takahashi, Ichiro; Terao, Keiji

    2013-11-01

    The ratio of genetic diversity on X chromosomes relative to autosomes in organisms with XX/XY sex chromosomes could provide fundamental insight into the process of genome evolution. Here we report this ratio for 24 cynomolgus monkeys (Macaca fascicularis) originating in Indonesia, Malaysia, and the Philippines. The average X/A diversity ratios in these samples was 0.34 and 0.20 in the Indonesian-Malaysian and Philippine populations, respectively, considerably lower than the null expectation of 0.75. A Philippine population supposed to derive from an ancestral population by founding events showed a significantly lower ratio than the parental population, suggesting a demographic effect for the reduction. Taking sex-specific mutation rate bias and demographic effect into account, expected X/A diversity ratios generated by computer simulations roughly agreed with the observed data in the intergenic regions. In contrast, silent sites in genic regions on X chromosomes showed strong reduction in genetic diversity and the observed X/A diversity ratio in the genic regions cannot be explained by mutation rate bias and demography, indicating that natural selection also reduces the level of polymorphism near genes. Whole-genome analysis of a female cynomolgus monkey also supported the notion of stronger reduction of genetic diversity near genes on the X chromosome.

  20. Lunar-based Ultraviolet Telescope study of the well-known Algol-type binary TW Dra

    NASA Astrophysics Data System (ADS)

    Liao, Wen-Ping; Qian, Sheng-Bang; Zejda, Miloslav; Zhu, Li-Ying; Li, Lin-Jia

    2016-06-01

    By using the Lunar-based Ultraviolet Telescope (LUT) from 2014 December 2 to December 4, the first near-UV light curve of the well-known Algol-type binary TW Dra is reported, which is analyzed with the 2013 version of the W-D code. Our solutions confirmed that TW Dra is a semi-detached binary system where the secondary component fills its Roche lobe. The mass ratio and a high inclination are obtained (q = 0.47, i = 86.68°). Based on 589 available data spanning more than one century, the complex period changes are studied. Secular increase and three cyclical changes are found in the corresponding orbital period analysis. The secular increase changes reveal mass transfer from the secondary component to the primary one at a rate of 6.8 × 10-7 M ⊙ yr-1. One large cyclical change of 116.04 yr may be caused by disturbance of visual component ADS 9706B orbiting TW Dra (ADS 9706A), while the other two cyclical changes with shorter periods of 22.47 and 37.27 yr can be explained as the result of two circumbinary companions that are orbiting around TW Dra, where the two companions are in simple 3 : 5 orbit-rotation resonances. TW Dra itself is a basic binary in a possible sextuple system with the configuration (1 + 1) + (1 + 1) + (1 + 1), which further suggests that multiplicity may be a fairly common phenomenon in close binary systems.

  1. Dark calcification and the daily rhythm of calcification in the scleractinian coral, Galaxea fascicularis

    NASA Astrophysics Data System (ADS)

    Al-Horani, F. A.; Tambutté, É.; Allemand, D.

    2007-09-01

    The rate of calcification in the scleractinian coral Galaxea fascicularis was followed during the daytime using 45Ca tracer. The coral began the day with a low calcification rate, which increased over time to a maximum in the afternoon. Since the experiments were carried out under a fixed light intensity, these results suggest that an intrinsic rhythm exists in the coral such that the calcification rate is regulated during the daytime. When corals were incubated for an extended period in the dark, the calcification rate was constant for the first 4 h of incubation and then declined, until after one day of dark incubation, calcification ceased, possibly as a result of the depletion of coral energy reserves. The addition of glucose and Artemia reduced the dark calcification rate for the short duration of the experiment, indicating an expenditure of oxygen in respiration. Artificial hypoxia reduced the rate of dark calcification to about 25% compared to aerated coral samples. It is suggested that G. fascicularis obtains its oxygen needs from the surrounding seawater during the nighttime, whereas during the day time the coral exports oxygen to the seawater.

  2. Isolation and Identification of Cytotoxic Compounds from Aeschynomene fascicularis, a Mayan Medicinal Plant.

    PubMed

    Caamal-Fuentes, Edgar E; Peraza-Sánchez, Sergio R; Torres-Tapia, Luis W; Moo-Puc, Rosa E

    2015-07-24

    The plant Aeschynomene fascicularis (Fabaceae) has been used in Mayan traditional medicine in the Yucatan peninsula. However, the compounds present in the plant responsible for its curative properties have not yet been investigated. Aeschynomene fascicularis root bark was extracted with 100% methanol to obtain a crude extract. The methanol extract was partitioned successively with solvents with increasing polarity to obtain the corresponding hexane (Hx), dichloromethane (DCM) and ethyl acetate fractions (EtOAc), as well as a residual water-alcoholic fraction. These fractions were tested for their cytotoxic activities using an MTT assay against Hep-2 cancer cell lines. The Hx fraction led to the isolation of spinochalcone C (1), spinochalcone A (2), isocordoin (3) and secundiflorol G (4). Their structures were identified based on spectroscopic evidence and chemical properties. All compounds were subjected to cytotoxicity and antiproliferative assays against a panel of seven cell lines, including one normal-type cell line. Spinochalcone A (2) exhibited cytotoxic activity against DU-145 cell line and antiproliferative activity against the KB cell line. Secundiflorol G (4) showed strong cytotoxic activity towards KB and Hep-2 cell lines. In addition, isocordoin (3) showed moderate activity on KB, Hep-2 and DU-145 cell lines. The active Compounds 2, 3 and 4 are potential therapeutic entities against cancer.

  3. Phylogenetic relationships of Malaysia’s long-tailed macaques, Macaca fascicularis, based on cytochrome b sequences

    PubMed Central

    Abdul-Latiff, Muhammad Abu Bakar; Ruslin, Farhani; Fui, Vun Vui; Abu, Mohd-Hashim; Rovie-Ryan, Jeffrine Japning; Abdul-Patah, Pazil; Lakim, Maklarin; Roos, Christian; Yaakop, Salmah; Md-Zain, Badrul Munir

    2014-01-01

    Abstract Phylogenetic relationships among Malaysia’s long-tailed macaques have yet to be established, despite abundant genetic studies of the species worldwide. The aims of this study are to examine the phylogenetic relationships of Macaca fascicularis in Malaysia and to test its classification as a morphological subspecies. A total of 25 genetic samples of M. fascicularis yielding 383 bp of Cytochrome b (Cyt b) sequences were used in phylogenetic analysis along with one sample each of M. nemestrina and M. arctoides used as outgroups. Sequence character analysis reveals that Cyt b locus is a highly conserved region with only 23% parsimony informative character detected among ingroups. Further analysis indicates a clear separation between populations originating from different regions; the Malay Peninsula versus Borneo Insular, the East Coast versus West Coast of the Malay Peninsula, and the island versus mainland Malay Peninsula populations. Phylogenetic trees (NJ, MP and Bayesian) portray a consistent clustering paradigm as Borneo’s population was distinguished from Peninsula’s population (99% and 100% bootstrap value in NJ and MP respectively and 1.00 posterior probability in Bayesian trees). The East coast population was separated from other Peninsula populations (64% in NJ, 66% in MP and 0.53 posterior probability in Bayesian). West coast populations were divided into 2 clades: the North-South (47%/54% in NJ, 26/26% in MP and 1.00/0.80 posterior probability in Bayesian) and Island-Mainland (93% in NJ, 90% in MP and 1.00 posterior probability in Bayesian). The results confirm the previous morphological assignment of 2 subspecies, M. f. fascicularis and M. f. argentimembris, in the Malay Peninsula. These populations should be treated as separate genetic entities in order to conserve the genetic diversity of Malaysia’s M. fascicularis. These findings are crucial in aiding the conservation management and translocation process of M. fascicularis populations

  4. Sulfate secretion and chloride absorption are mediated by the anion exchanger DRA (Slc26a3) in the mouse cecum.

    PubMed

    Whittamore, Jonathan M; Freel, Robert W; Hatch, Marguerite

    2013-07-15

    Inorganic sulfate (SO₄²⁻) is essential for a multitude of physiological processes. The specific molecular pathway has been identified for uptake from the small intestine but is virtually unknown for the large bowel, although there is evidence for absorption involving Na⁺-independent anion exchange. A leading candidate is the apical chloride/bicarbonate (Cl⁻/HCO₃⁻) exchanger DRA (down-regulated in adenoma; Slc26a3), primarily linked to the Cl⁻ transporting defect in congenital chloride diarrhea. The present study set out to characterize transepithelial ³⁵SO₄²⁻ and ³⁶Cl⁻ fluxes across the isolated, short-circuited cecum from wild-type (WT) and knockout (KO) mice and subsequently to define the contribution of DRA. The cecum demonstrated simultaneous net SO₄²⁻ secretion (-8.39 ± 0.88 nmol·cm⁻²·h⁻¹) and Cl⁻ absorption (10.85 ± 1.41 μmol·cm⁻²·h⁻¹). In DRA-KO mice, SO₄²⁻ secretion was reversed to net absorption via a 60% reduction in serosal to mucosal SO₄²⁻ flux. Similarly, net Cl⁻ absorption was abolished and replaced by secretion, indicating that DRA represents a major pathway for transcellular SO₄²⁻ secretion and Cl⁻ absorption. Further experiments including the application of DIDS (500 μM), bumetanide (100 μM), and substitutions of extracellular Cl⁻ or HCO₃⁻/CO₂ helped to identify specific ion dependencies and driving forces and suggested that additional anion exchangers were operating at both apical and basolateral membranes supporting SO₄²⁻ transport. In conclusion, DRA contributes to SO₄²⁻ secretion via DIDS-sensitive HCO₃⁻/SO₄²⁻ exchange, in addition to being the principal DIDS-resistant Cl⁻/HCO₃⁻ exchanger. With DRA linked to the pathogenesis of other gastrointestinal diseases extending its functional characterization offers a more complete picture of its role in the intestine.

  5. Rotational modulation and flares on RS CVn and BY Dra-type stars. I - Photometry and spot models for BY Dra, AU Mic, AR Lac, II Peg and V 711 Tau (= HR 1099)

    NASA Technical Reports Server (NTRS)

    Rodono, M.; Cutispoto, G.; Pazzani, V.; Catalano, S.; Byrne, P. B.

    1986-01-01

    Multicolor wide-band photometry of five active stars is presented. The observations were carried out at several places before, during and after the period of IUE observations for the purpose of determining the location, sizes, and evolution of photospheric spots at the time when chromospheric, transition region, and coronal activity data were obtained from UV and radio observations. II Peg, BY Dra, and AU Mic show fairly stable quasi-sinusoidal light curves, while AR Lac and V 711 Tau show double-peaked light curves. For V 711 Tau, a remarkable evolution of the spotted area extent and/or longitude distribution is found. Small, but definite color variations that are consistent with the cool spot hypothesis have also been detected for BY Dra, II Peg and V 711 Tau.

  6. Photometric analysis of overcontact binaries AK Her, HI Dra, V1128 Tau, and V2612 Oph

    SciTech Connect

    Çalışkan, Ş.; Özavcı, İ.; Baştürk, Ö.; Şenavcı, H. V.; Kılıçoğlu, T.; Yılmaz, M.; Selam, S. O.; Latković, O.; Djurašević, G.; Cséki, A. E-mail: ozavci@science.ankara.edu.tr E-mail: hvsenavci@ankara.edu.tr E-mail: mesutyilmaz@ankara.edu.tr E-mail: olivia@aob.rs E-mail: attila@aob.rs

    2014-12-01

    We analyze new, high quality multicolor light curves of four overcontact binaries: AK Her, HI Dra, V1128 Tau, and V2612 Oph, and determine their orbital and physical parameters using the modeling program of G. Djurasevic and recently published results of radial velocity studies. The achieved precision in absolute masses is between 10% and 20%, and the precision in absolute radii is between 5% and 10%. All four systems are W UMa-type binaries with bright or dark spots indicative of mass and energy transfer or surface activity. We estimate the distances and the ages of the systems using the luminosities computed through our analysis, and perform an O – C study for V1128 Tau, which reveals a complex period variation that can be interpreted in terms of mass loss/exchange and either the presence of the third body, or the magnetic activity on one of the components. We conclude that further observations of these systems are needed to deepen our understanding of their nature and variability.

  7. Geomorphology of Dra Abu el-Naga (Egypt): The basis of the funerary sacred landscape

    NASA Astrophysics Data System (ADS)

    Bardají, T.; Martínez-Graña, A.; Sánchez-Moral, S.; Pethen, H.; García-González, D.; Cuezva, S.; Cañaveras, J. C.; Jiménez-Higueras, A.

    2017-07-01

    A geological and geomorphological analysis has been performed in the necropolis of Dra Abu el-Naga in order to understand the role played by these two factors in the development of the sacred landscape. The investigation focuses upon two aspects of the development of the necropolis, the selection criteria for tomb location and the reconstruction of the ancient funerary landscape. Around 50 tombs were surveyed, analysing the characteristics of their host rock and classifying them according to a modified Rock Mass Rating Index, in order to understand how rock quality affected tomb construction. This analysis resulted in the definition of five rock-quality classes (I to V) from very good to very poor rock. The geological study also resulted in a proposed geological-geomorphological model for the evolution of this zone of the Theban necropolis that complements previous works by other authors. Due to the lack of precise dating evidence this chronology is a relative one and is based on the chronology given by other authors for similar deposits and events. Two catastrophic events, represented by mega-landslides, have been identified, the first one predates the deposition of early Pleistocene fluvial deposits, and the second one possibly occurred during the middle-late Pleistocene. Two weathering surfaces developed under wetter than present climatic conditions and have been tentatively correlated to the mid-late Pleistocene humid period and the African-Humid Period (early-mid Holocene).

  8. Long-term variations in the spottedness of BY Dra M dwarfs

    NASA Astrophysics Data System (ADS)

    Alekseev, I. Yu.; Kozhevnikova, A. V.

    2017-03-01

    The results of a spottedness study for twelve red dwarf stars covering several decades and based on a vast amount of photometric observations are presented. The analysis makes use of multicolor ( UBV RI) photometric monitoring of ten of these stars since 1991 at the Crimean Astrophysical Observatory, as well as data from the literature. The spottedness parameters for selected active BY Dra red dwarfs have been refined using an improved zonal model for the spotted stellar atmospheres to allow for the possible presence of two active longitudes on the stars. Time variations in the spot activity of these systems are analyzed in order to look for possible cycles. Three of the stars show a drift of their spots in the latitude towards the stellar poles; however, the magnitude of this latitude drift is a factor of two to three lower than the analogous value for sunspots. All the stars except for YZ CMi display relationships between the area of the spots and their latitude, with correlation coefficients R from 0.67 to 0.97. Evidence for the presence of activity cycles with durations from 25 to 40 years is found for six stars, which are characterized by synchronous variations in the areas and latitudes of their spots, as well as of the overall photometric brightness.

  9. Evaluating Semantic Relatedness and Similarity Measures with Standardized MedDRA Queries

    PubMed Central

    Bill, Robert W.; Liu, Ying; McInnes, Bridget T.; Melton, Genevieve B.; Pedersen, Ted; Pakhomov, Serguei

    2012-01-01

    A potential use of automated concept similarity and relatedness measures is to improve automatic detection of clinical text that relates to a condition indicative of an adverse drug reaction. This is also one of the purposes of the Medical Dictionary for Regulatory Activities (MedDRA) Standardized Queries (SMQ). An expert panel evaluates SMQs for their ability to detect a condition of interest and thus qualifies them as a reference standard for evaluating automated approaches. We compare similarity and relatedness measurement methods on rates of correctly identifying intra-category and inter-category concept pairs from SMQ data to create ROC curves of each method’s sensitivity and specificity. Results indicate an information content measure, specifically the Resnik method, achieved the highest results as measured by area under the curve, but using two different measures as predictors, Resnik and Lin, obtained the highest score. Overall, using SMQ data resulted in a productive method of evaluating automated semantic relatedness and similarity scores. PMID:23304271

  10. A novel Creb family gene telomeric of HLA-DRA in the HLA complex

    SciTech Connect

    Min, Jingjuan; Kozono, Haruo; Bronson, S.K.; Chaplin, D.D.; Shukla, Hridayabhiranjan; Weissman, S.M.

    1995-11-20

    cDNA selection was used to identify genes encoded by a 440-kb yeast artificial chromosome (YAC) clone that spanned from HLA-DRA to CYP21 in the HLA complex. An initially selected short cDNA was used to isolate a 2639-nucleotide, apparently full-length cDNA from a human tonsil library. This cDNA contained one extended open reading frame that predicted a protein of 700 amino acids with a basic region and a leucine zipper that is highly similar to members of the Creb/ATF subfamily. High-stringency Southern blotting of total human genomic DNA using this cDNA as the probe showed only a single locus that mapped to the selecting YAC clone. This gene, designated Creb-related protein (Creb-rp), is expressed ubiquitously and is evolutionarily conserved in mammals. It is located in the HLA Class III region 6-10 kb centromeric of the XB gene, which encodes a tenascin-like extracellular matrix protein. Homologous sequences are located in the Class II-Class III interval of the mouse H-2 complex. The amino acid sequence homology and general structural features of the predicted protein indicate that this gene encodes a general transcription factor belonging to the Creb/ATF subfamily of the bZip super family. 47 refs., 5 figs., 1 tab.

  11. Selective Serotonin Reuptake Inhibitor and Bleeding in a Cynomolgus Macaque (Macaca fascicularis)

    PubMed Central

    Silverstein, Marnie G; El-Amin, Colette Kirk; Shively, Carol A

    2014-01-01

    Selective serotonin reuptake inhibitors (SSRI) are associated with an increased bleeding risk in humans. This report describes a bleeding event in a cynomolgus macaque (Macaca fascicularis) treated with the SSRI sertraline HCl (Zoloft). During the treatment course, the subject presented with a maculopapular rash, cutaneous bleeding, epistaxis, bleeding from the eye, melena, and a severe thrombocytopenia. To our knowledge, this report is the first description of an SSRI-related adverse event in a nonhuman primate. This report demonstrates that the clinical presentation of SSRI-associated bleeding in cynomolgus macaques is consistent with that reported in humans and that complications from SSRI treatment should be considered as a differential diagnosis for maculopapular dermatitis or spontaneous bleeding in this species. PMID:24956214

  12. Incidence of ketamine-induced emesis in cynomologus monkeys (Macaca fascicularis) used for staphylococcal enterotoxin bioassay.

    PubMed Central

    Adesiyun, A. A.; Tatini, S. R.

    1982-01-01

    Ten (24%) of 41 cynomologus monkeys (Macaca fascicularis) showed emetic response to 2.5-20 mg/Kg of ketamine injected i.m. Reduction of the levels of ketamine to one half or less of the emetic level resulted in faster recovery from sedation yet provided adequate time for intubation and subsequent intragastric feeding of staphylococcal enterotoxin (SE) in only 6 of the 10 monkeys without emesis. The onset of the first emetic episode with ketamine was similar to that induced by staphylococcal enterotoxin A (SEA). Cynomologus monkeys showing emetic response to ketamine could still be used for SE bioassay if an experimentally determined non-emetic dose for individual monkeys is employed for sedation. PMID:7093145

  13. Polymerase Chain Reaction Detection of Trypanosoma cruzi in Macaca fascicularis Using Archived Tissues

    PubMed Central

    Williams, Jeff T.; Mubiru, James N.; Schlabritz-Loutsevitch, Natalia E.; Rubicz, Rohina C.; VandeBerg, John L.; Dick, Edward J.; Hubbard, Gene B.

    2009-01-01

    This study describes conventional and real-time polymerase chain reaction (PCR) methods developed to detect and quantify Trypanosoma cruzi DNA in cynomolgus monkeys (Macaca fascicularis) using formalin-fixed paraffin-embedded blocks archived for periods of up to 6 years. The highest concentration of T. cruzi DNA was found in the myocardium, urinary bladder, stomach, lymph node, adrenal gland, and colon. The concentration of T. cruzi DNA detected in cardiac tissues was 10–100-fold greater than found elsewhere; the mean concentrations of T. cruzi DNA in non-cardiac tissues were otherwise comparable. Trypanosoma cruzi DNA was amplified from cerebrum but not cerebellum or kidney. Successful use of DNA from formalin-fixed, paraffin-embedded blocks is important because most pathology laboratories routinely archive wax blocks. This archived resource can be used for further studies on the prevalence of this disease. PMID:19635875

  14. Light and scanning electron microscopical study of the cavernous sinus of the monkey, Macaca fascicularis.

    PubMed Central

    Rajendran, K; Ling, E A

    1985-01-01

    The cavernous sinus of Macaca fascicularis is in many respects similar to the human sinus. It consists predominantly of one main venous channel that, together with the internal carotid artery, occupies a meningo-endocranial compartment lateral to the pituitary gland. Trabeculae are few and do not in any way cause the sinus to appear cavernous. They are mostly flattened in the direction of the main venous channel. Cranial nerves three, four, six and the ophthalmic division of five are all located in the lateral wall of the meningo-endocranial compartment with cranial nerve six located most medially adjacent to the internal carotid artery. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:4077687

  15. Characterization of cement float buoyancy in the stalked barnacle Dosima fascicularis (Crustacea, Cirripedia)

    PubMed Central

    Zheden, Vanessa; Kovalev, Alexander; Gorb, Stanislav N.; Klepal, Waltraud

    2015-01-01

    Dosima fascicularis is the only barnacle which can drift autonomously at the water surface with a foam-like cement float. The cement secreted by the animal contains numerous gas-filled cells of different size. When several individuals share one float, their size and not their number is crucial for the production of both volume and mass of the float. The gas content within the cells of the foam gives positive static buoyancy to the whole float. The volume of the float, the gas volume and the positive static buoyancy are positively correlated. The density of the cement float without gas is greater than that of seawater. This study shows that the secreted cement consists of more than 90% water and the gas volume is on average 18.5%. Our experiments demonstrate that the intact foam-like cement float is sealed to the surrounding water. PMID:25657839

  16. Neuroblastoma at the trigeminal nerve in a cynomolgus monkey (Macaca fascicularis)

    PubMed Central

    Ide, Tetsuya; Moriyama, Akiko; Uchida, Kazuyuki; Chambers, James K.; Okazaki, Takanobu; Kobayashi, Kinji; Nakatsuji, Shunji; Matsumoto, Masahiro

    2016-01-01

    A male cynomolgus monkey (Macaca fascicularis) of 5 years and 11 months of age from the vehicle control group of a 4-week repeated oral dose toxicity study had a spontaneously occurring mass lesion directly attached to the proximal part of the left trigeminal nerve. Histologically, the mass was characterized by a multifocal nodular appearance. Nodular zones showed low to moderate cellularity and were composed of small round cells exhibiting nuclear uniformity. On the other hand, inter-nodular zones were composed of nerve fiber containing septa and closely aggregated highly pleomorphic cells. Immunohistochemically, the small round cells were strongly immunopositive for synaptophysin, neuN, and class III beta-tubulin, while the highly pleomorphic cells were weakly immunopositive for neuN and occasionally immunopositive for class III beta-tubulin and doublecortin, suggesting that the tumor had originated from a neuronal lineage cell. Based on these findings, the mass was diagnosed as a neuroblastoma at the trigeminal nerve. PMID:27559245

  17. Selective serotonin reuptake inhibitor and bleeding in a cynomolgus macaque (Macaca fascicularis).

    PubMed

    Silverstein, Marnie G; El-Amin, Colette Kirk; Shively, Carol A

    2014-06-01

    Selective serotonin reuptake inhibitors (SSRI) are associated with an increased bleeding risk in humans. This report describes a bleeding event in a cynomolgus macaque (Macaca fascicularis) treated with the SSRI sertraline HCl (Zoloft). During the treatment course, the subject presented with a maculopapular rash, cutaneous bleeding, epistaxis, bleeding from the eye, melena, and a severe thrombocytopenia. To our knowledge, this report is the first description of an SSRI-related adverse event in a nonhuman primate. This report demonstrates that the clinical presentation of SSRI-associated bleeding in cynomolgus macaques is consistent with that reported in humans and that complications from SSRI treatment should be considered as a differential diagnosis for maculopapular dermatitis or spontaneous bleeding in this species.

  18. Bilateral hamartomatous medullary lipoma within the nasal turbinate bones in a cynomolgus monkey (Macaca fascicularis)

    PubMed Central

    KATSUTA, Osamu; SHIBATA, Toru; KURIKI-YAMAMOTO, Yumi; MOCHIZUKI, Takaharu; YOSHIMI, Miwa; NOTO, Takahisa; MANO, Hidetoshi

    2016-01-01

    A 15-year-old male cynomolgus monkey (Macaca fascicularis) showed large bilateral masses in the maxillary sinus. In histopathological examination, both masses revealed benign medullary lipomas within the turbinate bones. The tumors were composed of well-developed lipocytes, trabecular bones and a few blood vessels. Although we initially diagnosed the tumor as bilateral lipomas in the nasal turbinates, it was not differentiated from lipomatous hamartoma. Findings, such as unique symmetrical proliferation, lack of border from the normal marrow and the intact surrounding tissue, indicated a lipomatous hamartoma/hamartomatous lipoma, thought to be a suitable diagnosis of the lesion. Of most interest was that such a proliferating lesion occurred in the nasal turbinate. PMID:27499062

  19. Peripheral Ossifying Fibroma and Juxtacortical Chondrosarcoma in Cynomolgus Monkeys (Macaca fascicularis)

    PubMed Central

    Schmelting, Barthel; Zöller, Martina; Kaspareit, Joachim

    2011-01-01

    Literature on spontaneous primary bone tumors in nonhuman primates is sparse. This case report describes 2 different neoplastic bone lesions in 2 adult cynomolgus monkeys (Macaca fascicularis), including macroscopic, radiographic, histologic, and immunohistochemical findings. In one monkey, a firm mass located at the palatogingival junction of the left rostral maxilla was confirmed to be a peripheral ossifying fibroma in light of its histologic and immunohistochemical characteristics. In another monkey, a lobulated tumor at the right distal femur that radiographically showed moderate radiopacity with splotchy areas of mineralization was confirmed to be a juxtacortical chondrosarcoma on histologic examination. The 2 neoplastic bone lesions revealed rare histologic and immunohistochemical characteristics and contribute to the known tumor spectrum of cynomolgus monkeys. PMID:21333171

  20. Characterization of cement float buoyancy in the stalked barnacle Dosima fascicularis (Crustacea, Cirripedia).

    PubMed

    Zheden, Vanessa; Kovalev, Alexander; Gorb, Stanislav N; Klepal, Waltraud

    2015-02-06

    Dosima fascicularis is the only barnacle which can drift autonomously at the water surface with a foam-like cement float. The cement secreted by the animal contains numerous gas-filled cells of different size. When several individuals share one float, their size and not their number is crucial for the production of both volume and mass of the float. The gas content within the cells of the foam gives positive static buoyancy to the whole float. The volume of the float, the gas volume and the positive static buoyancy are positively correlated. The density of the cement float without gas is greater than that of seawater. This study shows that the secreted cement consists of more than 90% water and the gas volume is on average 18.5%. Our experiments demonstrate that the intact foam-like cement float is sealed to the surrounding water.

  1. Analysis of Macular Drusen and Blood Test Results in 945 Macaca fascicularis

    PubMed Central

    Nishiguchi, Koji M.; Yokoyama, Yu; Fujii, Yusuke; Fujita, Kosuke; Tomiyama, Yusuke; Kawasaki, Ryo; Furukawa, Toshinori; Ono, Fumiko; Shimozawa, Nobuhiro; Togo, Mutsumi; Suzuki, Michihiro; Nakazawa, Toru

    2016-01-01

    Age-dependent formation of macular drusen caused by the focal accumulation of extracellular deposits beneath the retinal pigment epithelium precede the development of age-related macular degeneration (AMD), one of the leading causes of blindness worldwide. It is established that inflammation contributes to the pathogenesis of drusen and AMD. However, development of a preemptive therapeutic strategy targeting macular drusen and AMD has been impeded by the lack of relevant animal models because most laboratory animals lack macula, an anatomic feature present only in humans and a subset of monkeys. Reportedly, macular drusen and macular degeneration develop in monkeys in an age-dependent manner. In this study, we analyzed blood test results from 945 Macaca fascicularis, 317 with and 628 without drusen. First, a trend test for drusen frequency (the Cochran–Armitage test) was applied to the quartile data for each parameter. We selected variables with an increasing or decreasing trend with higher quartiles at P < 0.05, to which multivariate logistic regression analysis was applied. This revealed a positive association of age (odds ratio [OR]: 1.10 per year, 95% confidence interval [CI]: 1.07–1.12) and white blood cell count (OR: 1.01 per 1 × 103/μl, 95% CI: 1.00–1.01) with drusen. When the monkeys were divided by age, the association between drusen and white blood cell count was only evident in younger monkeys (OR: 1.01 per 1 × 103/μl, 95% CI: 1.00–1.02). In conclusion, age and white blood cell count may be associated with drusen development in M. fascicularis. Systemic inflammation may contribute to drusen formation in monkeys. PMID:27776188

  2. Infection by Brazilian and Dutch swine hepatitis E virus strains induces haematological changes in Macaca fascicularis

    PubMed Central

    2013-01-01

    Background Hepatitis E virus (HEV) has been described as an emerging pathogen in Brazil and seems to be widely disseminated among swine herds. An autochthonous human case of acute hepatitis E was recently reported. To obtain a better understanding of the phenotypic profiles of both human and swine HEV strains, a experimental study was conducted using the animal model, Macaca fascicularis. Methods Six cynomolgus monkeys (Macaca fascicularis) were inoculated intravenously with swine HEV genotype 3 that was isolated from naturally and experimentally infected pigs in Brazil and the Netherlands. Two other monkeys were inoculated with HEV genotype 3 that was recovered from Brazilian and Argentinean patients with locally acquired acute and fulminant hepatitis E. The haematological, biochemical, and virological parameters of all animals were monitored for 67 days. Results Subclinical hepatitis was observed in all monkeys after inoculation with HEV genotype 3 that was recovered from the infected swine and human patients. HEV RNA was detected in the serum and/or faeces of 6 out of the 8 cynomolgus monkeys between 5 and 53 days after inoculation. The mild inflammation of liver tissues and elevations of discrete liver enzymes were observed. Seroconversions to anti-HEV IgM and/or IgG were detected in 7 animals. Reactivities to anti-HEV IgA were also detected in the salivary samples of 3 animals. Interestingly, all of the infected monkeys showed severe lymphopenia and a trend toward monocytosis, which coincided with elevations in alanine aminotransferase and antibody titres. Conclusions The ability of HEV to cross the species barrier was confirmed for both the swine (Brazilian and Dutch) and human (Argentinean) strains, thus reinforcing the zoonotic risk of hepatitis E in South America. Cynomolgus monkeys that were infected with HEV genotype 3 developed subclinical hepatitis that was associated with haematological changes. Haematological approaches should be considered in

  3. Epizoic acoelomorph flatworms impair zooplankton feeding by the scleractinian coral Galaxea fascicularis

    PubMed Central

    Wijgerde, Tim; Schots, Pauke; Van Onselen, Eline; Janse, Max; Karruppannan, Eric; Verreth, Johan A. J.; Osinga, Ronald

    2013-01-01

    Summary Many scleractinian coral species host epizoic acoelomorph flatworms, both in aquaculture and in situ. These symbiotic flatworms may impair coral growth and health through light-shading, mucus removal and disruption of heterotrophic feeding. To quantify the effect of epizoic flatworms on zooplankton feeding, we conducted video analyses of single polyps of Galaxea fascicularis (Linnaeus 1767) grazing on Artemia nauplii in the presence and absence of symbiotic flatworms. 18S DNA analysis revealed that flatworms inhabiting G. fascicularis belonged to the genus Waminoa (Convolutidae), which were hosted at a density of 3.6±0.4 individuals polyp−1. Polyps hosting flatworms exhibited prey capture rates of 2.2±2.5, 3.4±4.5 and 2.7±3.4 nauplii polyp−1 30 min−1 at prey concentrations of 250, 500 and 1,000 nauplii L−1, respectively. Polyps that had their flatworms removed displayed prey capture rates of 2.7±1.6, 4.8±4.1 and 16.9±10.3 nauplii polyp−1 30 min−1. Significant main and interactive effects of flatworm presence and ambient prey concentration were found, reflected by the fact that flatworms significantly impaired host feeding rates at the highest prey density of 1,000 nauplii L−1. In addition, flatworms displayed kleptoparasitism, removing between 0.1±0.3 and 0.6±1.1 nauplii 30 min−1 from the oral disc of their host, or 5.3±3.3 to 50.0±2.1% of prey acquired by the coral. We suggest classifying the coral-associated Waminoa sp. as an epizoic parasite, as its presence may negatively affect growth and health of the host. PMID:23336072

  4. Epizoic acoelomorph flatworms impair zooplankton feeding by the scleractinian coral Galaxea fascicularis.

    PubMed

    Wijgerde, Tim; Schots, Pauke; Van Onselen, Eline; Janse, Max; Karruppannan, Eric; Verreth, Johan A J; Osinga, Ronald

    2013-01-15

    Many scleractinian coral species host epizoic acoelomorph flatworms, both in aquaculture and in situ. These symbiotic flatworms may impair coral growth and health through light-shading, mucus removal and disruption of heterotrophic feeding. To quantify the effect of epizoic flatworms on zooplankton feeding, we conducted video analyses of single polyps of Galaxea fascicularis (Linnaeus 1767) grazing on Artemia nauplii in the presence and absence of symbiotic flatworms. 18S DNA analysis revealed that flatworms inhabiting G. fascicularis belonged to the genus Waminoa (Convolutidae), which were hosted at a density of 3.6±0.4 individuals polyp(-1). Polyps hosting flatworms exhibited prey capture rates of 2.2±2.5, 3.4±4.5 and 2.7±3.4 nauplii polyp(-1) 30 min(-1) at prey concentrations of 250, 500 and 1,000 nauplii L(-1), respectively. Polyps that had their flatworms removed displayed prey capture rates of 2.7±1.6, 4.8±4.1 and 16.9±10.3 nauplii polyp(-1) 30 min(-1). Significant main and interactive effects of flatworm presence and ambient prey concentration were found, reflected by the fact that flatworms significantly impaired host feeding rates at the highest prey density of 1,000 nauplii L(-1). In addition, flatworms displayed kleptoparasitism, removing between 0.1±0.3 and 0.6±1.1 nauplii 30 min(-1) from the oral disc of their host, or 5.3±3.3 to 50.0±2.1% of prey acquired by the coral. We suggest classifying the coral-associated Waminoa sp. as an epizoic parasite, as its presence may negatively affect growth and health of the host.

  5. Transcriptome profiling of Galaxea fascicularis and its endosymbiont Symbiodinium reveals chronic eutrophication tolerance pathways and metabolic mutualism between partners

    PubMed Central

    Lin, Zhenyue; Chen, Mingliang; Dong, Xu; Zheng, Xinqing; Huang, Haining; Xu, Xun; Chen, Jianming

    2017-01-01

    In the South China Sea, coastal eutrophication in the Beibu Gulf has seriously threatened reef habitats by subjecting corals to chronic physiological stress. To determine how coral holobionts may tolerate such conditions, we examined the transcriptomes of healthy colonies of the galaxy coral Galaxea fascicularis and its endosymbiont Symbiodinium from two reef sites experiencing pristine or eutrophied nutrient regimes. We identified 236 and 205 genes that were differentially expressed in eutrophied hosts and symbionts, respectively. Both gene sets included pathways related to stress responses and metabolic interactions. An analysis of genes originating from each partner revealed striking metabolic integration with respect to vitamins, cofactors, amino acids, fatty acids, and secondary metabolite biosynthesis. The expression levels of these genes supported the existence of a continuum of mutualism in this coral-algal symbiosis. Additionally, large sets of transcription factors, cell signal transduction molecules, biomineralization components, and galaxin-related proteins were expanded in G. fascicularis relative to other coral species. PMID:28181581

  6. Transcriptome profiling of Galaxea fascicularis and its endosymbiont Symbiodinium reveals chronic eutrophication tolerance pathways and metabolic mutualism between partners.

    PubMed

    Lin, Zhenyue; Chen, Mingliang; Dong, Xu; Zheng, Xinqing; Huang, Haining; Xu, Xun; Chen, Jianming

    2017-02-09

    In the South China Sea, coastal eutrophication in the Beibu Gulf has seriously threatened reef habitats by subjecting corals to chronic physiological stress. To determine how coral holobionts may tolerate such conditions, we examined the transcriptomes of healthy colonies of the galaxy coral Galaxea fascicularis and its endosymbiont Symbiodinium from two reef sites experiencing pristine or eutrophied nutrient regimes. We identified 236 and 205 genes that were differentially expressed in eutrophied hosts and symbionts, respectively. Both gene sets included pathways related to stress responses and metabolic interactions. An analysis of genes originating from each partner revealed striking metabolic integration with respect to vitamins, cofactors, amino acids, fatty acids, and secondary metabolite biosynthesis. The expression levels of these genes supported the existence of a continuum of mutualism in this coral-algal symbiosis. Additionally, large sets of transcription factors, cell signal transduction molecules, biomineralization components, and galaxin-related proteins were expanded in G. fascicularis relative to other coral species.

  7. Reduced heterotrophy in the stony coral Galaxea fascicularis after life-long exposure to elevated carbon dioxide

    NASA Astrophysics Data System (ADS)

    Smith, Joy N.; Strahl, Julia; Noonan, Sam H. C.; Schmidt, Gertraud M.; Richter, Claudio; Fabricius, Katharina E.

    2016-06-01

    Ocean acidification imposes many physiological, energetic, structural and ecological challenges to stony corals. While some corals may increase autotrophy under ocean acidification, another potential mechanism to alleviate some of the adverse effects on their physiology is to increase heterotrophy. We compared the feeding rates of Galaxea fascicularis colonies that have lived their entire lives under ocean acidification conditions at natural carbon dioxide (CO2) seeps with colonies living under present-day CO2 conditions. When provided with the same quantity and composition of zooplankton as food, corals acclimatized to high CO2 showed 2.8 to 4.8 times depressed rates of zooplankton feeding. Results were consistent over four experiments, from two expeditions and both in field and chamber measurements. Unless replenished by other sources, reduced zooplankton uptake in G. fascicularis acclimatized to ocean acidification is likely to entail a shortage of vital nutrients, potentially jeopardizing their health and survival in future oceans.

  8. Transcriptome profiling of Galaxea fascicularis and its endosymbiont Symbiodinium reveals chronic eutrophication tolerance pathways and metabolic mutualism between partners

    NASA Astrophysics Data System (ADS)

    Lin, Zhenyue; Chen, Mingliang; Dong, Xu; Zheng, Xinqing; Huang, Haining; Xu, Xun; Chen, Jianming

    2017-02-01

    In the South China Sea, coastal eutrophication in the Beibu Gulf has seriously threatened reef habitats by subjecting corals to chronic physiological stress. To determine how coral holobionts may tolerate such conditions, we examined the transcriptomes of healthy colonies of the galaxy coral Galaxea fascicularis and its endosymbiont Symbiodinium from two reef sites experiencing pristine or eutrophied nutrient regimes. We identified 236 and 205 genes that were differentially expressed in eutrophied hosts and symbionts, respectively. Both gene sets included pathways related to stress responses and metabolic interactions. An analysis of genes originating from each partner revealed striking metabolic integration with respect to vitamins, cofactors, amino acids, fatty acids, and secondary metabolite biosynthesis. The expression levels of these genes supported the existence of a continuum of mutualism in this coral-algal symbiosis. Additionally, large sets of transcription factors, cell signal transduction molecules, biomineralization components, and galaxin-related proteins were expanded in G. fascicularis relative to other coral species.

  9. Reduced heterotrophy in the stony coral Galaxea fascicularis after life-long exposure to elevated carbon dioxide

    PubMed Central

    Smith, Joy N.; Strahl, Julia; Noonan, Sam H. C.; Schmidt, Gertraud M.; Richter, Claudio; Fabricius, Katharina E.

    2016-01-01

    Ocean acidification imposes many physiological, energetic, structural and ecological challenges to stony corals. While some corals may increase autotrophy under ocean acidification, another potential mechanism to alleviate some of the adverse effects on their physiology is to increase heterotrophy. We compared the feeding rates of Galaxea fascicularis colonies that have lived their entire lives under ocean acidification conditions at natural carbon dioxide (CO2) seeps with colonies living under present-day CO2 conditions. When provided with the same quantity and composition of zooplankton as food, corals acclimatized to high CO2 showed 2.8 to 4.8 times depressed rates of zooplankton feeding. Results were consistent over four experiments, from two expeditions and both in field and chamber measurements. Unless replenished by other sources, reduced zooplankton uptake in G. fascicularis acclimatized to ocean acidification is likely to entail a shortage of vital nutrients, potentially jeopardizing their health and survival in future oceans. PMID:27255977

  10. Long-Term Starspot Activity of Some Chromospherically Active Rs CVn and BY Dra Stars

    NASA Astrophysics Data System (ADS)

    Kozhevnikova, Alla; Ilya, Alekseev

    2016-10-01

    We present results of our long-term photometric observations of a sample of 15 chromospherically active BY Dra and RS CVn-type stars. Observations were carried out at a 70-cm telescope and multichannel photometer of Kourovka Astronomical Observatory of Ural Federal University and at a 1.25-m telescope of Crimean Astrophysical Observatory from 2003 to 2015 in Johnson B, V, R, I bands. We also use the previously published photometric data for all these stars to find the meaning of historical star's brightness, that we assume as a brightness of unspotted photosphere. Using a renewed zonal spot model for spotted stellar photospheres we determined spot parameters for all observational seasons, as our as published ones, that were spanning almost over 45 years for some stars (e.g. CG Cyg, WY Cnc, EV Lac, V 1396 Cyg). It is shown that the spots were located at low and middle latitudes up to 58 deg., are cooler than the surrounding photosphere by 200 - 2000 K according to the spectral class. The spotted area varied from season to season, comprising 13%-47% of the surface area of the star. Almost half of the stars display drifts of their spots towards the equator and poles during certain time intervals; however, the speeds of the spots' latitude drifts are lower than the analogous speeds for sunspots, by factors of 1.5-4, on average. Activity cycles lasting from 5 to 40 years have been determined or confirmed for majority of the studied stars. As a rule, cycles are expressed in synchronous variations of spot areas, spot latitudes and average photometric star's brightness.

  11. Jaw-muscle architecture and mandibular morphology influence relative maximum jaw gapes in the sexually dimorphic Macaca fascicularis.

    PubMed

    Terhune, Claire E; Hylander, William L; Vinyard, Christopher J; Taylor, Andrea B

    2015-05-01

    Maximum jaw gape is a performance variable related to feeding and non-feeding oral behaviors, such as canine gape displays, and is influenced by several factors including jaw-muscle fiber architecture, muscle position on the skull, and jaw morphology. Maximum gape, jaw length, and canine height are strongly correlated across catarrhine primates, but relationships between gape and other aspects of masticatory apparatus morphology are less clear. We examine the effects of jaw-adductor fiber architecture, jaw-muscle leverage, and jaw form on gape in an intraspecific sample of sexually dimorphic crab-eating macaques (Macaca fascicularis). As M. fascicularis males have relatively larger maximum gapes than females, we predict that males will have muscle and jaw morphologies that facilitate large gape, but these morphologies may come at some expense to bite force. Male crab-eating macaques have relatively longer jaw-muscle fibers, masseters with decreased leverage, and temporomandibular joint morphologies that facilitate the production of wide gapes. Because relative canine height is correlated with maximum gape in catarrhines, and males have relatively longer canines than females, these results support the hypothesis that male M. fascicularis have experienced selection to increase maximum gape. The sexes do not differ in relative masseter physiologic cross-sectional area (PCSA), but males compensate for a potential trade-off between muscle excursion versus muscle force with increased temporalis weight and PCSA. This musculoskeletal configuration is likely functionally significant for behaviors involving aggressive canine biting and displays in male M. fascicularis and provides additional evidence supporting the multifactorial nature of the catarrhine masticatory apparatus. Our results have implications for the evolution of craniofacial morphology in catarrhine primates and reinforce the importance of evaluating additional factors other than feeding behavior and diet

  12. Loss of the anion exchanger DRA (Slc26a3), or PAT1 (Slc26a6), alters sulfate transport by the distal ileum and overall sulfate homeostasis.

    PubMed

    Whittamore, Jonathan M; Hatch, Marguerite

    2017-09-01

    The ileum is considered the primary site of inorganic sulfate ([Formula: see text]) absorption. In the present study, we explored the contributions of the apical chloride/bicarbonate (Cl(-)/[Formula: see text]) exchangers downregulated in adenoma (DRA; Slc26a3), and putative anion transporter 1 (PAT1; Slc26a6), to the underlying transport mechanism. Transepithelial (35)[Formula: see text] and (36)Cl(-) fluxes were determined across isolated, short-circuited segments of the distal ileum from wild-type (WT), DRA-knockout (KO), and PAT1-KO mice, together with measurements of urine and plasma sulfate. The WT distal ileum supported net sulfate absorption [197.37 ± 13.61 (SE) nmol·cm(-2)·h(-1)], but neither DRA nor PAT1 directly contributed to the unidirectional mucosal-to-serosal flux ([Formula: see text]), which was sensitive to serosal (but not mucosal) DIDS, dependent on Cl(-), and regulated by cAMP. However, the absence of DRA significantly enhanced net sulfate absorption by one-third via a simultaneous rise in [Formula: see text] and a 30% reduction to the secretory serosal-to-mucosal flux ([Formula: see text]). We propose that DRA, together with PAT1, contributes to [Formula: see text] by mediating sulfate efflux across the apical membrane. Associated with increased ileal sulfate absorption in vitro, plasma sulfate was 61% greater, and urinary sulfate excretion (USO4) 2.2-fold higher, in DRA-KO mice compared with WT controls, whereas USO4 was increased 1.8-fold in PAT1-KO mice. These alterations to sulfate homeostasis could not be accounted for by any changes to renal sulfate handling suggesting that the source of this additional sulfate was intestinal. In summary, we characterized transepithelial sulfate fluxes across the mouse distal ileum demonstrating that DRA (and to a lesser extent, PAT1) secretes sulfate with significant implications for intestinal sulfate absorption and overall homeostasis.NEW & NOTEWORTHY Sulfate is an essential anion that is

  13. AG Dra is going into outburst again, of the hot type and the third in the present series

    NASA Astrophysics Data System (ADS)

    Munari, U.; Righetti, G. L.; Valisa, P.; Buzzi, L.; Moretti, S.

    2017-05-01

    The outbursts of the Halo symbiotic binary and super-soft X-ray source AG Dra are known to come in series (1932-1939, 1949-1955, 1963-1966, 1980-1986, 1993-2008, Leedjarv et al. 2016 MNRAS 456, 2558, Galis et al. 2017, OEJV 180, 24), usually started by a large amplitude eruption of the "cool" type, followed by a train of lower amplitude events of the "hot" type (Gonzalez-Riestra et al. 1999, A & A 1999, 347, 478).

  14. Emisión Hα en sistemas binarios cromosféricamente activos (RS CVn y BY Dra)

    NASA Astrophysics Data System (ADS)

    Fernández-Figueroa, M. J.; Montes, D.; de Castro, E.

    1992-05-01

    We report here high and medium resolution Balmer Hα line profiles for 11 chromospherically active binary systems including the class of RS Canum Venaticorum binaries (RS CVn) and BY Draconis (BY Dra) with a total range of rotation periods from 0.8 to 24 days. We have obtained different types of Hα line profiles: strong emission line, weak emission line with strong superposed absorption profile and filled-in absorption line profile. We have measured the Hα equivalent width of the program stars and the Hα core emission was determined by subtraction of the equivalent width of a presumably inactive star with the same spectral type and luminosity class.

  15. Coronal Temperature and Emission Measure Distributions for he Active G Supergiant Beta Dra and other ASCA Projects

    NASA Technical Reports Server (NTRS)

    Brown, Alexander

    1998-01-01

    This NASA grant supported my ASCA observing and data analysis programs during AOs 1-4. This research involved four Guest Observer projects. Analysis of data from all four programs has been completed. This grant included the following ASCA GO programs: AO1 - "Coronal Temperature and Emission Measure Distributions for the Active G Supergiant Beta Dra" AO2 - "Contemporaneous ASCA, EUVE, IUE, and VLA/AT Observations of Atmospheric Structure of the RS CVn Binary HR1099". AO3 - "Coronal Temperature and Emission Measure Distributions for the hybrid-chromosphere star alpha TrA". AO4-"Activity on the edge of convection: The atmosphere of Canopus (alpha Car, FO Ib-II)".

  16. Dra/AfaE adhesin of uropathogenic Dr/Afa+ Escherichia coli mediates mortality in pregnant rats.

    PubMed

    Wroblewska-Seniuk, K; Selvarangan, R; Hart, A; Pladzyk, R; Goluszko, P; Jafari, A; du Merle, L; Nowicki, S; Yallampalli, C; Le Bouguénec, C; Nowicki, B

    2005-11-01

    Escherichia coli bearing adhesins of the Dr/Afa family frequently causes urogenital infections during pregnancy in humans and has been associated with mortality in pregnant rats. Two components of the adhesin, Dra/AfaE and Dra/AfaD, considered virulence factors, are responsible for bacterial binding and internalization. We hypothesize that gestational mortality caused by Dr/Afa+ E. coli is mediated by one of these two proteins, Dra/AfaE or Dra/AfaD. In this study, using afaE and/or afaD mutants, we investigated the role of the afaE and afaD genes in the mortality of pregnant rats from intrauterine infection. Sprague-Dawley rats, on the 17th day of pregnancy, were infected with the E. coli afaE+ afaD and afaE afaD+ mutants. The clinical E. coli strain (afaE+ afaD+) and the afaE afaD double mutant were used as positive and negative controls, respectively. The mortality rate was evaluated 24 h after infection. The highest maternal mortality was observed in the group infected with the afaE+ afaD+ strain, followed by the group infected with the afaE+ afaD strain. The mortality was dose dependent. The afaE afaD double mutant did not cause maternal mortality, even with the highest infection dose. The in vivo studies corresponded with the invasion assay, where the afaE+ strains were the most invasive (afaE+ afaD strain > afaE+ afaD+ strain), while the afaE mutant strains (afaE afaD+ and afaE afaD strains) seemed to be noninvasive. This study shows for the first time that the afaE gene coding for the AfaE subunit of Dr/Afa adhesin is involved in the lethal outcome of gestational infection in rats. This lethal effect associated with AfaE correlates with the invasiveness of afaE+ E. coli strains in vitro.

  17. Dra/AfaE Adhesin of Uropathogenic Dr/Afa+ Escherichia coli Mediates Mortality in Pregnant Rats

    PubMed Central

    Wroblewska-Seniuk, K.; Selvarangan, R.; Hart, A.; Pladzyk, R.; Goluszko, P.; Jafari, A.; du Merle, L.; Nowicki, S.; Yallampalli, C.; Le Bouguénec, C.; Nowicki, B.

    2005-01-01

    Escherichia coli bearing adhesins of the Dr/Afa family frequently causes urogenital infections during pregnancy in humans and has been associated with mortality in pregnant rats. Two components of the adhesin, Dra/AfaE and Dra/AfaD, considered virulence factors, are responsible for bacterial binding and internalization. We hypothesize that gestational mortality caused by Dr/Afa+ E. coli is mediated by one of these two proteins, Dra/AfaE or Dra/AfaD. In this study, using afaE and/or afaD mutants, we investigated the role of the afaE and afaD genes in the mortality of pregnant rats from intrauterine infection. Sprague-Dawley rats, on the 17th day of pregnancy, were infected with the E. coli afaE+ afaD and afaE afaD+ mutants. The clinical E. coli strain (afaE+ afaD+) and the afaE afaD double mutant were used as positive and negative controls, respectively. The mortality rate was evaluated 24 h after infection. The highest maternal mortality was observed in the group infected with the afaE+ afaD+ strain, followed by the group infected with the afaE+ afaD strain. The mortality was dose dependent. The afaE afaD double mutant did not cause maternal mortality, even with the highest infection dose. The in vivo studies corresponded with the invasion assay, where the afaE+ strains were the most invasive (afaE+ afaD strain > afaE+ afaD+ strain), while the afaE mutant strains (afaE afaD+ and afaE afaD strains) seemed to be noninvasive. This study shows for the first time that the afaE gene coding for the AfaE subunit of Dr/Afa adhesin is involved in the lethal outcome of gestational infection in rats. This lethal effect associated with AfaE correlates with the invasiveness of afaE+ E. coli strains in vitro. PMID:16239563

  18. Engineering Macaca fascicularis cytochrome P450 2C20 to reduce animal testing for new drugs.

    PubMed

    Rua, Francesco; Sadeghi, Sheila J; Castrignanò, Silvia; Di Nardo, Giovanna; Gilardi, Gianfranco

    2012-12-01

    In order to develop in vitro methods as an alternative to P450 animal testing in the drug discovery process, two main requisites are necessary: 1) gathering of data on animal homologues of the human P450 enzymes, currently very limited, and 2) bypassing the requirement for both the P450 reductase and the expensive cofactor NADPH. In this work, P450 2C20 from Macaca fascicularis, homologue of the human P450 2C8 has been taken as a model system to develop such an alternative in vitro method by two different approaches. In the first approach called "molecular Lego", a soluble self-sufficient chimera was generated by fusing the P450 2C20 domain with the reductase domain of cytochrome P450 BM3 from Bacillus megaterium (P450 2C20/BMR). In the second approach, the need for the redox partner and also NADPH were both obviated by the direct immobilization of the P450 2C20 on glassy carbon and gold electrodes. Both systems were then compared to those obtained from the reconstituted P450 2C20 monooxygenase in presence of the human P450 reductase and NADPH using paclitaxel and amodiaquine, two typical drug substrates of the human P450 2C8. The K(M) values calculated for the 2C20 and 2C20/BMR in solution and for 2C20 immobilized on electrodes modified with gold nanoparticles were 1.9 ± 0.2, 5.9 ± 2.3, 3.0 ± 0.5 μM for paclitaxel and 1.2 ± 0.2, 1.6±0.2 and 1.4 ± 0.2 μM for amodiaquine, respectively. The data obtained not only show that the engineering of M. fascicularis did not affect its catalytic properties but also are consistent with K(M) values measured for the microsomal human P450 2C8 and therefore show the feasibility of developing alternative in vitro animal tests. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Role for draTG and rnf Genes in Reduction of 2,4-Dinitrophenol by Rhodobacter capsulatus

    PubMed Central

    Sáez, Lara P.; García, Patricia; Martínez-Luque, Manuel; Klipp, Werner; Blasco, Rafael; Castillo, Francisco

    2001-01-01

    The phototrophic bacterium Rhodobacter capsulatus is able to reduce 2,4-dinitrophenol (DNP) to 2-amino-4-nitrophenol enzymatically and thus can grow in the presence of this uncoupler. DNP reduction was switched off by glutamine or ammonium, but this short-term regulation did not take place in a draTG deletion mutant. Nevertheless, the target of DraTG does not seem to be the nitrophenol reductase itself since the ammonium shock did not inactivate the enzyme. In addition to this short-term regulation, ammonium or glutamine repressed the DNP reduction system. Mutants of R. capsulatus affected in ntrC or rpoN exhibited a 10-fold decrease in nitroreductase activity in vitro but almost no DNP activity in vivo. In addition, mutants affected in rnfA or rnfC, which are also under NtrC control and encode components involved in electron transfer to nitrogenase, were unable to metabolize DNP. These results indicate that NtrC regulates dinitrophenol reduction in R. capsulatus, either directly or indirectly, by controlling expression of the Rnf proteins. Therefore, the Rnf complex seems to supply electrons for both nitrogen fixation and DNP reduction. PMID:11160111

  20. Theta(1) and gamma Tauri: Understanding the coronal structure of Hyades giants. EUV spectroscopy of BY Dra systems

    NASA Technical Reports Server (NTRS)

    Stern, Robert A.

    1995-01-01

    These programs involve: (1) analysis and interpretation of EUVE spectrometer observations of the active giant beta Cet in comparison to the Hyades giant theta(1) Tau, and (2) analysis and interpretation of EUVE spectrometer observations of the BY Dra systems FK Aqr, DH Leo, and BH Lyn. EUVE carried out observations of beta Cet, but has yet to perform an observation of theta(1) Tau. In beta Cet, a number of Fe lines from high ionization species were observed, up to Fe XXIV. The spectrum overall resembles that seen in the active binary Capella (alpha Aur). All three BY Dra systems were observed by EUVE, and show evidence of high temperature (approximately 10(exp 7) K) plasma; FK Aqr and DH Leo show significant variability in their Deep Survey lightcurves. In FK Aqr, spectral differences between its 'quiescent' and 'active' states suggest possible differences in the plasma density. In DH Leo, the Deep Survey lightcurve, taken over nearly 8 days, shows a distinct period of approximately 1.05 days, similar to the photometric period. The emission measure distributions of all three systems are rather similar in shape, and can be well-represented by a power law with slope approximately 1.5 from 6.2-7.0 in log T.

  1. A structural study of the interaction between the Dr haemagglutinin DraE and derivatives of chloramphenicol

    PubMed Central

    Pettigrew, David M.; Roversi, Pietro; Davies, Stephen G.; Russell, Angela J.; Lea, Susan M.

    2009-01-01

    Dr adhesins are expressed on the surface of uropathogenic and diffusely adherent strains of Escherichia coli. The major adhesin subunit (DraE/AfaE) of these organelles mediates attachment of the bacterium to the surface of the host cell and possibly intracellular invasion through its recognition of the complement regulator decay-accelerating factor (DAF) and/or members of the carcinoembryonic antigen (CEA) family. The adhesin subunit of the Dr haemagglutinin, a Dr-family member, additionally binds type IV collagen and is inhibited in all its receptor interactions by the antibiotic chloram­phenicol (CLM). In this study, previous structural work is built upon by reporting the X-ray structures of DraE bound to two chloramphenicol derivatives: chloramphenicol succinate (CLS) and bromamphenicol (BRM). The CLS structure demonstrates that acylation of the 3-hydroxyl group of CLM with succinyl does not significantly perturb the mode of binding, while the BRM structure implies that the binding pocket is able to accommodate bulkier substituents on the N-­acyl group. It is concluded that modifications of the 3-­hydroxyl group would generate a potent Dr haemagglutinin inhibitor that would not cause the toxic side effects that are associated with the normal bacteriostatic activity of CLM. PMID:19465765

  2. Nutritional Composition of Fruits Selected by Long-Tailed Macaques (Macaca fascicularis) in Kuala Selangor, Malaysia.

    PubMed

    Kassim, Norazila; Hambali, Kamarul; Amir, Aainaa

    2017-01-01

    Proximate analysis of twelve species of fruits commonly consumed by long-tailed macaques (Macaca fascicularis), i.e., Arenga pinnata, Areca catechu, Terminalia catappa, Elaeis guineensis, Lagerstroemia tomentosa, Mangifera indica, Cascabela thevetia, Muntingia calabura, Musa sp., Artocarpus heterophyllus, Ficus tinctoria ssp. gibbosa and Ficus microcarpa, was conducted with the specific objective to determine the nutritional composition of the foodstuffs of long-tailed macaques. The results showed the following order of nutrients: fibre, protein, fat and ash. Based on the results of the chemical analysis, the highest percentage of fibre content (52.7%), protein (9.9%), fat (77.2%) and ash (8.5%) were found in A. catechu, T. catappa, E. guineensis and C. thevetia, respectively. The nutrient composition of these twelve fruit species was found to differ (ANOVA test: crude protein, F (11,24) = 87.978, p < 0.05; crude fibre, F (11,24) = 28.886, p < 0.05; crude fat, F (11,24) = 2081.396, p < 0.05 and ash, F (11,24) = 41.011, p < 0.05). Fibre was found in the highest amount among the four types of nutrients studied. Here, A. catechu had the highest relative fibre content of all tested fruits, E. guineensis had the highest fat content, T. catappa had the highest protein content, and the total mineral content was highest in C. thevetia.

  3. Genetic diversity and population structure of long-tailed macaque (Macaca fascicularis) populations in Peninsular Malaysia.

    PubMed

    Nikzad, Sonia; Tan, Soon Guan; Yong Seok Yien, Christina; Ng, Jillian; Alitheen, Noorjahan Banu; Khan, Razib; Rovie-Ryan, Jeffrine J; Valdiani, Alireza; Khajeaian, Parastoo; Kanthaswamy, Sree

    2014-12-01

    The genetic diversity and structure of long-tailed macaques (Macaca fascicularis) in Peninsular Malaysia, a widely used non-human primate species in biomedical research, have not been thoroughly characterized. Thirteen sites of wild populations of long-tailed macaques representing six states were sampled and analyzed with 18 STR markers. The Sunggala and Penang Island populations showed the highest genetic diversity estimates, while the Jerejak Island population was the most genetically discrete due to isolation from the mainland shelf. Concordant with pairwise F(st) estimates, STRUCTURE analyses of the seven PCA-correlated clusters revealed low to moderate differentiation among the sampling sites. No association between geographic and genetic distances exists, suggesting that the study sites, including island study sites, are genetically if not geographically contiguous. The status of the genetic structure and composition of long-tailed macaque populations require further scrutiny to develop this species as an important animal model in biomedical research. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Nutritional Composition of Fruits Selected by Long-Tailed Macaques (Macaca fascicularis) in Kuala Selangor, Malaysia

    PubMed Central

    Kassim, Norazila; Hambali, Kamarul; Amir, Aainaa

    2017-01-01

    Proximate analysis of twelve species of fruits commonly consumed by long-tailed macaques (Macaca fascicularis), i.e., Arenga pinnata, Areca catechu, Terminalia catappa, Elaeis guineensis, Lagerstroemia tomentosa, Mangifera indica, Cascabela thevetia, Muntingia calabura, Musa sp., Artocarpus heterophyllus, Ficus tinctoria ssp. gibbosa and Ficus microcarpa, was conducted with the specific objective to determine the nutritional composition of the foodstuffs of long-tailed macaques. The results showed the following order of nutrients: fibre, protein, fat and ash. Based on the results of the chemical analysis, the highest percentage of fibre content (52.7%), protein (9.9%), fat (77.2%) and ash (8.5%) were found in A. catechu, T. catappa, E. guineensis and C. thevetia, respectively. The nutrient composition of these twelve fruit species was found to differ (ANOVA test: crude protein, F (11,24) = 87.978, p < 0.05; crude fibre, F (11,24) = 28.886, p < 0.05; crude fat, F (11,24) = 2081.396, p < 0.05 and ash, F (11,24) = 41.011, p < 0.05). Fibre was found in the highest amount among the four types of nutrients studied. Here, A. catechu had the highest relative fibre content of all tested fruits, E. guineensis had the highest fat content, T. catappa had the highest protein content, and the total mineral content was highest in C. thevetia. PMID:28228918

  5. Biosorption of copper(II) from aqueous solutions by green alga Cladophora fascicularis.

    PubMed

    Deng, Liping; Zhu, Xiaobin; Wang, Xinting; Su, Yingying; Su, Hua

    2007-08-01

    Biosorption is an effective means of removal of heavy metals from wastewater. In this work the biosorption behavior of Cladophora fascicularis was investigated as a function of pH, amount of biosorbent, initial Cu2+ concentration, temperature, and co-existing ions. Adsorption equilibria were well described by Langmuir isotherm models. The enthalpy change for the biosorption process was found to be 6.86 kJ mol(-1) by use of the Langmuir constant b. The biosorption process was found to be rapid in the first 30 min. The presence of co-existing cations such as Na+, K+, Mg2+, and Ca2+ and anions such as chloride, nitrate, sulfate, and acetate did not significantly affect uptake of Cu2+ whereas EDTA substantially affected adsorption of the metal. When experiments were performed with different desorbents the results indicated that EDTA was an efficient desorbent for the recovery of Cu2+ from biomass. IR spectral analysis suggested amido or hydroxy, C=O, and C-O could combine strongly with Cu2+.

  6. Infinium Monkeys: Infinium 450K Array for the Cynomolgus macaque (Macaca fascicularis)

    PubMed Central

    Ong, Mei-Lyn; Tan, Peck Yean; MacIsaac, Julia L; Mah, Sarah M; Buschdorf, Jan Paul; Cheong, Clara Y; Stunkel, Walter; Chan, Louiza; Gluckman, Peter D.; Chng, Keefe; Kobor, Michael S.; Meaney, Michael J; Holbrook, Joanna D

    2014-01-01

    The Infinium Human Methylation450 BeadChip Array (Infinium 450K) is a robust and cost-efficient survey of genome-wide DNA methylation patterns. Macaca fascicularis (Cynomolgus macaque) is an important disease model; however, its genome sequence is only recently published, and few tools exist to interrogate the molecular state of Cynomolgus macaque tissues. Although the Infinium 450K is a hybridization array designed to the human genome, the relative conservation between the macaque and human genomes makes its use in macaques feasible. Here, we used the Infinium 450K array to assay DNA methylation in 11 macaque muscle biopsies. We showed that probe hybridization efficiency was related to the degree of sequence identity between the human probes and the macaque genome sequence. Approximately 61% of the Human Infinium 450K probes could be reliably mapped to the Cynomolgus macaque genome and contain a CpG site of interest. We also compared the Infinium 450K data to reduced representation bisulfite sequencing data generated on the same samples and found a high level of concordance between the two independent methodologies, which can be further improved by filtering for probe sequence identity and mismatch location. We conclude that the Infinium 450K array can be used to measure the DNA methylome of Cynomolgus macaque tissues using the provided filters. We also provide a pipeline for validation of the array in other species using a simple BLAST-based sequence identify filter. PMID:24815017

  7. Status of urban populations of the long-tailed macaque (Macaca fascicularis) in West Sumatra, Indonesia.

    PubMed

    Ilham, Kurnia; Rizaldi; Nurdin, Jabang; Tsuji, Yamato

    2017-04-01

    We studied long-tailed macaque (Macaca fascicularis) populations in Padang, West Sumatra, Indonesia, focusing on the effect of human provisioning on their demography and dietary composition. We conducted a field survey at three sites in the city: Gunung Meru, Gunung Padang, and Gunung Panggilun. Mean troop size (range 28-68) and infant ratio (range 0.38-1.00) were greater in Gunung Meru, where the macaques have been highly provisioned, than at the other two study sites (troop size 10-15; infant ratio 0.00-0.33). The macaques at all sites consumed both natural and human foods, but dependence on the latter differed among sites: three-quarters of the diet of macaques in Gunung Meru consisted of human foods, while human foods comprised less than 5% of the macaque diet at the other sites. The ability of macaques to modify the proportion of human food is a behavioral flexibility that facilitates the survival of the long-tailed macaque in urban habitats. Without restrictions on provisioning, the degree of dependence of macaques on human foods and population size could increase, especially in Gunung Meru, and human-macaque conflict could escalate. In order to create an effective management policy for urbanized monkeys, long-term quantitative data on macaque behavior and monitoring of population parameters are required.

  8. Infinium monkeys: Infinium 450K array for the Cynomolgus macaque (Macaca fascicularis).

    PubMed

    Ong, Mei-Lyn; Tan, Peck Yean; MacIsaac, Julia L; Mah, Sarah M; Buschdorf, Jan Paul; Cheong, Clara Y; Stunkel, Walter; Chan, Louiza; Gluckman, Peter D; Chng, Keefe; Kobor, Michael S; Meaney, Michael J; Holbrook, Joanna D

    2014-05-08

    The Infinium Human Methylation450 BeadChip Array (Infinium 450K) is a robust and cost-efficient survey of genome-wide DNA methylation patterns. Macaca fascicularis (Cynomolgus macaque) is an important disease model; however, its genome sequence is only recently published, and few tools exist to interrogate the molecular state of Cynomolgus macaque tissues. Although the Infinium 450K is a hybridization array designed to the human genome, the relative conservation between the macaque and human genomes makes its use in macaques feasible. Here, we used the Infinium 450K array to assay DNA methylation in 11 macaque muscle biopsies. We showed that probe hybridization efficiency was related to the degree of sequence identity between the human probes and the macaque genome sequence. Approximately 61% of the Human Infinium 450K probes could be reliably mapped to the Cynomolgus macaque genome and contain a CpG site of interest. We also compared the Infinium 450K data to reduced representation bisulfite sequencing data generated on the same samples and found a high level of concordance between the two independent methodologies, which can be further improved by filtering for probe sequence identity and mismatch location. We conclude that the Infinium 450K array can be used to measure the DNA methylome of Cynomolgus macaque tissues using the provided filters. We also provide a pipeline for validation of the array in other species using a simple BLAST-based sequence identify filter. Copyright © 2014 Ong et al.

  9. Whole-genome sequencing and analysis of the Malaysian cynomolgus macaque (Macaca fascicularis) genome.

    PubMed

    Higashino, Atsunori; Sakate, Ryuichi; Kameoka, Yosuke; Takahashi, Ichiro; Hirata, Makoto; Tanuma, Reiko; Masui, Tohru; Yasutomi, Yasuhiro; Osada, Naoki

    2012-07-02

    The genetic background of the cynomolgus macaque (Macaca fascicularis) is made complex by the high genetic diversity, population structure, and gene introgression from the closely related rhesus macaque (Macaca mulatta). Herein we report the whole-genome sequence of a Malaysian cynomolgus macaque male with more than 40-fold coverage, which was determined using a resequencing method based on the Indian rhesus macaque genome. We identified approximately 9.7 million single nucleotide variants (SNVs) between the Malaysian cynomolgus and the Indian rhesus macaque genomes. Compared with humans, a smaller nonsynonymous/synonymous SNV ratio in the cynomolgus macaque suggests more effective removal of slightly deleterious mutations. Comparison of two cynomolgus (Malaysian and Vietnamese) and two rhesus (Indian and Chinese) macaque genomes, including previously published macaque genomes, suggests that Indochinese cynomolgus macaques have been more affected by gene introgression from rhesus macaques. We further identified 60 nonsynonymous SNVs that completely differentiated the cynomolgus and rhesus macaque genomes, and that could be important candidate variants for determining species-specific responses to drugs and pathogens. The demographic inference using the genome sequence data revealed that Malaysian cynomolgus macaques have experienced at least three population bottlenecks. This list of whole-genome SNVs will be useful for many future applications, such as an array-based genotyping system for macaque individuals. High-quality whole-genome sequencing of the cynomolgus macaque genome may aid studies on finding genetic differences that are responsible for phenotypic diversity in macaques and may help control genetic backgrounds among individuals.

  10. Compete to Play: Trade-Off with Social Contact in Long-Tailed Macaques (Macaca fascicularis)

    PubMed Central

    Ballesta, Sébastien; Reymond, Gilles; Pozzobon, Mathieu; Duhamel, Jean-René

    2014-01-01

    Many animal species engage in various forms of solitary object play, but this activity seems to be of particular importance in primates. If playing objects constitute a valuable resource, and access to such objects is limited, a competitive context may arise. We inserted a unique toy within a mini-colony of long-tailed macaque (Macaca fascicularis) and compared their behaviors to sessions without playing object. An automatic color-based 3D video device was used to track the positions of each animal and the toy, and this data was categorized into 5 exclusive behaviors (resting, locomotion, foraging, social contact and object play). As expected, the delay to first access to the object reflected the hierarchy of the colony, indicating that a competition took place to own this unique resource of entertainment. In addition, we found that the amount of object play was not correlated with social or foraging behavior, suggesting independent motivational mechanisms. Conversely, object playing time was negatively correlated with idling time, thus indicating its relation to pastime activities. Interestingly, the amount of social contacts in the group was significantly reduced by the heightened competitive context, suggesting that competitors are more likely to be perceived as potential threat requiring caution, as shown in humans. Experimental manipulation of competitive contexts in primates reveals common mental processes involved in social judgment, and shows that access to valuable resources can be a sufficient cause for variations in group cohesion. PMID:25551755

  11. Population and landscape genetics of an introduced species (M. fascicularis) on the island of Mauritius.

    PubMed

    Satkoski Trask, Jessica; George, Debra; Houghton, Paul; Kanthaswamy, Sree; Smith, David Glenn

    2013-01-01

    The cynomolgus macaque, Macaca fascicularis, was introduced onto the island of Mauritius in the early 17(th) century. The species experienced explosive population growth, and currently exists at high population densities. Anecdotes collected from nonhuman primate trappers on the island of Mauritius allege that animals from the northern portion of the island are larger in body size than and superior in condition to their conspecifics in the south. Although previous genetic studies have reported Mauritian cynomolgus macaques to be panmictic, the individuals included in these studies were either from the southern/central or an unknown portion of the island. In this study, we sampled individuals broadly throughout the entire island of Mauritius and used spatial principle component analysis to measure the fine-scale correlation between geographic and genetic distance in this population. A stronger correlation between geographic and genetic distance was found among animals in the north than in those in the southern and central portions of the island. We found no difference in body weight between the two groups, despite anecdotal evidence to the contrary. We hypothesize that the increased genetic structure among populations in the north is related to a reduction in dispersal distance brought about by human habitation and tourist infrastructure, but too recent to have produced true genetic differentiation.

  12. Gene expression profiling in the Cynomolgus macaque Macaca fascicularis shows variation within the normal birth range.

    PubMed

    Emerald, Bright Starling; Chng, Keefe; Masuda, Shinya; Sloboda, Deborah M; Vickers, Mark H; Kambadur, Ravi; Gluckman, Peter D

    2011-10-16

    Although an adverse early-life environment has been linked to an increased risk of developing the metabolic syndrome, the molecular mechanisms underlying altered disease susceptibility as well as their relevance to humans are largely unknown. Importantly, emerging evidence suggests that these effects operate within the normal range of birth weights and involve mechanisms of developmental palsticity rather than pathology. To explore this further, we utilised a non-human primate model Macaca fascicularis (Cynomolgus macaque) which shares with humans the same progressive history of the metabolic syndrome. Using microarray we compared tissues from neonates in the average birth weight (50-75th centile) to those of lower birth weight (5-25th centile) and studied the effect of different growth trajectories within the normal range on gene expression levels in the umbilical cord, neonatal liver and skeletal muscle. We identified 1973 genes which were differentially expressed in the three tissue types between average and low birth weight animals (P < 0.05). Gene ontology analysis identified that these genes were involved in metabolic processes including cellular lipid metabolism, cellular biosynthesis, cellular macromolecule synthesis, cellular nitrogen metabolism, cellular carbohydrate metabolism, cellular catabolism, nucleotide and nucleic acid metabolism, regulation of molecular functions, biological adhesion and development. These differences in gene expression levels between animals in the upper and lower percentiles of the normal birth weight range may point towards early life metabolic adaptations that in later life result in differences in disease risk.

  13. Gene expression profiling in the Cynomolgus macaque Macaca fascicularis shows variation within the normal birth range

    PubMed Central

    2011-01-01

    Background Although an adverse early-life environment has been linked to an increased risk of developing the metabolic syndrome, the molecular mechanisms underlying altered disease susceptibility as well as their relevance to humans are largely unknown. Importantly, emerging evidence suggests that these effects operate within the normal range of birth weights and involve mechanisms of developmental palsticity rather than pathology. Method To explore this further, we utilised a non-human primate model Macaca fascicularis (Cynomolgus macaque) which shares with humans the same progressive history of the metabolic syndrome. Using microarray we compared tissues from neonates in the average birth weight (50-75th centile) to those of lower birth weight (5-25th centile) and studied the effect of different growth trajectories within the normal range on gene expression levels in the umbilical cord, neonatal liver and skeletal muscle. Results We identified 1973 genes which were differentially expressed in the three tissue types between average and low birth weight animals (P < 0.05). Gene ontology analysis identified that these genes were involved in metabolic processes including cellular lipid metabolism, cellular biosynthesis, cellular macromolecule synthesis, cellular nitrogen metabolism, cellular carbohydrate metabolism, cellular catabolism, nucleotide and nucleic acid metabolism, regulation of molecular functions, biological adhesion and development. Conclusion These differences in gene expression levels between animals in the upper and lower percentiles of the normal birth weight range may point towards early life metabolic adaptations that in later life result in differences in disease risk. PMID:21999700

  14. Experimental and postexperimental effects of posteriorly directed extraoral traction in adult Macaca fascicularis.

    PubMed

    Brandt, H C; Shapiro, P A; Kokich, V G

    1979-03-01

    The experimental, postexperimental, and postretention effects of continuous high-pull headgear force application to the maxilla were evaluated in four adult, nongrowing Macaca fascicularis monkeys. Force was applied at 450 grams per side to face-bows attached to cast maxillary splints with an implanted occipital plug for anchorage. The active experimental phase lasted from 84 days to 205 days, and its effects were documented histologically, cephalometrically, and with dry skull preparations. Postexperimental, retention, and postretention responses were documented cephalometrically. The findings of the present investigation lead to the following conclusions: 1. The termination active sutural growth is of little significance to the remodeling potential of the sutural articulations and the morphologic adaptability of the facial skeletal complex. 2. The length of time necessary for resorptive remodeling of the sutural bony projections is partially responsible for the slower rate of detectable skeletal movement in adult animals. 3. The sutural ligament in adult animals is initially less responsive to the effects of extraoral force application, possibly because of a diminished level of cellular activity at older ages. 4. Increases in age do not appear to affect the osteogenic potential of the periosteal envelope. 5. Retention aids in establishing a maintainable equilibrium following experimentally induced sutural and skeletal remodeling, but it is of little importance in maintaining the altered position of the denition. 6. The amount of postexperimental skeletal reorientation following force application to the maxilla may be related to the force level and the duration of force.

  15. Effect of soy isoflavones on thyroid hormones in intact and ovariectomized cynomolgus monkeys (Macaca fascicularis).

    PubMed

    Silverstein, Marnie G; Kaplan, Jay R; Appt, Susan E; Register, Thomas C; Shively, Carol A

    2014-10-01

    Soy isoflavones are commonly used to alleviate menopause-related symptoms. Postmenopausal women are at increased risk for hypothyroidism, and there are concerns that isoflavones may be detrimental to thyroid health. The aim of this study was to examine the effects of soy protein and isoflavones on thyroid function and the relationship between thyroid function and ovarian function. Adult female cynomolgus monkeys (Macaca fascicularis) were randomized to consume two diets differing only in protein source: casein-lactalbumin (n = 44) or soy protein with isoflavones (n = 41). After 34 months, all animals were ovariectomized via laparotomy. Half of the monkeys from each diet treatment group continued to consume their preovariectomy treatment phase diet (either isolated soy protein [n = 19] or casein-lactalbumin [n = 21]) for an additional 34 months. The remaining animals did not continue their diets and thus were not considered further. Circulating progesterone, triiodothyronine, thyroxine, and thyroid-stimulating hormone were measured at baseline. Thyroid hormones were remeasured during each treatment phase. Dietary soy increased triiodothyronine in preovariectomized monkeys and prevented a decline in thyroxine after surgical menopause (both P's < 0.05). Mean progesterone concentrations were positively correlated with triiodothyronine at baseline in preovariectomized monkeys (P < 0.01). Progesterone levels and triiodothyronine are positively correlated in macaques. Dietary soy increases triiodothyronine in preovariectomized monkeys and prevents a decline in thyroxine after surgical menopause. The outcomes observed in this study suggest that soy protein and isoflavone consumption does not adversely affect-and may even preserve-thyroid function in postmenopausal women.

  16. Pulmonary Embolization of Fat and Bone Marrow in Cynomolgus Macaques (Macaca fascicularis)

    PubMed Central

    Fong, Derek L.; Murnane, Robert D.; Hotchkiss, Charlotte E.; Green, Damian J.; Hukkanen, Renee R.

    2011-01-01

    Fat embolization (FE), the introduction of bone marrow elements into circulation, is a known complication of bone fractures. Although FE has been described in other animal models, this study represents the first reported cases of FE and bone marrow embolism in nonhuman primates. Histopathologic findings from cynomolgus macaques (Macaca fascicularis) indicated that in all 5 cases, fat and bone marrow embolization occurred subsequent to multiple bone marrow biopsies. In the most severe case, extensive embolization was associated pulmonary damage consistent with acute respiratory distress syndrome. Fat embolism syndrome (FES) is an infrequent clinical outcome of FE and is triggered by systemic biochemical and mechanical responses to fat in circulation. Although clinical criteria diagnostic of FES were not investigated at the time of death, this severe case may represent the fulminant form of FES, which occurs within 12 h after trauma. Bone marrow biopsy as an etiology of FES has been reported only once in humans. In addition, the association of embolization with bone marrow biopsies suggests that nonhuman primates may be a useful animal model of FE. FE and FES represent important research confounders and FES should be considered as a differential diagnosis for clinical complications subsequent to skeletal trauma. PMID:21819686

  17. Telomere length of the colonial coral Galaxea fascicularis at different developmental stages

    NASA Astrophysics Data System (ADS)

    Tsuta, H.; Hidaka, M.

    2013-06-01

    The ability to estimate coral age using soft tissue would be useful for population biology or aging studies on corals. In this study, we investigated whether telomere length can be used to estimate coral age. We applied single telomere length analysis to a colonial coral, Galaxea fascicularis, and estimated telomere lengths of specific coral chromosomes at different developmental stages. If the telomere shortened at each cell division, the telomere length of the coral would be longest in sperm and shortest in adult colonies. However, the mean telomere length of sperm, planula larvae, and polyps was approximately 4 kb, with no significant differences among the developmental stages. The telomerase restriction fragment (TRF) analysis also showed no significant difference in the mean TRF length among the developmental stages. Our results suggested that telomere length is maintained during developmental stages and that estimating the age of colonial coral based on telomere length may not be possible. However, our findings can be used to examine avoidance of aging and rejuvenation during regeneration and asexual reproduction in colonial corals.

  18. No costly prosociality among related long-tailed macaques (Macaca fascicularis).

    PubMed

    Sterck, Elisabeth H M; Olesen, Caroline U; Massen, Jorg J M

    2015-08-01

    Altruism, benefiting another at a cost to the donor, may be achieved through prosocial behavior. Studies of nonhuman animals typically investigate prosocial behavior with paradigms in which the donor can choose to give a recipient a food item, and the choice does not affect the donor's reward (which is either present or absent). In such tasks, long-tailed macaques (Macaca fascicularis) show prosocial behavior, especially toward kin. Here, we tested captive long-tailed macaques with related recipients in an alternative task, in which the donor had to give up a preferred reward to benefit the recipient; that is, they had to choose a lower valued reward for themselves to provide food to their kin. Overall, the macaques did not provide their kin with food. The task forced the donor to balance its prosocial behavior with its selfish choice for a higher value reward, a balance that turned out to favor selfish motives. Consequently, our study shows that a prosocial tendency is not sufficient to elicit costly prosocial behavior in long-tailed macaques. Subsequently, we feel that tasks in which the donor must choose a lower value reward to benefit another individual may allow the titration of the strength of prosocial behavior, and thus provides interesting possibilities for future comparative studies. (c) 2015 APA, all rights reserved).

  19. Influence of testosterone and a novel SARM on gene expression in whole blood of Macaca fascicularis.

    PubMed

    Riedmaier, Irmgard; Tichopad, Ales; Reiter, Martina; Pfaffl, Michael W; Meyer, Heinrich H D

    2009-04-01

    Anabolic hormones, including testosterone, have been suggested as a therapy for aging-related conditions, such as osteoporosis and sarcopenia. These therapies are sometimes associated with severe androgenic side effects. A promising alternative to testosterone replacement therapy are selective androgen receptor modulators (SARMs). SARMs have the potential to mimic the desirable central and peripheral androgenic anabolic effects of testosterone without having its side effects. In this study we evaluated the effects of LGD2941, in comparison to testosterone, on mRNA expression of selected target genes in whole blood in an non-human model. The regulated genes can act as potential blood biomarker candidates in future studies with AR ligands. Cynomolgus monkeys (Macaca fascicularis) were treated either with testosterone or LGD2941 for 90 days in order to compare their effects on mRNA expression in blood. Blood samples were taken before SARM application, on day 16 and on day 90 of treatment. Gene expression of 37 candidate genes was measured using quantitative real-time RT-PCR (qRT-PCR) technology. Our study shows that both testosterone and LGD2941 influence mRNA expression of 6 selected genes out of 37 in whole blood. The apoptosis regulators CD30L, Fas, TNFR1 and TNFR2 and the interleukins IL-12B and IL-15 showed significant changes in gene expression between control and the treatment groups and represent potential biomarkers for androgen receptor ligands in whole blood.

  20. Allele frequency of antiretroviral host factor TRIMCyp in wild-caught cynomolgus macaques (Macaca fascicularis)

    PubMed Central

    Saito, Akatsuki; Kawamoto, Yoshi; Higashino, Atsunori; Yoshida, Tomoyuki; Ikoma, Tomoko; Suzaki, Yuriko; Ami, Yasushi; Shioda, Tatsuo; Nakayama, Emi E.; Akari, Hirofumi

    2012-01-01

    A recent study showed that the frequency of an antiretroviral factor TRIM5 gene-derived isoform, TRIMCyp, in cynomolgus macaques (Macaca fascicularis) varies widely according to the particular habitat examined. However, whether the findings actually reflect the prevalence of TRIMCyp in wild cynomolgus macaques is still uncertain because the previous data were obtained with captive monkeys in breeding and rearing facilities. Here, we characterized the TRIM5 gene in cynomolgus macaques captured in the wild, and found that the frequency of the TRIMCyp allele was comparable to those in captive monkeys. This suggests that the previous results with captive monkeys do indeed reflect the natural allele frequency and that breeding and rearing facilities may not affect the frequency of TRIM5 alleles. Interestingly, the prevalence of a minor haplotype of TRIMCyp in wild macaques from the Philippines was significantly lower than in captive ones, suggesting that it is advantageous for wild monkeys to possess the major haplotype of TRIMCyp. Overall, our results add to our understanding of the geographic and genetic prevalence of cynomolgus macaque TRIMCyp. PMID:22969754

  1. Pharmacokinetics of 2 Formulations of Transdermal Fentanyl in Cynomolgus Macaques (Macaca fascicularis)

    PubMed Central

    Carlson, Amy M; Kelly, Richard; Fetterer, David P; Rico, Pedro J; Bailey, Emily J

    2016-01-01

    Fentanyl is a μ-opioid agonist that often is used as the analgesic component for balanced anesthesia in both human and veterinary patients. Minimal information has been published regarding appropriate dosing, and the pharmacokinetics of fentanyl are unknown in NHP. The pharmacokinetic properties of 2 transdermal fentanyl delivery methods, a solution (2.6 and 1.95 mg/kg) and a patch (25 µg/h), were determined when applied topically to the dorsal scapular area of cynomolgus macaques (Macaca fascicularis). Serum fentanyl concentrations were analyzed by using liquid chromatography–mass spectrometry. Compared with the patch, the transdermal fentanyl solution generated higher drug concentrations over longer time. Adverse reactions occurred in the macaques that received the transdermal fentanyl solution at 2.6 mg/kg. Both preparations showed significant interanimal variability in the maximal serum drug levels, time to achieve maximal fentanyl levels, elimination half-life, and AUC values. Both the maximal concentration and the time at which this concentration occurred were increased in macaques compared with most other species after application of the transdermal fentanyl patch and compared with dogs after application of the transdermal fentanyl solution. The pharmacokinetic properties of transdermal fentanyl in macaques are markedly different from those in other veterinary species and preclude its use as a long-acting analgesic drug in NHP. PMID:27423151

  2. Differential Radial Capillary Action of Ligand Assay (DRaCALA) for High-Throughput Detection of Protein-Metabolite Interactions in Bacteria.

    PubMed

    Orr, Mona W; Lee, Vincent T

    2017-01-01

    Bacteria rely on numerous nucleotide second messengers for signal transduction such as cyclic AMP, cyclic-di-GMP, and cyclic-di-AMP. Although a number of receptors responsible for known regulated phenotypes have been established, the completeness of protein receptors in any given organism remains elusive. We have developed a method called differential radial capillary action of ligand assay (DRaCALA) that allows for an unbiased, systematic high-throughput screen for the detection of ligand binding proteins encoded by a genome. DRaCALA permits interrogation of ligand binding directly to an overexpressed protein in a cell lysate and bypasses the need of protein purification. Gateway-cloning-compatible open reading frame libraries are available for a diverse range of bacterial species and permits generation of the lysates overexpressing each open reading frame. These lysates can be assessed by DRaCALA in a 96-well format to allow rapid identification of protein-ligand interactions, including previously unknown proteins. Here, we present the protocols for generating the expression library, conducting the DRaCALA screen, data analysis, and hit validation.

  3. Test Review: Beaver, J. M., & Carter, M. A. (2006). "The Developmental Reading Assessment--Second Edition" (DRA2). Upper Saddle River, NJ--Pearson

    ERIC Educational Resources Information Center

    McCarty, Allison M.; Christ, Theodore J.

    2010-01-01

    This article reviews the "Developmental Reading Assessment--Second Edition" (DRA2), a teacher-administered assessment that identifies students' instructional level, along with their strengths and weaknesses in reading. Once teachers calculate and interpret scores, the data can purportedly be used to inform, and possibly individualize,…

  4. Test Review: Beaver, J. M., & Carter, M. A. (2006). "The Developmental Reading Assessment--Second Edition" (DRA2). Upper Saddle River, NJ--Pearson

    ERIC Educational Resources Information Center

    McCarty, Allison M.; Christ, Theodore J.

    2010-01-01

    This article reviews the "Developmental Reading Assessment--Second Edition" (DRA2), a teacher-administered assessment that identifies students' instructional level, along with their strengths and weaknesses in reading. Once teachers calculate and interpret scores, the data can purportedly be used to inform, and possibly individualize,…

  5. Mechanism of ADP-ribosylation removal revealed by the structure and ligand complexes of the dimanganese mono-ADP-ribosylhydrolase DraG

    PubMed Central

    Berthold, Catrine L.; Wang, He; Nordlund, Stefan; Högbom, Martin

    2009-01-01

    ADP-ribosylation is a ubiquitous regulatory posttranslational modification involved in numerous key processes such as DNA repair, transcription, cell differentiation, apoptosis, and the pathogenic mechanism of certain bacterial toxins. Despite the importance of this reversible process, very little is known about the structure and mechanism of the hydrolases that catalyze removal of the ADP-ribose moiety. In the phototrophic bacterium Rhodospirillum rubrum, dinitrogenase reductase-activating glycohydrolase (DraG), a dimanganese enzyme that reversibly associates with the cell membrane, is a key player in the regulation of nitrogenase activity. DraG has long served as a model protein for ADP-ribosylhydrolases. Here, we present the crystal structure of DraG in the holo and ADP-ribose bound forms. We also present the structure of a reaction intermediate analogue and propose a detailed catalytic mechanism for protein de-ADP-ribosylation involving ring opening of the substrate ribose. In addition, the particular manganese coordination in DraG suggests a rationale for the enzyme's preference for manganese over magnesium, although not requiring a redox active metal for the reaction. PMID:19706507

  6. Experimental Infection of Cynomolgus Macaques (Macaca fascicularis) with Human Varicella-Zoster Virus

    PubMed Central

    Willer, David O.; Ambagala, Aruna P. N.; Pilon, Richard; Chan, Jacqueline K.; Fournier, Jocelyn; Brooks, James; Sandstrom, Paul

    2012-01-01

    Varicella-zoster virus (VZV) is a member of the alphaherpesvirus family and the causative agent of chickenpox and shingles. To determine the utility of cynomolgus macaques (Macaca fascicularis) as a nonhuman primate model to evaluate VZV-based simian immunodeficiency virus/human immunodeficiency virus (SIV/HIV) vaccines, we experimentally inoculated 10 animals with the parental Oka (Oka-P) strain of VZV derived from MeWo or Telo-RF cells. VZV DNA could be detected in the lungs as late as 4 days postinfection, with replicating virus detected by shell vial culture assay in one case. Infection did not result in any overt clinical symptoms but was characterized by humoral and cell-mediated immunity in a time frame and at a magnitude similar to those observed following VZV vaccination in humans. The cell line source of VZV inoculum influenced both the magnitude and polyfunctionality of cell-mediated immunity. Animals mounted a vigorous anamnestic antibody response following a second inoculation 12 weeks later. Inoculations resulted in transient increases in CD4+ T-cell activation and proliferation, as well as a sustained increase in CD4+ T cells coexpressing CCR5 and α4β7 integrin. In contrast to previous failed attempts to successfully utilize attenuated VZV-Oka as an SIV vaccine vector in rhesus macaques due to suboptimal infectivity and cellular immunogenicity, the ability to infect cynomolgus macaques with Oka-P VZV should provide a valuable tool for evaluating VZV-vectored SIV/HIV vaccines. PMID:22258257

  7. Two types of periglomerular cells in the olfactory bulb of the macaque monkey (Macaca fascicularis).

    PubMed

    Liberia, Teresa; Blasco-Ibáñez, José Miguel; Nácher, Juan; Varea, Emilio; Lanciego, José Luis; Crespo, Carlos

    2013-07-01

    The olfactory bulb (OB) of mammals is the brain region that receives the sensory information coming from the olfactory epithelium. The entrance of the olfactory information occurs in spherical structures of neuropil named olfactory glomeruli and is modulated by a population of interneurons known as periglomerular cells (PG). It has been demonstrated that there are two types of PG in the OB of some macrosmatic mammals, including rats and mice. Type 1 PG (PG-1) receive synapses from the olfactory nerve, whereas type 2 PG (PG-2) do not receive synapses from the olfactory axons. To date, the presence of the two types of PG has not been investigated in microsmatic mammals. In this context, we analyze the presence of PG-1 and PG-2 in the OB of the long-tailed macaque (Macaca fascicularis). For that, we used the enzyme tyrosine hydroxylase, the neuronal isoform of the enzyme nitric oxide synthase and the calcium-binding proteins calbindin D-28k and calretinin as neurochemical markers. Our results demonstrate that the OB of the macaque contains PG-1 and PG-2. A subpopulation of PG-1 expresses tyrosine hydroxylase and another expresses the neuronal isoform of nitric oxide synthase. In addition, a subpopulation of PG-2 expresses calbindin D-28k and another expresses calretinin. Double immunofluorescence demonstrates that there is no colocalization of two markers in the same PG. These results mimic those found in macrosmatic animals. The presence of two types of PG in the glomerular circuits seems to be a key principle for the organization of the OB of mammals.

  8. Whole-genome sequencing and analysis of the Malaysian cynomolgus macaque (Macaca fascicularis) genome

    PubMed Central

    2012-01-01

    Background The genetic background of the cynomolgus macaque (Macaca fascicularis) is made complex by the high genetic diversity, population structure, and gene introgression from the closely related rhesus macaque (Macaca mulatta). Herein we report the whole-genome sequence of a Malaysian cynomolgus macaque male with more than 40-fold coverage, which was determined using a resequencing method based on the Indian rhesus macaque genome. Results We identified approximately 9.7 million single nucleotide variants (SNVs) between the Malaysian cynomolgus and the Indian rhesus macaque genomes. Compared with humans, a smaller nonsynonymous/synonymous SNV ratio in the cynomolgus macaque suggests more effective removal of slightly deleterious mutations. Comparison of two cynomolgus (Malaysian and Vietnamese) and two rhesus (Indian and Chinese) macaque genomes, including previously published macaque genomes, suggests that Indochinese cynomolgus macaques have been more affected by gene introgression from rhesus macaques. We further identified 60 nonsynonymous SNVs that completely differentiated the cynomolgus and rhesus macaque genomes, and that could be important candidate variants for determining species-specific responses to drugs and pathogens. The demographic inference using the genome sequence data revealed that Malaysian cynomolgus macaques have experienced at least three population bottlenecks. Conclusions This list of whole-genome SNVs will be useful for many future applications, such as an array-based genotyping system for macaque individuals. High-quality whole-genome sequencing of the cynomolgus macaque genome may aid studies on finding genetic differences that are responsible for phenotypic diversity in macaques and may help control genetic backgrounds among individuals. PMID:22747675

  9. Oxygen and heterotrophy affect calcification of the scleractinian coral Galaxea fascicularis.

    PubMed

    Wijgerde, Tim; Jurriaans, Saskia; Hoofd, Marleen; Verreth, Johan A J; Osinga, Ronald

    2012-01-01

    Heterotrophy is known to stimulate calcification of scleractinian corals, possibly through enhanced organic matrix synthesis and photosynthesis, and increased supply of metabolic DIC. In contrast to the positive long-term effects of heterotrophy, inhibition of calcification has been observed during feeding, which may be explained by a temporal oxygen limitation in coral tissue. To test this hypothesis, we measured the short-term effects of zooplankton feeding on light and dark calcification rates of the scleractinian coral Galaxea fascicularis (n=4) at oxygen saturation levels ranging from 13 to 280%. Significant main and interactive effects of oxygen, heterotrophy and light on calcification rates were found (three-way factorial repeated measures ANOVA, p<0.05). Light and dark calcification rates of unfed corals were severely affected by hypoxia and hyperoxia, with optimal rates at 110% saturation. Light calcification rates of fed corals exhibited a similar trend, with highest rates at 150% saturation. In contrast, dark calcification rates of fed corals were close to zero under all oxygen saturations. We conclude that oxygen exerts a strong control over light and dark calcification rates of corals, and propose that in situ calcification rates are highly dynamic. Nevertheless, the inhibitory effect of heterotrophy on dark calcification appears to be oxygen-independent. We hypothesize that dark calcification is impaired during zooplankton feeding by a temporal decrease of the pH and aragonite saturation state of the calcifying medium, caused by increased respiration rates. This may invoke a transient reallocation of metabolic energy to soft tissue growth and organic matrix synthesis. These insights enhance our understanding of how oxygen and heterotrophy affect coral calcification, both in situ as well as in aquaculture.

  10. A natural model of behavioral depression in postpartum adult female cynomolgus monkeys (Macaca fascicularis).

    PubMed

    Chu, Xun-Xun; Dominic Rizak, Joshua; Yang, Shang-Chuan; Wang, Jian-Hong; Ma, Yuan-Ye; Hu, Xin-Tian

    2014-05-01

    Postpartum depression (PPD) is a modified form of major depressive disorders (MDD) that can exert profound negative effects on both mothers and infants than MDD. Within the postpartum period, both mothers and infants are susceptible; but because PPD typically occurs for short durations and has moderate symptoms, there exists challenges in exploring and addressing the underlying cause of the depression. This fact highlights the need for relevant animal models. In the present study, postpartum adult female cynomolgus monkeys (Macaca fascicularis) living in breeding groups were observed for typical depressive behavior. The huddle posture behavior was utilized as an indicator of behavioral depression postpartum (BDP) as it has been established as the core depressive-like behavior in primates. Monkeys were divided into two groups: A BDP group (n=6), which were found to spend more time huddling over the first two weeks postpartum than other individuals that formed a non-depression control group (n=4). The two groups were then further analyzed for locomotive activity, stressful events, hair cortisol levels and for maternal interactive behaviors. No differences were found between the BDP and control groups in locomotive activity, in the frequencies of stressful events experienced and in hair cortisol levels. These findings suggested that the postpartum depression witnessed in the monkeys was not related to external factors other than puerperium period. Interestingly, the BDP monkeys displayed an abnormal maternal relationship consisting of increased infant grooming. Taken together, these findings suggest that the adult female cynomolgus monkeys provide a natural model of behavioral postpartum depression that holds a number of advantages over commonly used rodent systems in PPD modeling. The cynomolgus monkeys have a highly-organized social hierarchy and reproductive characteristics without seasonal restriction-similar to humans-as well as much greater homology to humans

  11. Effects elicited by toxaphene in the cynomolgus monkey (Macaca fascicularis): a pilot study.

    PubMed

    Bryce, F; Iverson, F; Andrews, P; Barker, M; Cherry, W; Mueller, R; Pulido, O; Hayward, S; Fernie, S; Arnold, D L

    2001-12-01

    Toxaphene, which was added to glycerol/corn oil, was administered at a level of 1 mg/kg body weight/day in gelatin capsules to four healthy young adult cynomolgus (Macaca fascicularis) monkeys for 52 weeks. Four control monkeys ingested capsules containing only glycerol/corn oil. Each group had two males and two females. On a daily basis, each monkey's feed and water consumption was determined, its health was monitored and the females were swabbed to evaluate menstrual status. On a weekly basis, each monkey's body weight was determined and a detailed clinical evaluation was performed. At 4-week intervals, blood samples were taken for serum biochemistry, haematology and toxaphene analysis. Also, a local anaesthetic was administered to the nuchal fat pad area of each monkey, and adipose samples were obtained for toxaphene analysis. 1 day prior to the biopsies, a 24-h urine and faecal collection was obtained for toxaphene analysis. After 34 weeks of treatment, the immune system of the monkeys was evaluated. After 52 weeks of dosing, all treated and two control animals were necropsied. Liver samples were obtained and microsomal fractions were prepared immediately. A portion of liver and kidney was taken for toxaphene analysis. All of the major internal organs were weighed and bone marrow evaluations were conducted. Organ and tissue samples were fixed in 10% formalin and processed for light microscopy. There was no effect of treatment on body weight gain, feed consumption, water consumption or haematological parameters. Two major clinical findings were inflammation and/or enlargement of the tarsal gland and impacted diverticulae in the upper and lower eye lids. At necropsy, the relative spleen and thymus weights were greater for the treated monkeys than the controls. Toxaphene administration produced an increase in metabolism of aminopyrene, methoxyresorufin and ethoxyresorufin, three substrates that are altered specifically by cytochrome P450-based hepatic

  12. Effect of Soy Isoflavones on Thyroid Hormones in Intact and Ovariectomized Cynomolgus Monkeys (Macaca fascicularis)

    PubMed Central

    Silverstein, Marnie G.; Kaplan, Jay R.; Appt, Susan E.; Register, Thomas C.; Shively, Carol A.

    2014-01-01

    Objectives Soy isoflavones are commonly used to alleviate menopause-related symptoms. Menopausal women are at an increased risk for hypothyroidism and there are concerns that isoflavones may be detrimental to thyroid health. The aim of this study was to examine the effects of soy protein and isoflavones on thyroid function and the relationship between thyroid and ovarian function. Methods Adult female cynomolgus monkeys (Macaca fascicularis) were randomized to consume two diets differing only in protein source: casein-lactalbumin (n = 44) or soy protein with isoflavones (n = 41). After 34 months all animals were ovariectomized via laparotomy. Half of the monkeys from each diet treatment group continued to consume their Pre-Ovariectomy treatment phase diet (either SOY [n = 19] or CL [n = 21]) for an additional 34 months. The remaining animals did not continue their diets, and thus were not considered further. Circulating progesterone, triiodothyronine, thyroxine, and thyroid stimulating hormone were measured at baseline. Thyroid hormones were remeasured during each treatment phase. Results Dietary soy increased triiodothyronine in pre-ovariectomized monkeys and prevented a decline in thyroxine following surgical menopause (both p’s < 0.05). Mean progesterone concentrations were positively correlated with triiodothyronine at baseline in pre-ovariectomized monkeys (p < 0.01). Conclusions Progesterone levels and triiodothyronine are positively correlated in macaques. Dietary soy increases triiodothyronine in pre-ovariectomized monkeys and prevents a decline in thyroxine following surgical menopause. The outcomes observed in this study suggest soy protein and isoflavone consumption does not adversely affect and may even preserve thyroid function in postmenopausal women. PMID:24618766

  13. Oxygen and Heterotrophy Affect Calcification of the Scleractinian Coral Galaxea fascicularis

    PubMed Central

    Wijgerde, Tim; Jurriaans, Saskia; Hoofd, Marleen; Verreth, Johan A. J.; Osinga, Ronald

    2012-01-01

    Heterotrophy is known to stimulate calcification of scleractinian corals, possibly through enhanced organic matrix synthesis and photosynthesis, and increased supply of metabolic DIC. In contrast to the positive long-term effects of heterotrophy, inhibition of calcification has been observed during feeding, which may be explained by a temporal oxygen limitation in coral tissue. To test this hypothesis, we measured the short-term effects of zooplankton feeding on light and dark calcification rates of the scleractinian coral Galaxea fascicularis (n = 4) at oxygen saturation levels ranging from 13 to 280%. Significant main and interactive effects of oxygen, heterotrophy and light on calcification rates were found (three-way factorial repeated measures ANOVA, p<0.05). Light and dark calcification rates of unfed corals were severely affected by hypoxia and hyperoxia, with optimal rates at 110% saturation. Light calcification rates of fed corals exhibited a similar trend, with highest rates at 150% saturation. In contrast, dark calcification rates of fed corals were close to zero under all oxygen saturations. We conclude that oxygen exerts a strong control over light and dark calcification rates of corals, and propose that in situ calcification rates are highly dynamic. Nevertheless, the inhibitory effect of heterotrophy on dark calcification appears to be oxygen-independent. We hypothesize that dark calcification is impaired during zooplankton feeding by a temporal decrease of the pH and aragonite saturation state of the calcifying medium, caused by increased respiration rates. This may invoke a transient reallocation of metabolic energy to soft tissue growth and organic matrix synthesis. These insights enhance our understanding of how oxygen and heterotrophy affect coral calcification, both in situ as well as in aquaculture. PMID:23285159

  14. Masticatory loadings and cranial deformation in Macaca fascicularis: a finite element analysis sensitivity study

    PubMed Central

    Fitton, L C; Shi, J F; Fagan, M J; O’Higgins, P

    2012-01-01

    Biomechanical analyses are commonly conducted to investigate how craniofacial form relates to function, particularly in relation to dietary adaptations. However, in the absence of corresponding muscle activation patterns, incomplete muscle data recorded experimentally for different individuals during different feeding tasks are frequently substituted. This study uses finite element analysis (FEA) to examine the sensitivity of the mechanical response of a Macaca fascicularis cranium to varying muscle activation patterns predicted via multibody dynamic analysis. Relative to the effects of varying bite location, the consequences of simulated variations in muscle activation patterns and of the inclusion/exclusion of whole muscle groups were investigated. The resulting cranial deformations were compared using two approaches; strain maps and geometric morphometric analyses. The results indicate that, with bite force magnitude controlled, the variations among the mechanical responses of the cranium to bite location far outweigh those observed as a consequence of varying muscle activations. However, zygomatic deformation was an exception, with the activation levels of superficial masseter being most influential in this regard. The anterior portion of temporalis deforms the cranial vault, but the remaining muscles have less profound effects. This study for the first time systematically quantifies the sensitivity of an FEA model of a primate skull to widely varying masticatory muscle activations and finds that, with the exception of the zygomatic arch, reasonable variants of muscle loading for a second molar bite have considerably less effect on cranial deformation and the resulting strain map than does varying molar bite point. The implication is that FEA models of biting crania will generally produce acceptable estimates of deformation under load as long as muscle activations and forces are reasonably approximated. In any one FEA study, the biological significance of the

  15. Antimicrobial resistance in Campylobacter coli and Campylobacter jejuni in cynomolgus monkeys (Macaca fascicularis) and eradication regimens.

    PubMed

    Koga, Tetsufumi; Aoki, Wataru; Mizuno, Takashi; Wakazono, Kuniko; Ohno, Junki; Nakai, Tsunehiro; Nomiya, Takao; Fujii, Miki; Fusegawa, Keiichi; Kinoshita, Kazuya; Hamada, Takakazu; Ikeda, Yoshinori

    2017-02-01

    Campylobacter spp. are zoonotic pathogens, however, knowledge about their presence and antimicrobial resistance in nonhuman primates is limited. Our animal facility purchased cynomolgus monkeys (Macaca fascicularis) from various Asian countries: China, Cambodia, Indonesia, the Philippines, and Vietnam. Colonization by Campylobacter spp. was investigated in 238 of the monkeys from 2009 to 2012 and antimicrobial susceptibility testing was carried out for these isolates. Furthermore, we eradicated these pathogens from these monkeys. Campylobacter spp. were isolated from 47 monkeys from three specific countries: China, Cambodia, and Indonesia, with respective isolation rates of 15%, 36%, and 67%. Two monkeys, which were each infected with Campylobacter jejuni and Campylobacter coli, showed clinical symptoms of diarrhea and bloody feces. In total, 41 isolates of C. coli and 17 isolates of C. jejuni were detected. Antimicrobial susceptibility varied: in the monkeys from China, erythromycin (ERY)-, tetracycline (TET)-, and ciprofloxacin-resistant C. coli, in the monkeys from Cambodia, amoxicillin-intermediate, TET- and ciprofloxacin-resistant C. coli and amoxicillin- and ciprofloxacin-resistant C. jejuni, and in the monkeys from Indonesia, ciprofloxacin-resistant C. coli and TET- and ciprofloxacin-resistant C. jejuni were common (>75%). Multiresistant isolates of C. coli were found in monkeys from all countries and multiresistant isolates of C. jejuni were found in monkeys from Indonesia. The eradication rate with azithromycin was comparable to that with gentamicin (GEN) by oral administration, and was higher than those with amoxicillin-clavulanic acid (AMC) and chloramphenicol (CHL). From the perspective of zoonosis, we should acknowledge multiresistant Campylobacter spp. isolated from the monkeys as a serious warning. Copyright © 2015. Published by Elsevier B.V.

  16. Introducing SummerTime: A package for high-precision computation of sums appearing in DRA1 method

    NASA Astrophysics Data System (ADS)

    Lee, Roman N.; Mingulov, Kirill T.

    2016-06-01

    We present the Mathematica package SummerTime for arbitrary-precision computation of sums appearing in the results of DRA method (Lee, 2010). So far these results include the following families of the integrals: 3-loop onshell massless vertices, 3-loop onshell mass operator type integrals, 4-loop QED-type tadpoles, 4-loop massless propagators (Lee et al., 2010; Lee and Smirnov, 2011; Lee et al., 2011, 2012). The package can be used for high-precision numerical computation of the expansion of the integrals from the above families around arbitrary space-time dimension. In addition, this package contains convenient tools for the calculation of multiple zeta values, harmonic polylogarithms and other transcendental numbers expressed in terms of nested sums with factorized summand.

  17. Expression of HLA-DRA and CD74 mRNA in whole blood during the course of complicated and uncomplicated Staphylococcus aureus bacteremia.

    PubMed

    Rasmussen, Gunlög; Cajander, Sara; Bäckman, Anders; Källman, Jan; Söderquist, Bo; Strålin, Kristoffer

    2017-09-01

    In order to improve patient management in Staphylococcus aureus bacteremia (SAB), better understanding of host-pathogen interactions is needed. In vitro studies have shown that S. aureus bacteria induce a dose-dependent immunosuppression, in terms of reduced expression of major histocompatibility complex (MHC) class II on antigen presenting cells. Thus, we aimed to study if the expressions of the MHC class II-related genes HLA-DRA and CD74 are more reduced in complicated SAB, with probably higher loads of S. aureus, than in uncomplicated SAB. Adult patients with SAB were prospectively included and were sampled on the day of confirmed SAB (day 1) and on days 2, 3, 5, and 7. HLA-DRA and CD74 mRNA expressions were determined by quantitative reverse transcription PCR. Sepsis was defined according to the Sepsis-3 classification, and SAB was categorized as complicated in patients with deep-seated infection and/or haematogenous seeding. Twenty patients with SAB were enrolled and were sampled on all assessment days. HLA-DRA and CD74 expressions did not differ significantly between SAB patients with sepsis (n=13) and without sepsis (n=7) on any assessment day. However, patients with complicated SAB (n=14) had significantly lower HLA-DRA expressions on all five assessment days compared to patients with uncomplicated SAB (n=6), and they tended to have lower CD74 expressions. Neutrophil, monocyte, and leukocyte counts did not differ significantly between complicated and uncomplicated SAB. In conclusion, patients with complicated SAB showed lower HLA-DRA expression than patients with uncomplicated SAB during the first week of bacteremia. © 2017 The Societies and Wiley Publishing Asia Pty Ltd.

  18. Stimulus-Food Pairings Produce Stimulus-Directed Touch Screen Responding in Cynomolgus Monkeys ("Macaca Fascicularis") with or without a Positive Response Contingency

    ERIC Educational Resources Information Center

    Bullock, Christopher E.; Myers, Todd M.

    2009-01-01

    Acquisition and maintenance of touch-screen responding was examined in naive cynomolgus monkeys ("Macaca fascicularis") under automaintenance and classical conditioning arrangements. In the first condition of Experiment 1, we compared acquisition of screen touching to a randomly positioned stimulus (a gray square) that was either stationary or…

  19. Large-scale transcriptome sequencing and gene analyses in the crab-eating macaque (Macaca fascicularis) for biomedical research

    PubMed Central

    2012-01-01

    Background As a human replacement, the crab-eating macaque (Macaca fascicularis) is an invaluable non-human primate model for biomedical research, but the lack of genetic information on this primate has represented a significant obstacle for its broader use. Results Here, we sequenced the transcriptome of 16 tissues originated from two individuals of crab-eating macaque (male and female), and identified genes to resolve the main obstacles for understanding the biological response of the crab-eating macaque. From 4 million reads with 1.4 billion base sequences, 31,786 isotigs containing genes similar to those of humans, 12,672 novel isotigs, and 348,160 singletons were identified using the GS FLX sequencing method. Approximately 86% of human genes were represented among the genes sequenced in this study. Additionally, 175 tissue-specific transcripts were identified, 81 of which were experimentally validated. In total, 4,314 alternative splicing (AS) events were identified and analyzed. Intriguingly, 10.4% of AS events were associated with transposable element (TE) insertions. Finally, investigation of TE exonization events and evolutionary analysis were conducted, revealing interesting phenomena of human-specific amplified trends in TE exonization events. Conclusions This report represents the first large-scale transcriptome sequencing and genetic analyses of M. fascicularis and could contribute to its utility for biomedical research and basic biology. PMID:22554259

  20. HLA-DRA is associated with Parkinson's disease in Iranian population.

    PubMed

    Jamshidi, J; Movafagh, A; Emamalizadeh, B; Zare Bidoki, A; Manafi, A; Ghasemi Firouzabadi, S; Shahidi, G-A; Kazeminasab, S; Petramfar, P; Fazeli, A; Motallebi, M; Mortazavi-Tabatabaei, S A; Kowsari, A; Jafarian, Z; Darvish, H

    2014-12-01

    The rs3129882, a noncoding variant in HLA-DR, was found to be associated with Parkinson's disease (PD) using several genome-wide association studies. The aim of this replication study was to explore the relationship between this variant and PD in Iranian population. Genomic DNA was extracted from peripheral blood samples, and the rs3129882 SNP was genotyped using a PCR-RFLP method in 520 PD patients and 520 healthy Iranian controls. Significant differences were found in allele frequencies between patients and controls (χ(2) = 4.64, P = 0.031). Under additive and dominant models, the association of the SNP with PD risk is significant, where the A allele was observed to be protective. The results suggest that rs3129882 polymorphism may be a risk factor for PD in Iranian. This is the first study reporting such an association in this population. More replication studies are needed to confirm this data. © 2014 John Wiley & Sons Ltd.

  1. Mechanism of the pH-Induced Conformational Change in the Sensor Domain of the DraK Histidine Kinase via the E83, E105, and E107 Residues

    PubMed Central

    Jee, Jun-Goo; Lee, Jae Kyoung; Kim, Hyo Jeong; Park, Jin-Wan; Kim, Eun-Hee; Hwang, Eunha; Kim, Sang-Yoon; Lee, Eun-Gyeong; Kwon, Ohsuk; Cheong, Hae-Kap

    2014-01-01

    The DraR/DraK two-component system was found to be involved in the differential regulation of antibiotic biosynthesis in a medium-dependent manner; however, its function and signaling and sensing mechanisms remain unclear. Here, we describe the solution structure of the extracellular sensor domain of DraK and suggest a mechanism for the pH-dependent conformational change of the protein. The structure contains a mixed alpha-beta fold, adopting a fold similar to the ubiquitous sensor domain of histidine kinase. A biophysical study demonstrates that the E83, E105, and E107 residues have abnormally high pKa values and that they drive the pH-dependent conformational change for the extracellular sensor domain of DraK. We found that a triple mutant (E83L/E105L/E107A) is pH independent and mimics the low pH structure. An in vivo study showed that DraK is essential for the recovery of the pH of Streptomyces coelicolor growth medium after acid shock. Our findings suggest that the DraR/DraK two-component system plays an important role in the pH regulation of S. coelicolor growth medium. This study provides a foundation for the regulation and the production of secondary metabolites in Streptomyces. PMID:25203403

  2. Analysis of the unique structural and physicochemical properties of the DraD/AfaD invasin in the context of its belonging to the family of chaperone/usher type fimbrial subunits

    PubMed Central

    2011-01-01

    Background DraD invasin encoded by the dra operon possesses a classical structure characteristic to fimbrial subunits of the chaperone/usher type. The Ig-fold of the DraD possesses two major characteristics distinguishing it from the family of fimbrial subunits: 1) a distortion of the β-barrel structure in the region of the acceptor cleft, demonstrated by a disturbance of the main-chain hydrogen bonds network, and 2) an unusually located disulfide bond connecting B and F strands - the localization exclusively observed in the subfamily of DraD/AfaD-type subunits. Results To evaluate the influence of the DraD-sc specific structural features on its stability and mechanism of thermal denaturation, a series of DSC and FT-IR denaturation experiments were performed giving following conclusions. 1) The DraD-sc is characterized by a low stability (standard Gibbs free energy and enthalpy of unfolding of 18.4 ±1.4 kJ mol-1 and 131 ±25 kJ mol-1, respectively) that contrasts strongly with almost infinite stability of the described previously DraE-sc fimbrial protein. 2) The DraD-sc unfolds thermally according to the two state equilibrium model, in contrast to the irreversible kinetically controlled transition of the DraE-sc. 3) The DraD specific disulfide bond is crucial at the folding stage and has little stability effect in the mature protein. Conclusions Data published so far emphasize unique biological properties of the DraD invasin as fimbrial subunit: a chaperone independent folding, an usher independent surface localization and the possibility to exist in two forms: as unbound subunits and as loosely bound at fimbrial tip. Presented calorimetric and FT-IR stability data combined with structural correlations has underlined that the DraD invasin is also characterized by unique physicochemical and structural attributes in the context of its belonging to the family of fimbrial subunits. PMID:21575181

  3. Pharmacokinetics of 2 Formulations of Buprenorphine in Macaques (Macaca mulatta and Macaca fascicularis)

    PubMed Central

    Nunamaker, Elizabeth A; Halliday, Lisa C; Moody, David E; Fang, Wenfang B; Lindeblad, Matthew; Fortman, Jeffrey D

    2013-01-01

    Buprenorphine is the cornerstone of pain management in nonhuman primates, but the pharmacokinetics of this widely used drug are unknown. The purpose of this study was to evaluate the pharmacokinetic profiles of buprenorphine (0.01 and 0.03 mg/kg IM) and sustained-release buprenorphine (0.2 mg/kg SC) in 2 macaque species (M. mulatta and M. fascicularis) by using mass spectrometry. The pharmacokinetics did not differ significantly between species, and buprenorphine was dose-proportional at the tested doses. The low and high doses of buprenorphine had elimination half-lives of 2.6 ± 0.7 and 5.3 ± 2.0 h, respectively, but the low-dose data were constrained by the sensitivity of the analytical method. Sustained-release buprenorphine had an elimination half-life of 42.6 ± 26.2 h. The AUC0-Tlast of buprenorphine were 9.1 ± 4.3 and 39.0 ± 25.1 ng×h/mL for the low and high doses, respectively, and sustained-release buprenorphine had an AUC0-Tlast of 177 ± 74 ng×h/mL. Assuming a hypothesized therapeutic buprenorphine plasma concentration threshold of 0.1 ng/mL in macaques, these results suggest that buprenorphine doses of 0.01 mg/kg IM should be administered every 6 to 8 h, whereas doses of 0.03 mg/kg IM can be administered every 12 h. These results further demonstrate that a single 0.2-mg/kg SC injection of sustained-release buprenorphine maintains plasma concentrations above 0.1 ng/mL for 5 d in macaques. These findings support a new dosing strategy using sustained-release buprenorphine to improve pain management, decrease animal stress, improve animal welfare, and simplify the postoperative management of nonhuman primates in laboratory animal and zoological settings. PMID:23562033

  4. Studies on the Structure of Low Density Lipoproteins Isolated from Macaca Fascicularis Fed an Atherogenic Diet

    PubMed Central

    Tall, Alan R.; Small, Donald M.; Atkinson, David; Rudel, Lawrence L.

    1978-01-01

    Cynomolgus monkeys, Macaca fascicularis, fed cholesterol-containing saturated-fat diets develop increased levels of high molecular weight plasma low density lipoproteins (LDL), associated with accelerated atherosclerosis. To study the composition and structure of these abnormal particles, LDL from monkeys, fed atherogenic and control diets, were characterized chemically and examined by differential scanning calorimetry and low-angle X-ray scattering. LDL from animals on the experimental diet showed an increase in molecular weight (4.0 to 7.0 × 106, experimental diet compared with 3.0 to 3.7 × 106, control diet) associated with a large increase in cholesterol ester content and concomitant smaller increases in protein, phospholipid, and free cholesterol. There was a strong positive correlation between molecular weight and the number of saturated and monounsaturated cholesterol esters in the particle. In contrast, particle content of polyunsaturated cholesterol esters remained constant despite large changes in total particle cholesterol esters. When examined by calorimetry and X-ray scattering, LDL from monkeys on both diets diplayed a reversible transition of cholesterol esters from an ordered smeticlike (layered) structure to a more disordered state. For all animals on the experimental diet, the peak temperature of the cholesterol-ester transition (42-48°C) was above body temperature (39°C), but below body temperature on the control diet (34-38.5°C). In the experimental group, the transition temperature was correlated with the LDL molecular weight. However, after thermal disruption of LDL, liquid-crystalline transitions of LDL cholesterol esters were observed in the same temperature range as in the intact lipoprotein, which shows that changes in particle size had little effect on the cholesterol-ester transition temperature. Rather, the transition temperature was determined by the degree of saturation of the LDL cholesterol ester fatty acids and the LDL

  5. Linking MedDRA(®)-Coded Clinical Phenotypes to Biological Mechanisms by the Ontology of Adverse Events: A Pilot Study on Tyrosine Kinase Inhibitors.

    PubMed

    Sarntivijai, Sirarat; Zhang, Shelley; Jagannathan, Desikan G; Zaman, Shadia; Burkhart, Keith K; Omenn, Gilbert S; He, Yongqun; Athey, Brian D; Abernethy, Darrell R

    2016-07-01

    A translational bioinformatics challenge exists in connecting population and individual clinical phenotypes in various formats to biological mechanisms. The Medical Dictionary for Regulatory Activities (MedDRA(®)) is the default dictionary for adverse event (AE) reporting in the US Food and Drug Administration Adverse Event Reporting System (FAERS). The ontology of adverse events (OAE) represents AEs as pathological processes occurring after drug exposures. The aim of this work was to establish a semantic framework to link biological mechanisms to phenotypes of AEs by combining OAE with MedDRA(®) in FAERS data analysis. We investigated the AEs associated with tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (mAbs) targeting tyrosine kinases. The five selected TKIs/mAbs (i.e., dasatinib, imatinib, lapatinib, cetuximab, and trastuzumab) are known to induce impaired ventricular function (non-QT) cardiotoxicity. Statistical analysis of FAERS data identified 1053 distinct MedDRA(®) terms significantly associated with TKIs/mAbs, where 884 did not have corresponding OAE terms. We manually annotated these terms, added them to OAE by the standard OAE development strategy, and mapped them to MedDRA(®). The data integration to provide insights into molecular mechanisms of drug-associated AEs was performed by including linkages in OAE for all related AE terms to MedDRA(®) and the existing ontologies, including the human phenotype ontology (HP), Uber anatomy ontology (UBERON), and gene ontology (GO). Sixteen AEs were shared by all five TKIs/mAbs, and each of 17 cardiotoxicity AEs was associated with at least one TKI/mAb. As an example, we analyzed "cardiac failure" using the relations established in OAE with other ontologies and demonstrated that one of the biological processes associated with cardiac failure maps to the genes associated with heart contraction. By expanding the existing OAE ontological design, our TKI use case demonstrated that the combination

  6. RNA sequencing (RNA-Seq) of lymph node, spleen, and thymus transcriptome from wild Peninsular Malaysian cynomolgus macaque (Macaca fascicularis)

    PubMed Central

    Ee Uli, Joey; Yong, Christina Seok Yien; Yeap, Swee Keong; Rovie-Ryan, Jeffrine J.; Mat Isa, Nurulfiza; Tan, Soon Guan

    2017-01-01

    The cynomolgus macaque (Macaca fascicularis) is an extensively utilised nonhuman primate model for biomedical research due to its biological, behavioural, and genetic similarities to humans. Genomic information of cynomolgus macaque is vital for research in various fields; however, there is presently a shortage of genomic information on the Malaysian cynomolgus macaque. This study aimed to sequence, assemble, annotate, and profile the Peninsular Malaysian cynomolgus macaque transcriptome derived from three tissues (lymph node, spleen, and thymus) using RNA sequencing (RNA-Seq) technology. A total of 174,208,078 paired end 70 base pair sequencing reads were obtained from the Illumina Hi-Seq 2500 sequencer. The overall mapping percentage of the sequencing reads to the M. fascicularis reference genome ranged from 53–63%. Categorisation of expressed genes to Gene Ontology (GO) and KEGG pathway categories revealed that GO terms with the highest number of associated expressed genes include Cellular process, Catalytic activity, and Cell part, while for pathway categorisation, the majority of expressed genes in lymph node, spleen, and thymus fall under the Global overview and maps pathway category, while 266, 221, and 138 genes from lymph node, spleen, and thymus were respectively enriched in the Immune system category. Enriched Immune system pathways include Platelet activation pathway, Antigen processing and presentation, B cell receptor signalling pathway, and Intestinal immune network for IgA production. Differential gene expression analysis among the three tissues revealed 574 differentially expressed genes (DEG) between lymph and spleen, 5402 DEGs between lymph and thymus, and 7008 DEGs between spleen and thymus. Venn diagram analysis of expressed genes revealed a total of 2,630, 253, and 279 tissue-specific genes respectively for lymph node, spleen, and thymus tissues. This is the first time the lymph node, spleen, and thymus transcriptome of the Peninsular

  7. RNA sequencing (RNA-Seq) of lymph node, spleen, and thymus transcriptome from wild Peninsular Malaysian cynomolgus macaque (Macaca fascicularis).

    PubMed

    Ee Uli, Joey; Yong, Christina Seok Yien; Yeap, Swee Keong; Rovie-Ryan, Jeffrine J; Mat Isa, Nurulfiza; Tan, Soon Guan; Alitheen, Noorjahan Banu

    2017-01-01

    The cynomolgus macaque (Macaca fascicularis) is an extensively utilised nonhuman primate model for biomedical research due to its biological, behavioural, and genetic similarities to humans. Genomic information of cynomolgus macaque is vital for research in various fields; however, there is presently a shortage of genomic information on the Malaysian cynomolgus macaque. This study aimed to sequence, assemble, annotate, and profile the Peninsular Malaysian cynomolgus macaque transcriptome derived from three tissues (lymph node, spleen, and thymus) using RNA sequencing (RNA-Seq) technology. A total of 174,208,078 paired end 70 base pair sequencing reads were obtained from the Illumina Hi-Seq 2500 sequencer. The overall mapping percentage of the sequencing reads to the M. fascicularis reference genome ranged from 53-63%. Categorisation of expressed genes to Gene Ontology (GO) and KEGG pathway categories revealed that GO terms with the highest number of associated expressed genes include Cellular process, Catalytic activity, and Cell part, while for pathway categorisation, the majority of expressed genes in lymph node, spleen, and thymus fall under the Global overview and maps pathway category, while 266, 221, and 138 genes from lymph node, spleen, and thymus were respectively enriched in the Immune system category. Enriched Immune system pathways include Platelet activation pathway, Antigen processing and presentation, B cell receptor signalling pathway, and Intestinal immune network for IgA production. Differential gene expression analysis among the three tissues revealed 574 differentially expressed genes (DEG) between lymph and spleen, 5402 DEGs between lymph and thymus, and 7008 DEGs between spleen and thymus. Venn diagram analysis of expressed genes revealed a total of 2,630, 253, and 279 tissue-specific genes respectively for lymph node, spleen, and thymus tissues. This is the first time the lymph node, spleen, and thymus transcriptome of the Peninsular

  8. Nuclear Thermal Rocket/Vehicle Characteristics And Sensitivity Trades For NASA's Mars Design Reference Architecture (DRA) 5.0 Study

    NASA Technical Reports Server (NTRS)

    Borowski, Stanley K.; McCurdy, David R.; Packard, Thomas W.

    2009-01-01

    This paper summarizes Phase I and II analysis results from NASA's recent Mars DRA 5.0 study which re-examined mission, payload and transportation system requirements for a human Mars landing mission in the post-2030 timeframe. Nuclear thermal rocket (NTR) propulsion was again identified as the preferred in-space transportation system over chemical/aerobrake because of its higher specific impulse (I(sub sp)) capability, increased tolerance to payload mass growth and architecture changes, and lower total initial mass in low Earth orbit (IMLEO) which is important for reducing the number of Ares-V heavy lift launches and overall mission cost. DRA 5.0 features a long surface stay (approximately 500 days) split mission using separate cargo and crewed Mars transfer vehicles (MTVs). All vehicles utilize a common core propulsion stage with three 25 klbf composite fuel NERVA-derived NTR engines (T(sub ex) approximately 2650 - 2700 K, p(sub ch) approximately 1000 psia, epsilon approximately 300:1, I(sub sp) approximately 900 - 910 s, engine thrust-toweight ratio approximately 3.43) to perform all primary mission maneuvers. Two cargo flights, utilizing 1-way minimum energy trajectories, pre-deploy a cargo lander to the surface and a habitat lander into a 24-hour elliptical Mars parking orbit where it remains until the arrival of the crewed MTV during the next mission opportunity (approximately 26 months later). The cargo payload elements aerocapture (AC) into Mars orbit and are enclosed within a large triconicshaped aeroshell which functions as payload shroud during launch, then as an aerobrake and thermal protection system during Mars orbit capture and subsequent entry, descent and landing (EDL) on Mars. The all propulsive crewed MTV is a 0-gE vehicle design that utilizes a fast conjunction trajectory that allows approximately 6-7 month 1-way transit times to and from Mars. Four 12.5 kW(sub e) per 125 square meter rectangular photovoltaic arrays provide the crewed MTV with

  9. Pre- and Post-harvest Influences on Seed Dormancy Status of an Australian Goodeniaceae species, Goodenia fascicularis

    PubMed Central

    Hoyle, Gemma L.; Steadman, Kathryn J.; Daws, Matthew I.; Adkins, Steve W.

    2008-01-01

    Background and Aims The period during which seeds develop on the parent plant has been found to affect many seed characteristics, including dormancy, through interactions with the environment. Goodenia fascicularis (Goodeniaceae) seeds were used to investigate whether seeds of an Australian native forb, harvested from different environments and produced at different stages of the reproductive period, differ in dormancy status. Methods During the reproductive phase, plants were grown ex situ in warm (39/21 °C) or cool (26/13 °C) conditions, with adequate or limited water availability. The physiological dormancy of resulting seeds was measured in terms of the germination response to warm stratification (34/20 °C, 100 % RH, darkness). Key Results Plants in the cool environment were tall and had high above-ground biomass, yet yielded fewer seeds over a shorter, later harvest period when compared with plants in the warm environment. Seeds from the cool environment also had higher viability and greater mass, despite a significant proportion (7 % from the cool-wet environment) containing no obvious embryo. In the warm environment, the reproductive phase was accelerated and plants produced more seeds despite being shorter and having lower above-ground biomass than those in the cool environment. Ten weeks of warm stratification alleviated physiological dormancy in seeds from all treatments resulting in 80–100 % germination. Seeds that developed at warm temperatures were less dormant (i.e. germination percentages were higher) than seeds from the cool environment. Water availability had less effect on plant and seed traits than air temperature, although plants with reduced soil moisture were shorter, had lower biomass and produced fewer, less dormant seeds than plants watered regularly. Conclusions Goodenia fascicularis seeds are likely to exhibit physiological dormancy regardless of the maternal environment. However, seeds collected from warm, dry environments are

  10. Déformation hercynienne et relation socle/couverture dans le domaine du Bas-Draˆa (Anti-Atlas occidental, Maroc)

    NASA Astrophysics Data System (ADS)

    Soulaimani, A.; Le Corre, Cl.; Farazdaq, R.

    1997-04-01

    Hercynian deformations in the western anti-Atlas area are controlled by the reactivation of faults in the Precambrain basement. The Bas-Draˆa anticline zone forms the southernmost Precambian basement massif covered by Infracambrian and Palaeozoic sedimentary formations. Relative motions of basement blocks induce in the cover an heterogeneous ductile deformation associated with a SE vergence. Structural data and finite strain measurements suggest the basement-cover relationships and late Cabboniferous age of the regional tectonics. The uplift of the Bas-Draˆa basement associated with the southeast thrusting induced a punching motion in the cover. A dextral shear component locally involved the rotation of structures or en echelon folding. The deformation is very intense near the basement boundaries, but decreases away from the boundary, as well as upwards within the sedimentary cover. To the southeast the deformation is very weak in the Carboniferous on the Saharan domain. The Bas-Draˆa area represents the last mobile block of Hercynian Belt foreland near the stable West African Craton. Vertical m movements are dominant versus wrench shifting.

  11. Trypanosoma cruzi in non-human primates with a history of stillbirths: a retrospective study (Papio hamadryas spp.) and case report (Macaca fascicularis)

    PubMed Central

    Grieves, Jessica L.; Hubbard, Gene B.; Williams, Jeff T.; VandeBerg, John L.; Dick, Edward J.; López-Alvarenga, Juan C.; Schlabritz-Loutsevitch, Natalia E.

    2011-01-01

    Background Congenital transmission of Trypanosoma cruzi has been described in humans and experimental work has been conducted with mice, but not with non-human primates (NHPs). Methods We conducted a retrospective study of female baboons (Papio hamadryas spp.) naturally seropositive or seronegative for T. cruzi with history of fetal loss, and we report a stillbirth in a cynomolgus macaque (Macaca fascicularis) with placental T. cruzi amastigotes. Results There were no differences in menstrual cycle parameters and the number of fetal losses between seropositive and seronegative baboons with history of fetal loss. The amount of parasite DNA detected using quantitative polymerase chain reaction (Q-PCR) in M. fascicularis placenta was within the range detected in infected baboon tissues. Conclusions There is no evidence that chronic maternal T. cruzi infection causes fetal loss in baboons. Q-PCR is a useful diagnostic tool to study archived NHP placentas. PMID:18671769

  12. Stimulus-Food Pairings Produce Stimulus-Directed Touch-Screen Responding in Cynomolgus Monkeys (MACACA Fascicularis) With or Without a Positive Response Contingency

    DTIC Science & Technology

    2009-07-01

    Experimental Analysis of Behavior, 37, 461–484. Cawthon-Lang, K. A. (2006). Primate Factsheets: Long-tailed macaque (Macaca fascicularis) Taxonomy , Morphology... Ecology . ,http://pin.primate.wisc.edu/factsheets/entry/ long-tailed_macaque.. Cleland, G. G., & Davey, G. C. L. (1983). Autoshaping in the rat: The...2003). Diet of Macaca fasicicularis in a mangrove forest, Vietnam. Laboratory Primate Newsletter, 42, 1–5. Staddon, J. E. R., & Simmelhag, V. L. (1971

  13. Antibody responses of Macaca fascicularis against a new inactivated polio vaccine derived from Sabin strains (sIPV) in DTaP-sIPV vaccine.

    PubMed

    Sato, Y; Shiosaki, K; Goto, Y; Sonoda, K; Kino, Y

    2013-05-01

    Antibody responses of Macaca fascicularis against a new tetravalent vaccine composed of diphtheria toxoid, tetanus toxoid, acellular pertussis antigens, and inactivated poliovirus derived from Sabin strains (sIPV) was investigated to predict an optimal dose of sIPV in a new tetravalent vaccine (DTaP-sIPV) prior to conducting a dose-defined clinical study. Monkeys were inoculated with DTaP-sIPVs containing three different antigen units of sIPVs: Vaccine A (types 1:2:3 = 3:100:100 DU), Vaccine B (types 1:2:3 = 1.5:50:50 DU), and Vaccine C (types 1:2:3 = 0.75:25:25 DU). There was no difference in the average titers of neutralizing antibody against the attenuated or virulent polioviruses between Vaccines A and B. The average neutralizing antibody titers of Vaccine C tended to be lower than those of Vaccines A and B. The sIPV antigens did not affect the anti-diphtheria or anti-tetanus antibody titers of DTaP-sIPV. Furthermore, the average neutralizing antibody titers of Vaccine A against the attenuated and virulent polioviruses were comparable between M. fascicularis and humans. These results suggest that M. fascicularis may be a useful animal model for predicting the antibody responses to sIPVs in humans, and that it may be likely to reduce the amount of sIPVs contained in DTaP-sIPVs, even for humans.

  14. Morphologic-anthropological investigations in tomb K93.12 at Dra' Abu el-Naga (Western Thebes, Egypt).

    PubMed

    Lösch, Sandra; Moghaddam, Negahnaz; Paladin, Alice; Rummel, Ute; Hower-Tilmann, Estelle; Zink, Albert

    2014-01-01

    In this study we present the analysis of the human remains from tomb K93.12 in the Ancient Egyptian necropolis of Dra' Abu el-Naga, located opposite the modern city of Luxor in Upper Egypt on the western bank of the Nile. Archaeological findings indicate that the rock tomb was originally built in the early 18th dynasty. Remains of two tomb-temples of the 20th dynasty and the looted burial of the High Priest of Amun Amenhotep have been identified. After the New Kingdom the tomb was reused as a burial place until the 26th dynasty. The skeletal and mummified material of the different tomb areas underwent a detailed anthropological and paleopathological analysis. The human remains were mostly damaged and scattered due to extensive grave robberies. In total, 79 individuals could be partly reconstructed and investigated. The age and sex distribution revealed a male predominance and a high percentage of young children (< 6 years) and adults in the range of 20 to 40 years. The paleopathological analysis showed a high prevalence of stress markers such as cribra orbitalia in the younger individuals, and other pathological conditions such as dental diseases, degenerative diseases and a possible case of ankylosing spondylitis. Additionally, 13 mummies of an intrusive waste pit could be attributed to three different groups belonging to earlier time periods based on their style of mummification and materials used. The study revealed important information on the age and sex distribution and diseases of the individuals buried in tomb K93.12.

  15. Crystallographic structure of the human leukocyte antigen DRA, DRB3*0101: models of a directional alloimmune response and autoimmunity.

    PubMed

    Parry, Christian S; Gorski, Jack; Stern, Lawrence J

    2007-08-10

    We describe structural studies of the human leukocyte antigen DR52a, HLA-DRA/DRB3*0101, in complex with an N-terminal human platelet integrin alphaII(B)betaIII glycoprotein peptide which contains a Leu/Pro dimorphism. The 33:Leu dimorphism is the epitope for the T cell directed response in neonatal alloimmune thrombocytopenia and post-transfusion purpura in individuals with the alphaII(B)betaIII 33:Pro allele, and defines the unidirectional alloimmune response. This condition is always associated with DR52a. The crystallographic structure has been refined to 2.25 A. There are two alphabeta heterodimers to the asymmetric unit in space group P4(1)2(1)2. The molecule is characterized by two prominent hydrophobic pockets at either end of the peptide binding cleft and a deep, narrower and highly charged P4 opening underneath the beta 1 chain. Further, the peptide in the second molecule displays a sharp upward turn after pocket P9. The structure reveals the role of pockets and the distinctive basic P4 pocket, shared by DR52a and DR3, in selecting their respective binding peptide repertoire. We observe an interesting switch in a residue from the canonically assigned pocket 6 seen in prior class II structures to pocket 4. This occludes the P6 pocket helping to explain the distinctive "1-4-9" peptide binding motif. A beta57 Asp-->Val substitution abrogates the salt-bridge to alpha76 Arg and along with a hydrophobic beta37 is important in shaping the P9 pocket. DRB3*0101 and DRB1*0301 belong to an ancestral haplotype and are associated with many autoimmune diseases linked to antigen presentation, but whereas DR3 is susceptible to type 1 diabetes DR52a is not. This dichotomy is explored for clues to the disease.

  16. Crystallographic Structure of the Human Leukocyte Antigen DRA, DRB3*0101: Models of a Directional Alloimmune Respone and Autoimmunity

    SciTech Connect

    Parry,C.; Gorski, J.; Stern, L.

    2007-01-01

    We describe structural studies of the human leukocyte antigen DR52a, HLA-DRA/DRB3*0101, in complex with an N-terminal human platelet integrin {alpha}II{sub B}{beta}III glycoprotein peptide which contains a Leu/Pro dimorphism. The 33:Leu dimorphism is the epitope for the T cell directed response in neonatal alloimmune thrombocytopenia and post-transfusion purpura in individuals with the {alpha}II{sub B}{beta}III 33:Pro allele, and defines the unidirectional alloimmune response. This condition is always associated with DR52a. The crystallographic structure has been refined to 2.25 {angstrom}. There are two {alpha}{beta} heterodimers to the asymmetric unit in space group P4{sub 1}2{sub 1}2. The molecule is characterized by two prominent hydrophobic pockets at either end of the peptide binding cleft and a deep, narrower and highly charged P4 opening underneath the beta 1 chain. Further, the peptide in the second molecule displays a sharp upward turn after pocket P9. The structure reveals the role of pockets and the distinctive basic P4 pocket, shared by DR52a and DR3, in selecting their respective binding peptide repertoire. We observe an interesting switch in a residue from the canonically assigned pocket 6 seen in prior class II structures to pocket 4. This occludes the P6 pocket helping to explain the distinctive '1-4-9' peptide binding motif. A {beta}57 Asp {yields} Val substitution abrogates the salt-bridge to {alpha}76 Arg and along with a hydrophobic {beta}37 is important in shaping the P9 pocket. DRB3*0101 and DRB1*0301 belong to an ancestral haplotype and are associated with many autoimmune diseases linked to antigen presentation, but whereas DR3 is susceptible to type 1 diabetes DR52a is not. This dichotomy is explored for clues to the disease.

  17. An integrated restriction fragment length polymorphism--amplified fragment length polymorphism linkage map for cultivated sunflower.

    PubMed

    Gedil, M A; Wye, C; Berry, S; Segers, B; Peleman, J; Jones, R; Leon, A; Slabaugh, M B; Knapp, S J

    2001-04-01

    Restriction fragment length polymorphism (RFLP) maps have been constructed for cultivated sunflower (Helianthus annuus L.) using three independent sets of RFLP probes. The aim of this research was to integrate RFLP markers from two sets with RFLP markers for resistance gene candidate (RGC) and amplified fragment length polymorphism (AFLP) markers. Genomic DNA samples of HA370 and HA372, the parents of the F2 population used to build the map, were screened for AFLPs using 42 primer combinations and RFLPs using 136 cDNA probes (RFLP analyses were performed on DNA digested with EcoRI, HindIII, EcoRV, or DraI). The AFLP primers produced 446 polymorphic and 1101 monomorphic bands between HA370 and HA372. The integrated map was built by genotyping 296 AFLP and 104 RFLP markers on 180 HA370 x HA372 F2 progeny (the AFLP marker assays were performed using 18 primer combinations). The HA370 x HA372 map comprised 17 linkage groups, presumably corresponding to the 17 haploid chromosomes of sunflower, had a mean density of 3.3 cM, and was 1326 cM long. Six RGC RFLP loci were polymorphic and mapped to three linkage groups (LG8, LG13, and LG15). AFLP markers were densely clustered on several linkage groups, and presumably reside in centromeric regions where recombination is reduced and the ratio of genetic to physical distance is low. Strategies for targeting markers to euchromatic DNA need to be tested in sunflower. The HA370 x HA372 map integrated 14 of 17 linkage groups from two independent RFLP maps. Three linkage groups were devoid of RFLP markers from one of the two maps.

  18. Drug-Induced Liver Injury Associated With Antidepressive Psychopharmacotherapy: An Explorative Assessment Based on Quantitative Signal Detection Using Different MedDRA Terms.

    PubMed

    Gahr, Maximilian; Zeiss, René; Lang, Dirk; Connemann, Bernhard J; Hiemke, Christoph; Schönfeldt-Lecuona, Carlos

    2016-06-01

    Drug-induced liver injury is a major problem of pharmacotherapy and is also frequent with antidepressive psychopharmacotherapy. However, there are only few studies using a consistent methodologic approach to study hepatotoxicity of a larger group of antidepress ants. We performed a quantitative signal detection analysis using data from the Uppsala Monitoring Centre from the WHO that records adverse drug reaction (ADR) data from worldwide sources; we retrieved substance- and country-specific (Australia, France, Germany, Italy, Spain, the United Kingdom, and the United States) ADR data and calculated reporting odds ratios as measures for disproportionality within a case/noncase approach. To allow for identification of agents that cause severe forms of hepatotoxic ADRs, we used 2 terms of the MedDRA ("drug-related hepatic disorders-comprehensive search" [DRHD-CS] and "… -severe events only" [DRHD-SEO]). Distribution of signals was heterogeneous throughout the different data sets, and consistent findings were present for only a few substances: agomelatine (AGM) and tianeptine as well as both positive control agents (amineptine, nefazodone) generated signals related to DRHD-CS and DRHD-SEO in all analyzed data sets. Tri- and tetracyclic antidepressants (here amitriptyline, clomipramine, mianserin, mirtazapine, trimipramine) were associated with hepatotoxicity in several data sets. Using 2 MedDRA terms did not allow for detection of agents that cause severe hepatotoxic ADR. Our results support the findings of previous, primarily literature-based, systematic analyses of hepatotoxicity related to antidepressive psychopharmacotherapy. No new safety information could be generated. Application of 2 MedDRA terms did not increase the substance-specific safety information.

  19. On the Origin of the Raman Scattered O VI 1032 Å Line During Outbursts and Quiescent Phases of the Symbiotic Binary AG Dra

    NASA Astrophysics Data System (ADS)

    Kreibiková, Z.; Skopal, A.

    2015-07-01

    We investigate the effect of Raman scattering of photons from the O VI 1032 Å line on neutral atoms of hydrogen in the symbiotic binary AG Dra. We found that the profile of the Raman scattered O VI 6825 Å line can be fitted by two Gaussians. We have investigated the behavior of their parameters (position, flux at maximum, FWHM, and the corresponding total flux of the line) as a function of orbital phase and the level of activity. Differences in some parameters as measured during quiescent and active phases suggest a significant variation of the ionization structure of the binary as a function of the activity level.

  20. Automated segmentation of cerebral vasculature with aneurysms in 3DRA and TOF-MRA using geodesic active regions: An evaluation study

    SciTech Connect

    Bogunovic, Hrvoje; Pozo, Jose Maria; Villa-Uriol, Maria Cruz; and others

    2011-01-15

    Purpose: To evaluate the suitability of an improved version of an automatic segmentation method based on geodesic active regions (GAR) for segmenting cerebral vasculature with aneurysms from 3D x-ray reconstruction angiography (3DRA) and time of flight magnetic resonance angiography (TOF-MRA) images available in the clinical routine. Methods: Three aspects of the GAR method have been improved: execution time, robustness to variability in imaging protocols, and robustness to variability in image spatial resolutions. The improved GAR was retrospectively evaluated on images from patients containing intracranial aneurysms in the area of the Circle of Willis and imaged with two modalities: 3DRA and TOF-MRA. Images were obtained from two clinical centers, each using different imaging equipment. Evaluation included qualitative and quantitative analyses of the segmentation results on 20 images from 10 patients. The gold standard was built from 660 cross-sections (33 per image) of vessels and aneurysms, manually measured by interventional neuroradiologists. GAR has also been compared to an interactive segmentation method: isointensity surface extraction (ISE). In addition, since patients had been imaged with the two modalities, we performed an intermodality agreement analysis with respect to both the manual measurements and each of the two segmentation methods. Results: Both GAR and ISE differed from the gold standard within acceptable limits compared to the imaging resolution. GAR (ISE) had an average accuracy of 0.20 (0.24) mm for 3DRA and 0.27 (0.30) mm for TOF-MRA, and had a repeatability of 0.05 (0.20) mm. Compared to ISE, GAR had a lower qualitative error in the vessel region and a lower quantitative error in the aneurysm region. The repeatability of GAR was superior to manual measurements and ISE. The intermodality agreement was similar between GAR and the manual measurements. Conclusions: The improved GAR method outperformed ISE qualitatively as well as

  1. Attenuation of neurovirulence, biodistribution, and shedding of a poliovirus:rhinovirus chimera after intrathalamic inoculation in Macaca fascicularis.

    PubMed

    Dobrikova, Elena Y; Goetz, Christian; Walters, Robert W; Lawson, Sarah K; Peggins, James O; Muszynski, Karen; Ruppel, Sheryl; Poole, Karyol; Giardina, Steven L; Vela, Eric M; Estep, James E; Gromeier, Matthias

    2012-03-01

    A dependence of poliovirus on an unorthodox translation initiation mode can be targeted selectively to drive viral protein synthesis and cytotoxicity in malignant cells. Transformed cells are naturally susceptible to poliovirus, due to widespread ectopic upregulation of the poliovirus receptor, Necl-5, in ectodermal/neuroectodermal cancers. Viral tumor cell killing and the host immunologic response it engenders produce potent, lasting antineoplastic effects in animal tumor models. Clinical application of this principle depends on unequivocal demonstration of safety in primate models for paralytic poliomyelitis. We conducted extensive dose-range-finding, toxicity, biodistribution, shedding, and neutralizing antibody studies of the prototype oncolytic poliovirus recombinant, PVS-RIPO, after intrathalamic inoculation in Macaca fascicularis. These studies suggest that intracerebral PVS-RIPO inoculation does not lead to viral propagation in the central nervous system (CNS), does not cause histopathological CNS lesions or neurological symptoms that can be attributed to the virus, is not associated with extraneural virus dissemination or replication and does not induce shedding of virus with stool. Intrathalamic PVS-RIPO inoculation induced neutralizing antibody responses against poliovirus serotype 1 in all animals studied.

  2. Use of Contrast-Enhanced Sonography to Investigate Intraneural Vascularity in a Cohort of Macaca fascicularis With Suspected Median Mononeuropathy

    PubMed Central

    Evans, Kevin D.; Volz, Kevin R.; Pargeon, Rachel L.; Fout, Larry T.; Buford, John; Roll, Shawn C.

    2014-01-01

    Objectives The purpose of this study was to provide clinical evidence of the use of contrast-enhanced sonography in detecting and quantifying changes in intraneural vascularity due to median mononeuropathy. Methods Five Macaca fascicularis monkeys were exposed to 20 weeks of repetitive work to increase their risk of developing median mononeuropathy. Contrast-enhanced sonograms were obtained in 30-second increments for 7 minutes while a contrast agent was being delivered. Data were collected immediately at the conclusion of the 20-week work exposure and then again during a recovery phase approximately 3 months after the completion of work. Quantitative analysis and trend graphs were used to analyze median nerve perfusion intensity. This study also compared the use of both manual counting of pixels and semiautomatic measurement using specialized software. Results Based on the average data, maximum intensity values were identified as the best indicators of nerve hyperemia. Paired t tests demonstrated significantly higher maximum intensities in the working stage for 4 of the 5 subjects (P < .01). Conclusions This study provides preliminary evidence that (1) in a controlled exposure model, a change in intraneural vascularity of the median nerve between working and recovery can be observed; (2) this vascular change can be measured using an objective technique that quantifies the intensity of vascularity; and (3) contrast-enhanced sonography may improve the ability to reliably capture and measure low-flow microvascularity. PMID:24371104

  3. Highly heterogeneous bacterial communities associated with the South China Sea reef corals Porites lutea, Galaxea fascicularis and Acropora millepora.

    PubMed

    Li, Jie; Chen, Qi; Zhang, Si; Huang, Hui; Yang, Jian; Tian, Xin-Peng; Long, Li-Juan

    2013-01-01

    Coral harbor diverse and specific bacteria play significant roles in coral holobiont function. Bacteria associated with three of the common and phylogenetically divergent reef-building corals in the South China Sea, Porites lutea, Galaxea fascicularis and Acropora millepora, were investigated using 454 barcoded-pyrosequencing. Three colonies of each species were sampled, and 16S rRNA gene libraries were constructed individually. Analysis of pyrosequencing libraries showed that bacterial communities associated with the three coral species were more diverse than previous estimates based on corals from the Caribbean Sea, Indo-Pacific reefs and the Red Sea. Three candidate phyla, including BRC1, OD1 and SR1, were found for the first time in corals. Bacterial communities were separated into three groups: P. lutea and G. fascicular, A. millepora and seawater. P. lutea and G. fascicular displayed more similar bacterial communities, and bacterial communities associated with A. millepora differed from the other two coral species. The three coral species shared only 22 OTUs, which were distributed in Alphaproteobacteria, Deltaproteobacteria, Gammaproteobacteria, Chloroflexi, Actinobacteria, Acidobacteria and an unclassified bacterial group. The composition of bacterial communities within each colony of each coral species also showed variation. The relatively small common and large specific bacterial communities in these corals implies that bacterial associations may be structured by multiple factors at different scales and that corals may associate with microbes in terms of similar function, rather than identical species.

  4. Ancestry, Plasmodium cynomolgi prevalence and rhesus macaque admixture in cynomolgus macaques (Macaca fascicularis) bred for export in Chinese breeding farms.

    PubMed

    Zhang, Xinjun; Meng, Yuhuan; Houghton, Paul; Liu, Mingyu; Kanthaswamy, Sreetharan; Oldt, Robert; Ng, Jillian; Trask, Jessica Satkoski; Huang, Ren; Singh, Balbir; Du, Hongli; Smith, David Glenn

    2017-04-01

    Most cynomolgus macaques (Macaca fascicularis) used in the United States as animal models are imported from Chinese breeding farms without documented ancestry. Cynomolgus macaques with varying rhesus macaque ancestry proportions may exhibit differences, such as susceptibility to malaria, that affect their suitability as a research model. DNA of 400 cynomolgus macaques from 10 Chinese breeding farms was genotyped to characterize their regional origin and rhesus ancestry proportion. A nested PCR assay was used to detect Plasmodium cynomolgi infection in sampled individuals. All populations exhibited high levels of genetic heterogeneity and low levels of inbreeding and genetic subdivision. Almost all individuals exhibited an Indochinese origin and a rhesus ancestry proportion of 5%-48%. The incidence of P. cynomolgi infection in cynomolgus macaques is strongly associated with proportion of rhesus ancestry. The varying amount of rhesus ancestry in cynomolgus macaques underscores the importance of monitoring their genetic similarity in malaria research. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Immunoglobulins A, G, and M in serum and in some secretions of monkeys (Macaca fascicularis syn. irus).

    PubMed Central

    Cole, M F; Bowen, W H

    1976-01-01

    The purpose of this investigation was to study the distribution and levels of the following immunoglobulins, IgA, IgG, and IgM ,in sera and in some secretions of monkeys (M. fascicularis). IgG, IgA, and IgM were isolated from monkey serum and secretory IgA was separated from monkey milk by combined gel filtration and ion-exchange chromatography. These pure preparations served as standards to quantitate immunoglobulins in sera and secretions by single radial immunodiffusion. Antisera were raised in the rabbit against the pure immunoglobulins and also against the whole secretions to identify the immunoglobulins in immunoelectrophoresis. In common with humans, the major immunoglobulin in serum and amniotic fluid is IgG and the IgG/IgA ratio is greater than unity. In secretions IgA is the dominant immunoglobulin and the IgG/IgA ratio is less than 1. In general, the levels of immunoglobulins in the sera and secretions of monkeys paralleled the levels found in humans. No age-related increase in immunoglobulin levels was detected in the sera of monkeys. PMID:818024

  6. Morphology of the cement apparatus and the cement of the buoy barnacle Dosima fascicularis (Crustacea, Cirripedia, Thoracica, Lepadidae).

    PubMed

    Zheden, Vanessa; Von Byern, Janek; Kerbl, Alexandra; Leisch, Nikolaus; Staedler, Yannick; Grunwald, Ingo; Power, Anne Marie; Klepal, Waltraud

    2012-10-01

    Barnacles produce a proteinaceous adhesive called cement to attach permanently to rocks or to other hard substrata. The stalked barnacle Dosima fascicularis is of special interest as it produces a large amount of foam-like cement that can be used as a float. The morphology of the cement apparatus and of the polymerized cement of this species is almost unknown. The current study aims at filling these gaps in our knowledge using light and electron microscopy as well as x-ray microtomography. The shape of the cement gland cells changes from round to ovoid during barnacle development. The cytoplasm of the gland cells, unlike that of some other barnacles, does not have distinct secretory and storage regions. The cement canals, which transport the cement from the gland cells to the base of the stalk, end at different positions in juvenile and mature animals. With increasing size of the cement float, the exit of the cement canals shift from the centrally positioned attachment disk of the vestigial antennules to more lateral positions on the stalk. The bubbles enclosed in the foam-like float are most likely filled with CO(2) that diffuses from the hemolymph into the cement canal system and from there into the cement.

  7. Visible lesion laser thresholds in Cynomolgus (Macaca fascicularis) retina with a 1064 nm 12-ns pulsed laser

    NASA Astrophysics Data System (ADS)

    Oliver, Jeffrey W.; Stolarski, David J.; Noojin, Gary D.; Hodnett, Harvey M.; Imholte, Michelle L.; Rockwell, Benjamin A.; Kumru, Semih S.

    2007-02-01

    A series of experiments in a new animal model for retinal damage, cynomolgus monkeys (Macaca fascicularis), have been conducted to determine the damage threshold for 12.5-nanosecond laser exposures at 1064 nm. These results provide a direct comparison to threshold values obtained in rhesus monkey (Macaca mulatta), which is the model historically used in establishing retinal maximum permissible exposure (MPE) limits. In this study, the irradiance level of a collimated Gaussian laser beam of 2.5 mm diameter at the cornea was randomly varied to produce a rectangular grid of exposures on the retina. Exposures sites were fundoscopically evaluated at post-irradiance intervals of 1 hour and 24 hours. Probit analysis was performed on dose-response data to obtain probability of response curves. The 50% probability of damage (ED50) values for 1 and 24 hours post-exposure are 28.5(22.7-38.4) μJ and 17.0(12.9-21.8) μJ, respectively. These values compare favorably to data obtained with the rhesus model, 28.7(22.3-39.3) μJ and 19.1(13.6-24.4) μJ, suggesting that the cynomolgus monkey may be a suitable replacement for rhesus monkey in photoacoustic minimum visible lesion threshold studies.

  8. Pharmacokinetics of cefovecin in cynomolgus macaques (Macaca fascicularis), olive baboons (Papio anubis), and rhesus macaques (Macaca mulatta).

    PubMed

    Raabe, Brigitte M; Lovaglio, Jamie; Grover, G Scott; Brown, Scott A; Boucher, Joseph F; Yuan, Yang; Civil, Jacqueline R; Gillhouse, Kimberly A; Stubbs, Makeida N; Hoggatt, Amber F; Halliday, Lisa C; Fortman, Jeffrey D

    2011-05-01

    Cefovecin sodium is a long-acting, third-generation, cephalosporin antibiotic approved for the treatment of skin infections in dogs and cats. The pharmacokinetic properties of cefovecin were evaluated in cynomolgus macaques (Macaca fascicularis), olive baboons (Papio anubis), and rhesus macaques (Macaca mulatta) by using a single-dose (8 mg/kg SC) dosing regimen. Plasma cefovecin concentrations were determined by using ultra-performance liquid chromatography with tandem mass spectrometry, and a noncompartmental model was used to determine pharmacokinetic parameters. The half-life of cefovecin was 4.95 ± 1.47 h in cynomolgus macaques, 9.17 ± 1.84 h in olive baboons, and 8.40 ± 2.53 h in rhesus macaques. These values are considerably lower than the half-lives previously published for dogs (133 h) and cats (166 h). The extended half-life of cefovecin in dogs and cats is speculated to be due to active reabsorption of drug in the kidney tubules because plasma clearance is well below the normal glomerular filtration rate. In nonhuman primates, renal clearance rates approximated plasma clearance rates, suggesting that active renal reabsorption of cefovecin does not occur in these species. The pharmacokinetic properties of cefovecin in nonhuman primates are vastly different from the pharmacokinetic properties in dogs and cats, precluding its use as a long-acting antibiotic in nonhuman primates. This study highlights the importance of performing pharmacokinetic studies prior to extralabel drug usage.

  9. Investigating biogeographic boundaries of the Sunda shelf: A phylogenetic analysis of two island populations of Macaca fascicularis.

    PubMed

    Klegarth, A R; Sanders, S A; Gloss, A D; Lane-deGraaf, K E; Jones-Engel, L; Fuentes, A; Hollocher, H

    2017-08-01

    Cyclical submergence and re-emergence of the Sunda Shelf throughout the Pleistocene served as a dynamic biogeographic landscape, across which long-tailed macaques (Macaca fascicularis) have migrated and evolved. Here, we tested the integrity of the previously reported continental-insular haplotype divide reported among Y and mitochondrial DNA lineages across multiple studies. The continental-insular haplotype divide was tested by heavily sampling wild macaques from two important biogeographic regions within Sundaland: (1) Singapore, the southernmost tip of continental Asia and (2) Bali, Indonesia, the southeastern edge of the Indonesian archipelago, immediately west of Wallace's line. Y DNA was haplotyped for samples from Bali, deep within the Indonesian archipelago. Mitochondrial D-loop from both islands was analyzed against existing data using Maximum Likelihood and Bayesian approaches. We uncovered both "continental" and "insular" Y DNA haplotypes in Bali. Between Singapore and Bali we found 52 unique mitochondrial haplotypes, none of which had been previously described. Phylogenetic analyses confirmed a major haplogroup division within Singapore and identified five new Singapore subclades and two primary subclades in Bali. While we confirmed the continental-insular divide among mtDNA haplotypes, maintenance of both Y DNA haplotypes on Bali, deep within the Indonesian archipelago calls into question the mechanism by which Y DNA diversity has been maintained. It also suggests the continental-insular designation is less appropriate for Y DNA, leading us to propose geographically neutral Y haplotype designations. © 2017 Wiley Periodicals, Inc.

  10. Pharmacokinetics of Cefovecin in Cynomolgus Macaques (Macaca fascicularis), Olive Baboons (Papio anubis), and Rhesus Macaques (Macaca mulatta)

    PubMed Central

    Raabe, Brigitte M.; Lovaglio, Jamie.; Grover, G Scott.; Brown, Scott A.; Boucher, Joseph F.; Yuan, Yang.; Civil, Jacqueline R.; Gillhouse, Kimberly A.; Stubbs, Makeida N.; Hoggatt, Amber F.; Halliday, Lisa C.; Fortman, Jeffrey D.

    2011-01-01

    Cefovecin sodium is a long-acting, third-generation, cephalosporin antibiotic approved for the treatment of skin infections in dogs and cats. The pharmacokinetic properties of cefovecin were evaluated in cynomolgus macaques (Macaca fascicularis), olive baboons (Papio anubis), and rhesus macaques (Macaca mulatta) by using a single-dose (8 mg/kg SC) dosing regimen. Plasma cefovecin concentrations were determined by using ultra-performance liquid chromatography with tandem mass spectrometry, and a noncompartmental model was used to determine pharmacokinetic parameters. The half-life of cefovecin was 4.95 ± 1.47 h in cynomolgus macaques, 9.17 ± 1.84 h in olive baboons, and 8.40 ± 2.53 h in rhesus macaques. These values are considerably lower than the half-lives previously published for dogs (133 h) and cats (166 h). The extended half-life of cefovecin in dogs and cats is speculated to be due to active reabsorption of drug in the kidney tubules because plasma clearance is well below the normal glomerular filtration rate. In nonhuman primates, renal clearance rates approximated plasma clearance rates, suggesting that active renal reabsorption of cefovecin does not occur in these species. The pharmacokinetic properties of cefovecin in nonhuman primates are vastly different from the pharmacokinetic properties in dogs and cats, precluding its use as a long-acting antibiotic in nonhuman primates. This study highlights the importance of performing pharmacokinetic studies prior to extralabel drug usage. PMID:21640036

  11. Pharmacokinetics of Cefovecin in Cynomolgus Macaques (Macaca fascicularis), Olive Baboons (Papio anubis), and Rhesus Macaques (Macaca mulatto)

    SciTech Connect

    Raabe, Brigitte M.; Lovaglio, Jamie A.; Grover, GScott; Brown, Scott A.; Boucher, Joseph F.; Yuan, Yang; Civil, Jacqueline R.; Gillhouse, Kimberly A.; Stubbs, Makeida N.; Hoggatt, Amber F.; Halliday, Lisa C.; Fortman, Jeffrey D.

    2011-05-01

    Cefovecin sodium is a long-acting, third-generation, cephalosporin antibiotic approved for the treatment of skin infections in dogs and cats. The pharmacokinetic properties of cefovecin were evaluated in cynomolgus macaques (Macaca fascicularis), olive baboons (Papio anubis), and rhesus macaques (Macaca mulatto) by using a single-dose (8 mg/kg SC) dosing regimen. Plasma cefovecin concentrations were determined by using ultra-performance liquid chromatography with tandem mass spectrometry, and a noncompartmental model was used to determine pharmacokinetic parameters. The half-life of cefovecin was 4.95 {+-} 1.47 h in cynomolgus macaques, 9.17 {+-} 1.84 h in olive baboons, and 8.40 {+-} 2.53 h in rhesus macaques. These values are considerably lower than the half-lives previously published for dogs (133 h) and cats (166 h). The extended half-life of cefovecin in dogs and cats is speculated to be due to active reabsorption of drug in the kidney tubules because plasma clearance is well below the normal glomerular filtration rate. In nonhuman primates, renal clearance rates approximated plasma clearance rates, suggesting that active renal reabsorption of cefovecin does not occur in these species. The pharmacokinetic properties of cefovecin in nonhuman primates are vastly different from the pharmacokinetic properties in dogs and cats, precluding its use as a long-acting antibiotic in nonhuman primates. This study highlights the importance of performing pharmacokinetic studies prior to extralabel drug usage.

  12. Highly Heterogeneous Bacterial Communities Associated with the South China Sea Reef Corals Porites lutea, Galaxea fascicularis and Acropora millepora

    PubMed Central

    Li, Jie; Chen, Qi; Zhang, Si; Huang, Hui; Yang, Jian; Tian, Xin-Peng; Long, Li-Juan

    2013-01-01

    Coral harbor diverse and specific bacteria play significant roles in coral holobiont function. Bacteria associated with three of the common and phylogenetically divergent reef-building corals in the South China Sea, Porites lutea, Galaxea fascicularis and Acropora millepora, were investigated using 454 barcoded-pyrosequencing. Three colonies of each species were sampled, and 16S rRNA gene libraries were constructed individually. Analysis of pyrosequencing libraries showed that bacterial communities associated with the three coral species were more diverse than previous estimates based on corals from the Caribbean Sea, Indo-Pacific reefs and the Red Sea. Three candidate phyla, including BRC1, OD1 and SR1, were found for the first time in corals. Bacterial communities were separated into three groups: P. lutea and G. fascicular, A. millepora and seawater. P. lutea and G. fascicular displayed more similar bacterial communities, and bacterial communities associated with A. millepora differed from the other two coral species. The three coral species shared only 22 OTUs, which were distributed in Alphaproteobacteria, Deltaproteobacteria, Gammaproteobacteria, Chloroflexi, Actinobacteria, Acidobacteria and an unclassified bacterial group. The composition of bacterial communities within each colony of each coral species also showed variation. The relatively small common and large specific bacterial communities in these corals implies that bacterial associations may be structured by multiple factors at different scales and that corals may associate with microbes in terms of similar function, rather than identical species. PMID:23940737

  13. Attenuation of Neurovirulence, Biodistribution, and Shedding of a Poliovirus:Rhinovirus Chimera after Intrathalamic Inoculation in Macaca fascicularis

    PubMed Central

    Dobrikova, Elena Y.; Goetz, Christian; Walters, Robert W.; Lawson, Sarah K.; Peggins, James O.; Muszynski, Karen; Ruppel, Sheryl; Poole, Karyol; Giardina, Steven L.; Vela, Eric M.; Estep, James E.

    2012-01-01

    A dependence of poliovirus on an unorthodox translation initiation mode can be targeted selectively to drive viral protein synthesis and cytotoxicity in malignant cells. Transformed cells are naturally susceptible to poliovirus, due to widespread ectopic upregulation of the poliovirus receptor, Necl-5, in ectodermal/neuroectodermal cancers. Viral tumor cell killing and the host immunologic response it engenders produce potent, lasting antineoplastic effects in animal tumor models. Clinical application of this principle depends on unequivocal demonstration of safety in primate models for paralytic poliomyelitis. We conducted extensive dose-range-finding, toxicity, biodistribution, shedding, and neutralizing antibody studies of the prototype oncolytic poliovirus recombinant, PVS-RIPO, after intrathalamic inoculation in Macaca fascicularis. These studies suggest that intracerebral PVS-RIPO inoculation does not lead to viral propagation in the central nervous system (CNS), does not cause histopathological CNS lesions or neurological symptoms that can be attributed to the virus, is not associated with extraneural virus dissemination or replication and does not induce shedding of virus with stool. Intrathalamic PVS-RIPO inoculation induced neutralizing antibody responses against poliovirus serotype 1 in all animals studied. PMID:22171271

  14. Sex-dependent expression of mRNA encoding a major egg protein in the gonochoric coral Galaxea fascicularis

    NASA Astrophysics Data System (ADS)

    Hayakawa, H.; Nakano, Y.; Andoh, T.; Watanabe, T.

    2005-11-01

    A cDNA encoding a major egg protein was cloned in Galaxea fascicularis, a hermatypic coral with a gonochoric breeding system, and gene expression at the transcriptional level was compared between female and functional male colonies. In an electrophoretic analysis, four soluble proteins were present in high abundance in the female egg, but not in the pseudo-eggs of functional males. Partial amino acid sequences of one of the major proteins named GfEP-1 (88 kDa) were determined, and a cDNA fragment of about 2 kb containing a partial GfEP-1 sequence was isolated. The deduced amino acid sequence exhibited sequence similarities to vertebrate and invertebrate vitellogenins. GfEP-1 transcripts were detected in both sexes 0 1 month before spawning. However, the mRNA levels were significantly higher in females than in functional males. The expression of GfEP-1 may be utilized in sexing and also monitoring effects of environmental and anthropogenic factors on vitellogenesis and sex determination.

  15. Voloshina I.B., Metlov V.G., Shugarov S.Yu., Golovin A.V., Antoniuk O.I. Positive and Negative Superhumps of the Dwarf Nova MN Dra

    NASA Astrophysics Data System (ADS)

    Samsonov, D. A.; Pavlenko, E. P.; Andreev, M. V.; Sklyanov, A.; Zubareva, A. M.

    2010-12-01

    We present the result of O-C analysis of the dwarf nova MN Dra. It is based on the multi-site photometric observations that were made over 77 nights in August - November, 2009. The total exposure was 433 hours. During this time binary underwent two superoutbursts and five normal outbursts. In superoutbursts the positive superhumps decreased with extremely large P = -(3 - 8) x 10-4 for SU UMa-like dwarf novae, confirming the known behavior of MN Dra in 2003. MN Dra displayed large-amplitude (up to 1.4m in quiescence and 0.1m-0.2m in normal outbursts) negative superhumps. The improved value of negative superhump period is 0.095952(4) d.

  16. Comparison of Methods for Determining ABO Blood Type in Cynomolgus Macaques (Macaca fascicularis).

    PubMed

    Kim, Tae M; Park, Hyojun; Cho, Kahee; Kim, Jong S; Park, Mi K; Choi, Ju Y; Park, Jae B; Park, Wan J; Kim, Sung J

    2015-05-01

    Thorough examination of ABO blood type in cynomolgus monkeys is an essential experimental step to prevent humoral rejection during transplantation research. In the present study, we evaluated current methods of ABO blood-antigen typing in cynomolgus monkeys by comparing the outcomes obtained by reverse hemagglutination, single-nucleotide polymorphism (SNP) analysis, and buccal mucosal immunohistochemistry. Among 21 animals, 5 were type A regardless of the method. However, of 8 serologically type B animals, 3 had a heterozygous type AB SNP profile, among which 2 failed to express A antigen, as shown by immunohistochemical analysis. Among 8 serologically type AB animals, 2 appeared to be type A by SNP analysis and immunohistochemistry. None of the methods identified any type O subjects. We conclude that the expression of ABO blood-group antigens is regulated by an incompletely understood process and that using both SNP and immunohistochemistry might minimize the risk of incorrect results obtained from the conventional hemagglutination assay.

  17. The infrared flux method and its use for study of Alpha Boo, MU HER and Beta Dra; relation to the VEGA 1.2-5 micron infrared excess

    NASA Astrophysics Data System (ADS)

    Blackwell, D. E.; Booth, A. J.; Petford, A. D.; Leggett, S. K.; Mountain, C. M.; Selby, M. J.

    1986-07-01

    The effective temperatures of α Boo, μ Her, and β Dra are determined using the infrared flux method. The determinations are based on the high-quality spectrophotometric data obtained from an aircraft by Strecker, Erickson & Witteborn, the new infrared calibration of Vega obtained from observations made at Tenerife between 1979 and 1983, the use of a Reticon spectrometer to determine the integrated fluxes in the region 370-950 nm, and the use of model atmospheres constructed with the MARCS code developed by Gustafsson et al. Temperatures for α Boo and β Her are also given using the Dreiling & Bell (DB) Vega calibration in association with the Hanbury-Brown, Davis & Allen angular diameter for Vega. The large and uncertain reddening for β Dra prevents the accurate determination of a reliable temperature for this star. The Tenerife and Dreiling & Bell infrared calibrations for Vega are considered in relation to the apparent variation of effective temperature with wavelength for α Boo and μ Her given by the infrared flux method, in an effort to distinguish between them. It is concluded that improved spectrophotometry is needed for this, with particular attention paid to the proper identification of continuum windows.

  18. The role of anthropic, ecological, and social factors in sleeping site choice by long-tailed macaques (Macaca fascicularis).

    PubMed

    Brotcorne, Fany; Maslarov, Cindy; Wandia, I Nengah; Fuentes, Agustin; Beudels-Jamar, Roseline C; Huynen, Marie-Claude

    2014-12-01

    When choosing their sleeping sites, primates make adaptive trade-offs between various biotic and abiotic constraints. In human-modified environments, anthropic factors may play a role. We assessed the influence of ecological (predation), social (intergroup competition), and anthropic (proximity to human settlements) factors in sleeping site choice by long-tailed macaques (Macaca fascicularis) occupying a habitat at the interface of natural forests and human-modified zones in Bali Barat National Park, Indonesia. Over the course of 56 nights, we collected data relating to physical features of sleeping trees, patterns of the use of sleeping sites within the home range, pre-sleep behavior, diurnal ranging patterns and availability of natural and human food. Overall, the macaques used 17 sleeping sites with 37 sleeping trees. When the monkeys slept in forest zones, they selected sleeping trees that had larger trunks but were not significantly taller than surrounding trees. Though the macaques rarely re-used sleeping sites on consecutive nights, they frequently re-used four sites over the study period. The group favored sleeping within the core area of its home range, despite the occurrence of frequent agonistic intergroup encounters there. Macaques preferentially selected sleeping trees located within or near human-modified zones, especially when human food was abundant and natural food was scarce. These results partially support the hypothesis that long-tailed macaques choose their sleeping sites to avoid predation; proximity to human settlements appears to be the primary factor influencing sleeping site choice in this primate species. Our results reflect the strong influence that anthropic factors have on primates, which subsist in increasingly human-dominated landscapes.

  19. The effect of different flow regimes on the growth and metabolic rates of the scleractinian coral Galaxea fascicularis

    NASA Astrophysics Data System (ADS)

    Schutter, M.; Crocker, J.; Paijmans, A.; Janse, M.; Osinga, R.; Verreth, A. J.; Wijffels, R. H.

    2010-09-01

    To study the effect of water flow on coral growth, four series of ten coral nubbins of Galaxea fascicularis were exposed to four different flow regimes (0, 10, 20, and 25 cm s-1, bidirectional flow) for 42 weeks. Buoyant weight, surface area, and polyp number were measured at regular intervals. Net photosynthesis and dark respiration were measured at the corresponding flow speeds, and daily amount of photosynthetic carbon left for coral growth was calculated. Finally, skeletal density and CN content, chlorophyll concentration and dry weight of coral tissue were determined for each coral. Specific growth rate (in day-1) decreased with time in each flow treatment. Absence of flow resulted in significantly lower growth rates. Average specific growth rate calculated over the entire experiment was not significantly different between 10 and 20 cm s-1, while it was significantly higher at 25 cm s-1. From 10 to 25 cm s-1, average net photosynthetic rate decreased and average dark respiration rate did not change significantly. Scope for growth based on phototrophic carbon decreased with increasing flow. Growth was not positively correlated with either photosynthesis or respiration, or scope for growth. It is suggested that higher flow rates reduce the chance of disturbance of coral growth by competing algae or cyanobacteria, allowing corals to grow more readily with the maximum specific growth rate possible under the given environmental conditions. Notably, other effects of increased flow, such as increased respiratory rates and increased (in)organic nutrient uptake, might have been equally responsible for the increased growth of the corals in 25 cm s-1.

  20. Morphometric studies on the structural development of the lung in Macaca fascicularis during fetal and postnatal life.

    PubMed Central

    Hislop, A; Howard, S; Fairweather, D V

    1984-01-01

    The structural development of the normal monkey lung (Macaca fascicularis) from 61 days of gestation to 14 days postnatal age has been described using quantitative morphometric techniques. The lung of the adult monkey has also been studied. The airway and arterial branching pattern has been traced using serial sections. The alveolar number and size have been estimated and the structure of the arteries after postmortem arterial injection has been assessed. Comparison of lung morphology in monkey and man shows that there are similarities in segmental arrangement, structure and branching pattern of airways, in arterial structure and in changes in the arteries after birth. Although there are differences in the number of lobes, the number of generations of different types of airways and the number and size of alveoli, the overall structure in the monkey is more similar to that in man than is the structure of the lung in species such as sheep, pig or rat. During fetal life the monkey lung passes through the same stages of development as the human fetus but at birth the monkey has a full complement of airways and mature alveoli. Postnatal growth of airways and alveoli is due to increase in size rather than to multiplication. In man there is an increase in the number of alveoli and alveolar ducts after birth as well as an increase in size. Despite the differences between the species it seems appropriate to use the monkey in experimental studies on the lung. Images Fig. 1 (cont.) Fig. 1 Fig. 4 (cont.) Fig. 4 PMID:6706842

  1. Population Recovery of Nicobar Long-Tailed Macaque Macaca fascicularis umbrosus following a Tsunami in the Nicobar Islands, India

    PubMed Central

    Velankar, Avadhoot D.; Kumara, Honnavalli N.

    2016-01-01

    Natural disasters pose a threat to isolated populations of species with restricted distributions, especially those inhabiting islands. The Nicobar long tailed macaque.Macaca fascicularis umbrosus, is one such species found in the three southernmost islands (viz. Great Nicobar, Little Nicobar and Katchal) of the Andaman and Nicobar archipelago, India. These islands were hit by a massive tsunami (Indian Ocean tsunami, 26 December 2004) after a 9.2 magnitude earthquake. Earlier studies [Umapathy et al. 2003; Sivakumar, 2004] reported a sharp decline in the population of M. f. umbrosus after thetsunami. We studied the distribution and population status of M. f. umbrosus on thethree Nicobar Islands and compared our results with those of the previous studies. We carried out trail surveys on existing paths and trails on three islands to get encounter rate as measure of abundance. We also checked the degree of inundation due to tsunami by using Normalized Difference Water Index (NDWI) on landsat imageries of the study area before and after tsunami. Theencounter rate of groups per kilometre of M. f. umbrosus in Great Nicobar, Little Nicobar and Katchal was 0.30, 0.35 and 0.48 respectively with the mean group size of 39 in Great Nicobar and 43 in Katchal following the tsunami. This was higher than that reported in the two earlier studies conducted before and after the tsunami. Post tsunami, there was a significant change in the proportion of adult males, adult females and immatures, but mean group size did not differ as compared to pre tsunami. The results show that population has recovered from a drastic decline caused by tsunami, but it cannot be ascertained whether it has reached stability because of the altered group structure. This study demonstrates the effect of natural disasters on island occurring species. PMID:26886197

  2. Population Recovery of Nicobar Long-Tailed Macaque Macaca fascicularis umbrosus following a Tsunami in the Nicobar Islands, India.

    PubMed

    Velankar, Avadhoot D; Kumara, Honnavalli N; Pal, Arijit; Mishra, Partha Sarathi; Singh, Mewa

    2016-01-01

    Natural disasters pose a threat to isolated populations of species with restricted distributions, especially those inhabiting islands. The Nicobar long tailed macaque.Macaca fascicularis umbrosus, is one such species found in the three southernmost islands (viz. Great Nicobar, Little Nicobar and Katchal) of the Andaman and Nicobar archipelago, India. These islands were hit by a massive tsunami (Indian Ocean tsunami, 26 December 2004) after a 9.2 magnitude earthquake. Earlier studies [Umapathy et al. 2003; Sivakumar, 2004] reported a sharp decline in the population of M. f. umbrosus after thetsunami. We studied the distribution and population status of M. f. umbrosus on thethree Nicobar Islands and compared our results with those of the previous studies. We carried out trail surveys on existing paths and trails on three islands to get encounter rate as measure of abundance. We also checked the degree of inundation due to tsunami by using Normalized Difference Water Index (NDWI) on landsat imageries of the study area before and after tsunami. Theencounter rate of groups per kilometre of M. f. umbrosus in Great Nicobar, Little Nicobar and Katchal was 0.30, 0.35 and 0.48 respectively with the mean group size of 39 in Great Nicobar and 43 in Katchal following the tsunami. This was higher than that reported in the two earlier studies conducted before and after the tsunami. Post tsunami, there was a significant change in the proportion of adult males, adult females and immatures, but mean group size did not differ as compared to pre tsunami. The results show that population has recovered from a drastic decline caused by tsunami, but it cannot be ascertained whether it has reached stability because of the altered group structure. This study demonstrates the effect of natural disasters on island occurring species.

  3. Improvement of Adeno-Associated Virus-Mediated Liver Transduction Efficacy by Regional Administration in Macaca fascicularis.

    PubMed

    Zabaleta, Nerea; Salas, David; Paramo, Maria; Hommel, Mirja; Sier-Ferreira, Valerie; Hernandez-Alcoceba, Ruben; Prieto, Jesus; Bilbao, Jose I; Gonzalez-Aseguinolaza, Gloria

    2017-06-01

    The liver is a central organ in metabolism and can be affected by numerous inherited metabolic disorders. Recombinant adeno-associated virus (AAV)-based gene therapy represents a promising therapeutic approach for such diseases. AAVs have been demonstrated to be safe, and resulted in high and long-term expression in preclinical and clinical studies. However, there are still some concerns regarding the expression levels that can be achieved and the percentage of hepatocytes that can be transduced. Because of the cell-autonomous nature of most metabolic liver disorders, a high percentage of hepatocytes needs to be corrected in order to achieve a therapeutic effect. The goal of our work was to improve transduction efficacy of the liver by conveying the vector directly to hepatic tissue. Interventional radiology procedures were used to administer an AAV5 vector expressing a secreted form of human embryonic alkaline phosphatase (hSEAP) under the control of a liver-specific promoter to a clinically relevant animal model, Macaca fascicularis. Balloon occlusion of the regional hepatic venous flow was performed while injecting the vector either into the hepatic artery (HA) or, against flow, via the suprahepatic vein (SHV). In both cases the vector was injected into the right hepatic lobules, and the two routes were compared with conventional intravenous administration. Higher hSEAP levels were obtained when the vector was administered via SHV or HA than after intravenous injection. Furthermore, higher expression levels correlated with a higher number of vector genomes in the injected lobules. In conclusion, direct administration of AAV vectors via the hepatic blood flow with simultaneous balloon occlusion of the hepatic outflow increases liver transduction efficacy in comparison with systemic delivery and can be further improved in bigger animals or humans, where it would be technically feasible to inject the vector into the hepatic vasculature in the generality of lobules.

  4. Glial response and myelin clearance in areas of wallerian degeneration after spinal cord hemisection in the monkey Macaca fascicularis.

    PubMed

    Shi, Fujun; Zhu, Hui; Yang, Senfu; Liu, Yansheng; Feng, Yaping; Shi, Jihong; Xu, Dingze; Wu, Wutian; You, Siwei; Ma, Zhengwen; Zou, Jian; Lu, Peihua; Xu, Xiao-Ming

    2009-11-01

    Spinal cord injury (SCI) in mammals not only damages the focal area, but also leads to wallerian degeneration (WD) of axons and myelin distal to the injury. In the present study, we investigated cellular responses within areas of WD of a sensory pathway, the fasciculus gracilis, after a T8-9 lateral spinal hemisection in the adult monkey Macaca fascicularis. Spinal cord segments rostral and caudal to the injury at two clinically-relevant time points, 1 week and 4 weeks post-SCI, representing subacute and chronic stages, respectively, were examined. We observed marked axon degeneration in the areas of WD at the subacute stage, and minimal axonal neurofilament staining at the chronic stage. At the ultrastructural level, however, many degenerating axonal profiles remained at the chronic stage. Myelin breakdown was a much-delayed process. A large number of residual myelin sheaths was observed at the chronic stage. In contrast to rodents, a substantial astrogliotic response was not found in the WD regions up to 4 weeks post-injury. Microglia activation was evident in the WD areas at the subacute stage, and was enhanced at the chronic stage. However, the lack of round reactive microglia/macrophages in these regions suggests that microglial activation was either delayed or incomplete. Thus it appears that many pathological characteristics of WD in monkeys are much delayed compared to those in rodents, but are similar to those in humans. Our results suggest that non-human primate SCI models are useful for evaluating repair strategies before they are translated to clinical trials of human SCI.

  5. Axonal and glial responses to a mid-thoracic spinal cord hemisection in the Macaca fascicularis monkey.

    PubMed

    Wu, Wenjie; Wu, Wei; Zou, Jian; Shi, Fujun; Yang, Senfu; Liu, Yansheng; Lu, Peihua; Ma, Zhengwen; Zhu, Hui; Xu, Xiao-Ming

    2013-05-15

    A comprehensive understanding of the pathology of spinal cord injury (SCI) in non-human primates may facilitate greatly the development of new strategies to promote recovery in humans with SCI. Relatively few studies, however, have been conducted to systemically examine pathological changes in the monkey, a non-human primate, after SCI. We report axonal, glial, and fibrotic responses in the spinal cord of monkey Macaca fascicularis after a thoracic (T) 8-9 lateral hemisection. We examined these changes at three regions--i.e., the lesion epicenter, the peri-lesion area, and the lateral white matter of the intact, contralateral hemicord at 7 (subacute) and 30 (early chronic) days post-injury. The lateral hemisection resulted in a marked axon and myelin loss, along with tissue loss, at the lesion epicenter at both time points. Unexpectedly, axonal loss and myelin degeneration, along with reactive gliosis and microglia/macrophages activation, were also observed in the contralateral spared hemicord, indicating a spread of the initial damage to the contralateral side. In addition, activated microglia/macrophages were found both within the injury epicenter and the peri-lesion area, indicating that they participate in injury-induced immune responses that may exacerbate the secondary damage. In contrast to rodents, substantial reactive astrocytic responses at the lesion border were not observed in the monkey. Conversely, a deposit of robust fibrotic scar was observed at the injury epicenter, which filled the space originally created by the hemisection. Thus, understanding the pathology of monkey SCI may provide clinically relevant information in designing repair strategies targeting specific problems associated with human SCIs.

  6. Experimental hepatitis A virus (HAV) infection in cynomolgus monkeys (Macaca fascicularis): evidence of active extrahepatic site of HAV replication

    PubMed Central

    Amado, Luciane A; Marchevsky, Renato S; de Paula, Vanessa S; Hooper, Cleber; Freire, Marcos da S; Gaspar, Ana Maria C; Pinto, Marcelo A

    2010-01-01

    This work studied the replication sites of hepatitis A virus (HAV) in cynomolgus monkeys (Macaca fascicularis) after intravenous inoculation. The cynomolgus monkeys were inoculated with the Brazilian hepatitis A virus strain (HAF-203). Monkeys were euthanized on days 15, 30, 45 and 60 postinoculation (pi). Liver samples, submandibular salivary gland, mesenteric lymph node and tonsils were removed for virological and pathological evaluation. Immunofluorescence analyses on liver and salivary gland sections using confocal laser scanning microscopy revealed the presence of HAV antigen (HAV Ag). The presence of HAV genome was monitored by real-time PCR. The HAV RNA was detected at 7 days postinoculation (dpi), concomitantly in serum, saliva and faeces. The highest HAV viral load was observed in faeces at 15 dpi (105 copies/ml), followed by serum viral load of 104 copies/ml at 20 dpi and saliva viral load of 103copies/ml at 7 dpi. The animals showed first histological and biochemical signs of hepatitis at 15 dpi. The HAV antigen (Ag) was present from day 7 until day 60 pi in the liver and salivary glands. The HAV replicative intermediate was also detected in the liver (4.5 × 104 copies/mg), salivary glands (1.9 × 103 copies/mg), tonsils (4.2 × 101 copies/mg) and lymph nodes (3.4 × 101 copies/mg). Our data demonstrated that the salivary gland as an extrahepatic site of early HAV replication could create a potential risk of saliva transmitted infection. In addition, the cynomolgus monkey was confirmed as a suitable model to study the pathogenesis of HAV human infection. PMID:20096073

  7. Diurnal pituitary-adrenal activity during schedule-induced polydipsia of water and ethanol in cynomolgus monkeys (Macaca fascicularis)

    PubMed Central

    Helms, Christa M.; Gonzales, Steven W.; Green, Heather L.; Szeliga, Kendall T.; Rogers, Laura S.M.; Grant, Kathleen A.

    2013-01-01

    Rationale Intermittent delivery of an important commodity (e.g., food pellets) generates excessive behaviors as an adjunct to the schedule of reinforcement (adjunctive behaviors) that are hypothesized to be due to conflict between engaging and escaping a situation where reinforcement is delivered, but at sub-optimal rates. Objectives This study characterized the endocrine correlates during schedule-induced polydipsia (SIP) of water and ethanol using a longitudinal approach in non-human primates. Methods Plasma adrenocorticotropic hormone (ACTH) and cortisol were measured in samples from awake cynomolgus monkeys (Macaca fascicularis, 11 adult males) obtained at the onset, midday and offset of their 12-h light cycle. The monkeys were induced to drink water and ethanol (4% w/v, in water) using a fixed time (FT) 300-s interval schedule of pellet delivery. The induction fluid changed every 30 sessions in the following order: water, 0.5 g/kg ethanol, 1.0 g/kg ethanol, and 1.5 g/kg ethanol. Following induction, ethanol and water were concurrently available for 22 h/d. Results The FT300-s schedule gradually increased ACTH, but not cortisol, during water induction to a plateau sustained throughout ethanol induction in every monkey. Upon termination of the schedule, ACTH decreased to baseline and cortisol below baseline. Diurnal ACTH and cortisol were unrelated to the dose of ethanol, but ACTH rhythm flattened at 0.5 g/kg/d and remained flattened. Conclusions The coincidence of elevated ACTH with the initial experience of drinking to intoxication may have altered the mechanisms involved in the transition to heavy drinking. PMID:23508555

  8. Analysis of sea almond (Terminalia catappa) cracking sites used by wild Burmese long-tailed macaques (Macaca fascicularis aurea).

    PubMed

    Falótico, Tiago; Spagnoletti, Noemi; Haslam, Michael; Luncz, Lydia V; Malaivijitnond, Suchinda; Gumert, Michael

    2017-01-05

    Nut-cracking is shared by all non-human primate taxa that are known to habitually use percussive stone tools in the wild: robust capuchins (Sapajus spp.), western chimpanzees (Pan troglodytes verus), and Burmese long-tailed macaques (Macaca fascicularis aurea). Despite opportunistically processing nuts, Burmese long-tailed macaques predominantly use stone tools to process mollusks in coastal environments. Here, we present the first comprehensive survey of sea almond (Terminalia catappa) nut-cracking sites created by macaques. We mapped T. catappa trees and nut-cracking sites that we encountered along the intertidal zone and forest border on the coasts of Piak Nam Yai Island, Thailand. For each nut-cracking site, we measured the physical properties (i.e., size, weight, use-wear) of hammer stones and anvils. We found that T. catappa trees and nut-cracking sites primarily occurred on the western coast facing the open sea, and cracking sites clusters around the trees. We confirmed previous results that nut cracking tools are among the heaviest tools used by long-tailed macaques; however, we found our sample of T. catappa stone tools lighter than a previously collected sea almond sample that, unlike our sample, was collected immediately after use within the intertidal zone. The difference was likely the result of tidal influences on tool-use sites. We also found that tool accumulations above the intertidal region do not resemble those within them, possibly leading to incomplete assessments of macaque stone tools through archaeological techniques that would use these durable sites.

  9. Genomic diversity and interspecies host infection of Macaca fascicularis papillomaviruses (MfPVs) within the alpha papillomavirus α12 species

    PubMed Central

    Chen, Zigui; van Doorslaer, Koenraad; DeSalle, Rob; Wood, Charles E.; Kaplan, Jay R.; Wagner, Janice D.; Burk, Robert D.

    2009-01-01

    Alpha human papillomaviruses (HPVs) are among the most common sexually transmitted agents of which a subset causes cervical neoplasia and cancer in humans. Alpha-PVs have also been identified in non-human primates although few studies have systematically characterized such mucosal PVs. We cloned and characterized 10 distinct types of PVs from exfoliated cervicovaginal cells from different populations of female cynomolgus macaques (Macaca fascicularis) originating from China and Indonesia. These include 5 novel genotypes and 5 previously identified genotypes found in rhesus (Macaca mulatta) (RhPV-1, RhPV-a, RhPV-b and RhPV-d) and cynomolgus macaques (MfPV-a). Type-specific primers were designed to amplify the complete PV genomes using an overlapping PCR method. Four MfPVs were associated with cervical intraepithelial neoplasia (CIN). The most prevalent virus type was MfPV-3 (formerly RhPV-d), which was identified in 60% of animals with CIN. In addition, the complete genomes of variants of MfPV-3 and RhPV-1 were characterized. These variants are 97.1% and 97.7% similar across the L1 nucleotide sequences with the prototype genomes, respectively. Sequence comparisons and phylogenetic analyses indicate that these novel MfPVs cluster together within the alpha PV α12 species closely related to the α9 (e.g., HPV16) and α11 species (e.g., HPV34), and all share a most recent common ancestor. Our data expand the molecular diversity of non-human primate PVs and suggest the recent expansion of alpha PV species groups. Moreover, identification of an overlapping set of MfPVs in rhesus and cynomolgus macaques indicates that non-human primate alpha PVs might not be strictly species specific and that “subtypes” may represent recent divergence of host species or past interspecies infection. PMID:19716580

  10. Polymorphous light eruption

    MedlinePlus

    Polymorphous light eruption (PMLE) is a common skin reaction in people who are sensitive to sunlight (ultraviolet light). ... Polymorphic light eruption; Photodermatosis; PMLE; Benign summer light eruption

  11. Novel cynomolgus macaque MHC-DPB1 polymorphisms in three South-East Asian populations.

    PubMed

    Sano, K; Shiina, T; Kohara, S; Yanagiya, K; Hosomichi, K; Shimizu, S; Anzai, T; Watanabe, A; Ogasawara, K; Torii, R; Kulski, J K; Inoko, H

    2006-04-01

    Cynomolgus macaques (Macaca fascicularis, Mafa), alias the crab-eating monkeys or long-tailed macaques, live across a vast range of South-East Asia. These non-human primates have emerged as important animal models in infectious and chronic diseases and transplantation studies, necessitating a more extensive characterization of their major histocompatibility complex polymorphic regions. The current information on the polymorphic variation or diversity of the Mafa-DPB1 locus is largely limited in comparison with the more commonly studied rhesus macaque DPB1 locus. In this article, to better elucidate the degree and types of polymorphisms and genetic differences of Mafa-DPB1 locus among three South-East Asian populations and to investigate how the allele differences between macaques and humans might affect their respective immune responses, we identified 40 alleles within exon 2 of the Mafa-DPB1 locus by DNA sequencing using 217 individuals. We also performed evolutionary and population analyses using these sequences to reveal some population-specific alleles and trans-species allelic conservation between the cynomolgus macaques and the rhesus macaques. Of the 40 new alleles, eight belong to a newly identified lineage group not previously found in the rhesus macaque species. This allele information will be useful for medical researchers using the cynomolgus macaques in disease and immunological studies.

  12. Association between metabolic gene polymorphisms and susceptibility to peripheral nerve damage in workers exposed to n-hexane: a preliminary study.

    PubMed

    Zhang, Y; Liu, Q; Liu, Q; Duan, H; Cheng, J; Jiang, S; Huang, X; Leng, S; He, F; Zheng, Y

    2006-01-01

    Chronic exposure to n-hexane may result in peripheral neuropathy. 2,5-Hexanedione (2,5-HD) has been identified as a toxic metabolite of n-hexane. The CYP2E1, CYP1A1 and GST genes are involved in the formation of 2,5-hexanedione from n-hexane as well as the elimination of 2,5-HD-formed electrophile, and these genes are highly polymorphic in the general population. A nested case-control study in an industrial cohort was conducted to evaluate the associations between polymorphisms in these metabolic genes and n-hexane-induced peripheral nerve damage. The study subjects included 22 cases, who worked in a printing factory with symptoms of peripheral nerve damage, and 163 controls, who came from the same factory of cases. DNA was extracted from blood samples and genotyping was conducted for CYP2E1 Pst, CYP2E1 Dra, CYP2E1 Ins96, CYP1A1 Msp, GSTT1 null, GSTM1 null and GSTP1 105V. Unconditional logistic regression was applied to estimate the odds ratio and 95% confidence intervals. There were no significant differences between the two groups regarding age, sex, smoking and alcohol status. A significant association between Dra polymorphism and peripheral nerve damage was found. The frequency of CYP2E1 Dra homozygous mutation in the case group (18.2%) was higher than that in the control group (3.7%, p=0.015). Individuals with homozygote genotype (CC) of CYP2E1 Dra had a significantly higher risk of peripheral nerve damage compared with those with DD genotype (adjusted OR=?.58, 95% CI=1.32-23.65) after n-hexane exposure duration, sex, age, smoking and alcohol status were adjusted. No significant association was found that CYP2E1 Pst, CYP2E1 Ins96, CYP1A1 Msp, GSTT1, GSTM1, GSTP gene polymorphisms associated with the susceptibility of peripheral nerve damage. These findings suggested that CYP2E1 gene might increase the susceptibility to n-hexane-induced peripheral damage.

  13. Characterization of Major Histocompatibility Complex (MHC) DRB Exon 2 and DRA Exon 3 Fragments in a Primary Terrestrial Rabies Vector (Procyon lotor)

    PubMed Central

    Castillo, Sarrah; Srithayakumar, Vythegi; Meunier, Vanessa; Kyle, Christopher J.

    2010-01-01

    The major histocompatibility complex (MHC) presents a unique system to explore links between genetic diversity and pathogens, as diversity within MHC is maintained in part by pathogen driven selection. While the majority of wildlife MHC studies have investigated species that are of conservation concern, here we characterize MHC variation in a common and broadly distributed species, the North American raccoon (Procyon lotor). Raccoons host an array of broadly distributed wildlife diseases (e.g., canine distemper, parvovirus and raccoon rabies virus) and present important human health risks as they persist in high densities and in close proximity to humans and livestock. To further explore how genetic variation influences the spread and maintenance of disease in raccoons we characterized a fragment of MHC class II DRA exon 3 (250bp) and DRB exon 2 (228 bp). MHC DRA was found to be functionally monomorphic in the 32 individuals screened; whereas DRB exon 2 revealed 66 unique alleles among the 246 individuals screened. Between two and four alleles were observed in each individual suggesting we were amplifying a duplicated DRB locus. Nucleotide differences between DRB alleles ranged from 1 to 36 bp (0.4–15.8% divergence) and translated into 1 to 21 (1.3–27.6% divergence) amino acid differences. We detected a significant excess of nonsynonymous substitutions at the peptide binding region (P = 0.005), indicating that DRB exon 2 in raccoons has been influenced by positive selection. These data will form the basis of continued analyses into the spatial and temporal relationship of the raccoon rabies virus and the immunogenetic response in its primary host. PMID:20706587

  14. Characterization of major histocompatibility complex (MHC) DRB exon 2 and DRA exon 3 fragments in a primary terrestrial rabies vector (Procyon lotor).

    PubMed

    Castillo, Sarrah; Srithayakumar, Vythegi; Meunier, Vanessa; Kyle, Christopher J

    2010-08-10

    The major histocompatibility complex (MHC) presents a unique system to explore links between genetic diversity and pathogens, as diversity within MHC is maintained in part by pathogen driven selection. While the majority of wildlife MHC studies have investigated species that are of conservation concern, here we characterize MHC variation in a common and broadly distributed species, the North American raccoon (Procyon lotor). Raccoons host an array of broadly distributed wildlife diseases (e.g., canine distemper, parvovirus and raccoon rabies virus) and present important human health risks as they persist in high densities and in close proximity to humans and livestock. To further explore how genetic variation influences the spread and maintenance of disease in raccoons we characterized a fragment of MHC class II DRA exon 3 (250 bp) and DRB exon 2 (228 bp). MHC DRA was found to be functionally monomorphic in the 32 individuals screened; whereas DRB exon 2 revealed 66 unique alleles among the 246 individuals screened. Between two and four alleles were observed in each individual suggesting we were amplifying a duplicated DRB locus. Nucleotide differences between DRB alleles ranged from 1 to 36 bp (0.4-15.8% divergence) and translated into 1 to 21 (1.3-27.6% divergence) amino acid differences. We detected a significant excess of nonsynonymous substitutions at the peptide binding region (P = 0.005), indicating that DRB exon 2 in raccoons has been influenced by positive selection. These data will form the basis of continued analyses into the spatial and temporal relationship of the raccoon rabies virus and the immunogenetic response in its primary host.

  15. Toward reduction in animal sacrifice for drugs: molecular modeling of Macaca fascicularis P450 2C20 for virtual screening of Homo sapiens P450 2C8 substrates.

    PubMed

    Rua, Francesco; Di Nardo, Giovanna; Sadeghi, Sheila J; Gilardi, Gianfranco

    2012-01-01

    Macaca fascicularis P450 2C20 shares 92% identity with human cytochrome P450 2C8, which is involved in the metabolism of more than 8% of all prescribed drugs. To date, only paclitaxel and amodiaquine, two substrate markers of the human P450 2C8, have been experimentally confirmed as M. fascicularis P450 2C20 drugs. To bridge the lack of information on the ligands recognized by M. fascicularis P450 2C20, in this study, a three-dimensional homology model of this enzyme was generated on the basis of the available crystal structure of the human homologue P450 2C8 using YASARA. The results indicated that 90.0%, 9.0%, 0.5%, and 0.5% of the residues of the P450 2C20 model were located in the most favorable, allowed, generously allowed, and disallowed regions, respectively. The root-mean-square deviation of the C-alpha superposition of the M. fascicularis P450 2C20 model with the Homo sapiens P450 2C8 was 0.074 Å, indicating a very high similarity of the two structures. Subsequently, the 2C20 model was used for in silico screening of 58 known P450 2C8 substrates and 62 inhibitors. These were also docked in the active site of the crystal structure of the human P450 2C8. The affinity of each compound for the active site of both cytochromes proved to be very similar, meaning that the few key residues that are mutated in the active site of the M. fascicularis P450 do not prevent the P450 2C20 from recognizing the same substrates as the human P450 2C8.

  16. Increased atherosclerosis and glomerulonephritis in cynomolgus monkeys (Macaca fascicularis) given injections of BSA over an extended period of time.

    PubMed Central

    Stills, H. F.; Bullock, B. C.; Clarkson, T. B.

    1983-01-01

    A study was conducted to compare the effects of experimental immune complex disease on the development of glomerulonephritis and aortic and coronary artery atherosclerosis. Fourteen adult male macaques (Macaca fascicularis) were fed a mildly atherogenic diet. Ten of these animals were given repeated intravenous injections of bovine serum albumin (BSA), and the remaining 4 were given similar injections of saline. Three of the monkeys given BSA responded with a high antibody titer, 4 with a moderate titer, and 3 with a low level titer to BSA. In all 4 monkeys with the moderate antibody response glomerulonephritis developed, characterized by increased glomerular cellularity, electron-dense deposits in the glomerular capillary basal lamina, and deposits of IgG, IgM, C3, C4, and BSA. Glomerulonephritis was not seen in the other 6 monkeys given BSA or the 4 control monkeys. Aortic lesions seen at necropsy consisted of a few fatty intimal streaks with no differences between test monkeys (given BSA) and control monkeys (given saline). There was no correlation between total serum cholesterol concentration, high-density lipoprotein cholesterol concentration, or BSA antibody levels and the degree of aortic atherosclerosis. Immunochemical stains for immunoglobulins and complement components revealed increased intimal staining when intimal thickness increased. Medial staining for immunoglobulin and complement components appeared to be slightly increased in monkeys with moderately high-level titers of BSA. The extent of atherosclerosis in the coronary arteries of monkeys given BSA was greater than in the control animals. Differences in the extent and severity of the atherosclerotic lesions were most pronounced in the proximal portions of the main coronary arteries, suggesting an increased susceptibility of this site to immune-complex-exacerbated atherosclerosis. In addition to the increased lesion severity in monkeys given BSA, there were numerous granulocytes seen within

  17. Use of photogrammetry as a means to assess hybrids of rhesus (Macaca mulatta) and long-tailed (M. fascicularis) macaques.

    PubMed

    Jadejaroen, Janya; Hamada, Yuzuru; Kawamoto, Yoshi; Malaivijitnond, Suchinda

    2015-01-01

    Rhesus (Macaca mulatta) and long-tailed (M. fascicularis) macaques are the most commonly used non-human primate models for biomedical research, but it is difficult to identify these two species in the hybrid zone (15-20°N). In this work, we used morphological values obtained via photogrammetry to assess hybrids of rhesus and long-tailed macaques at Khao Khieow Open Zoo (KKZ; 13°21'N, 101°06'E), eastern Thailand. Long-tailed and rhesus macaques have species-specific tail lengths and contrasts of their yellowish pelages. The accuracy and precision of the relative tail length (%RTL) and the contrast of the yellow hue (Cb*) of the pelage, as obtained from photographs, were compared with the corresponding direct measurements (morphometrics). The photogrammetric and morphometric measurements of %RTL and Cb* were highly significantly correlated (r = 0.989 and 0.980, p < 0.001), and there were no significant differences between the two datasets (t test, p = 0.13 and 0.41; n = 42 and 17 for %RTL and Cb*, respectively). The reproducibilities of the %RTL and Cb* measurements (calculated in the photogrammetric case by taking photographs of the same macaques in two different environments) were significantly correlated between the datasets (r = 0.983 and 0.914, p < 0.001 and 0.005), and there were no significant differences between the datasets (t test, p = 0.539 and 0.344; n = 30 each for %RTL and Cb*, respectively). The %RTL and Cb* data were combined with data on the crown and cheek hair patterns and sex skin reddening of the macaques, and this combined data set was then analyzed by multiple correspondence analysis and agglomerative hierarchical cluster analysis, leading to the categorization of the rhesus macaques, long-tailed macaques, and hybrids at KKZ into five groups. Thus, photogrammetry can be utilized to identify macaque species or hybrids when species identification relies mainly on tail length and pelage color.

  18. Muscle force recruitment and biomechanical modeling: an analysis of masseter muscle function during mastication in Macaca fascicularis.

    PubMed

    Hylander, W L; Johnson, K R; Crompton, A W

    1992-07-01

    The main purpose of this study is to test the hypothesis that as subjects chew with increasing levels of force, the ratio of the working- to balancing-side jaw-muscle force (W/B) decreases and begins to approach 1.0. We did this by analyzing relative masseter force in Macaca fascicularis using both strain gage and surface electromyographic (EMG) techniques. In addition, we also analyzed: 1) the relationship between jaw position using cineradiographic techniques and relative masseter force, 2) the timing differences between relative masseter force from the working and balancing sides, and 3) the loading and unloading characteristics of the masseter muscle. Our findings indicate that when macaques increase the amount of overall masticatory force during chewing, the W/B ratio for masseter force frequently (but not always) decreases and begins to approach 1.0. Therefore, our working hypothesis is not completely supported because the W/B ratio does not decrease with increasing levels of force in all subjects. The data also demonstrate timing differences in masseter force. During apple-skin mastication, the average peak masseter force on the working side occurs immediately at or slightly after the initial occurrence of maximum intercuspation, whereas the average peak masseter force on the balancing side occurs well before maximum intercuspation. On average, we found that peak force from the balancing-side masseter precedes the working-side masseter by about 26 msec. The greater the asynchrony between working- and balancing-side masseter force, the greater the difference in the relative magnitude of these forces. For example, in the subject with the greatest asynchrony, the balancing-side masseter had already fallen to about one-half of peak force when the working-side masseter reached peak force. Our data also indicate that the loading and unloading characteristics of the masseter differ between the working and balancing sides. Loading (from 50 to 100% of peak force) and

  19. Sequence length polymorphisms within primate amelogenin and amelogenin-like genes: usefulness in sex determination.

    PubMed

    Morrill, Benson H; Rickords, Lee F; Schafstall, Heather J

    2008-10-01

    Sequence length polymorphisms between the amelogenin (AMELX) and the amelogenin-like (AMELY) genes both within and between several mammalian species have been identified and utilized for sex determination, species identification, and to elucidate evolutionary relationships. Sex determination via polymerase chain reaction (PCR) assays of the AMELX and AMELY genes has been successful in greater apes, prosimians, and two species of old world monkeys. To date, no sex determination PCR assay using AMELX and AMELY has been developed for new world monkeys. In this study, we present partial AMELX and AMELY sequences for five old world monkey species (Mandrillus sphinx, Macaca nemestrina, Macaca fuscata, Macaca mulatta, and Macaca fascicularis) along with primer sets that can be used for sex determination of these five species. In addition, we compare the sequences we generated with other primate AMELX and AMELY sequences available on GenBank and discuss sequence length polymorphisms and their usefulness in sex determination within primates. The mandrill and four species of macaque all share two similar deletion regions with each other, the human, and the chimpanzee in the region sequenced. These two deletion regions are 176-181 and 8 nucleotides in length. In analyzing existing primate sequences on GenBank, we also discovered that a separate six-nucleotide polymorphism located approximately 300 nucleotides upstream of the 177 nucleotide polymorphism in sequences of humans and chimps was also present in two species of new world monkeys (Saimiri boliviensis and Saimiri sciureus). We designed primers that incorporate this polymorphism, creating the first AMELX and AMELY PCR primer set that has been used successfully to generate two bands in a new world monkey species.

  20. Antagonism of TCDD-induced ethoxyresorufin-O-deethylation activity by polybrominated diphenyl ethers (PBDEs) in primary cynomolgus monkey (Macaca fascicularis) hepatocytes.

    PubMed

    Peters, A K; Sanderson, J T; Bergman, A; van den Berg, M

    2006-07-01

    Polybrominated diphenyl ethers (PBDEs) are widespread environmental pollutants, and the levels of certain congeners have been increasing in biota and abiota in recent decades. Some PBDEs are lipophilic and persistent, resulting in bioaccumulation in the environment. Their structural similarity to other polyhalogenated aromatic hydrocarbons (PHAHs) such as polychlorinated biphenyls (PCBs) has raised concerns that PBDEs might act as agonists for the aryl hydrocarbon receptor (AhR). Recent studies in our laboratory with human and rat cell lines indicated no AhR mediated CYP1A1 induction for PBDEs. However, an earlier in vitro study by Van der Burght et al. (1999) [Van der Burght, A.S., Clijsters, P.J., Horbach, G.J., Andersson, P.L., Tysklind, M., van den Berg, M., 1999. Structure-dependent induction of CYP1A by polychlorinated biphenyls in hepatocytes of cynomolgus monkeys (Macaca fascicularis). Toxicol. Appl. Pharmacol. 155, 13-23] indicated that in cynomolgus monkey (M. fascicularis) hepatocytes PCBs with a non-planar configuration could induce CYP1A. As PBDEs show a structural similarity with non-planar (ortho substituted) PCBs, our present study focused on the possible CYP1A induction by PBDEs (BDE-47, -99, -100, -153, -154, -183, and -77) in individual preparations (n=4) of primary hepatocytes of cynomolgus monkeys (M. fascicularis). 7-Ethoxyresorufin-O-deethylase (EROD) was used as a marker for CYP1A-mediated catalytic activity. Cells were exposed for 48 h to various PBDE concentrations (0.01-10 microM), positive controls 2,3,7,8-TCDD (0.001-2.5 nM) and PCB-126 (0.01-10nM), and negative control (DMSO vehicle alone). No statistically significant induction of CYP1A was observed in the hepatocytes after 48 h of exposure to all environmentally relevant PBDEs. After exposing hepatocytes to PBDEs in combination with TCDD, a concentration-dependent decrease in TCDD-induced EROD activity was observed. All PBDEs tested showed a similar reduction in each of four

  1. Identification of microRNAs in Macaca fascicularis (Cynomolgus Monkey) by Homology Search and Experimental Validation by Small RNA-Seq and RT-qPCR Using Kidney Cortex Tissues.

    PubMed

    Veeranagouda, Yaligara; Rival, Pierrick; Prades, Catherine; Mariet, Claire; Léonard, Jean-François; Gautier, Jean-Charles; Zhou, Xiaobing; Wang, Jufeng; Li, Bo; Ozoux, Marie-Laure; Boitier, Eric

    2015-01-01

    MicroRNAs (miRNAs) present in tissues and biofluids are emerging as sensitive and specific safety biomarkers. MiRNAs have not been thoroughly described in M. fascicularis, an animal model used in pharmaceutical industry especially in drug safety evaluation. Here we investigated the miRNAs in M. fascicularis. For Macaca mulatta, a closely related species of M. fascicularis, 619 stem-loop precursor miRNAs (pre-miRNAs) and 914 mature miRNAs are available in miRBase version 21. Using M. mulatta miRNAs as a reference list and homology search tools, we identified 604 pre-miRNAs and 913 mature miRNAs in the genome of M. fascicularis. In order to validate the miRNAs identified by homology search we attempted to sequence miRNAs expressed in kidney cortex from M. fascicularis. MiRNAs expressed in kidney cortex may indeed be released in urine upon kidney cortex damage and be potentially used to monitor drug induced kidney injury. Hence small RNA sequencing libraries were prepared using kidney cortex tissues obtained from three naive M. fascicularis and sequenced. Analysis of sequencing data indicated that 432 out of 913 mature miRNAs were expressed in kidney cortex tissues. Assigning these 432 miRNAs to pre-miRNAs revealed that 273 were expressed from both the -5p and -3p arms of 150 pre-miRNAs and 159 miRNAs expressed from either the -5p or -3p arm of 176 pre-miRNAs. Mapping sequencing reads to pre-miRNAs also facilitated the detection of twenty-two new miRNAs. To substantiate miRNAs identified by small RNA sequencing, 313 miRNAs were examined by RT-qPCR. Expression of 262 miRNAs in kidney cortex tissues ware confirmed by TaqMan microRNA RT-qPCR assays. Analysis of kidney cortex miRNA targeted genes suggested that they play important role in kidney development and function. Data presented in this study may serve as a valuable resource to assess the renal safety biomarker potential of miRNAs in Cynomolgus monkeys.

  2. Identification of microRNAs in Macaca fascicularis (Cynomolgus Monkey) by Homology Search and Experimental Validation by Small RNA-Seq and RT-qPCR Using Kidney Cortex Tissues

    PubMed Central

    Veeranagouda, Yaligara; Rival, Pierrick; Prades, Catherine; Mariet, Claire; Léonard, Jean-François; Gautier, Jean-Charles; Zhou, Xiaobing; Wang, Jufeng; Li, Bo; Ozoux, Marie-Laure; Boitier, Eric

    2015-01-01

    MicroRNAs (miRNAs) present in tissues and biofluids are emerging as sensitive and specific safety biomarkers. MiRNAs have not been thoroughly described in M. fascicularis, an animal model used in pharmaceutical industry especially in drug safety evaluation. Here we investigated the miRNAs in M. fascicularis. For Macaca mulatta, a closely related species of M. fascicularis, 619 stem-loop precursor miRNAs (pre-miRNAs) and 914 mature miRNAs are available in miRBase version 21. Using M. mulatta miRNAs as a reference list and homology search tools, we identified 604 pre-miRNAs and 913 mature miRNAs in the genome of M. fascicularis. In order to validate the miRNAs identified by homology search we attempted to sequence miRNAs expressed in kidney cortex from M. fascicularis. MiRNAs expressed in kidney cortex may indeed be released in urine upon kidney cortex damage and be potentially used to monitor drug induced kidney injury. Hence small RNA sequencing libraries were prepared using kidney cortex tissues obtained from three naive M. fascicularis and sequenced. Analysis of sequencing data indicated that 432 out of 913 mature miRNAs were expressed in kidney cortex tissues. Assigning these 432 miRNAs to pre-miRNAs revealed that 273 were expressed from both the -5p and -3p arms of 150 pre-miRNAs and 159 miRNAs expressed from either the -5p or -3p arm of 176 pre-miRNAs. Mapping sequencing reads to pre-miRNAs also facilitated the detection of twenty-two new miRNAs. To substantiate miRNAs identified by small RNA sequencing, 313 miRNAs were examined by RT-qPCR. Expression of 262 miRNAs in kidney cortex tissues ware confirmed by TaqMan microRNA RT-qPCR assays. Analysis of kidney cortex miRNA targeted genes suggested that they play important role in kidney development and function. Data presented in this study may serve as a valuable resource to assess the renal safety biomarker potential of miRNAs in Cynomolgus monkeys. PMID:26562842

  3. Physical volcanology, geochemistry and basin evolution of the Ediacaran volcano-sedimentary succession in the Bas Draâ inlier (Ouarzazate Supergroup, Western Anti-Atlas, Morocco)

    NASA Astrophysics Data System (ADS)

    Karaoui, Brahim; Breitkreuz, Christoph; Mahmoudi, Abdelkader; Youbi, Nasrrddine

    2014-11-01

    New geologic mapping, lithofacies and granulometric analysis, and geochemistry from the volcano-sedimentary successions of the central part of the Bas Draâ inlier, Western Anti-Atlas, constrain the Ediacaran Ouarzazate Supergroup evolution during the post-collisional stage of the Pan-African orogeny. Volcanosedimentary facies analysis is the key aspect of the present contribution. We distinguished sixteen terrestrial volcanosedimentary lithofacies in the Bas Draâ succession (BDS), which reaches a total thickness of 2000 m. BDS evolution can be grouped into four units (Aouinet Aït Oussa I to IV, AO I-AO IV). The earliest volcanic activity produced rhyolitic ignimbrite sheets (AO I), which had been considered as lava flows by previous workers, and which were presumably related to caldera system(s). During AO II, a complex of high-silica andesitic and rhyolitic lavas formed, punctuated by the explosive eruption of a high-temperature silica-rich magma leading to the formation of parataxitic ignimbrite. AO III consists of basalt and andesite lava fields and small explosive, in parts phreatomagmatic volcanic vents. It is dissected by fluvial systems depositing external non-volcanic and local volcanic debris. BDS evolution terminated with the formation of a large SiO2-rich lava dome complex (AO IV), accompanied by small basalt effusive event. Volcanosedimentary facies analysis infers that the BDS evolved in a continental extensional setting developing in a low topography under humid paleoclimatic conditions. Alteration textures are dominated by a piemontite-calcite-albite-quartz (+ iron oxides) assemblage. Chemical analysis of BDS volcanic and subvolcanic rocks belongs to high-k calc-alkaline and alkali-calcic to alkaline magmatic trend typical for a post-collision setting. Trace elements spidergrams show a pattern typical for subduction-related suites of orogenic belts. REE patterns show moderate enrichment in LREE relative to flat HREE, with strong negative Eu

  4. Monitoring low benzene exposure: comparative evaluation of urinary biomarkers, influence of cigarette smoking, and genetic polymorphisms.

    PubMed

    Fustinoni, Silvia; Consonni, Dario; Campo, Laura; Buratti, Marina; Colombi, Antonio; Pesatori, Angela C; Bonzini, Matteo; Bertazzi, Pier A; Foà, Vito; Garte, Seymour; Farmer, Peter B; Levy, Leonard S; Pala, Mauro; Valerio, Federico; Fontana, Vincenzo; Desideri, Arianna; Merlo, Domenico F

    2005-09-01

    Benzene is a human carcinogen and an ubiquitous environmental pollutant. Identification of specific and sensitive biological markers is critical for the definition of exposure to low benzene level and the evaluation of the health risk posed by this exposure. This investigation compared urinary trans,trans-muconic acid (t,t-MA), S-phenylmercapturic acid, and benzene (U-benzene) as biomarkers to assess benzene exposure and evaluated the influence of smoking and the genetic polymorphisms CYP2E1 (RsaI and DraI) and NADPH quinone oxidoreductase-1 on these indices. Gas station attendants, urban policemen, bus drivers, and two groups of controls were studied (415 subjects). Median benzene exposure was 61, 22, 21, 9 and 6 microg/m(3), respectively, with higher levels in workers than in controls. U-benzene, but not t,t-MA and S-phenylmercapturic acid, showed an exposure-related increase. All the biomarkers were strongly influenced by cigarette smoking, with values up to 8-fold higher in smokers compared with nonsmokers. Significant correlations of the biomarkers with each other and with urinary cotinine were found. A possible influence of genetic polymorphism of CYP2E1 (RsaI and/or DraI) on t,t-MA and U-benzene in subjects with a variant allele was found. Multiple linear regression analysis correlated the urinary markers with exposure, smoking status, and CYP2E1 (RsaI; R(2) up to 0.55 for U-benzene). In conclusion, in the range of investigated benzene levels (<478 micro/m(3) or <0.15 ppm), smoking may be regarded as the major source of benzene intake; among the study indices, U-benzene is the marker of choice for biomonitoring low-level occupational and environmental benzene exposure.

  5. Effects of Implantation and Reimplantation of Cochlear Implant Electrodes in an In Vivo Animal Experimental Model (Macaca fascicularis).

    PubMed

    de Abajo, Jorge; Manrique-Huarte, Raquel; Sanhueza, Ignacio; Alvarez-Gómez, Laura; Zulueta-Santos, Cristina; Calavia, Diego; Ramírez, Fernando; Manrique, Manuel

    The objectives of this study were to evaluate the effect of reimplanting a cochlear implant electrode in animal normal-hearing cochlea to propose measures that may prevent cochlear injury and, given its close phylogenetic proximity to humans, to evaluate the macaque as a model for electroacoustic stimulation. Simultaneous, bilateral surgical procedures in a group of 5 normal-hearing specimens (Macaca fascicularis) took place in a total of 10 ears. Periodic bilateral auditory testing (distortion product otoacoustic emissions and auditory brainstem evoked responses [ABR]) took place during a 6-month follow-up period. Subsequently, unilateral explantation and reimplantation was performed. Auditory follow-up continued up to 12 months, after which animals were sacrificed and both temporal bones extracted for histological analysis. Implantation and reimplantation surgeries were performed without complications in 9 of 10 cases. Full insertion depth was achieved at reimplantation in four of five ears. Auditory evaluation: Statistically significant differences between implanted and reimplanted were observed for the frequencies 2000 and 11,000 Hz, the remaining frequencies showed no differences for distortion product otoacoustic emission. Before the procedure, average thresholds with click-stimuli ABR of the five animals were 40 dB SPL (implanted group) and 40 dB SPL (reimplanted group). One week after first implantation, average thresholds were 55 dB SPL and 60 dB, respectively. After 12 months of follow-up, the average thresholds were 72.5 dB SPL (implanted group) and 65 dB SPL (reimplanted group). Hearing loss appeared during the first weeks after the first implantation and no deterioration was observed thereafter. Differences for ABR under click stimulus were not significant between the two ear groups. Similar results were observed with tone-burst ABR. A 15 dB shift was observed for the implanted group preoperatively versus 1-week post surgery and an additional 17.5 d

  6. Données nouvelles sur le contenu organique des dépôts phosphatés du gisement de Ras-Draâ (Tunisie)

    NASA Astrophysics Data System (ADS)

    Ben Hassen, Aida; Trichet, Jean; Disnar, Jean-Robert; Belayouni, Habib

    2009-04-01

    The study of the organic matter (OM) content of phosphatic sediments from the Ras-Draâ deposit, Tunisia, was carried on the two separated lithological fractions constituting the bulk sediments, namely phosphatic grains (pellets) and their associated matrices. The geochemical characterization of the OM present in pellets and in their matrices by CNS elemental analysis and RE pyrolysis indicates that: (i) the TOC content is higher in matrices (where it reaches 4.00%), than in pellets in the same strata where it does not exceed 1.62%; (ii) the presence of more or less oxidized marine planktonic OM in both fractions; (iii) a low degree of diagenetic evolution of the OM in both fractions (RE Tmax globally < than 430 °C). The chemical extraction of the humic substances (HS) from both fractions followed by the separation of fractions according to the IHSS procedure, systematically indicates a higher abundance of extractable humic compounds (HC) in the pellets (C HC ˜ 70% of the sum of TOC in the separated fractions, TOCfr) and a variable but lower extraction yield in matrices (C HC ˜ 18% TOCfr). This significant difference between both fractions excludes the possibility that pellets formed authigenically from, and within, their matrix. This is consistent with recent findings suggesting that these pellets could be fish feces.

  7. Lack of Association between Polymorphisms of Hepatic Lipase with Lipid Profile in Young Jordanian Adults.

    PubMed

    Khabour, Omar F; Alomari, Mahmoud A; Alzoubi, Karem H; Gharaibeh, Mohammad Y; Alhashimi, Farah H

    2014-01-01

    The human hepatic lipase (LIPC) gene encodes hepatic lipase, an enzyme involved in lipoprotein metabolism and regulation. Therefore, variants in LIPC gene may influence plasma lipoprotein levels. In this study, the association of LIPC C-514T and G-250A polymorphisms with plasma lipid profiles in 348 young Jordanians was investigated. Genotyping of C-514T and G-250A was performed by polymerase chain reaction and subsequent digestion with DraI and NiaIII restriction enzymes, respectively, while Roche analyzer was used to determine plasma total cholesterol, triglycerides, low-and high-density lipoprotein. The G-250 and C-514 alleles were most abundant in Jordanians with 79 and 80% frequencies, respectively. Additionally, no difference was found in the lipid-lipoprotein profile between the different genotype groups of C-514T or G-250A polymorphisms, even when males and females were examined separately (P > 0.05). In young Jordanian adults, the examined LIPC polymorphisms seem to play a limited role in determining the lipid profile.

  8. Emergence and evolution of inter-specific segregating retrocopies in cynomolgus monkey (Macaca fascicularis) and rhesus macaque (Macaca mulatta)

    PubMed Central

    Zhang, Xu; Zhang, Qu; Su, Bing

    2016-01-01

    Retroposition is an RNA-mediated mechanism to generate gene duplication, and is believed to play an important role in genome evolution and phenotypic adaptation in various species including primates. Previous studies suggested an elevated rate of recent retroposition in the rhesus macaque genome. To better understand the impact of retroposition on macaque species which have undergone an adaptive radiation approximately 3–6 million years ago, we developed a bioinformatics pipeline to identify recently derived retrocopies in cynomolgus monkeys. As a result, we identified seven experimentally validated young retrocopies, all of which are polymorphic in cynomolgus monkeys. Unexpectedly, five of them are also present in rhesus monkeys and are still segregating. Molecular evolutionary analysis indicates that the observed inter-specific polymorphism is attribute to ancestral polymorphism. Further population genetics analysis provided strong evidence of balancing selection on at least one case (Crab-eating monkey retrocopy 6, or CER6) in both species. CER6 is in adjacent with an immunoglobulin related gene and may be involved in host-pathogen interaction, a well-known target of balancing selection. Altogether, our data support that retroposition is an important force to shape genome evolution and species adaptation. PMID:27600022

  9. Novel experimental methods for investigating high speed friction of titanium-aluminum-vanadium/tool steel interface and dynamic failure of extrinsically toughened DRA composites

    NASA Astrophysics Data System (ADS)

    Irfan, Mohammad Abdulaziz

    effects the sliding resistance of the interface. The experimental results deduced from the response of the sliding interface to step changes in normal pressure and the applied shear stress reinforce the importance of including frictional memory in the development of rate dependent state variable friction models. The second part of the thesis presents an investigation into the dynamic deformation and failure of extrinsically toughened DRA composites. Experiments were conducted using the split Hopkinson pressure bar to investigate the deformation and flow behavior under dynamic compression loading. A modified Hopkinson bar apparatus was used to explore the dynamic fracture behavior of three different extrinsically toughened DRA composites. The study was paralleled by systematic exploration of the failure modes in each composite. For all the composites evaluated the dynamic crack propagation characteristics of the composites are observed to be strongly dependent on the volume fraction of the ductile phase reinforcement in the composite, the yield stress of the ductile phase reinforcement, the micro-structural arrangement of the ductile phase reinforcements with respect to the notch, and the impact velocity employed in the particular experiment.

  10. Polymorphous computing fabric

    DOEpatents

    Wolinski, Christophe Czeslaw [Los Alamos, NM; Gokhale, Maya B [Los Alamos, NM; McCabe, Kevin Peter [Los Alamos, NM

    2011-01-18

    Fabric-based computing systems and methods are disclosed. A fabric-based computing system can include a polymorphous computing fabric that can be customized on a per application basis and a host processor in communication with said polymorphous computing fabric. The polymorphous computing fabric includes a cellular architecture that can be highly parameterized to enable a customized synthesis of fabric instances for a variety of enhanced application performances thereof. A global memory concept can also be included that provides the host processor random access to all variables and instructions associated with the polymorphous computing fabric.

  11. A new assay based on terminal restriction fragment length polymorphism of homocitrate synthase gene fragments for Candida species identification.

    PubMed

    Szemiako, Kasjan; Śledzińska, Anna; Krawczyk, Beata

    2017-08-01

    Candida sp. have been responsible for an increasing number of infections, especially in patients with immunodeficiency. Species-specific differentiation of Candida sp. is difficult in routine diagnosis. This identification can have a highly significant association in therapy and prophylaxis. This work has shown a new application of the terminal restriction fragment length polymorphism (t-RFLP) method in the molecular identification of six species of Candida, which are the most common causes of fungal infections. Specific for fungi homocitrate synthase gene was chosen as a molecular target for amplification. The use of three restriction enzymes, DraI, RsaI, and BglII, for amplicon digestion can generate species-specific fluorescence labeled DNA fragment profiles, which can be used to determine the diagnostic algorithm. The designed method can be a cost-efficient high-throughput molecular technique for the identification of six clinically important Candida species.

  12. Analysis with a Combination of Macrorestriction Endonucleases Reveals a High Degree of Polymorphism among Bordetella pertussis Isolates in Eastern France

    PubMed Central

    Prevost, G.; Freitas, F. I. S.; Stoessel, P.; Meunier, O.; Haubensack, M.; Monteil, H.; Scheftel, J. M.

    1999-01-01

    From 1990 to 1996, routine screening for whooping cough identified 399 patients with a calmodulin-dependent adenylate cyclase-positive test result and yielded 69 Bordetella pertussis isolates. None of the patients were fully vaccinated, and most were less than 6 months old. Analysis of total DNA by pulsed-field gel electrophoresis (PFGE) after XbaI, SpeI, or DraI macrorestriction yielded 19, 15, and 5 different patterns, respectively, whereas ribotyping failed to demonstrate any strain polymorphism. Discrimination among the isolates was improved by combining the PFGE profiles. Some patterns were more frequent, but the corresponding patients were not clearly epidemiologically related. The patterns for two strains obtained during a 3-month period from patients who were neighbors differed by the length of a single DNA fragment. These data strongly suggest that one type of isolate is widely spread throughout the world and is carried by individuals other than patients who develop a true illness. PMID:10074527

  13. Comparison of Saliva Collection Methods for the Determination of Salivary Cortisol Levels in Rhesus Macaques (Macaca mulatta), Cynomolgus Macaques (Macaca fascicularis), and African Green Monkeys (Chlorocebus aethiops).

    PubMed

    Rapp-Santos, Kamala J; Altamura, Louis A; Norris, Sarah L; Lugo-Roman, Luis A; Rico, Pedro J; Hofer, Christian C

    2017-03-01

    The ability to quickly and accurately determine cortisol as a biomarker for stress is a valuable tool in assessing the wellbeing of NHP. In this study, 2 methods of collecting saliva (a commercial collection device and passive drool) and the resulting free salivary cortisol levels were compared with total serum cortisol concentration in rhesus macaques (Macaca mulatta), cynomolgus macaques (Macaca fascicularis) and African green monkeys (Chlorocebus aethiops) at 2 collection time points. Serum and salivary cortisol levels were determined using a competitive quantitative ELISA. In addition, both saliva collection methods were evaluated for volume collected and ease of use. Compared with passive drool, the experimental collection device was more reliable in collecting sufficient volumes of saliva, and the resulting salivary cortisol values demonstrated stronger correlation with serum cortisol concentration in all species and collection days except cynomolgus macaques on day 1. This saliva collection device allows quick and reliable sample collection for the determination of salivary cortisol levels. In addition, the results might provide a useful tool for evaluating hypothalamic-pituitary-adrenal axis activity or the physiologic stress reaction in NHP as well as a biomarker of psychologic stress states in a variety of situations.

  14. STIMULUS–FOOD PAIRINGS PRODUCE STIMULUS-DIRECTED TOUCH-SCREEN RESPONDING IN CYNOMOLGUS MONKEYS (MACACA FASCICULARIS) WITH OR WITHOUT A POSITIVE RESPONSE CONTINGENCY

    PubMed Central

    Bullock, Christopher E; Myers, Todd M

    2009-01-01

    Acquisition and maintenance of touch-screen responding was examined in naïve cynomolgus monkeys (Macaca fascicularis) under automaintenance and classical conditioning arrangements. In the first condition of Experiment 1, we compared acquisition of screen touching to a randomly positioned stimulus (a gray square) that was either stationary or moving under automaintenance (i.e., banana pellet delivery followed an 8-s stimulus presentation or immediately upon a stimulus touch). For all subjects stimulus touching occurred within the first session and increased to at least 50% of trials by the end of four sessions (320 trials). In the subsequent condition, stimulus touching further increased under a similar procedure in which pellets were only delivered if a stimulus touch occurred (fixed ratio 1 with 8-s limited hold). In Experiment 2, 6 naive subjects were initially exposed to a classical conditioning procedure (8-s stimulus preceded pellet delivery). Despite the absence of a programmed response contingency, all subjects touched the stimulus within the first session and responded on about 50% or more of trials by the second session. Responding was also sensitive to negative, neutral, and positive response contingencies introduced in subsequent conditions. Similar to other species, monkeys engaged in stimulus-directed behavior when stimulus presentations were paired with food delivery. However, stimulus-directed behavior quickly conformed to response contingencies upon subsequent introduction. Video recordings of sessions showed topographies of stimulus-directed behavior that resembled food acquisition and consumption. PMID:20119521

  15. The effects of thermal and high-CO2 stresses on the metabolism and surrounding microenvironment of the coral Galaxea fascicularis.

    PubMed

    Agostini, Sylvain; Fujimura, Hiroyuki; Higuchi, Tomihiko; Yuyama, Ikuko; Casareto, Beatriz E; Suzuki, Yoshimi; Nakano, Yoshikatsu

    2013-08-01

    The effects of elevated temperature and high pCO2 on the metabolism of Galaxea fascicularis were studied with oxygen and pH microsensors. Photosynthesis and respiration rates were evaluated from the oxygen fluxes from and to the coral polyps. High-temperature alone lowered both photosynthetic and respiration rates. High pCO2 alone did not significantly affect either photosynthesis or respiration rates. Under a combination of high-temperature and high-CO2, the photosynthetic rate increased to values close to those of the controls. The same pH in the diffusion boundary layer was observed under light in both (400 and 750 ppm) CO2 treatments, but decreased significantly in the dark as a result of increased CO2. The ATP contents decreased with increasing temperature. The effects of temperature on the metabolism of corals were stronger than the effects of increased CO2. The effects of acidification were minimal without combined temperature stress. However, acidification combined with higher temperature may affect coral metabolism due to the amplification of diel variations in the microenvironment surrounding the coral and the decrease in ATP contents.

  16. Colour cues for leaf food selection by long-tailed macaques (Macaca fascicularis) with a new suggestion for the evolution of trichromatic colour vision.

    PubMed

    Lucas, P W; Darvell, B W; Lee, P K; Yuen, T D; Choong, M F

    1998-01-01

    Leaf colour, size and toughness were investigated in five plant species important in the diet of Macaca fascicularis in Singapore. Leaf colour and size were examined as potential visual cues for food selection, whereas toughness mirrored fibre content, the inverse of food quality. As leaves matured, they changed colour and toughened. Leaf lightness and yellowness were strongly negatively correlated with toughness, but variation in both the red-green axis of the CIE Lab colour space and leaf size were not. Leaves selected as food by the macaques were distinguished by being very light, yellow to slightly green. Some leaves were dappled with red. The literature suggests that these leaves are relatively rich in protein without being tough and therefore would be sought after by primates. We argue that leaf colour is an important indicator of the nutritive value of leaves. Trichromatic vision is an important advantage in finding those palatable leaves that are dappled red. These would appear dark to dichromatic primates and be deceptive by making leaves look older (lower in quality) than they actually are. This would decrease the perceived window of feeding opportunity for such primates who would be at a disadvantage in trying to find these leaves. It is possible that trichromatic vision in catarrhine primates may have originally evolved for the detection of red coloration in the leaves of shade-tolerant tropical plants, enabling the better exploitation of a food resource.

  17. Trace elements found to be variable in two coral reef species, Heliofungia actiniformis and Galaxea fascicularis, collected from the Ryukyu Islands.

    PubMed

    Yamada, G; Fujimori, K; Yamada, M; Minami, T; Tohno, S; Tohno, Y

    1998-11-01

    Biominerals and metals of intertidal corals of two species (Heliofungia actiniformis, Quoy and Gaimard; Galaxea fascicularis, Linnaeus), collected from the Iriomote Island of Ryukyu, were examined with an inductively coupled plasma atomic emission spectrometer (ICP-AES). Twelve elements were detectable in the coralline skeletons dissected radially along the growth axis. The relative content (RC) of Hg periodically fluctuated and was minimum at the hollow sites of the coralline slab of Heliofungia sp., corresponding to the cyclic growth. There were two types of elements: constant elements and variable elements along the growth axis. RCs of Ca, Mg, Al, Si, and P were nearly constant. RCs of Fe, Mn, Cu, and Ba were variable, but not as regularly changed as Hg. There were positive mass correlations of Hg to Mn, Cu and Zn, but not to Ba and Fe. In contrast, these relationships were not prominent and were likely degraded by aging in the skeleton of Galaxea sp., suggesting a different mode from that of the Heliofungia sp.

  18. Polymorphism and solvatomorphism 2008.

    PubMed

    Brittain, Harry G

    2010-09-01

    Papers and patents that deal with polymorphism and solvatomorphism have been summarized in an annual review. The review is divided into sections that cover articles of general interest, computational and theoretical studies, preparative and isolation methods, structural characterization and properties of polymorphic and solvatomorphic systems, studies of phase transformations, effects associated with secondary processing, and United States patents issued during 2008.

  19. Polymorphism in Carbamazepine Cocrystals

    PubMed Central

    Porter, William W.; Elie, Sophia C.; Matzger, Adam J.

    2009-01-01

    Cocrystals of carbamazepine with nicotinamide and saccharin are shown to be polymorphic. Two polymorphs of carbamazepine-nicotinamide (CBZ-NCT) cocrystals and two polymorphs of carbamazepine-saccharin (CBZ-SAC) cocrystals were grown from solution in the presence of polymer heteronuclei. The two CBZ-NCT polymorphs, CBZ-NCT I and a polymer nucleated (PN) form of CBZ-NCT, were characterized by Raman spectroscopy and powder X-ray diffraction. CBZ-SAC II, a new polymorph, was found to be in the monoclinic space group C2/c with a = 35.72 Å, b = 6.84 Å, c = 16.11 Å, and β = 98.03°. The unique feature of CBZ-SAC II is the formation of a heterosynthon between the carbamazepine and saccharin. These results are notable because CBZ-NCT and CBZ-SAC are among the most widely studied pharmaceutical cocrystals. PMID:19367342

  20. There Is More than One Way to Crack an Oyster: Identifying Variation in Burmese Long-Tailed Macaque (Macaca fascicularis aurea) Stone-Tool Use.

    PubMed

    Tan, Amanda; Tan, Say Hoon; Vyas, Dhaval; Malaivijitnond, Suchinda; Gumert, Michael D

    2015-01-01

    We explored variation in patterns of percussive stone-tool use on coastal foods by Burmese long-tailed macaques (Macaca fascicularis aurea) from two islands in Laem Son National Park, Ranong, Thailand. We catalogued variation into three hammering classes and 17 action patterns, after examining 638 tool-use bouts across 90 individuals. Hammering class was based on the stone surface used for striking food, being face, point, and edge hammering. Action patterns were discriminated by tool material, hand use, posture, and striking motion. Hammering class was analyzed for associations with material and behavioural elements of tool use. Action patterns were not, owing to insufficient instances of most patterns. We collected 3077 scan samples from 109 macaques on Piak Nam Yai Island's coasts, to determine the proportion of individuals using each hammering class and action pattern. Point hammering was significantly more associated with sessile foods, smaller tools, faster striking rates, smoother recoil, unimanual use, and more varied striking direction, than were face and edge hammering, while both point and edge hammering were significantly more associated with precision gripping than face hammering. Edge hammering also showed distinct differences depending on whether such hammering was applied to sessile or unattached foods, resembling point hammering for sessile foods and face hammering for unattached foods. Point hammering and sessile edge hammering compared to prior descriptions of axe hammering, while face and unattached edge hammering compared to pound hammering. Analysis of scans showed that 80% of individuals used tools, each employing one to four different action patterns. The most common patterns were unimanual point hammering (58%), symmetrical-bimanual face hammering (47%) and unimanual face hammering (37%). Unimanual edge hammering was relatively frequent (13%), compared to the other thirteen rare action patterns (<5%). We compare our study to other stone

  1. Assessing natural introgression in 2 biomedical model species, the rhesus macaque (Macaca mulatta) and the long-tailed macaque (Macaca fascicularis).

    PubMed

    Bonhomme, Maxime; Cuartero, Sergi; Blancher, Antoine; Crouau-Roy, Brigitte

    2009-01-01

    Rhesus macaque (Macaca mulatta) and long-tailed macaque (Macaca fascicularis) are the 2 most commonly used primate model species in biomedical sciences. Although morphological studies have revealed a weak hybridization at the interspecific contact zone, in the north of Indochina, a molecular study has suggested an ancient introgression from rhesus to long-tailed macaque into the Indo-Chinese peninsula. However, the gene flow between these 2 taxa has never been quantified using genetic data and theoretical models. In this study, we have examined genetic variation within and between the parapatric Chinese rhesus macaque and Indo-Chinese long-tailed macaque populations, using 13 autosomal, 5 sex-linked microsatellite loci and mitochondrial DNA sequence data. From these data, we assessed genetic structure and estimated gene flow using a Bayesian clustering approach and the "Isolation with Migration" model. Our results reveal a weak interspecific genetic differentiation at both autosomal and sex-linked loci, suggesting large population sizes and/or gene flow between populations. According to the Bayesian clustering, Chinese rhesus macaque is a highly homogeneous gene pool that contributes strongly to the current Indo-Chinese long-tailed macaque genetic makeup, whether or not current admixture is assumed. Coalescent simulations, which integrated the characteristics of the loci, pointed out 1) a higher effective population size in rhesus macaque, 2) no mitochondrial gene flow, and 3) unilateral and male-mediated nuclear gene flow of approximately 10 migrants per generation from rhesus to long-tailed macaque. These patterns of genetic structure and gene flow suggest extensive ancient introgression from Chinese rhesus macaque into the Indo-Chinese long-tailed macaque population.

  2. There Is More than One Way to Crack an Oyster: Identifying Variation in Burmese Long-Tailed Macaque (Macaca fascicularis aurea) Stone-Tool Use

    PubMed Central

    Tan, Amanda; Tan, Say Hoon; Vyas, Dhaval; Malaivijitnond, Suchinda; Gumert, Michael D.

    2015-01-01

    We explored variation in patterns of percussive stone-tool use on coastal foods by Burmese long-tailed macaques (Macaca fascicularis aurea) from two islands in Laem Son National Park, Ranong, Thailand. We catalogued variation into three hammering classes and 17 action patterns, after examining 638 tool-use bouts across 90 individuals. Hammering class was based on the stone surface used for striking food, being face, point, and edge hammering. Action patterns were discriminated by tool material, hand use, posture, and striking motion. Hammering class was analyzed for associations with material and behavioural elements of tool use. Action patterns were not, owing to insufficient instances of most patterns. We collected 3077 scan samples from 109 macaques on Piak Nam Yai Island’s coasts, to determine the proportion of individuals using each hammering class and action pattern. Point hammering was significantly more associated with sessile foods, smaller tools, faster striking rates, smoother recoil, unimanual use, and more varied striking direction, than were face and edge hammering, while both point and edge hammering were significantly more associated with precision gripping than face hammering. Edge hammering also showed distinct differences depending on whether such hammering was applied to sessile or unattached foods, resembling point hammering for sessile foods and face hammering for unattached foods. Point hammering and sessile edge hammering compared to prior descriptions of axe hammering, while face and unattached edge hammering compared to pound hammering. Analysis of scans showed that 80% of individuals used tools, each employing one to four different action patterns. The most common patterns were unimanual point hammering (58%), symmetrical-bimanual face hammering (47%) and unimanual face hammering (37%). Unimanual edge hammering was relatively frequent (13%), compared to the other thirteen rare action patterns (<5%). We compare our study to other stone

  3. The Vgamma2/Vdelta2 T-cell repertoire in Macaca fascicularis: functional responses to phosphoantigen stimulation by the Vgamma2/Jgamma1.2 subset.

    PubMed

    Cairo, Cristiana; Propp, Nadia; Hebbeler, Andrew M; Colizzi, Vittorio; Pauza, C David

    2005-06-01

    Circulating Vgamma2/Vdelta2 T cells in human and non-human primates respond to small molecular weight non-peptidic phosphoantigens in a major histocompatibility complex (MHC)-unrestricted manner. These responses are encoded by the Vgamma2/Jgamma1.2 chain of the T-cell receptor and are positively selected during early development to create a biased repertoire in adults. We characterized the Vgamma2 chain in cynomolgus macaques (Macaca fascicularis) to develop a non-human primate model for studying the effects of infection and therapy on the circulating Vgamma2/Vdelta2 T-cell subset. The cynomolgus macaque Vgamma2 chain was highly homologous to the Vgamma2 chain from human beings and rhesus macaques (Macaca mulatta), though we noted conserved substitutions in critical residues within the CDR3 for both macaque species. Despite these substitutions, Vgamma2/Vdelta2+ T cells from cynomolgus monkeys exhibited polyclonal responses to two different phosphoantigens. Proliferative responses were observed with both isopentenylpyrophosphate and alendronate, but stronger interferon-gamma secretory responses were observed with isopentenylpyrophosphate. In vitro stimulation and expansion led to selective outgrowth of the Vgamma2/Jgamma1.2 subset, with a marked shift in the Vgamma2 spectratype. As a result of the less biased starting repertoire for Vgamma2, the cynomolgus macaque constitutes a sensitive model for examining the effects of in vitro or in vivo treatments on the Vgamma2/Vdelta2 T-cell population. Our studies establish the value of cynomolgus macaques as a model for Vgamma2/Vdelta2 T-cell responses to non-peptidic antigens, and further evidence the remarkable evolutionary conservation of this unusual, phosphoantigen-responsive T-cell subset that is found only in primate species.

  4. The Vγ2/Vδ2 T-cell repertoire in Macaca fascicularis: functional responses to phosphoantigen stimulation by the Vγ2/Jγ1.2 subset

    PubMed Central

    Cairo, Cristiana; Propp, Nadia; Hebbeler, Andrew M; Colizzi, Vittorio; Pauza, C David

    2005-01-01

    Circulating Vγ2/Vδ2 T cells in human and non-human primates respond to small molecular weight non-peptidic phosphoantigens in a major histocompatibility complex (MHC)-unrestricted manner. These responses are encoded by the Vγ2/Jγ1.2 chain of the T-cell receptor and are positively selected during early development to create a biased repertoire in adults. We characterized the Vγ2 chain in cynomolgus macaques (Macaca fascicularis) to develop a non-human primate model for studying the effects of infection and therapy on the circulating Vγ2/Vδ2 T-cell subset. The cynomolgus macaque Vγ2 chain was highly homologous to the Vγ2 chain from human beings and rhesus macaques (Macaca mulatta), though we noted conserved substitutions in critical residues within the CDR3 for both macaque species. Despite these substitutions, Vγ2/Vδ2+ T cells from cynomolgus monkeys exhibited polyclonal responses to two different phosphoantigens. Proliferative responses were observed with both isopentenylpyrophosphate and alendronate, but stronger interferon-γ secretory responses were observed with isopentenylpyrophosphate. In vitro stimulation and expansion led to selective outgrowth of the Vγ2/Jγ1.2 subset, with a marked shift in the Vγ2 spectratype. As a result of the less biased starting repertoire for Vγ2, the cynomolgus macaque constitutes a sensitive model for examining the effects of in vitro or in vivo treatments on the Vγ2/Vδ2 T-cell population. Our studies establish the value of cynomolgus macaques as a model for Vγ2/Vδ2 T-cell responses to non-peptidic antigens, and further evidence the remarkable evolutionary conservation of this unusual, phosphoantigen-responsive T-cell subset that is found only in primate species. PMID:15885125

  5. A novel wireless recording and stimulating multichannel epicortical grid for supplementing or enhancing the sensory-motor functions in monkey (Macaca fascicularis)

    PubMed Central

    Zippo, Antonio G.; Romanelli, Pantaleo; Torres Martinez, Napoleon R.; Caramenti, Gian C.; Benabid, Alim L.; Biella, Gabriele E. M.

    2015-01-01

    Artificial brain-machine interfaces (BMIs) represent a prospective step forward supporting or replacing faulty brain functions. So far, several obstacles, such as the energy supply, the portability and the biocompatibility, have been limiting their effective translation in advanced experimental or clinical applications. In this work, a novel 16 channel chronically implantable epicortical grid has been proposed. It provides wireless transmission of cortical recordings and stimulations, with induction current recharge. The grid has been chronically implanted in a non-human primate (Macaca fascicularis) and placed over the somato-motor cortex such that 13 electrodes recorded or stimulated the primary motor cortex and three the primary somatosensory cortex, in the deeply anaesthetized animal. Cortical sensory and motor recordings and stimulations have been performed within 3 months from the implant. In detail, by delivering motor cortex epicortical single spot stimulations (1–8 V, 1–10 Hz, 500 ms, biphasic waves), we analyzed the motor topographic precision, evidenced by tunable finger or arm movements of the anesthetized animal. The responses to light mechanical peripheral sensory stimuli (blocks of 100 stimuli, each single stimulus being <1 ms and interblock intervals of 1.5–4 s) have been analyzed. We found 150–250 ms delayed cortical responses from fast finger touches, often spread to nearby motor stations. We also evaluated the grid electrical stimulus interference with somatotopic natural tactile sensory processing showing no suppressing interference with sensory stimulus detection. In conclusion, we propose a chronically implantable epicortical grid which can accommodate most of current technological restrictions, representing an acceptable candidate for BMI experimental and clinical uses. PMID:26029061

  6. A novel wireless recording and stimulating multichannel epicortical grid for supplementing or enhancing the sensory-motor functions in monkey (Macaca fascicularis).

    PubMed

    Zippo, Antonio G; Romanelli, Pantaleo; Torres Martinez, Napoleon R; Caramenti, Gian C; Benabid, Alim L; Biella, Gabriele E M

    2015-01-01

    Artificial brain-machine interfaces (BMIs) represent a prospective step forward supporting or replacing faulty brain functions. So far, several obstacles, such as the energy supply, the portability and the biocompatibility, have been limiting their effective translation in advanced experimental or clinical applications. In this work, a novel 16 channel chronically implantable epicortical grid has been proposed. It provides wireless transmission of cortical recordings and stimulations, with induction current recharge. The grid has been chronically implanted in a non-human primate (Macaca fascicularis) and placed over the somato-motor cortex such that 13 electrodes recorded or stimulated the primary motor cortex and three the primary somatosensory cortex, in the deeply anaesthetized animal. Cortical sensory and motor recordings and stimulations have been performed within 3 months from the implant. In detail, by delivering motor cortex epicortical single spot stimulations (1-8 V, 1-10 Hz, 500 ms, biphasic waves), we analyzed the motor topographic precision, evidenced by tunable finger or arm movements of the anesthetized animal. The responses to light mechanical peripheral sensory stimuli (blocks of 100 stimuli, each single stimulus being <1 ms and interblock intervals of 1.5-4 s) have been analyzed. We found 150-250 ms delayed cortical responses from fast finger touches, often spread to nearby motor stations. We also evaluated the grid electrical stimulus interference with somatotopic natural tactile sensory processing showing no suppressing interference with sensory stimulus detection. In conclusion, we propose a chronically implantable epicortical grid which can accommodate most of current technological restrictions, representing an acceptable candidate for BMI experimental and clinical uses.

  7. CpG site degeneration triggered by the loss of functional constraint created a highly polymorphic macaque drug-metabolizing gene, CYP1A2

    PubMed Central

    2011-01-01

    Background Elucidating the pattern of evolutionary changes in drug-metabolizing genes is an important subject not only for evolutionary but for biomedical research. We investigated the pattern of divergence and polymorphisms of macaque CYP1A1 and CYP1A2 genes, which are major drug-metabolizing genes in humans. In humans, CYP1A2 is specifically expressed in livers while CYP1A1 has a wider gene expression pattern in extrahepatic tissues. In contrast, macaque CYP1A2 is expressed at a much lower level than CYP1A1 in livers. Interestingly, a previous study has shown that Macaca fascicularis CYP1A2 harbored unusually high genetic diversity within species. Genomic regions showing high genetic diversity within species is occasionally interpreted as a result of balancing selection, where natural selection maintains highly diverged alleles with different functions. Nevertheless many other forces could create such signatures. Results We found that the CYP1A1/2 gene copy number and orientation has been highly conserved among mammalian genomes. The signature of gene conversion between CYP1A1 and CYP1A2 was detected, but the last gene conversion event in the simian primate lineage occurred before the Catarrhini-Platyrrhini divergence. The high genetic diversity of macaque CYP1A2 therefore cannot be explained by gene conversion between CYP1A1 and CYP1A2. By surveying CYP1A2 polymorphisms in total 91 M. fascicularis and M. mulatta, we found several null alleles segregating in these species, indicating functional constraint on CYP1A2 in macaques may have weakened after the divergence between humans and macaques. We propose that the high genetic diversity in macaque CYP1A2 is partly due to the degeneration of CpG sites, which had been maintained at a high level by purifying selection, and the rapid degeneration process was initiated by the loss of functional constraint on macaque CYP1A2. Conclusions Our findings show that the highly polymorphic CYP1A2 gene in macaques has not been

  8. Familial dysalbuminemic hyperthyroxinemia: a rare example of albumin polymorphism and its rapid molecular diagnosis.

    PubMed

    AvRuskin, Theodore W; Juan, Christina S; Weiss, Roy E

    2002-06-01

    Familial dysalbuminemic hyperthyroxinemia (FDH) is the most common cause of euthyroid hyperthyroxinemia, although a rare example of albumin polymorphism. FDH is inherited in an autosomal dominant manner and is characterized by enhanced binding of thyroxine to a mutant form of albumin, probably at Site 1, subdomain 11A. Previous laboratory tests of FDH have been cumbersome, rarely available, and required demonstration of anti-albumin precipitable T4, isoelectric focusing of serum for albumin in presence of labeled T4 and, occasionally, comparison of the concentrations of metabolites of T4 that have different binding affinities to the abnormal albumin. Recent studies have shown that the same mutation in the albumin gene that results in FDH has been found in 13 unrelated families. A G-->A transition in codon 218 of the albumin gene resulted in the replacement of arginine with histidine. An intragenic Sac-1 polymorphic site was found in association with the specific FDH mutation, suggesting a founder effect. FDH in our Hispanic family was confirmed by isoelectric focusing of serum. Results of thyroid function tests in our affected patients were typical for the phenotype: high total T4 and normal total T3. Genomic DNA was amplified by PCR using a mismatched oligonucleotide primer that produced a unique restriction site (Dra III) only if the DNA sample contained the mutation in codon 218: CGC (Arg) to CAC (His). In affected individuals of this family expression of the FDH phenotype was associated with the presence of His218 in one of the two alleles. Analysis linking the FDH mutation to the Sac-1 polymorphism in this family was not informative. DNA analysis is a rapid and simple method to diagnose FDH in individuals with euthyroid hyperthyroxinemia.

  9. Disappearing Polymorphs Revisited

    PubMed Central

    Bučar, Dejan-Krešimir; Lancaster, Robert W; Bernstein, Joel

    2015-01-01

    Nearly twenty years ago, Dunitz and Bernstein described a selection of intriguing cases of polymorphs that disappear. The inability to obtain a crystal form that has previously been prepared is indeed a frustrating and potentially serious problem for solid-state scientists. This Review discusses recent occurrences and examples of disappearing polymorphs (as well as the emergence of elusive crystal forms) to demonstrate the enduring relevance of this troublesome, but always captivating, phenomenon in solid-state research. A number of these instances have been central issues in patent litigations. This Review, therefore, also highlights the complex relationship between crystal chemistry and the law. PMID:26031248

  10. Evaluation of the bioeffects of prenatal ultrasound exposure in the cynomolgus macaque (Macaca fascicularis): II. Growth and behavior during the first year.

    PubMed

    Tarantal, A F; Hendrickx, A G

    1989-02-01

    The extensive use of ultrasonography for the prenatal assessment of growth and development continues to present questions regarding biological effects. We are currently evaluating a nonhuman primate model (Macaca fascicularis) exposed to ultrasound from gestational day (GD) 21 to 152 +/- 2. Exposures were performed with a commercial real-time sector scanner (ATL, MK 600); animals were scanned five times weekly on GD 21-35 +/- 2, three times weekly on GD 36-60 +/- 2, and once weekly on GD 61-150 +/- 2. The length of exposure was approximately the same as human exposure (GD 21-60 +/- 2 = 10 min/exam and GD 61-150 +/- 2 = 20 min/exam) although the frequency of the examinations was considerably greater. Initial reports indicated differences between control and treated animals including lower birth weight, higher simian Apgar scores, and changes in select hematologic parameters. Follow-up evaluations of growth during the first year included measurements of body weight, hand and foot lengths, humerus and femur lengths, biparietal and occipitofrontal diameters, head circumference, arm circumference, chest circumference, skinfold thickness, and crown-rump length. Results indicated a significant reduction in body weight in treated animals during the first three months, with nonsignificant differences during the following nine months. Hematologic analysis including complete blood counts (CBC) and clinical biochemistry at 6, 9, and 12 months of age were not significantly different. A series of behavioral evaluations including a neurobehavioral test battery (NBT) and tests assessing motor and cognitive skills were included. The NBT revealed increased muscle tone in treated animals at one, two, and four days. In an observation cage (week 1-14) more quiet activities were displayed by treated animals. Group differences in performance of motor and cognitive tasks were observed and may be attributable to agitation and difficulties in adjusting to test environments. There were no

  11. Polymorphism of sorbitol

    NASA Astrophysics Data System (ADS)

    Nezzal, Amale; Aerts, Luc; Verspaille, Marleen; Henderickx, Geert; Redl, Andreas

    2009-07-01

    The polymorphism of sorbitol was investigated, confirming the existence of four anhydrous crystalline phases plus the hydrate. The crystallised melt (CM), the alpha form, and the gamma form were obtained via a dry route. The CM was confirmed to be a crystalline state with a spherulite morphology. The alpha form was obtained via direct conversion from the CM, in contrast to more complicated routes previously reported, and was found to have a very high crystallinity. Gamma crystals were obtained by seeding the melt at high temperature; however, crystallinity was clearly less than for alpha crystals. Despite its lower crystallinity, the gamma polymorph was found to be the most stable of the anhydrous crystalline forms; this was confirmed by its high melting point and low hygroscopicity. In contrast, the alpha polymorph has a relatively high melting point but lacks moisture stability at high relative humidity. The hydrate form has the same resistance to moisture as the gamma form, but melts at a lower temperature. The combination of both a high melting point and high stability in the presence of water makes the gamma polymorph best suited for confectionary applications.

  12. Polymorphous Perversity in Texts

    ERIC Educational Resources Information Center

    Johnson-Eilola, Johndan

    2012-01-01

    Here's the tricky part: If we teach ourselves and our students that texts are made to be broken apart, remixed, remade, do we lose the polymorphous perversity that brought us pleasure in the first place? Does the pleasure of transgression evaporate when the borders are opened?

  13. Enzyme polymorphisms in Canarium

    USDA-ARS?s Scientific Manuscript database

    Fifty-two accessions of Canarium involving seven species, C. ovatum, C. album, C. megalanthum, C. harveyi, C. indicum, C. mehenbethene, and C. odontophyllum were studied for isozyme polymorphisms. Starch gel electrophoresis with a histidine-citrate buffer system (pH 6.5) was employed to assay six en...

  14. Investigation of Uranium Polymorphs

    SciTech Connect

    Sweet, Lucas E.; Henager, Charles H.; Hu, Shenyang Y.; Johnson, Timothy J.; Meier, David E.; Peper, Shane M.; Schwantes, Jon M.

    2011-08-01

    The UO3-water system is complex and has not been fully characterized, even though these species are common throughout the nuclear fuel cycle. As an example, most production schemes for UO3 result in a mixture of up to six or more different polymorphic phases, and small differences in these conditions will affect phase genesis that ultimately result in measureable changes to the end product. As a result, this feature of the UO3-water system may be useful as a means for determining process history. This research effort attempts to better characterize the UO3-water system with a variety of optical techniques for the purpose of developing some predictive capability for estimating process history in polymorphic phases of unknown origin. Three commercially relevant preparation methods for the production of UO3 were explored. Previously unreported low temperature routes to β- and γ-UO3 were discovered. Raman and fluorescence spectroscopic libraries were established for pure and mixed polymorphic forms of UO3 in addition to the common hydrolysis products of UO3. An advantage of the sensitivity of optical fluorescence microscopy over XRD has been demonstrated. Preliminary aging studies of the α and γ forms of UO3 have been conducted. In addition, development of a 3-D phase field model used to predict phase genesis of the system was initiated. Thermodynamic and structural constants that will feed the model have been gathered from the literature for most of the UO3 polymorphic phases.

  15. Polymorphism in Energetic Materials

    DTIC Science & Technology

    2008-01-01

    salicylic acid ) was first prepared by Charles Frederic Gerhardt in 1853, a second polymorph of this drug was not discovered until 2005. Studies have...the crystallization conditions post- synthesis were not recorded, reproducing the condi- tions resulting in the analyzed sample was not possible. All

  16. Abnormal glucose tolerance and insulin resistance in polycystic ovary syndrome amongst the Taiwanese population- not correlated with insulin receptor substrate-1 Gly972Arg/Ala513Pro polymorphism

    PubMed Central

    Lin, Ta-Chin; Yen, Jui-Mei; Gong, Kum-Bing; Kuo, Tsung-Cheng; Ku, Dong-Chi; Liang, Shu-Fen; Wu, Ming-Jiuan

    2006-01-01

    Background Insulin resistance and glucose dysmetabolism in polycystic ovary syndrome (PCOS) are related with the polymorphisms in the genes encoding the insulin receptor substrate (IRS) proteins, especially Gly972Arg/Ala513Pro polymorphism being reported to be associated with type-2 diabetes and PCOS. We intended to assess the prevalence of abnormal glucose tolerance (AGT) and insulin resistance in Taiwanese PCOS women. We also tried to assess whether the particular identity of Gly972Arg/Ala513Pro polymorphic alleles of the IRS-1 gene mutation can be used as an appropriate diagnostic indicator for PCOS. Methods We designed a prospective clinical study. Forty-seven Taiwanese Hoklo and Hakka women, diagnosed with PCOS were enrolled in this study as were forty-five healthy Hoklo and Hakka women as the control group. Insulin resistance was evaluated with fasting insulin, fasting glucose/insulin ratio, and homeostasis model assessment index for insulin resistance (HOMAIR). The genomic DNA of the subjects was amplified by PCR and digested by restriction fragmented length polymorphism (RFLP) with Bst N1 used for codon 972 and Dra III for codon 513. Results AGT was found in 46.8% of these PCOS patients and was significantly related to high insulin resistance rather than the low insulin resistance. Those patients with either insulin resistance or AGT comprised the majority of PCOS affected patients (AGT + fasting insulin ≥17: 83%, AGT + glucose/insulin ratio ≥6.5: 85.1%, AGT + HOMAIR ≥ 2: 87.2%, and AGT + HOMAIR ≥ 3.8: 72.3%). None of the tested samples revealed any polymorphism due to the absence of any Dra III recognition site or any Bst N1 recognition site in the amplified PCR fragment digested by restriction fragmented length polymorphism. Conclusion There is significantly high prevalence of AGT and insulin resistance in PCOS women, but Gly972Arg and Ala513Pro polymorphic alleles of IRS-1 are rare and are not associated with the elevated risk of PCOS amongst

  17. The sweet taste quality is linked to a cluster of taste fibers in primates: lactisole diminishes preference and responses to sweet in S fibers (sweet best) chorda tympani fibers of M. fascicularis monkey

    PubMed Central

    Wang, Yiwen; Danilova, Vicktoria; Cragin, Tiffany; Roberts, Thomas W; Koposov, Alexey; Hellekant, Göran

    2009-01-01

    Background Psychophysically, sweet and bitter have long been considered separate taste qualities, evident already to the newborn human. The identification of different receptors for sweet and bitter located on separate cells of the taste buds substantiated this separation. However, this finding leads to the next question: is bitter and sweet also kept separated in the next link from the taste buds, the fibers of the taste nerves? Previous studies in non-human primates, P. troglodytes, C. aethiops, M. mulatta, M. fascicularis and C. jacchus, suggest that the sweet and bitter taste qualities are linked to specific groups of fibers called S and Q fibers. In this study we apply a new sweet taste modifier, lactisole, commercially available as a suppressor of the sweetness of sugars on the human tongue, to test our hypothesis that sweet taste is conveyed in S fibers. Results We first ascertained that lactisole exerted similar suppression of sweetness in M. fascicularis, as reported in humans, by recording their preference of sweeteners and non- sweeteners with and without lactisole in two-bottle tests. The addition of lactisole significantly diminished the preference for all sweeteners but had no effect on the intake of non-sweet compounds or the intake of water. We then recorded the response to the same taste stimuli in 40 single chorda tympani nerve fibers. Comparison between single fiber nerve responses to stimuli with and without lactisole showed that lactisole only suppressed the responses to sweeteners in S fibers. It had no effect on the responses to any other stimuli in all other taste fibers. Conclusion In M. fascicularis, lactisole diminishes the attractiveness of compounds, which taste sweet to humans. This behavior is linked to activity of fibers in the S-cluster. Assuming that lactisole blocks the T1R3 monomer of the sweet taste receptor T1R2/R3, these results present further support for the hypothesis that S fibers convey taste from T1R2/R3 receptors, while

  18. The sweet taste quality is linked to a cluster of taste fibers in primates: lactisole diminishes preference and responses to sweet in S fibers (sweet best) chorda tympani fibers of M. fascicularis monkey.

    PubMed

    Wang, Yiwen; Danilova, Vicktoria; Cragin, Tiffany; Roberts, Thomas W; Koposov, Alexey; Hellekant, Göran

    2009-02-18

    Psychophysically, sweet and bitter have long been considered separate taste qualities, evident already to the newborn human. The identification of different receptors for sweet and bitter located on separate cells of the taste buds substantiated this separation. However, this finding leads to the next question: is bitter and sweet also kept separated in the next link from the taste buds, the fibers of the taste nerves? Previous studies in non-human primates, P. troglodytes, C. aethiops, M. mulatta, M. fascicularis and C. jacchus, suggest that the sweet and bitter taste qualities are linked to specific groups of fibers called S and Q fibers. In this study we apply a new sweet taste modifier, lactisole, commercially available as a suppressor of the sweetness of sugars on the human tongue, to test our hypothesis that sweet taste is conveyed in S fibers. We first ascertained that lactisole exerted similar suppression of sweetness in M. fascicularis, as reported in humans, by recording their preference of sweeteners and non- sweeteners with and without lactisole in two-bottle tests. The addition of lactisole significantly diminished the preference for all sweeteners but had no effect on the intake of non-sweet compounds or the intake of water. We then recorded the response to the same taste stimuli in 40 single chorda tympani nerve fibers. Comparison between single fiber nerve responses to stimuli with and without lactisole showed that lactisole only suppressed the responses to sweeteners in S fibers. It had no effect on the responses to any other stimuli in all other taste fibers. In M. fascicularis, lactisole diminishes the attractiveness of compounds, which taste sweet to humans. This behavior is linked to activity of fibers in the S-cluster. Assuming that lactisole blocks the T1R3 monomer of the sweet taste receptor T1R2/R3, these results present further support for the hypothesis that S fibers convey taste from T1R2/R3 receptors, while the impulse activity in non

  19. Molecular typing of Stenotrophomonas (Xanthomonas) maltophilia by DNA macrorestriction analysis and random amplified polymorphic DNA analysis.

    PubMed Central

    Yao, J D; Conly, J M; Krajden, M

    1995-01-01

    Stenotrophomonas (Xanthomonas) maltophilia is a multidrug-resistant, nosocomial pathogen for which optimal typing methods in epidemiologic investigations of nosocomial outbreaks have not been defined. We compared DNA macrorestriction analysis by pulsed-field gel electrophoresis (PFGE) with random amplified polymorphic DNA (RAPD) analysis by arbitrarily primed PCR for molecular typing of 109 multidrug-resistant strains of S. maltophilia from multiple outbreaks at our institution over a 10-month period in 1993. PFGE after digestion with restriction endonuclease DraI revealed 62 unique DNA restriction profiles among the 109 strains, with 23, 11, 6, 6, and 3 strains having concordant profiles in each of five types. There were four concordant profiles among 8 strains (2 strains with each profile), while unique profiles were present in each of the remaining 52 strains. Further RAPD analysis with a decanucleotide primer showed the same number of distinct strain types as PFGE but more subtype diversity within each clonal type. We concluded that DNA macrorestriction analysis and RAPD analysis are sufficiently discriminatory and useful for differentiation of S. maltophilia strains in epidemiologic investigations of nosocomial outbreaks. However, RAPD analysis by arbitrarily primed PCR is faster and less laborious method of molecular typing. PMID:7559978

  20. Polymorphism of phosphoric oxide

    USGS Publications Warehouse

    Hill, W.L.; Faust, G.T.; Hendricks, S.B.

    1943-01-01

    The melting points and monotropic relationship of three crystalline forms of phosphoric oxide were determined by the method of quenching. Previous vapor pressure data are discussed and interpreted to establish a pressure-temperature diagram (70 to 600??) for the one-component system. The system involves three triple points, at which solid, liquid and vapor (P4O10) coexist in equilibrium, namely: 420?? and 360 cm., 562?? and 43.7 cm. and 580?? and 55.5 cm., corresponding to the hexagonal, orthorhombic and stable polymorphs, respectively, and at least two distinct liquids, one a stable polymer of the other, which are identified with the melting of the stable form and the hexagonal modification, respectively. Indices of refraction of the polymorphs and glasses were determined. The density and the thermal, hygroscopic and structural properties of the several phases are discussed.

  1. Facts and fictions about polymorphism.

    PubMed

    Cruz-Cabeza, Aurora J; Reutzel-Edens, Susan M; Bernstein, Joel

    2015-12-07

    We present new facts about polymorphism based on (i) crystallographic data from the Cambridge Structural Database (CSD, a database built over 50 years of community effort), (ii) 229 solid form screens conducted at Hoffmann-La Roche and Eli Lilly and Company over the course of 8+ and 15+ years respectively and (iii) a dataset of 446 polymorphic crystals with energies and properties computed with modern DFT-d methods. We found that molecular flexibility or size has no correlation with the ability of a compound to be polymorphic. Chiral molecules, however, were found to be less prone to polymorphism than their achiral counterparts and compounds able to hydrogen bond exhibit only a slightly higher propensity to polymorphism than those which do not. Whilst the energy difference between polymorphs is usually less than 1 kcal mol(-1), conformational polymorphs are capable of differing by larger values (up to 2.5 kcal mol(-1) in our dataset). As overall statistics, we found that one in three compounds in the CSD are polymorphic whilst at least one in two compounds from the Roche and Lilly set display polymorphism with a higher estimate of up to three in four when compounds are screened intensively. Whilst the statistics provide some guidance of expectations, each compound constitutes a new challenge and prediction and realization of targeted polymorphism still remains a holy grail of materials sciences.

  2. Crystallographic and Computational Studies of a Class II MHC Complex with a Nonconforming Peptide: HLA-DRA/DRB3*0101

    NASA Astrophysics Data System (ADS)

    Parry, Christian S.; Gorski, Jack; Stern, Lawrence J.

    2003-03-01

    The stable binding of processed foreign peptide to a class II major histocompatibility (MHC) molecule and subsequent presentation to a T cell receptor is a central event in immune recognition and regulation. Polymorphic residues on the floor of the peptide binding site form pockets that anchor peptide side chains. These and other residues in the helical wall of the groove determine the specificity of each allele and define a motif. Allele specific motifs allow the prediction of epitopes from the sequence of pathogens. There are, however, known epitopes that do not satisfy these motifs: anchor motifs are not adequate for predicting epitopes as there are apparently major and minor motifs. We present crystallographic studies into the nature of the interactions that govern the binding of these so called nonconforming peptides. We would like to understand the role of the P10 pocket and find out whether the peptides that do not obey the consensus anchor motif bind in the canonical conformation observed in in prior structures of class II MHC-peptide complexes. HLA-DRB3*0101 complexed with peptide crystallized in unit cell 92.10 x 92.10 x 248.30 (90, 90, 90), P41212, and the diffraction data is reliable to 2.2ÅWe are complementing our studies with dynamical long time simulations to answer these questions, particularly the interplay of the anchor motifs in peptide binding, the range of protein and ligand conformations, and water hydration structures.

  3. Molecular composition of drusen and possible involvement of anti-retinal autoimmunity in two different forms of macular degeneration in cynomolgus monkey (Macaca fascicularis).

    PubMed

    Umeda, Shinsuke; Suzuki, Michihiro T; Okamoto, Haru; Ono, Fumiko; Mizota, Atsushi; Terao, Keiji; Yoshikawa, Yasuhiro; Tanaka, Yasuhiko; Iwata, Takeshi

    2005-10-01

    We have previously reported a cynomolgus monkey (Macaca fascicularis) pedigree with early onset macular degeneration that develops drusen at 2 yr after birth. In this study, the molecular composition of drusen in monkeys affected with late onset and early onset macular degeneration was both characterized. Involvement of anti-retinalautoimmunity in the deposition of drusen and the pathogenesis of the disease was also evaluated. Funduscopic and histological examinations were performed on 278 adult monkeys (mean age=16.94 yr) for late onset macular degeneration. The molecular composition of drusen was analyzed by immunohistochemistry and/or direct proteome analysis using liquid chromatography tandem mass spectroscopy (LC-MS/MS). Anti-retinal autoantibodies in sera were screened in 20 affected and 10 age-matched control monkeys by Western blot techniques. Immunogenic molecules were identified by 2D electrophoresis and LC-MS/MS. Relative antibody titer against each antigen was determined by ELISA in sera from 42 affected (late onset) and 41 normal monkeys. Yellowish-white spots in the macular region were observed in 90 (32%) of the late onset monkeys that were examined. Histological examination demonstrated that drusen or degenerative retinal pigment epithelium (RPE) cells were associated with the pigmentary abnormalities. Drusen in both late and early onset monkeys showed immunoreactivities for apolipoprotein E, amyloid P component, complement component C5, the terminal C5b-9 complement complex, vitronectin, and membrane cofactor protein. LC-MS/MS analyses identified 60 proteins as constituents of drusen, including a number of common components in drusen of human age-related macular degeneration (AMD), such as annexins, crystallins, immunoglobulins, and complement components. Half of the affected monkeys had single or multiple autoantibodies against 38, 40, 50, and 60 kDa retinal proteins. The reacting antigens of 38 and 40 kDa were identified as annexin II and mu

  4. Stability of Polymeric Crystalline Polymorphs

    NASA Astrophysics Data System (ADS)

    Sinkovits, Daniel W.; Kumar, Sanat K.

    2014-03-01

    In the search for polymeric materials with novel properties, such as high dielectric constant and low loss, an important attribute of a material is its crystal structure. Most polymers can crystallize into multiple polymorphs whose properties vary. Therefore, the question of which polymorphs are thermodynamically preferred under what conditions is of great importance. We generate polymorphs using atomistic molecular dynamics simulations and tackle the question of stability using a combination of molecular dynamics and Monte Carlo techniques. Multidisciplinary University Research Initiative (MURI).

  5. The Third Ambient Aspirin Polymorph

    DOE PAGES

    Shtukenberg, Alexander G.; Hu, Chunhua T.; Zhu, Qiang; ...

    2017-05-17

    Polymorphism in aspirin (acetylsalicylic acid), one of the most widely consumed medications, was equivocal until the structure of a second polymorph II, similar in structure to the original form I, was reported in 2005. Here, the third ambient polymorph of aspirin is described. Lastly, it was crystallized from the melt and its structure was determined using a combination of X-ray powder diffraction analysis and crystal structure prediction algorithms.

  6. Greater expression of TLR2, TLR4, and IL6 due to negative energy balance is associated with lower expression of HLA-DRA and HLA-A in bovine blood neutrophils after intramammary mastitis challenge with Streptococcus uberis.

    PubMed

    Moyes, Kasey M; Drackley, James K; Morin, Dawn E; Loor, Juan J

    2010-03-01

    Our objectives were to compare gene expression profiles in blood polymorphonuclear cells (PMN) during a Streptococcus uberis intramammary challenge between lactating cows subjected to feed restriction to induce negative energy balance (NEB; n=5) and cows fed ad libitum to maintain positive energy balance (PEB; n=5). After 5 days of feed restriction, one rear mammary quarter of each cow was inoculated with 5,000 cfu of S. uberis. Blood PMN were isolated at 24 h post-inoculation from all cows for mRNA expression via quantitative polymerase chain reaction for 20 genes associated with immune response and metabolism. A total of 12 genes were differentially expressed in blood PMN in NEB versus PEB cows. Upregulated genes by NEB were ALOX5AP, CPNE3, IL1R2, IL6, TLR2, TLR4, and THY1, and downregulated genes were HLA-DRA, HLA-A, IRAK1, SOD1, and TNF. Network analysis revealed that TNF was associated with several of the affected genes in NEB cows compared with PEB cows. Results showed that 24 h after intramammary challenge with S. uberis, cows in NEB had altered PMN expression of genes involved with immune response. Our data provide new information on transcriptomic mechanisms associated with NEB and the corresponding inhibition of immune response in lactating dairy cows.

  7. Polymorphic Electronic Circuits

    NASA Technical Reports Server (NTRS)

    Stoica, Adrian

    2004-01-01

    Polymorphic electronics is a nascent technological discipline that involves, among other things, designing the same circuit to perform different analog and/or digital functions under different conditions. For example, a circuit can be designed to function as an OR gate or an AND gate, depending on the temperature (see figure). Polymorphic electronics can also be considered a subset of polytronics, which is a broader technological discipline in which optical and possibly other information- processing systems could also be designed to perform multiple functions. Polytronics is an outgrowth of evolvable hardware (EHW). The basic concepts and some specific implementations of EHW were described in a number of previous NASA Tech Briefs articles. To recapitulate: The essence of EHW is to design, construct, and test a sequence of populations of circuits that function as incrementally better solutions of a given design problem through the selective, repetitive connection and/or disconnection of capacitors, transistors, amplifiers, inverters, and/or other circuit building blocks. The evolution is guided by a search-and-optimization algorithm (in particular, a genetic algorithm) that operates in the space of possible circuits to find a circuit that exhibits an acceptably close approximation of the desired functionality. The evolved circuits can be tested by computational simulation (in which case the evolution is said to be extrinsic), tested in real hardware (in which case the evolution is said to be intrinsic), or tested in random sequences of computational simulation and real hardware (in which case the evolution is said to be mixtrinsic).

  8. Energetics of kaolin polymorphs

    SciTech Connect

    Ligny, D. de; Navrotsky, A.

    1999-04-01

    The enthalpy of formation of kaolin polymorphs at 298 K has been determined by drop-solution calorimetry into molten lead borate at 975 K. Corrections have been made for impurities in the samples. The standard enthalpy of formation from the elements is: kaolinite {minus}4120.2 {+-} 6.6 kJ/mol, dickite {minus}4107.6 {+-} 5.7 kJ/mol, nacrite {minus}4104.0 {+-} 7.6 kJ/mol, and halloysite {minus}4097.5 {+-} 5.6 kJ/mol. Using entropy data from the literature, the standard free energy of formation from the elements at 298 K is /{minus}3799.4 {+-} 6.4 kJ/mol for kaolinite, {minus}3785.1 {+-} 5.6 kJ/mol for dickite, and {minus}3776.8 {+-} 5.8 kJ/mol for halloysite. The effect of crystallinity (Hinckley index ranging from 1.6 to 0.4) on the enthalpy of formation of kaolinite is smaller than 5 kJ/mol, the experimental error. The relative stability of the polymorphs probably does not change significantly with pressure and temperature over their range of occurrence. Thus the geological occurrence of halloysite, nacrite, and dickite, which are metastable phases, must be interpreted in terms of kinetics or as the result of a specific synthesis path, rather than as resulting from changes in the thermodynamically stable phase assemblage.

  9. Polymorphic Evolutionary Games.

    PubMed

    Fishman, Michael A

    2016-06-07

    In this paper, I present an analytical framework for polymorphic evolutionary games suitable for explicitly modeling evolutionary processes in diploid populations with sexual reproduction. The principal aspect of the proposed approach is adding diploid genetics cum sexual recombination to a traditional evolutionary game, and switching from phenotypes to haplotypes as the new game׳s pure strategies. Here, the relevant pure strategy׳s payoffs derived by summing the payoffs of all the phenotypes capable of producing gametes containing that particular haplotype weighted by the pertinent probabilities. The resulting game is structurally identical to the familiar Evolutionary Games with non-linear pure strategy payoffs (Hofbauer and Sigmund, 1998. Cambridge University Press), and can be analyzed in terms of an established analytical framework for such games. And these results can be translated into the terms of genotypic, and whence, phenotypic evolutionary stability pertinent to the original game.

  10. Gene Polymorphisms in Chronic Periodontitis

    PubMed Central

    Laine, Marja L.; Loos, Bruno G.; Crielaard, W.

    2010-01-01

    We aimed to conduct a review of the literature for gene polymorphisms associated with chronic periodontitis (CP) susceptibility. A comprehensive search of the literature in English was performed using the keywords: periodontitis, periodontal disease, combined with the words genes, mutation, or polymorphism. Candidate gene polymorphism studies with a case-control design and reported genotype frequencies in CP patients were searched and reviewed. There is growing evidence that polymorphisms in the IL1, IL6, IL10, vitamin D receptor, and CD14 genes may be associated with CP in certain populations. However, carriage rates of the rare (R)-allele of any polymorphism varied considerably among studies and most of the studies appeared under-powered and did not correct for other risk factors. Larger cohorts, well-defined phenotypes, control for other risk factors, and analysis of multiple genes and polymorphisms within the same pathway are needed to get a more comprehensive insight into the contribution of gene polymorphisms in CP. PMID:20339487

  11. SOD2 polymorphisms: unmasking the effect of polymorphism on splicing

    PubMed Central

    Shao, Jing; Chen, Lishan; Marrs, Brian; Lee, Lin; Huang, Hai; Manton, Kenneth G; Martin, George M; Oshima, Junko

    2007-01-01

    Background The SOD2 gene encodes an antioxidant enzyme, mitochondrial superoxide dismutase. SOD2 polymorphisms are of interest because of their potential roles in the modulation of free radical-mediated macromolecular damage during aging. Results We identified a new splice variant of SOD2 in human lymphoblastoid cell lines (LCLs). The alternatively spliced product was originally detected by exon trapping of a minigene in order to examine the consequences of an intronic polymorphism found upstream of exon 4 (nucleotide 8136, 10T vs 9T). Examination of the transcripts derived from the endogenous loci in five LCLs with or without the intron 3 polymorphism revealed low levels of an in-frame deletion of exon 4 that were different from those detected by the exon trap assay. This suggested that exon trapping of the minigene unmasked the effect of the 10T vs 9T polymorphism on the splicing of the adjacent exon. We also determined the frequencies of single nucleotide polymorphisms in a sample of US African-Americans and non-African-Americans ages 65 years and older who participated in the 1999 wave of the National Long Term Care Survey (NLTCS). Particularly striking differences between African-Americans and non-African-Americans were found for the frequencies of genotypes at the 10T/9T intron 3 polymorphism. Conclusion Exon trapping can unmask in vitro splicing differences caused by a 10T/9T intron 3 polymorphism. Given the recent evidence that SOD2 is in a region on chromosome 6 linked to susceptibility to hypertension, it will be of interest to investigate possible associations of this polymorphism with cardiovascular disorders. PMID:17331249

  12. Preferential Nucleation during Polymorphic Transformations

    NASA Astrophysics Data System (ADS)

    Sharma, H.; Sietsma, J.; Offerman, S. E.

    2016-08-01

    Polymorphism is the ability of a solid material to exist in more than one phase or crystal structure. Polymorphism may occur in metals, alloys, ceramics, minerals, polymers, and pharmaceutical substances. Unresolved are the conditions for preferential nucleation during polymorphic transformations in which structural relationships or special crystallographic orientation relationships (OR’s) form between the nucleus and surrounding matrix grains. We measured in-situ and simultaneously the nucleation rates of grains that have zero, one, two, three and four special OR’s with the surrounding parent grains. These experiments show a trend in which the activation energy for nucleation becomes smaller - and therefore nucleation more probable - with increasing number of special OR’s. These insights contribute to steering the processing of polymorphic materials with tailored properties, since preferential nucleation affects which crystal structure forms, the average grain size and texture of the material, and thereby - to a large extent - the final properties of the material.

  13. Preferential Nucleation during Polymorphic Transformations

    PubMed Central

    Sharma, H.; Sietsma, J.; Offerman, S. E.

    2016-01-01

    Polymorphism is the ability of a solid material to exist in more than one phase or crystal structure. Polymorphism may occur in metals, alloys, ceramics, minerals, polymers, and pharmaceutical substances. Unresolved are the conditions for preferential nucleation during polymorphic transformations in which structural relationships or special crystallographic orientation relationships (OR’s) form between the nucleus and surrounding matrix grains. We measured in-situ and simultaneously the nucleation rates of grains that have zero, one, two, three and four special OR’s with the surrounding parent grains. These experiments show a trend in which the activation energy for nucleation becomes smaller – and therefore nucleation more probable - with increasing number of special OR’s. These insights contribute to steering the processing of polymorphic materials with tailored properties, since preferential nucleation affects which crystal structure forms, the average grain size and texture of the material, and thereby - to a large extent - the final properties of the material. PMID:27484579

  14. Preferential Nucleation during Polymorphic Transformations.

    PubMed

    Sharma, H; Sietsma, J; Offerman, S E

    2016-08-03

    Polymorphism is the ability of a solid material to exist in more than one phase or crystal structure. Polymorphism may occur in metals, alloys, ceramics, minerals, polymers, and pharmaceutical substances. Unresolved are the conditions for preferential nucleation during polymorphic transformations in which structural relationships or special crystallographic orientation relationships (OR's) form between the nucleus and surrounding matrix grains. We measured in-situ and simultaneously the nucleation rates of grains that have zero, one, two, three and four special OR's with the surrounding parent grains. These experiments show a trend in which the activation energy for nucleation becomes smaller - and therefore nucleation more probable - with increasing number of special OR's. These insights contribute to steering the processing of polymorphic materials with tailored properties, since preferential nucleation affects which crystal structure forms, the average grain size and texture of the material, and thereby - to a large extent - the final properties of the material.

  15. Taenia saginata: differential diagnosis of human taeniasis by polymerase chain reaction-restriction fragment length polymorphism assay.

    PubMed

    Nunes, Cáris Maroni; Dias, Ana Karina Kerche; Dias, Francisca Elda Ferreira; Aoki, Sérgio Moraes; de Paula, Henrique Borges; Lima, Luis Gustavo Ferraz; Garcia, José Fernando

    2005-08-01

    Speciation of Taenia in human stool is important because of their different clinical and epidemiological features. DNA analysis has recently become possible which overcomes the problems of differentiating human taeniid cestodes morphologically. In the present study, we evaluated PCR coupled to restriction fragment length polymorphism to differentiate Taenia solium from Taenia saginata eggs present in fecal samples from naturally infected patients. A different DraI-RFLP pattern: a two-band pattern (421 and 100 bp) for T. saginata and a three-band pattern (234, 188, and 99 bp) for T. solium was observed allowing the two species to be separated. The lower detection limit of the PCR-RFLP using a non-infected fecal sample prepared with a given number of T. saginata eggs was 34 eggs in 2 g stool sediment. The 521 bp mtDNA fragment was detected in 8 out of 12 Taenia sp. carriers (66.6%). Of these, three showed a T. solium pattern and five a T. saginata pattern.

  16. Analyse quantitative des foraminifères benthiques actuels de la marge atiantique marocaine entre Cap Draˆa et Cap Juby: reponses fauniques aux changements de l'environnement

    NASA Astrophysics Data System (ADS)

    Rezqi, H.; Oujidi, M.; Boutakiout, M.; Labraimi, M.

    2000-02-01

    La population des foraminifères benthiques actuels de la marge atlantique marocaine, entre Cap Draˆa et Cap Juby, aétéétudiée dans 58 prélèvements parmi 430 répartis suivant un système de radiales perpendiculaireàla ligne de rivage. Quarante-sept espèces parmi 104 appartenantà58 genres et 28 familles ontétéreconnues. Les abondances absolues de chacune des espèces ontétécomparées dans les différents prélèvements ainsi que les indices biocénotiques (richesse spécifique, abondance, indice de pélagisme, nombre d'espèces benthiques enroulées, nombre d'espèces benthiques costulées) et les paramètres abiotiques (nature de substrat et profondeur). L'analyse factorielle des correspond ances, complétée par la classification hiérarchique et la projection des paramètres biotiques et abiotiques en tant que colonnes supplémentaires ont révéléclue la profondeur est le facteur principal de la distribution des espèces et des prélèvements. En effet, elle oppose les associations d'espèces infralittorales enroulées lisses aux associations d'espècesépibathyales rectilignes ornées, les espèces circalittorales occupent une position intermédiaire. Le facteur secondare correspondàla nature du substrat, oppose les associations d'espèces vasicoles aux associations d'espèces sabulicoles aussi bien celles de l'environnement infralittoral que celles de l'épibathyal.

  17. Crystallization and preliminary X-ray analysis of a monomeric mutant of Azami-Green (mAG), an Aequorea victoria green fluorescent protein-like green-emitting fluorescent protein from the stony coral Galaxea fascicularis.

    PubMed

    Ebisawa, Tatsuki; Yamamura, Akihiro; Kameda, Yasuhiro; Hayakawa, Kou; Nagata, Koji; Tanokura, Masaru

    2009-12-01

    Monomeric Azami-Green (mAG) from the stony coral Galaxea fascicularis is the first monomeric green-emitting fluorescent protein that is not a derivative of Aequorea victoria green fluorescent protein (avGFP). mAG and avGFP are 27% identical in amino-acid sequence. Diffraction-quality crystals of recombinant mAG were obtained by the sitting-drop vapour-diffusion method using PEG 3350 as the precipitant. The mAG crystal diffracted X-rays to 2.20 A resolution on beamline AR-NW12A at the Photon Factory (Tsukuba, Japan). The crystal belonged to space group P1, with unit-cell parameters a = 41.78, b = 51.72, c = 52.89 A, alpha = 90.96, beta = 103.41, gamma = 101.79 degrees. The Matthews coefficient (V(M) = 2.10 A(3) Da(-1)) indicated that the crystal contained two mAG molecules per asymmetric unit.

  18. Crystallization and preliminary X-ray analysis of a monomeric mutant of Azami-Green (mAG), an Aequorea victoria green fluorescent protein-like green-emitting fluorescent protein from the stony coral Galaxea fascicularis

    PubMed Central

    Ebisawa, Tatsuki; Yamamura, Akihiro; Kameda, Yasuhiro; Hayakawa, Kou; Nagata, Koji; Tanokura, Masaru

    2009-01-01

    Monomeric Azami-Green (mAG) from the stony coral Galaxea fascicularis is the first monomeric green-emitting fluorescent protein that is not a derivative of Aequorea victoria green fluorescent protein (avGFP). mAG and avGFP are 27% identical in amino-acid sequence. Diffraction-quality crystals of recombinant mAG were obtained by the sitting-drop vapour-diffusion method using PEG 3350 as the precipitant. The mAG crystal diffracted X-rays to 2.20 Å resolution on beamline AR-NW12A at the Photon Factory (Tsukuba, Japan). The crystal belonged to space group P1, with unit-cell parameters a = 41.78, b = 51.72, c = 52.89 Å, α = 90.96, β = 103.41, γ = 101.79°. The Matthews coefficient (V M = 2.10 Å3 Da−1) indicated that the crystal contained two mAG molecules per asymmetric unit. PMID:20054132

  19. New polymorphous computing fabric.

    SciTech Connect

    Wolinski, C.; Gokhale, M.; McCabe, K. P.

    2002-01-01

    This paper introduces a new polymorphous computing Fabric well suited to DSP and Image Processing and describes its implementation on a Configurable System on a Chip (CSOC). The architecture is highly parameterized and enables customization of the synthesized Fabric to achieve high performance for a specific class of application. For this reason it can be considered to be a generic model for hardware accelerator synthesis from a high level specification. Another important innovation is the Fabric uses a global memory concept, which gives the host processor random access to all the variables and instructions on the Fabric. The Fabric supports different computing models including MIMD, SPMD and systolic flow and permits dynamic reconfiguration. We present a specific implementation of a bank of FIR filters on a Fabric composed of 52 cells on the Altera Excalibur ARM running at 33 MHz. The theoretical performance of this Fabric is 1.8 GMACh. For the FIR application we obtain 1.6 GMAC/s real performance. Some automatic tools have been developed like the tool to provide a host access utility and assembler.

  20. Polymorphous light eruption.

    PubMed

    Hölzle, E; Plewig, G; von Kries, R; Lehmann, P

    1987-03-01

    Polymorphous light eruption (PLE) is a common photodermatosis of unknown etiology. It afflicts mainly fair-skinned patients, with a preponderance of young females. There is, however, no absolute restriction as to age, sex, or race. Clinical variants include the papular, vesiculo-bullous, and hemorrhagic variety, as well as plaque, erythema multiforme-like, and insect bite (strophulus)-like types. Skin lesions appear only in certain exposed areas hours or a few days after intense sunshine, and are nearly always monomorphous in the same patient. The rash subsides spontaneously within several days without leaving scars. The histopathologic picture is characteristic and shows a perivascular lymphocytic infiltrate in the upper and middle corium with subepidermal edema, vacuolization of basal cells, and spongiosis in the lower epidermis. The most important differential diagnoses are solar urticaria, photosensitive erythema multiforme, and lupus erythematosus. The action spectrum of PLE is under debate. Reproduction of skin lesions has been reported with UVB, UVA, and, rarely, visible light, with UVA probably being the most effective part of the spectrum. More important than treatment of PLE is prophylaxis. UVA- and UVB-effective sunscreens are of some help. Phototherapy and especially photochemotherapy (psoralen + UVA; PUVA) offer effective ways to decrease light sensitivity. Systemic treatment with chloroquine or beta-carotene has been disappointing.

  1. [Effect of genetic polymorphisms of microsomal epoxide hydrolase on urinary 1-hydroxypyrene levels in coke oven workers].

    PubMed

    Leng, Shu-Guang; Zheng, Yu-Xin; Huang, Chuan-Feng; Dai, Yu-Fei; Li, Xiao-Hua; Niu, Yong; Pan, Zu-Fei; Li, Tao; He, Feng-Sheng

    2004-08-01

    To investigate the associations of polymorphisms of metabolic enzyme genes with urinary 1-hydroxypyrene levels in coke oven workers. One hundred and forty-eight workers from a coke oven plant and 69 controls without occupational PAHs exposure were selected in this study. Urinary 1-hydroxypyrene was detected by high performance liquid chromatography with florescence detector. The genotypes at I462V site in exon 7 of CYP1A1 gene, GSTM1, GSTT1, I105V site in GSTP1gene, Pst1 and Dra1 sites in CYP2E1 gene, P187S site in NQO1 gene, Kpn1, BamH1 and Taq1 sites in NAT2 gene, and H113Y, R139H sites in mEH gene were determined by PCR-based methods. Personal information including occupational exposure history, age, sex, smoking and drinking status was collected by the questionnaire. The level of urinary 1-hydroxypyrene in coke oven workers [(5.61 +/- 1.04) mol/mol Cr] was higher than that in control [(0.74 +/- 0.32) micro mol/mol Cr]. After adjusting external occupational exposure category and smoking, coke oven workers with variant homozygotes at H113Y site of mEH gene had significantly higher urinary 1-hydroxypyrene concentrations than those with heterozygotes, and wild homozygotes (6.41 +/- 1.09 vs. 6.24 +/- 1.08, and 4.62 +/- 0.95 micro mol/mol Cr, P < 0.05), and gene-gene interaction was found between CYP1A1 and mEH. Genetic polymorphism of mEH gene could be a susceptible biomarker in coke oven workers which was involved in the individual susceptibility on metabolism of PAHs.

  2. [Polymorph transformation of solid drugs].

    PubMed

    Zhang, Qi; Mei, Xue-feng

    2015-05-01

    For the minimized phase transtorming risk, the most stable polymorph is generally considered as the desirable solid form for pharmaceutical applications. However, occasionally, the stable form may have some shortcomings such as low solubility, dissolution rate and bioavailability, etc. In that case, the metastable form which is kinetically stable at room or lower temperature could be selected. Using metastable form may result in polymorph transformation in pharmaceutical manufacture and storage. Hence, the knowledge of the transformation between solid forms is essential to the development of the drug materials. In this paper, we will review the recent studies in the area of crystal conversion of polymorphs and hydrates, to illustrate some cases to introduce the types, conditions and mechanisms of the crystalline solid transformation.

  3. Polymorphic light eruption sine eruption.

    PubMed

    Dover, J S; Hawk, J L

    1988-01-01

    We describe seven patients, four female and three male, who developed intense pruritus on sun-exposed skin without visible change. The clinical features resembled those of polymorphic light eruption (PLE) without rash. Four patients also occasionally developed typical PLE upon sun exposure, but sun-induced pruritus alone occurred most frequently. No patient was taking any drug therapy. One patient developed similar pruritus following solar simulated irradiation, and one following PUVA therapy. All other laboratory investigations were negative. Treatment with low dose UVB phototherapy or PUVA therapy was effective. The condition, which we have called polymorphic light eruption sine eruptione (PLESE), appears to be a variant of PLE not previously reported.

  4. Crystal Polymorphs of Barbital: News about a Classic Polymorphic System

    PubMed Central

    2013-01-01

    Barbital is a hypnotic agent that has been intensely studied for many decades. The aim of this work was to establish a clear and comprehensible picture of its polymorphic system. Four of the six known solid forms of barbital (denoted I0, III, IV, and V) were characterized by various analytical techniques, and the thermodynamic relationships between the polymorph phases were established. The obtained data permitted the construction of the first semischematic energy/temperature diagram for the barbital system. The modifications I0, III, and V are enantiotropically related to one another. Polymorph IV is enantiotropically related to V and monotropically related to the other two forms. The transition points for the pairs I0/III, I0/V, and III/IV lie below 20 °C, and the transition point for IV/V is above 20 °C. At room temperature, the order of thermodynamic stability is I0 > III > V > IV. The metastable modification III is present in commercial samples and has a high kinetic stability. The solid-state NMR spectra provide information on aspects of crystallography (viz., the asymmetric units and the nature of hydrogen bonding). The known correlation between specific N–H···O=C hydrogen bonding motifs of barbiturates and certain IR characteristics was used to predict the H-bonded pattern of polymorph IV. PMID:24283960

  5. Triclinic polymorph of dibenzotetra-thia-fulvalene.

    PubMed

    Mamada, Masashi; Yamashita, Yoshiro

    2009-08-08

    Crystals of the title compound (DBTTF), C(14)H(8)S(4), feature a triclinic polymorph different from two known monoclinic polymorphs. In this form, there are two independent centrosymmetric half-mol-ecules in the asymmetric unit. Although the mol-ecular orientations are relatively similar to one of monoclinic polymorphs, the packing motif is different.

  6. Preferential nucleation during polymorphic transformations

    SciTech Connect

    Sharma, H.; Sietsma, J.; Offerman, S. E.

    2016-08-03

    Polymorphism is the ability of a solid material to exist in more than one phase or crystal structure. Polymorphism may occur in metals, alloys, ceramics, minerals, polymers, and pharmaceutical substances. Unresolved are the conditions for preferential nucleation during polymorphic transformations in which structural relationships or special crystallographic orientation relationships (OR’s) form between the nucleus and surrounding matrix grains. We measured in-situ and simultaneously the nucleation rates of grains that have zero, one, two, three and four special OR’s with the surrounding parent grains. These experiments show a trend in which the activation energy for nucleation becomes smaller – and therefore nucleation more probable - with increasing number of special OR’s. As a result, these insights contribute to steering the processing of polymorphic materials with tailored properties, since preferential nucleation affects which crystal structure forms, the average grain size and texture of the material, and thereby - to a large extent - the final properties of the material.

  7. Preferential nucleation during polymorphic transformations

    DOE PAGES

    Sharma, H.; Sietsma, J.; Offerman, S. E.

    2016-08-03

    Polymorphism is the ability of a solid material to exist in more than one phase or crystal structure. Polymorphism may occur in metals, alloys, ceramics, minerals, polymers, and pharmaceutical substances. Unresolved are the conditions for preferential nucleation during polymorphic transformations in which structural relationships or special crystallographic orientation relationships (OR’s) form between the nucleus and surrounding matrix grains. We measured in-situ and simultaneously the nucleation rates of grains that have zero, one, two, three and four special OR’s with the surrounding parent grains. These experiments show a trend in which the activation energy for nucleation becomes smaller – and thereforemore » nucleation more probable - with increasing number of special OR’s. As a result, these insights contribute to steering the processing of polymorphic materials with tailored properties, since preferential nucleation affects which crystal structure forms, the average grain size and texture of the material, and thereby - to a large extent - the final properties of the material.« less

  8. Polymorphism in regulatory gene sequences

    PubMed Central

    Mitchison, N A

    2001-01-01

    The extensive polymorphism revealed in non-coding gene-regulatory sequences, particularly in the immune system, suggests that this type of genetic variation is functionally and evolutionarily far more important than has been suspected, and provides a lead to new therapeutic strategies. PMID:11178274

  9. Characterization of polymorphic ampicillin forms.

    PubMed

    Baraldi, C; Tinti, A; Ottani, S; Gamberini, M C

    2014-11-01

    In this work polymorphs of α-aminobenzylpenicillin (ampicillin), a β-lactamic antibiotic, were prepared and investigated by several experimental and theoretical methods. Amorphous monohydrate and three crystalline forms, the trihydrate, the crystal form I and the crystal form II, were investigated by FT-IR and micro-Raman. Also data obtained by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray powder diffraction (XRPD) and hot-stage Raman spectroscopy are reported. Finally, quantum mechanical calculations were performed by density functional theory (DFT) to assist the assignment of spectroscopic experimental bands. For the first time, the ampicillin molecule in its zwitterionic form was studied at the B3LYP/aug-cc-pVDZ level and the corresponding theoretical vibrational spectra were computed. In fact, ampicillin in the crystal is in zwitterionic form and concentrations of this same form are quite relevant in solutions at physiological pH. Experimental and theoretical results allowed identification of specific features for polymorph characterization. Bands typical of the different polymorphs are identified both in IR and Raman spectra: in particular in the NH stretching region (IR), in the amide I+δNH region (both techniques), in the 1520-1490cm(-1) region (IR), in the 1320-1300cm(-1) and 1280-1220cm(-1) (IR), in the 1200-1170cm(-1) (Raman), in the amide V region (IR), and, finally, in the 715-640cm(-1) and 220-200cm(-1) (Raman). Interconversion among different polymorphs was investigated by hot-stage Raman spectroscopy and thermal analysis, clarifying the complex pattern of transformations undergone as a function of temperature and heating rate. In particular, DSC scans show how the trihydrate crystals transform into anhydrous forms on heating. Finally, stability tests demonstrated, after a two years period, that no transformation or degradation of the polymorphs occurred. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Analysis of the bacterial diversity existing on animal hide and wool: development of a preliminary PCR-restriction fragment length polymorphism fingerprint database for identifying isolates.

    PubMed

    Chen, Yu; Gao, Hongwei; Zhang, Yanming; Deng, Mingjun; Wu, Zhenxing; Zhu, Laihua; Duan, Qing; Xu, Biao; Liang, Chengzhu; Yue, Zhiqin; Xiao, Xizhi

    2012-01-01

    Twenty-one bacterial strains were isolated from imported cattle hide and rabbit wool using two types of media, nutrient broth, and nutrient broth with serum. The bacteria identified were Brevibacillus laterosporus, Leclercia adecarboxylata, Peptococcus niger, Bacillus circulans, Raoultella ornithinolytica, Bacillus subtilis, Bacillus cereus, Bacillus thermobacillus, Bacillus choshinensis, Bacillus sphaericus, Acinetobacter haemolyticus, Sphingomonas paucimobilis, Bacillus thuringiensis, Staphylococcus intermedius, Mycobacteria, Moraxella, Klebsiella pneumoniae, Ralstonia pickettii, Staphylococcus chromogenes, Comamonas testosteroni, and Cupriavidus pauculus. The 16s rDNA gene of each bacterium was amplified using the universal primers 27f and 1492r. The amplicons were digested with AvaI, BamHI, BgII, DraI, EcoRI, EcoRV, HindIII, HinfI, HpaI, PstI, SmaI, TaqII, XbaI, XmaI, AluI, XhoI, and PvuI individually. A specific fingerprint from the PCR-restriction fragment length polymorphism method based on 16s rDNA was obtained for each bacterium. The results showed that the method developed was useful not only for bacterial identification but also for the etiological investigation of pathogens in imported animal hair and wool.

  11. Development of species-specific PCR and PCR-restriction fragment length polymorphism assays for L.infantum/L.donovani discrimination.

    PubMed

    Oshaghi, Mohammad A; Ravasan, Naseh Maleki; Hide, Mallorie; Javadian, Ezat-Aldin; Rassi, Yavar; Sedaghat, Mohammad M; Mohebali, Mehdi; Hajjaran, Homa

    2009-05-01

    Discrimination of Leishmania infantum and L. donovani, the members of the L. (L.) donovani complex, is important for diagnosis and epidemiological studies of visceral leishmaniasis (VL). We have developed two molecular tools including a restriction fragment length polymorphisms of amplified DNA (PCR-RFLP) and a PCR that are capable to discriminate L. donovani from L. infantum. Typing of the complex was performed by a simple PCR of cysteine protease B (cpb) gene followed by digestion with DraIII. The enzyme cuts the 741-bp amplicon of L. donovani into 400 and 341 bp fragments whereas the 702 bp of L. infantum remains intact. The designed PCR species-specific primer pair is specific for L. donovani and is capable of amplifying a 317 bp of 3' end of cpb gene of L. donovani whereas it does not generate an amplicon for L. infantum. The species-specific primers and the restriction enzyme were designed based on a 39 bp insertion/deletion (indel) in the middle of the cpb gene. Both assays could differentiate correctly the two species and are reliable and high-throughput alternatives for molecular diagnosis and epidemiological studies of VL in various foci.

  12. Identification of Cryptosporidium spp. Oocysts in United Kingdom Noncarbonated Natural Mineral Waters and Drinking Waters by Using a Modified Nested PCR-Restriction Fragment Length Polymorphism Assay

    PubMed Central

    Nichols, R. A. B.; Campbell, B. M.; Smith, H. V.

    2003-01-01

    We describe a nested PCR-restriction fragment length polymorphism (RFLP) method for detecting low densities of Cryptosporidium spp. oocysts in natural mineral waters and drinking waters. Oocysts were recovered from seeded 1-liter volumes of mineral water by filtration through polycarbonate membranes and from drinking waters by filtration, immunomagnetizable separation, and filter entrapment, followed by direct extraction of DNA. The DNA was released from polycarbonate filter-entrapped oocysts by disruption in lysis buffer by using 15 cycles of freeze-thawing (1 min in liquid nitrogen and 1 min at 65°C), followed by proteinase K digestion. Amplicons were readily detected from two to five intact oocysts on ethidium bromide-stained gels. DNA extracted from Cryptosporidium parvum oocysts, C. muris (RN 66), C. baileyi (Belgium strain, LB 19), human-derived C. meleagridis, C. felis (DNA from oocysts isolated from a cat), and C. andersoni was used to demonstrate species identity by PCR-RFLP after simultaneous digestion with the restriction enzymes DraI and VspI. Discrimination between C. andersoni and C. muris isolates was confirmed by a separate, subsequent digestion with DdeI. Of 14 drinking water samples tested, 12 were found to be positive by microscopy, 8 were found to be positive by direct PCR, and 14 were found to be positive by using a nested PCR. The Cryptosporidium species detected in these finished water samples was C. parvum genotype 1. This method consistently and routinely detected >5 oocysts per sample. PMID:12839797

  13. Superhard monoclinic polymorph of carbon.

    PubMed

    Li, Quan; Ma, Yanming; Oganov, Artem R; Wang, Hongbo; Wang, Hui; Xu, Ying; Cui, Tian; Mao, Ho-Kwang; Zou, Guangtian

    2009-05-01

    We report a novel phase of carbon possessing a monoclinic C2/m structure (8 atoms/cell) identified using an ab initio evolutionary structural search. This polymorph, which we call M-carbon, is related to the (2x1) reconstruction of the (111) surface of diamond and can also be viewed as a distorted (through sliding and buckling of the sheets) form of graphite. It is stable over cold-compressed graphite above 13.4 GPa. The simulated x-ray diffraction pattern and near K-edge spectroscopy are in satisfactory agreement with the experimental data [W. L. Mao, Science 302, 425 (2003)10.1126/science.1089713] on overcompressed graphite. The hardness and bulk modulus of this new carbon polymorph are calculated to be 83.1 and 431.2 GPa, respectively, which are comparable to those of diamond.

  14. Superhard Monoclinic Polymorph of Carbon

    SciTech Connect

    Li, Quan; Ma, Yanming; Oganov, Artem R.; Wang, Hongbo; Wang, Hui; Xu, Ying; Cui, Tian; Mao, Ho-Kwang; Zou, Guangtian; Jilin; SBU; CIW

    2009-05-08

    We report a novel phase of carbon possessing a monoclinic C2/m structure (8 atoms/cell) identified using an ab initio evolutionary structural search. This polymorph, which we call M-carbon, is related to the (2x1) reconstruction of the (111) surface of diamond and can also be viewed as a distorted (through sliding and buckling of the sheets) form of graphite. It is stable over cold-compressed graphite above 13.4 GPa. The simulated x-ray diffraction pattern and near K-edge spectroscopy are in satisfactory agreement with the experimental data [W.L. Mao et al., Science 302, 425 (2003)] on overcompressed graphite. The hardness and bulk modulus of this new carbon polymorph are calculated to be 83.1 and 431.2 GPa, respectively, which are comparable to those of diamond.

  15. IPD: the Immuno Polymorphism Database.

    PubMed

    Robinson, James; Marsh, Steven G E

    2007-01-01

    The Immuno Polymorphism Database (IPD) (http://www.ebi.ac.uk/ipd/) is a set of specialist databases related to the study of polymorphic genes in the immune system. IPD currently consists of four databases: IPD-KIR, contains the allelic sequences of killer cell immunoglobulin-like receptors (KIRs); IPD-MHC, a database of sequences of the major histocompatibility complex (MHC) of different species; IPD-HPA, alloantigens expressed only on platelets; and IPD-ESTAB, which provides access to the European Searchable Tumour Cell Line Database, a cell bank of immunologically characterized melanoma cell lines. The IPD project works with specialist groups or nomenclature committees who provide and curate individual sections before they are submitted to IPD for online publication. The IPD project stores all the data in a set of related databases. Those sections with similar data, such as IPD-KIR and IPD-MHC, share the same database structure.

  16. Lipid Polymorphisms and Membrane Shape

    PubMed Central

    Frolov, Vadim A.; Shnyrova, Anna V.; Zimmerberg, Joshua

    2011-01-01

    Morphological plasticity of biological membrane is critical for cellular life, as cells need to quickly rearrange their membranes. Yet, these rearrangements are constrained in two ways. First, membrane transformations may not lead to undesirable mixing of, or leakage from, the participating cellular compartments. Second, membrane systems should be metastable at large length scales, ensuring the correct function of the particular organelle and its turnover during cellular division. Lipids, through their ability to exist with many shapes (polymorphism), provide an adequate construction material for cellular membranes. They can self-assemble into shells that are very flexible, albeit hardly stretchable, which allows for their far-reaching morphological and topological behaviors. In this article, we will discuss the importance of lipid polymorphisms in the shaping of membranes and its role in controlling cellular membrane morphology. PMID:21646378

  17. The Single Nucleotide Polymorphism Consortium

    NASA Technical Reports Server (NTRS)

    Morgan, Michael

    2003-01-01

    I want to discuss both the Single Nucleotide Polymorphism (SNP) Consortium and the Human Genome Project. I am afraid most of my presentation will be thin on law and possibly too high on rhetoric. Having been engaged in a personal and direct way with these issues as a trained scientist, I find it quite difficult to be always as objective as I ought to be.

  18. Explicit Polymorphism and CPS Conversion,

    DTIC Science & Technology

    1992-10-01

    programming language design , the concepts of polymorphism [14, 28, 39] and continuation-passing [38, 41, 43] are of particular interest. The use of...Principles of Programming Languages, January 1991. [9] Matthias Felleisen . The Calculi of X.-CS Conversion: A Syntactic Theory of Control and State in...Imperative Higher-Order Programming Languages. PhD thesis, Indiana University, Bloomington, IN, 1987. 18 [10] Matthias Felleisen and Daniel Friedman

  19. Chemical substitution in silica polymorph

    NASA Technical Reports Server (NTRS)

    Smith, J. V.; Steele, I. M.

    1984-01-01

    Ion and electron probe analyses are presented for trace elements (Al, Na, K, Li, Ti) in quartz, tridymite, cristobalite and melanophlogite. Quartz and melanophlogite show low levels of trace elements relative to tridymite and cristobalite. The previously determined alpha-beta inversion temperature decreases as the Al content of quartz increases. For all silica polymorphs, Al is greater than or equal to Na + K + Li on an atom basis, with the excess Al probably balanced by H.

  20. The Single Nucleotide Polymorphism Consortium

    NASA Technical Reports Server (NTRS)

    Morgan, Michael

    2003-01-01

    I want to discuss both the Single Nucleotide Polymorphism (SNP) Consortium and the Human Genome Project. I am afraid most of my presentation will be thin on law and possibly too high on rhetoric. Having been engaged in a personal and direct way with these issues as a trained scientist, I find it quite difficult to be always as objective as I ought to be.

  1. Electrostatic control of phospholipid polymorphism.

    PubMed

    Tarahovsky, Y S; Arsenault, A L; MacDonald, R C; McIntosh, T J; Epand, R M

    2000-12-01

    A regular progression of polymorphic phase behavior was observed for mixtures of the anionic phospholipid, cardiolipin, and the cationic phospholipid derivative, 1, 2-dioleoyl-sn-glycero-3-ethylphosphocholine. As revealed by freeze-fracture electron microscopy and small-angle x-ray diffraction, whereas the two lipids separately assume only lamellar phases, their mixtures exhibit a symmetrical (depending on charge ratio and not polarity) sequence of nonlamellar phases. The inverted hexagonal phase, H(II,) formed from equimolar mixtures of the two lipids, i.e., at net charge neutrality (charge ratio (CR((+/-))) = 1:1). When one type of lipid was in significant excess (CR((+/-)) = 2:1 or CR((+/-)) = 1:2), a bicontinuous cubic structure was observed. These cubic phases were very similar to those sometimes present in cellular organelles that contain cardiolipin. Increasing the excess of cationic or anionic charge to CR((+/-)) = 4:1 or CR((+/-)) = 1:4 led to the appearance of membrane bilayers with numerous interlamellar contacts, i.e., sponge structures. It is evident that interactions between cationic and anionic moieties can influence the packing of polar heads and hence control polymorphic phase transitions. The facile isothermal, polymorphic interconversion of these lipids may have important biological and technical implications.

  2. Chromosomal polymorphism in mammals: an evolutionary perspective.

    PubMed

    Dobigny, Gauthier; Britton-Davidian, Janice; Robinson, Terence J

    2017-02-01

    Although chromosome rearrangements (CRs) are central to studies of genome evolution, our understanding of the evolutionary consequences of the early stages of karyotypic differentiation (i.e. polymorphism), especially the non-meiotic impacts, is surprisingly limited. We review the available data on chromosomal polymorphisms in mammals so as to identify taxa that hold promise for developing a more comprehensive understanding of chromosomal change. In doing so, we address several key questions: (i) to what extent are mammalian karyotypes polymorphic, and what types of rearrangements are principally involved? (ii) Are some mammalian lineages more prone to chromosomal polymorphism than others? More specifically, do (karyotypically) polymorphic mammalian species belong to lineages that are also characterized by past, extensive karyotype repatterning? (iii) How long can chromosomal polymorphisms persist in mammals? We discuss the evolutionary implications of these questions and propose several research avenues that may shed light on the role of chromosome change in the diversification of mammalian populations and species.

  3. Temporal Expression of Peripheral Blood Leukocyte Biomarkers in a Macaca fascicularis Infection Model of Tuberculosis; Comparison with Human Datasets and Analysis with Parametric/Non-parametric Tools for Improved Diagnostic Biomarker Identification

    PubMed Central

    Wareham, Alice; Lewandowski, Kuiama S.; Williams, Ann; Dennis, Michael J.; Sharpe, Sally; Vipond, Richard; Silman, Nigel; Ball, Graham

    2016-01-01

    A temporal study of gene expression in peripheral blood leukocytes (PBLs) from a Mycobacterium tuberculosis primary, pulmonary challenge model Macaca fascicularis has been conducted. PBL samples were taken prior to challenge and at one, two, four and six weeks post-challenge and labelled, purified RNAs hybridised to Operon Human Genome AROS V4.0 slides. Data analyses revealed a large number of differentially regulated gene entities, which exhibited temporal profiles of expression across the time course study. Further data refinements identified groups of key markers showing group-specific expression patterns, with a substantial reprogramming event evident at the four to six week interval. Selected statistically-significant gene entities from this study and other immune and apoptotic markers were validated using qPCR, which confirmed many of the results obtained using microarray hybridisation. These showed evidence of a step-change in gene expression from an ‘early’ FOS-associated response, to a ‘late’ predominantly type I interferon-driven response, with coincident reduction of expression of other markers. Loss of T-cell-associate marker expression was observed in responsive animals, with concordant elevation of markers which may be associated with a myeloid suppressor cell phenotype e.g. CD163. The animals in the study were of different lineages and these Chinese and Mauritian cynomolgous macaque lines showed clear evidence of differing susceptibilities to Tuberculosis challenge. We determined a number of key differences in response profiles between the groups, particularly in expression of T-cell and apoptotic makers, amongst others. These have provided interesting insights into innate susceptibility related to different host `phenotypes. Using a combination of parametric and non-parametric artificial neural network analyses we have identified key genes and regulatory pathways which may be important in early and adaptive responses to TB. Using comparisons

  4. Polymorphism and tautomeric preference in fenobam and the utility of NLO response to detect polymorphic impurities.

    PubMed

    Thomas, Sajesh P; Nagarajan, K; Row, T N Guru

    2012-11-04

    Crystal structures of polymorphs and solvatomorphs of the potential anxiolytic drug fenobam exhibit an exclusive preference for one of the two possible tautomeric structures. A novel methodology based on nonlinear optical response has been successfully employed to detect the presence of a polymorphic impurity in a mixture of polymorphs.

  5. Parasitic polymorphism of Coccidioides spp

    PubMed Central

    2014-01-01

    Background Coccidioides spp. is the ethiological agent of coccidioidomycosis, an infection that can be fatal. Its diagnosis is complicated, due to that it shares clinical and histopathological characteristics with other pulmonary mycoses. Coccidioides spp. is a dimorphic fungus and, in its saprobic phase, grows as a mycelium, forming a large amount of arthroconidia. In susceptible persons, arthroconidia induce dimorphic changes into spherules/endospores, a typical parasitic form of Coccidioides spp. In addition, the diversity of mycelial parasitic forms has been observed in clinical specimens; they are scarcely known and produce errors in diagnosis. Methods We presented a retrospective study of images from specimens of smears with 15% potassium hydroxide, cytology, and tissue biopsies of a histopathologic collection from patients with coccidioidomycosis seen at a tertiary-care hospital in Mexico City. Results The parasitic polymorphism of Coccidioides spp. observed in the clinical specimens was as follows: i) spherules/endospores in different maturation stages; ii) pleomorphic cells (septate hyphae, hyphae composed of ovoid and spherical cells, and arthroconidia), and iii) fungal ball formation (mycelia with septate hyphae and arthroconidia). Conclusions The parasitic polymorphism of Coccidioides spp. includes the following: spherules/endospores, arthroconidia, and different forms of mycelia. This knowledge is important for the accurate diagnosis of coccidioidomycosis. In earlier studies, we proposed the integration of this diversity of forms in the Coccidioides spp. parasitic cycle. The microhabitat surrounding the fungus into the host would favor the parasitic polymorphism of this fungus, and this environment may assist in the evolution toward parasitism of Coccidioides spp. PMID:24750998

  6. Calcium acamprosate: a triclinic polymorph.

    PubMed

    Maccaroni, Elisabetta; Panzeri, Walter; Malpezzi, Luciana

    2011-12-01

    The title compound, poly[bis-(μ(3)-4-acetamido-propane-sulfon-ato)-calcium], [Ca(C(5)H(10)NO(4)S)(2)](n), is a triclinic polymorph of the previously reported monoclinic structure [Toffoli et al. (1988 ▶). Acta Cryst. C44, 1493-1494]. The triclinic modification was found to have an all-trans configuration of the acetamido-propane chain, in contrast with the monoclinic polymorph which shows an angle of 74.66 (8)° between the S-C-C-C chain plane and that of the amide group. The Ca(2+) cation is situated on an inversion centre and is hexa-coordinated by six O atoms belonging to different anions in a distorted octa-hedral geometry. This arrangement leads to a layered structure parallel to (011). The layers are held together by N-H⋯O hydrogen bonds and by short C-H⋯O inter-actions, both involving the sulfonate O atoms not coordinated to the Ca(2+) cations. The structure was determined from a crystal twinned by non-merohedry [twin law ([Formula: see text]00, 0[Formula: see text]0, -0.335 -0.85 1), with a fractional contribution of the minor twin domain of 46.7 (1)%].

  7. Spinning up the polymorphs of calcium carbonate

    PubMed Central

    Boulos, Ramiz A.; Zhang, Fei; Tjandra, Edwin S.; Martin, Adam D.; Spagnoli, Dino; Raston, Colin L.

    2014-01-01

    Controlling the growth of the polymorphs of calcium carbonate is important in understanding the changing environmental conditions in the oceans. Aragonite is the main polymorph in the inner shells of marine organisms, and can be readily converted to calcite, which is the most stable polymorph of calcium carbonate. Both of these polymorphs are significantly more stable than vaterite, which is the other naturally occurring polymorph of calcium carbonate, and this is reflected in its limited distribution in nature. We have investigated the effect of high shear forces on the phase behaviour of calcium carbonate using a vortex fluidic device (VFD), with experimental parameters varied to explore calcium carbonate mineralisation. Variation of tilt angle, rotation speed and temperature allow for control over the size, shape and phase of the resulting calcium carbonate. PMID:24448077

  8. Investigation of the riddle of sulfathiazole polymorphism.

    PubMed

    Abu Bakar, Mohd R; Nagy, Zoltan K; Rielly, Chris D; Dann, Sandy E

    2011-07-29

    Since the discovery of sulfathiazole as an antimicrobial agent in 1939, numerous works in the screening for its different polymorphic forms, which is an essential part of drug development, have been conducted and published. These works consequently result in the availability of various methods for generating a particular polymorph. By following these methods, however, one cannot be guaranteed to obtain the intended pure polymorph because most of the methods do not clearly and adequately describe the crystallisation conditions, such as cooling rates and initial solute concentrations. In this paper, the available methods for generating all the known polymorphs of sulfathiazole are reviewed and selected methods for generating certain polymorphs, performed with their processes monitored using process analytical technology tools, i.e. focussed beam reflectance measurement and attenuated total reflectance ultraviolet spectroscopy, are presented. The properties of the obtained crystals, examined using various characterisation methods, are also presented and whenever possible, are compared with those of other workers.

  9. Lactose: a definitive guide to polymorph determination.

    PubMed

    Kirk, J H; Dann, S E; Blatchford, C G

    2007-04-04

    Lactose is a well-known molecule capable of forming a number of different polymorphs with varied chemical and physical properties. To date, no definitive guide for distinguishing between polymorphs using simple analytical techniques has been available. The information presented in this article aims to provide a conclusive guide for identifying the polymorphs of lactose and to successfully unravel years of contradictory research. Data have been collected on single phase polymorphs, prepared from an identical source, adopting the use of in situ and ex situ powder X-ray diffraction, CCD-Raman, FT-IR and (13)C-(1)H cross-polarisation magic angle spinning NMR (CP-MASNMR) spectroscopy, in order to provide simple methods to discriminate between the polymorphs.

  10. The "polymorphous" history of a polymorphous skull bone: the sphenoid.

    PubMed

    Costea, Claudia; Turliuc, Serban; Cucu, Andrei; Dumitrescu, Gabriela; Carauleanu, Alexandru; Buzduga, Catalin; Sava, Anca; Costache, Irina; Turliuc, Dana

    2017-03-27

    For a long time, because of its location at the skull base level, the sphenoid bone was rather mysterious as it was too difficult for anatomists to reach and to elucidate its true configuration. The configuration of the sphenoid bone led to confusion regarding its sutures with the other skull bones, its shape, its detailed anatomy, and the vascular and nervous structures that cross it. This article takes the reader on a journey through time and space, charting the evolution of anatomists' comprehension of sphenoid bone morphology from antiquity to its conception as a bone structure in the eighteenth century, and ranging from ancient Greece to modern Italy and France. The journey illustrates that many anatomists have attempted to name and to best describe the structural elements of this polymorphous bone.

  11. Genetic Polymorphisms and Peritoneal Membrane Function

    PubMed Central

    Siddique, Imad; Brimble, K. Scott; Walkin, Louise; Summers, Angela; Brenchley, Paul; Herrick, Sarah; Margetts, Peter J.

    2015-01-01

    ♦ Background: Outcomes for peritoneal dialysis (PD) patients are affected by the characteristics of the peritoneal membrane, which may be determined by genetic variants. We carried out a systematic review of the literature to identify studies which assessed the association between genetic polymorphisms, peritoneal membrane solute transport, and clinical outcomes for PD patients. ♦ Methods: The National Library of Medicine was searched using a variety of strategies. Studies which met our inclusion criteria were reviewed and data abstracted. Our outcomes of interest included: high transport status peritoneal membrane, risk for peritonitis, encapsulating peritoneal sclerosis (EPS), patient and technique survival. We combined data from studies which evaluated the same genetic polymorphism and the same outcome. ♦ Results: We evaluated 18 relevant studies. All studies used a candidate gene approach. Gene polymorphisms in the interleukin (IL)-6 gene were associated with peritoneal membrane solute transport in several studies in different ethnic populations. Associations with solute transport and polymorphisms in endothelial nitric oxide synthase and receptor for advanced glycation end product genes were also identified. There was evidence of a genetic predisposition for peritonitis found in 2 studies, and for EPS in 1 study. Survival was found to be associated with a polymorphism in vascular endothelial growth factor and technique failure was associated with a polymorphism in the IL-1 receptor antagonist. ♦ Conclusions: There is evidence that characteristics of the peritoneal membrane and clinical outcomes for PD patients have genetic determinants. The most consistent association was between IL-6 gene polymorphisms and peritoneal membrane solute transport. PMID:25395500

  12. Vibrational study of tamoxifen citrate polymorphism

    NASA Astrophysics Data System (ADS)

    Gamberini, M. C.; Baraldi, C.; Tinti, A.; Palazzoli, F.; Ferioli, V.

    2007-09-01

    The trans isomer of ( Z)-2-[ p-(1,2-diphenyl-butenyl)phenoxy]- N, N-dimethyletylamine (tamoxifen) is well known for its endocrine activity as an antiestrogenic agent. Its citrate salt, a widely used pharmaceutical agent, appears in three main polymorphic forms, two of which are well known (I and II) and another form not yet well evidenced. A vibrational study has been conducted for identifying the two known polymorphic forms of tamoxifen citrate (I and II) and for characterising the other form (form III) examined in this study. Other techniques for the characterization of the different polymorphs, such as XRDP, have been used.

  13. Rivastigmine hydrogen tartrate polymorphs: Solid-state characterisation of transition and polymorphic conversion via milling

    NASA Astrophysics Data System (ADS)

    Amaro, Maria Inês; Simon, Alice; Cabral, Lúcio Mendes; de Sousa, Valéria Pereira; Healy, Anne Marie

    2015-11-01

    Rivastigmine (RHT) is an active pharmaceutical ingredient that is used for the treatment of mild to moderately severe dementia in Alzheimer's disease, and is known to present two polymorphic forms and to amorphise upon granulation. To date there is no information in the scientific or patent literature on polymorphic transition and stability. Hence, the aim of the current study was to gain a fundamental understanding of the polymorphic forms by (1) evaluating RHT thermodynamic stability (monotropy or enantiotropy) and (2) investigating the potential for polymorphic transformation upon milling. The two polymorphic and amorphous forms were characterised using X-ray powder diffractometry, thermal analyses, infra-red spectroscopy and water sorption analysis. The polymorphic transition was found to be spontaneous (ΔG0 < 0) and exothermic (ΔH0 < 0), indicative of a monotropic polymorph pair. The kinetic studies showed a fast initial polymorphic transition characterised by a heterogeneous nucleation, followed by a slow crystal growth. Ball milling can be used to promote the polymorphic transition and for the production of RHT amorphous form.

  14. Purification of polymorphic components of complex genomes

    DOEpatents

    Stodolsky, M.

    1988-01-21

    A method for processing related subject and reference macromolecule composed of complementary strand into their respective subject and reference populations of representative fragments and effectuating purification of unique polymorphic subject fragments. 1 fig.

  15. Purification of polymorphic components of complex genomes

    DOEpatents

    Stodolsky, M.

    1991-07-16

    A method is disclosed for processing related subject and reference macromolecule populations composed of complementary strands into their respective subject and reference populations of representative fragments and effectuating purification of unique polymorphic subject fragments. 1 figure.

  16. Purification of polymorphic components of complex genomes

    DOEpatents

    Stodolsky, Marvin

    1991-01-01

    A method is disclosed for processing related subject and reference macromolecule populations composed of complementary strands into their respective subject and reference populations of representative fragments and effectuating purification of unique polymorphic subject fragments.

  17. Polymorph Discrimination using Low Wavenumber Raman Spectroscopy

    PubMed Central

    Roy, Saikat; Chamberlin, Brianna; Matzger, Adam J.

    2016-01-01

    Characterization of crystalline polymorphs and their quantitation has become an integral part of the pre-clinical drug development process. Raman spectroscopy is a powerful technique for the rapid identification of phases of pharmaceuticals. In the present work we demonstrate the use of low wavenumber Raman vibrational spectroscopy (including phonon measurement) for discrimination among polymorphs. A total of 10 polymorphic pharmaceuticals were employed to conduct a critical assessment. Raman scattering in the low frequency region (10–400 cm−1), which includes crystal lattice vibrations, has been analyzed and the results indicate lattice phonon Raman scattering can be used for rapid discrimination of polymorphic phases with additional discriminating power compared to conventional collection strategies. Moreover structural insight and conformational changes can be detected with this approach. PMID:27642248

  18. Gene polymorphisms and chronic obstructive pulmonary disease.

    PubMed

    Wu, Xiaodan; Yuan, Bowei; López, Elena; Bai, Chunxue; Wang, Xiangdong

    2014-01-01

    The genetic component was suggested to contribute to the development of chronic obstructive pulmonary disease (COPD), a major and growing public health burden. The present review aims to characterize the evidence that gene polymorphisms contribute to the aetiology of COPD and related traits, and explore the potential relationship between certain gene polymorphisms and COPD susceptibility, severity, lung function, phenotypes, or drug effects, even though limited results from related studies lacked consistency. Most of these studies were association studies, rather than confirmatory studies. More large-sized and strictly controlled studies are needed to prove the relationship between gene polymorphisms and the reviewed traits. More importantly, prospective confirmatory studies beyond initial association studies will be necessary to evaluate true relationships between gene polymorphisms and COPD and help individualized treatment for patients with COPD.

  19. Polymorphism Control of Poly(vinylidene fluoride)

    NASA Astrophysics Data System (ADS)

    Zheng, Jianfen; He, Aihua; Li, Junxing; Han, Charles C.

    2008-03-01

    Poly(vinylidene fluoride) (PVDF) is well-known for its polymorphism, and can exhibit five different polymorphs depending on its processing conditions. The α-phase is the most common and stable polymorph and the β-phase is the most important one due to its piezoelectric and pyroelectric properties. Polymorphism control of PVDF has been realized through electrospinning. PVDF fibrous membranes with fiber diameter in the range of 100 nm to several micrometers were produced by electrospinning and the crystal phase of electrospun PVDF fibers can be adjusted at the same time. Through the control of electrospinning parameters such as the solvent and electrospinning temperature, PVDF fibrous membranes containing mainly α- or β- or γ-phase could be fabricated successfully.

  20. Tetrazolium Oxidase Polymorphism in Rainbow Trout

    PubMed Central

    Cederbaum, Stephen D.; Yoshida, Akira

    1972-01-01

    Tetrazolium oxidase from the blood and liver of rainbow trout was found to be genetically polymorphic. The inheritance pattern of the liver enzyme was compatible only with a one locus-two allele hypothesis. The enzymes in the blood while having an electrophoretically identical polymorphism could differ genotypically from that of the liver in a given fish. The significance of these findings to the understanding of the evolution of the salmonid genome is discussed. PMID:4675090

  1. DNA polymorphism identity determination using flow cytometry

    DOEpatents

    Nolan, John P.; White, P. Scott; Cai, Hong

    2001-01-01

    DNA polymorphism identity determination using flow cytometry. Primers designed to be immobilized on microspheres are allowed to anneal to the DNA strand under investigation, and are extended by either DNA polymerase using fluorescent dideoxynucleotides or ligated by DNA ligase to fluorescent reporter oligonucleotides. The fluorescence of either the dideoxynucleotide or the reporter oligonucleotide attached to the immobilized primer is measured by flow cytometry, thereby identifying the nucleotide polymorphism on the DNA strand.

  2. Impact polymorphs of quartz: experiments and modelling

    NASA Astrophysics Data System (ADS)

    Price, M. C.; Dutta, R.; Burchell, M. J.; Cole, M. J.

    2013-09-01

    We have used the light gas gun at the University of Kent to perform a series of impact experiments firing quartz projectiles onto metal, quartz and sapphire targets. The aim is to quantify the amount of any high pressure quartz polymorphs produced, and use these data to develop our hydrocode modelling to enable the predict ion of the quantity of polymorphs produced during a planetary scale impact.

  3. Polymorphic crystals selected in the nucleation stage

    NASA Astrophysics Data System (ADS)

    Zhang, Hui-Jun; Peng, Shu-Ming; Zhou, Xiao-Song; Ju, Xin

    2014-08-01

    Molecular dynamics simulations are used to explore the atomic mechanism of formation of polymorphic crystals. Cooling the Lennard-Jones systems, we observe that the system almost always evolves into a polymorphic crystal with either fivefold-symmetric stacking faults or single-direction stacking faults. The detailed analysis reveals that such an evolution depends on the configuration of fcc/hcp concomitance in the nucleation stage. A defect-induced model is then introduced to illustrate these two evolution routes. Through calculating the formation energies of the defective critical nuclei, we find that the polymorphic crystals seem to be determined by their critical nuclei, in which the relatively lower formation energy ensures the preponderance of the fivefold-symmetric cluster. Before the nucleation, we observe that thermal fluctuations prefer hcp-like particles over fcc-like ones while in the nucleation and growth stage this preference reverses. Notably, an extended step rule of Ostwald is seemingly suitable to characterise the growth process because of the temporary hcp layers appearing among fcc layers in the growth stage. Although the crystalline cluster with single-direction stacking faults has higher growth rate and structural order than its competitor, the component (fcc and hcp) proportion of the final crystals is almost always constant regardless of the polymorphic type. Our finding renews the understanding of the polymorphism of crystals, and possibly draws more attention of people intending to control the polymorphic structures through nucleation.

  4. Neotame anhydrate polymorphs I: preparation and characterization.

    PubMed

    Doug, Zedong; Padden, Brian E; Salsbury, Jonathon S; Munson, Eric J; Schroeder, Steve A; Prakash, Indra; Grant, David J W

    2002-03-01

    To prepare, characterize, and compare polymorphs of neotame anhydrate. Neotame anhydrate polymorphs were prepared from amorphous or crystalline anhydrate by crystallization or suspension in various organic solvents, or by dehydration of neotame monohydrate. The following techniques were used for characterization: differential scanning calorimetry, thermogravimetry, hot-stage microscopy, powder X-ray diffractometry (PXRD), 13C solid-state nuclear magnetic resonance (SSNMR) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy, dynamic water vapor sorption/desorption, and density measurements. Seven polymorphs (Forms A-G) of neotame anhydrate were prepared and show different thermal properties and PXRD patterns. Two enantiotropically related pairs were identified: B and C; E and A. 13C SSNMR and FTIR spectroscopy clearly distinguish between Forms A, D, F, and G, which show similar needle-shaped morphology but distinct differences in dynamic water vapor sorption/desorption and density. The 13C SSNMR chemical shifts suggest conformational polymorphism. The stability in the presence of water vapor follows the rank order, G > A > D approximately = F, which resembles the rank orders of the molar volume and of the polarity of the solvents from which they crystallized. The neotame anhydrate polymorphs appear to show different molecular conformations. The less dense polymorphic structures crystallize from solvents of greater polarity and sorb water vapor less rapidly and less completely. Two enantiotropic pairs were discerned.

  5. Extended Polymorphism of Two-Dimensional Material.

    PubMed

    Yoshida, Masaro; Ye, Jianting; Zhang, Yijin; Imai, Yasuhiko; Kimura, Shigeru; Fujiwara, Akihiko; Nishizaki, Terukazu; Kobayashi, Norio; Nakano, Masaki; Iwasa, Yoshihiro

    2017-09-13

    When controlling electronic properties of bulk materials, we usually assume that the basic crystal structure is fixed. However, in two-dimensional (2D) materials, atomic structure or polymorph is attracting growing interest as a controlling parameter to functionalize their properties. Various polymorphs can exist in transition metal dichalcogenides (TMDCs) from which 2D materials are generated, and polymorphism has drastic impacts on the electronic states. Here we report the discovery of an unprecedented polymorph of a TMDC 2D material. By mechanical exfoliation, we made thin flakes from a single crystal of 2Ha-type tantalum disulfide (TaS2), a metallic TMDC with a charge-density-wave (CDW) phase. Microbeam X-ray diffraction measurements and electrical transport measurements indicate that thin flakes possess a polymorph different from any one known in TaS2 bulk crystals. Moreover, the flakes with the unique polymorph displayed the dramatically enhanced CDW ordering temperature. The present results suggest the potential existence of diverse structural and electronic phases accessible only in 2D materials.

  6. Sequence polymorphism and evolution of three cetacean MHC genes.

    PubMed

    Xu, Shi Xia; Ren, Wen Hua; Li, Shu Zhen; Wei, Fu Wen; Zhou, Kai Ya; Yang, Guang

    2009-09-01

    Sequence variability at three major histocompatibility complex (MHC) genes (DQB, DRA, and MHC-I) of cetaceans was investigated in order to get an overall understanding of cetacean MHC evolution. Little sequence variation was detected at the DRA locus, while extensive and considerable variability were found at the MHC-I and DQB loci. Phylogenetic reconstruction and sequence comparison revealed extensive sharing of identical MHC alleles among different species at the three MHC loci examined. Comparisons of phylogenetic trees for these MHC loci with the trees reconstructed only based on non-PBR sites revealed that allelic similarity/identity possibly reflected common ancestry and were not due to adaptive convergence. At the same time, trans-species evolution was also evidenced that the allelic diversity of the three MHC loci clearly pre-dated species divergence events according to the relaxed molecular clock. It may be the forces of balancing selection acting to maintain the high sequence variability and identical alleles in trans-specific manner at the MHC-I and DQB loci.

  7. Polymorphism in Bacterial Flagella Suspensions

    NASA Astrophysics Data System (ADS)

    Schwenger, Walter J.

    Bacterial flagella are a type of biological polymer studied for its role in bacterial motility and the polymorphic transitions undertaken to facilitate the run and tumble behavior. The naturally rigid, helical shape of flagella gives rise to novel colloidal dynamics and material properties. This thesis studies methods in which the shape of bacterial flagella can be controlled using in vitro methods and the changes the shape of the flagella have on both single particle dynamics and bulk material properties. We observe individual flagellum in both the dilute and semidilute regimes to observe the effects of solvent condition on the shape of the filament as well as the effect the filament morphology has on reptation through a network of flagella. In addition, we present rheological measurements showing how the shape of filaments effects the bulk material properties of flagellar suspensions. We find that the individual particle dynamics in suspensions of flagella can vary with geometry from needing to reptate linearly via rotation for helical filaments to the prevention of long range diffusion for block copolymer filaments. Similarly, for bulk material properties of flagella suspensions, helical geometries show a dramatic enhancement in elasticity over straight filaments while block copolymers form an elastic gel without the aid of crosslinking agents.

  8. Stability and metastability of bromine clathrate polymorphs.

    PubMed

    Nguyen, Andrew H; Molinero, Valeria

    2013-05-23

    Clathrate hydrates are crystals in which water forms a network of fully hydrogen-bonded polyhedral cages that contain small guests. Clathrate hydrates occur mostly in two cubic crystal polymorphs, sI and sII. Bromine is one of two guests that yield a hydrate with the tetragonal structure (TS), the topological dual of the Frank-Kasper σ phase. There has been a long-standing disagreement on whether bromine hydrate also forms metastable sI and sII crystals. To date there are no data on the thermodynamic range of stability (e.g., the melting temperatures) of the metastable polymorphs. Here we use molecular dynamics simulations with the coarse-grained model of water mW to (i) investigate the thermodynamic stability of the empty and guest-filled the sI, sII, TS, and HS-I hydrate polymorphs, (ii) develop a coarse-grained model of bromine compatible with mW water, and (iii) evaluate the stability of the bromine hydrate polymorphs. The mW model predicts the same relative energy of the empty clathrate polymorphs and the same phase diagram as a function of water-guest interaction than the fully atomistic TIP4P water model. There is a narrow region in water-guest parameter space for which TS is marginally more stable than sI or sII. We parametrize a coarse-grained model of bromine compatible with mW water and use it to determine the order of stability of the bromine hydrate polymorphs. The melting temperatures of the bromine hydrate polymorphs predicted by the coarse-grained model are 281 ± 1 K for TS, 279 ± 1 K for sII, and 276 ± 1 K for sI. The closeness of the melting temperatures supports the plausibility of formation of metastable sII and sI bromine hydrates.

  9. Cytochrome P450 gene polymorphism and cancer.

    PubMed

    Agundez, Jose A G

    2004-06-01

    Human cytochrome P450 (CYP) enzymes play a key role in the metabolism of drugs and environmental chemicals. Several CYP enzymes metabolically activate procarcinogens to genotoxic intermediates. Phenotyping analyses revealed an association between CYP enzyme activity and the risk to develop several forms of cancer. Research carried out in the last decade demonstrated that several CYP enzymes are polymorphic due to single nucleotide polymorphisms, gene duplications and deletions. As genotyping procedures became available for most human CYP, an impressive number of association studies on CYP polymorphisms and cancer risk were conducted. Here we review the findings obtained in these studies regarding CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A5, CYP3A7, CYP8A1 and CYP21 gene polymorphisms. Consistent evidences for association between CYP polymorphisms and lung, head and neck, and liver cancer were reported. Controversial findings suggest that colorectal and prostate cancers may be associated to CYP polymorphisms, whereas no evidences for a relevant association with breast or bladder cancers were reported. We summarize the available information related to the association of CYP polymorphisms with leukaemia, lymphomas and diverse types of cancer that were investigated only for some CYP genes, including brain, esophagus, stomach, pancreas, pituitary, cervical epithelium, melanoma, ovarian, kidney, anal and vulvar cancers. This review discusses on causes of heterogeneity in the proposed associations, controversial findings on cancer risk, and identifies topics that require further investigation. In addition, some recommendations on study design, in order to obtain more conclusive findings in further studies, are provided.

  10. MHC polymorphism under host-pathogen coevolution.

    PubMed

    Borghans, José A M; Beltman, Joost B; De Boer, Rob J

    2004-02-01

    The genes encoding major histocompatibility (MHC) molecules are among the most polymorphic genes known for vertebrates. Since MHC molecules play an important role in the induction of immune responses, the evolution of MHC polymorphism is often explained in terms of increased protection of hosts against pathogens. Two selective pressures that are thought to be involved are (1) selection favoring MHC heterozygous hosts, and (2) selection for rare MHC alleles by host-pathogen coevolution. We have developed a computer simulation of coevolving hosts and pathogens to study the relative impact of these two mechanisms on the evolution of MHC polymorphism. We found that heterozygote advantage per se is insufficient to explain the high degree of polymorphism at the MHC, even in very large host populations. Host-pathogen coevolution, on the other hand, can easily account for realistic polymorphisms of more than 50 alleles per MHC locus. Since evolving pathogens mainly evade presentation by the most common MHC alleles in the host population, they provide a selective pressure for a large variety of rare MHC alleles. Provided that the host population is sufficiently large, a large set of MHC alleles can persist over many host generations under host-pathogen coevolution, despite the fact that allele frequencies continuously change.

  11. Fractalkine receptor polymorphism and chronic tonsillitis.

    PubMed

    Babakurban, Seda Turkoglu; Erbek, Selim S; Terzi, Yunus Kasim; Arslan, Fatih; Sahin, Feride I

    2014-07-01

    The objective of this study is to examine whether there is an association of fractalkine gene receptor polymorphisms with chronic tonsillitis. This is a cross-sectional study in the setting of a tertiary referral center. The study group included 79 patients with chronic tonsillitis and 76 controls without history of chronic tonsillitis. Genotypes were identified by restriction fragment length polymorphism analyses after polymerase chain reaction. c.745G>A (V249I) single nucleotide polymorphism and the frequencies of the G and A alleles did not differ in the patient and control groups (p = 0.363; p = 0.743, respectively). c.839C>T (T280M) single nucleotide polymorphism was found to be higher in controls than in the patients with chronic tonsillitis (p < 0.001). Consistent with this result, T allele frequency was higher in controls than in the patients with chronic tonsillitis (p < 0.001). In this study, we suggested that fractalkine gene receptor c.839C>T (T280M) single nucleotide polymorphism could be associated with a reduced risk of chronic tonsillitis.

  12. Prdm9 polymorphism unveils mouse evolutionary tracks.

    PubMed

    Kono, Hiromitsu; Tamura, Masaru; Osada, Naoki; Suzuki, Hitoshi; Abe, Kuniya; Moriwaki, Kazuo; Ohta, Kunihiro; Shiroishi, Toshihiko

    2014-06-01

    PR/SET domain containing 9 (Prdm9) mediates histone modifications such as H3K4me3 and marks hotspots of meiotic recombination. In many mammalian species, the Prdm9 gene is highly polymorphic. Prdm9 polymorphism is assumed to play two critical roles in evolution: to diversify the spectrum of meiotic recombination hotspots and to cause male hybrid sterility, leading to reproductive isolation and speciation. Nevertheless, information about Prdm9 sequences in natural populations is very limited. In this study, we conducted a comprehensive population survey on Prdm9 polymorphism in the house mouse, Mus musculus. Overall M. musculus Prdm9 displays an extraordinarily high level of polymorphism, particularly in regions encoding zinc finger repeats, which recognize recombination hotspots. Prdm9 alleles specific to various M. musculus subspecies dominate in subspecies territories. Moreover, introgression into other subspecies territories was found for highly divergent Prdm9 alleles associated with t-haplotype. The results of our phylogeographical analysis suggest that the requirement for hotspot diversity depends on geographical range and time span in mouse evolution, and that Prdm9 polymorphism has not been maintained by a simple balanced selection in the population of each subspecies.

  13. Crystal structure of neotame anhydrate polymorph G.

    PubMed

    Dong, Zedong; Young, Victor G; Sheth, Agam; Munson, Eric J; Schroeder, Steve A; Prakash, Indra; Grant, David J W

    2002-10-01

    To determine the crystal structure of the neotame anhydrate polymorph G and to evaluate X-ray powder diffractometry (XRPD) with molecular modeling as an alternative method for determining the crystal structure of this conformationally flexible dipeptide. The crystal structure of polymorph G was determined by single crystal X-ray crystallography (SCXRD) and also from the X-ray powder diffraction (XRPD) pattern using molecular modeling (Cerius2, Powder Solve module). From SCXRD, polymorph G crystals are orthorhombic with space group of P2(1)2(1)2(1) with Z = 4, unit cell constants: a = 5.5999(4), b = 11.8921(8), c = 30.917(2) A, and one neotame molecule per asymmetric unit. The XRPD pattern of polymorph G, analyzed by Cerius2 software, led to the same P2(1)2(1)2(1) space group and almost identical unit cell dimensions. However, with 13 rigid bodies defined, Cerius2 gives a conformation of the neotame molecule, which is different from that determined by SCXRD. For neotame anhydrate polymorph G, the unit cell dimensions calculated from XRPD were almost identical to those determined by SCXRD. However, the crystal structure determined by XRPD closely resembled that determined by SCXRD, only when the correct conformation of the neotame molecule had been chosen before detailed analysis of the XRPD pattern.

  14. Solvable model for polymorphic dynamics of biofilaments.

    PubMed

    Mohrbach, Hervé; Kulić, Igor M

    2012-03-01

    We investigate an analytically tractable toy model for thermally induced polymorphic dynamics of cooperatively rearranging biofilaments-like microtubules. The proposed four-block model, which can be seen as a coarse-grained approximation of the full polymorphic tube model, permits a complete analytical treatment of all thermodynamic properties including correlation functions and angular Fourier mode distributions. Due to its mathematical tractability the model straightforwardly leads to some physical insights in recently discussed phenomena like the "length dependent persistence length." We show that a polymorphic filament can disguise itself as a classical worm-like chain on small and on large scales and yet display distinct anomalous tell-tale features indicating an inner switching dynamics on intermediate length scales.

  15. Human FcR Polymorphism and Disease

    PubMed Central

    Li, Xinrui; Gibson, Andrew W.; Kimberly, Robert P.

    2014-01-01

    Fc receptors play a central role in maintaining the homeostatic balance in the immune system. Our knowledge of the structure and function of these receptors and their naturally occurring polymorphisms, including single nucleotide polymorphisms and/or copy number variations, continues to expand. Through studies of their impact on human biology and clinical phenotype, the contributions of these variants to the pathogenesis, progression, and/or treatment outcome of many diseases that involve immunoglobulin have become evident. They affect susceptibility to bacterial and viral pathogens, constitute as risk factors for IgG or IgE mediated inflammatory diseases, and impact the development of many autoimmune conditions. In this chapter, we will provide an overview of these genetic variations in classical FcγRs, FcRLs, and other Fc receptors, as well as challenges in achieving an accurate and comprehensive understanding of the FcR polymorphisms and genomic architecture. PMID:25116105

  16. Human FcR polymorphism and disease.

    PubMed

    Li, Xinrui; Gibson, Andrew W; Kimberly, Robert P

    2014-01-01

    Fc receptors play a central role in maintaining the homeostatic balance in the immune system. Our knowledge of the structure and function of these receptors and their naturally occurring polymorphisms, including single nucleotide polymorphisms and/or copy number variations, continues to expand. Through studies of their impact on human biology and clinical phenotype, the contributions of these variants to the pathogenesis, progression, and/or treatment outcome of many diseases that involve immunoglobulin have become evident. They affect susceptibility to bacterial and viral pathogens, constitute as risk factors for IgG or IgE mediated inflammatory diseases, and impact the development of many autoimmune conditions. In this chapter, we will provide an overview of these genetic variations in classical FcγRs, FcRLs, and other Fc receptors, as well as challenges in achieving an accurate and comprehensive understanding of the FcR polymorphisms and genomic architecture.

  17. Single Nucleotide Polymorphisms and Osteoarthritis

    PubMed Central

    Wang, Ting; Liang, Yuting; Li, Hong; Li, Haibo; He, Quanze; Xue, Ying; Shen, Cong; Zhang, Chunhua; Xiang, Jingjing; Ding, Jie; Qiao, Longwei; Zheng, Qiping

    2016-01-01

    Abstract Osteoarthritis (OA) is a complex disorder characterized by degenerative articular cartilage and is largely attributed to genetic risk factors. Single nucleotide polymorphisms (SNPs) are common DNA variants that have shown promising and efficiency, compared with positional cloning, to map candidate genes of complex diseases, including OA. In this study, we aim to provide an overview of multiple SNPs from a number of genes that have recently been linked to OA susceptibility. We also performed a comprehensive meta-analysis to evaluate the association of SNP rs7639618 of double von Willebrand factor A domains (DVWA) gene with OA susceptibility. A systematic search of studies on the association of SNPs with susceptibility to OA was conducted in PubMed and Google scholar. Studies subjected to meta-analysis include human and case-control studies that met the Hardy–Weinberg equilibrium model and provide sufficient data to calculate an odds ratio (OR). A total of 9500 OA cases and 9365 controls in 7 case-control studies relating to SNP rs7639618 were included in this study and the ORs with 95% confidence intervals (CIs) were calculated. Over 50 SNPs from different genes have been shown to be associated with either hip (23), or knee (20), or both (13) OA. The ORs of these SNPs for OA and the subtypes are not consistent. As to SNP rs7639618 of DVWA, increased knee OA risk was observed in all genetic models analyzed. Specifically, people from Asian with G-allele showed significantly increased risk of knee OA (A versus G: OR = 1.28, 95% CI 1.13–1.46; AA versus GG: OR = 1.60, 95% CI 1.25–2.05; GA versus GG: OR = 1.31, 95% CI 1.18–1.44; AA versus GA+GG: OR = 1.34, 95% CI 1.12–1.61; AA+GA versus GG: OR = 1.40, 95% CI 1.19–1.64), but not in Caucasians or with hip OA. Our results suggest that multiple SNPs play different roles in the pathogenesis of OA and its subtypes; SNP rs7639618 of DVWA gene is associated with a significantly increased

  18. Polymorphic Phase Transition in Superhydrous Phase B

    SciTech Connect

    Koch-Muller,M.; Dera, P.; Fei, Y.; Hellwig, H.; Liu, Z.; Van Orman, J.; Wirth, R.

    2005-01-01

    We synthesized superhydrous phase B (shy-B) at 22 GPa and two different temperatures: 1200 C (LT) and 1400 C (HT) using a multi-anvil apparatus. The samples were investigated by transmission electron microscopy (TEM), single crystal X-ray diffraction, Raman and IR spectroscopy. The IR spectra were collected on polycrystalline thin-films and single crystals using synchrotron radiation, as well as a conventional IR source at ambient conditions and in situ at various pressures (up to 15 GPa) and temperatures (down to -180 C). Our studies show that shy-B exists in two polymorphic forms. As expected from crystal chemistry, the LT polymorph crystallizes in a lower symmetry space group (Pnn2), whereas the HT polymorph assumes a higher symmetry space group (Pnnm). TEM shows that both modifications consist of nearly perfect crystals with almost no lattice defects or inclusions of additional phases. IR spectra taken on polycrystalline thin films exhibit just one symmetric OH band and 29 lattice modes for the HT polymorph in contrast to two intense but asymmetric OH stretching bands and at least 48 lattice modes for the LT sample. The IR spectra differ not only in the number of bands, but also in the response of the bands to changes in pressure. The pressure derivatives for the IR bands are higher for the HT polymorph indicating that the high symmetry form is more compressible than the low symmetry form. Polarized, low-temperature single-crystal IR spectra indicate that in the LT-polymorph extensive ordering occurs not only at the Mg sites but also at the hydrogen sites.

  19. Mitochondrial DNA polymorphism in mitochondrial myopathy.

    PubMed

    Holt, I J; Harding, A E; Morgan-Hughes, J A

    1988-05-01

    In order to test the hypothesis that mitochondrial myopathy may be caused by mutation of the mitochondrial (mt) genome, restriction fragment length polymorphism in leucocyte mt DNA has been studied in 38 patients with mitochondrial myopathy, 44 of their unaffected matrilineal relatives, and 35 normal control subjects. Previously unreported mt DNA polymorphisms were identified in both patients and controls. No differences in restriction fragment patterns were observed between affected and unaffected individuals in the same maternal line, and there was no evidence of major deletion of mt DNA in patients. This study provides no positive evidence of mitochondrial inheritance in mitochondrial myopathy, but this has not been excluded.

  20. Microfluidic screening of potassium nitrate polymorphism

    NASA Astrophysics Data System (ADS)

    Laval, Philippe; Giroux, Céline; Leng, Jacques; Salmon, Jean-Baptiste

    2008-06-01

    We developed a microfluidic device for the investigation of crystallization kinetics from solution. The device allows to store hundreds of ≈100 nL droplets containing a given solute and to control their temperature within 0.1 °C. Upon cooling, we observe independent and mononuclear crystallization events; crystal dissolution occurs as the temperature is raised. For potassium nitrate (KNO 3) in water, these thermal cycles reveal the existence of two concomitant polymorphic forms. We measured, for the first time, the solubility curves of both these polymorphs, defined unambiguously the metastability extent of the solution and described why these results essentially stem from the miniaturized scale of the crystallization reactors.

  1. Clinical applications of Genome Polymorphism Scans

    PubMed Central

    Weber, James L

    2006-01-01

    Applications of Genome Polymorphism Scans range from the relatively simple such as gender determination and confirmation of biological relationships, to the relatively complex such as determination of autozygosity and propagation of genetic information throughout pedigrees. Unlike nearly all other clinical DNA tests, the Scan is a universal test – it covers all people and all genes. In balance, I argue that the Genome Polymorphism Scan is the most powerful, affordable clinical DNA test available today. Reviewers: This article was reviewed by Scott Weiss (nominated by Neil Smalheiser), Roberta Pagon (nominated by Jerzy Jurka) and Val Sheffield (nominated by Neil Smalheiser). PMID:16756678

  2. Polymorphs calcium carbonate on temperature reaction

    SciTech Connect

    Chong, Kai-Yin; Chia, Chin-Hua; Zakaria, Sarani

    2014-09-03

    Calcium carbonate (CaCO{sub 3}) has three different crystal polymorphs, which are calcite, aragonite and vaterite. In this study, effect of reaction temperature on polymorphs and crystallite structure of CaCO{sub 3} was investigated. X-ray powder diffraction (XRD), fourier transform infrared (FTIR), and variable pressure scanning electron microscope (VPSEM) were used to characterize the obtained CaCO{sub 3} particles. The obtained results showed that CaCO{sub 3} with different crystal and particle structures can be formed by controlling the temperature during the synthesis process.

  3. Migraine and genetic polymorphisms: an overview.

    PubMed

    Pizza, Vincenzo; Agresta, Anella; Agresta, Antonio; Lamaida, Eros; Lamaida, Norman; Infante, Francesco; Capasso, Anna

    2012-01-01

    The relationship between genetic polymorphisms and migraine as a cause of an increased risk of thrombotic disorders development is still debated In this respect, factor V Leiden, factor V (H1299R), prothrombin G20210A, factor XIII (V34L), β-fibrinogen, MTHFR (C677T), MTHFR (A1298C), APO E, PAI-1, HPA-1 and ACE I/D seem to play a determinant role in vascular diseases related to migraine. The present review analyzes both the incidence of the above genetic vascular mutations in migraineurs and the most re-cent developments related to genetic polymorphisms and migraine.

  4. Migraine and Genetic Polymorphisms: An Overview

    PubMed Central

    Pizza, Vincenzo; Agresta, Anella; Agresta, Antonio; Lamaida, Eros; Lamaida, Norman; Infante, Francesco; Capasso, Anna

    2012-01-01

    The relationship between genetic polymorphisms and migraine as a cause of an increased risk of thrombotic disorders development is still debated In this respect, factor V Leiden, factor V (H1299R), prothrombin G20210A, factor XIII (V34L), β-fibrinogen, MTHFR (C677T), MTHFR (A1298C), APO E, PAI-1, HPA-1 and ACE I/D seem to play a determinant role in vascular diseases related to migraine. The present review analyzes both the incidence of the above genetic vascular mutations in migraineurs and the most re-cent developments related to genetic polymorphisms and migraine. PMID:22962564

  5. Polymorphic transformation of helical flagella of bacteria

    NASA Astrophysics Data System (ADS)

    Lim, Sookkyung; Howard Berg Collaboration; William Ko Collaboration; Yongsam Kim Collaboration; Wanho Lee Collaboration; Charles Peskin Collaboration

    2016-11-01

    Bacteria such as E. coli swim in an aqueous environment by utilizing the rotation of flagellar motors and alternate two modes of motility, runs and tumbles. Runs are steady forward swimming driven by bundles of flagellar filaments whose motors are turning CCW; tumbles involve a reorientation of the direction of swimming triggered by motor reversals. During tumbling, the helical flagellum undergoes polymorphic transformations, which is a local change in helical pitch, helical radius, and handedness. In this work, we investigate the underlying mechanism of structural conformation and how this polymorphic transition plays a role in bacterial swimming. National Science Foundation.

  6. TNF-alpha polymorphisms and breast cancer.

    PubMed

    Yang, Yu; Feng, Rennan; Bi, Sheng; Xu, Yuqing

    2011-09-01

    Tumor necrosis factor-α (TNF-α) is an important pro-inflammatory cytokine in the development and progress in human cancer. TNF-α polymorphisms have been confirmed to influence the risk for several types of cancer, however, the associations between TNF-α polymorphisms and breast cancer (BC) remain controversial and ambiguous. The aim of this meta-analysis is to explore more precise estimations regarding this point. Electronic searches of several databases were conducted for all online publications on the associations between TNF-α-238, -308, -857, -863, -1031, -1210 polymorphisms and BC through March 2011. Odds ratios (OR) with 95% confidence intervals (95% CI) were calculated to assess the strength of these associations in fixed- and random-effect models with Review manager 5.0. A total of 17 studies with 44,442 BC patients and 49,926 controls involved were identified. This meta-analysis showed no significant association between TNF-α-308 polymorphism and BC (AA + GA vs. GG: OR = 0.95, 95% CI = 0.82-1.09) in overall and (OR = 1.44, 95% CI = 0.61-3.40) Asian populations, however, a negative association was shown in Caucasian subgroup (OR = 0.91, 95% CI = 0.85-0.97). As regards the TNF-α-238 polymorphism, the OR values (95% CI) were 0.99 (0.94-1.05), 0.94 (0.78-1.14), and 1.00 (0.95-1.05) for the overall, Asian, and Caucasian studies, respectively. No significant associations were found for other polymorphisms. Furthermore, there was a coincidence in the sensitivity analysis of these associations. No publication bias was detected in this study. To sum up, no significant associations were found between the TNF-α-308, -238, -857, -863, -1031, -1210 polymorphisms and the risk for BC in overall populations, whereas a negative association was found between TNF-α-308 polymorphism and BC in Caucasian populations.

  7. Speciation as a sieve for ancestral polymorphism.

    PubMed

    Guerrero, Rafael F; Hahn, Matthew W

    2017-08-09

    Because they are considered rare, balanced polymorphisms are often discounted as crucial constituents of genome-wide variation in sequence diversity. Despite its perceived rarity, however, long-term balancing selection can elevate genetic diversity and significantly affect observed divergence between species. Here, we discuss how ancestral balanced polymorphisms can be "sieved" by the speciation process, which sorts them unequally across descendant lineages. After speciation, ancestral balancing selection is revealed by genomic regions of high divergence between species. This signature, which resembles that of other evolutionary processes, can potentially confound genomic studies of population divergence and inferences of "islands of speciation." © 2017 John Wiley & Sons Ltd.

  8. Simultaneous detection of the exon 10 polymorphism and a novel intronic single base insertion polymorphism in the XPD gene using single strand conformation polymorphism.

    PubMed

    Kumar, Rajiv; Angelini, Sabrina; Hemminki, Kari

    2003-03-01

    We developed a new method based on the single strand conformation polymorphism (SSCP) technique for the detection of a G23591A (Asp312Asn) polymorphism in exon 10 of the XPD gene. In the process we also identified a novel polymorphism 23623C-ins (IVS10+17C-ins) in intron 10 of the same gene. With this newly developed SSCP-based method of genotyping we could detect both polymorphisms in the same assay and thus consequently determine the haplotype. In order to determine the population frequency of the novel polymorphism and the haplotype frequency, 302 healthy individuals were genotyped. The allelic frequency of the 23623C-ins intronic polymorphism was 0.16, whereas the frequency of the variant allele for the G23591A polymorphism was 0.39. Forty-three individuals (14%) were heterozygous for both polymorphisms but none carried polymorphic variants for both G23591A and 23623C-ins on the same allele. The effect of the novel intronic insertion polymorphism, which is located 16 nt downstream of the 3'-end of exon 10 of the XPD gene and involves a mononucleotide C repeat sequence, on expression remains to be determined.

  9. Phase transformation in conformational polymorphs of nimesulide.

    PubMed

    Sanphui, Palash; Sarma, Bipul; Nangia, Ashwini

    2011-06-01

    Nimesulide is a nonsteroidal anti-inflammatory drug (NSAID) and a COX-2 inhibitor. The native crystal structure of nimesulide (or Form I) has been characterized in the literature by X-ray powder diffraction (XRPD) lines, whereas full three-dimensional coordinates are known for a second polymorph (Form II). A detailed structural characterization and phase stability of nimesulide polymorphs were carried out. Rod-like crystals of Form I (space group Pca2(1); number of symmetry-independent molecules, Z' = 2) were crystallized from EtOH concomitantly with Form II (C2/c, Z' = 1). These conformational polymorphs have different torsion angles at the phenoxy and sulfonamide groups. The crystal structures are stabilized by N-H · · · O hydrogen bonds and C-H · · · O, C-H · · · π interactions. Phase transition from the metastable Form (II) to the stable modification (I) was studied using differential scanning calorimetry, hot-stage microscopy, solid-state grinding, solvent-drop grinding, and slurry crystallization. The phase transition was monitored by infrared, Raman, and ss-nuclear magnetic resonance spectroscopy; and XRPD and single-crystal X-ray diffraction. The stable polymorph I was obtained in excess during solution crystallization, grinding, and slurry methods. Intrinsic dissolution and equilibrium solubility experiments showed that the metastable Form II dissolves much faster than the stable Form I. Copyright © 2011 Wiley-Liss, Inc.

  10. Difficulties in Learning Inheritance and Polymorphism

    ERIC Educational Resources Information Center

    Liberman, Neomi; Beeri, Catriel; Kolikant, Yifat Ben-David

    2011-01-01

    This article reports on difficulties related to the concepts of inheritance and polymorphism, expressed by a group of 22 in-service CS teachers with an experience with the procedural paradigm, as they coped with a course on OOP. Our findings are based on the analysis of tests, questionnaires that the teachers completed in the course, as well as on…

  11. Polymorphism in a high-entropy alloy

    DOE PAGES

    Zhang, Fei; Wu, Yuan; Lou, Hongbo; ...

    2017-06-01

    Polymorphism, which describes the occurrence of different lattice structures in a crystalline material, is a critical phenomenon in materials science and condensed matter physics. Recently, configuration disorder was compositionally engineered into single lattices, leading to the discovery of high-entropy alloys and high-entropy oxides. For these novel entropy-stabilized forms of crystalline matter with extremely high structural stability, is polymorphism still possible? Here by employing in situ high-pressure synchrotron radiation X-ray diffraction, we reveal a polymorphic transition from face-centred-cubic (fcc) structure to hexagonal-close-packing (hcp) structure in the prototype CoCrFeMnNi high-entropy alloy. The transition is irreversible, and our in situ high-temperature synchrotron radiationmore » X-ray diffraction experiments at different pressures of the retained hcp high-entropy alloy reveal that the fcc phase is a stable polymorph at high temperatures, while the hcp structure is more thermodynamically favourable at lower temperatures. Lastly, as pressure is increased, the critical temperature for the hcp-to-fcc transformation also rises.« less

  12. Idealized powder diffraction patterns for cellulose polymorphs

    USDA-ARS?s Scientific Manuscript database

    Cellulose samples are routinely analyzed by X-ray diffraction to determine their crystal type (polymorph) and crystallinity. However, the connection is seldom made between those efforts and the crystal structures of cellulose that have been determined with synchrotron X-radiation and neutron diffrac...

  13. Molecular basis for amyloid-[beta] polymorphism

    SciTech Connect

    Colletier, Jacques-Philippe; Laganowsky, Arthur; Landau, Meytal; Zhao, Minglei; Soriaga, Angela B.; Goldschmidt, Lukasz; Flot, David; Cascio, Duilio; Sawaya, Michael R.; Eisenberga, David

    2011-10-19

    Amyloid-beta (A{beta}) aggregates are the main constituent of senile plaques, the histological hallmark of Alzheimer's disease. A{beta} molecules form {beta}-sheet containing structures that assemble into a variety of polymorphic oligomers, protofibers, and fibers that exhibit a range of lifetimes and cellular toxicities. This polymorphic nature of A{beta} has frustrated its biophysical characterization, its structural determination, and our understanding of its pathological mechanism. To elucidate A{beta} polymorphism in atomic detail, we determined eight new microcrystal structures of fiber-forming segments of A{beta}. These structures, all of short, self-complementing pairs of {beta}-sheets termed steric zippers, reveal a variety of modes of self-association of A{beta}. Combining these atomic structures with previous NMR studies allows us to propose several fiber models, offering molecular models for some of the repertoire of polydisperse structures accessible to A{beta}. These structures and molecular models contribute fundamental information for understanding A{beta} polymorphic nature and pathogenesis.

  14. Treatment of asymptomatic catecholaminergic polymorphic ventricular tachycardia.

    PubMed

    Obeyesekere, Manoj N; Sy, Raymond W; Leong-Sit, Peter; Gula, Lorne J; Yee, Raymond; Skanes, Allan C; Klein, George J; Krahn, Andrew D

    2012-05-01

    Catecholaminergic polymorphic ventricular tachycardia is a rare genetic disorder caused by mutations in genes involved in the intracellular calcium homeostasis of cardiac cells. Affected patients typically present with life-threatening ventricular arrhythmias precipitated by emotional/physical stress. The diagnosis is based on the demonstration of polymorphic or bidirectional ventricular tachycardia associated with adrenergic stress. Genetic testing can be confirmatory in some patients. Treatment for catecholaminergic polymorphic ventricular tachycardia includes medical and surgical efforts to suppress the effects of epinephrine at the myocardial level and/or modulation of calcium homeostasis. Mortality is high when untreated and sudden cardiac death may be the first manifestation of the disease. First-degree relatives of a proband should be offered genetic testing if the causal mutation is known. If the family mutation is not known, relatives should be clinically evaluated with provocative testing. In the absence of rigorous trials, prophylactic treatment of the asymptomatic catecholaminergic polymorphic ventricular tachycardia patient appears to reduce morbidity and mortality.

  15. Difficulties in Learning Inheritance and Polymorphism

    ERIC Educational Resources Information Center

    Liberman, Neomi; Beeri, Catriel; Kolikant, Yifat Ben-David

    2011-01-01

    This article reports on difficulties related to the concepts of inheritance and polymorphism, expressed by a group of 22 in-service CS teachers with an experience with the procedural paradigm, as they coped with a course on OOP. Our findings are based on the analysis of tests, questionnaires that the teachers completed in the course, as well as on…

  16. Polymorphism in a high-entropy alloy

    NASA Astrophysics Data System (ADS)

    Zhang, Fei; Wu, Yuan; Lou, Hongbo; Zeng, Zhidan; Prakapenka, Vitali B.; Greenberg, Eran; Ren, Yang; Yan, Jinyuan; Okasinski, John S.; Liu, Xiongjun; Liu, Yong; Zeng, Qiaoshi; Lu, Zhaoping

    2017-06-01

    Polymorphism, which describes the occurrence of different lattice structures in a crystalline material, is a critical phenomenon in materials science and condensed matter physics. Recently, configuration disorder was compositionally engineered into single lattices, leading to the discovery of high-entropy alloys and high-entropy oxides. For these novel entropy-stabilized forms of crystalline matter with extremely high structural stability, is polymorphism still possible? Here by employing in situ high-pressure synchrotron radiation X-ray diffraction, we reveal a polymorphic transition from face-centred-cubic (fcc) structure to hexagonal-close-packing (hcp) structure in the prototype CoCrFeMnNi high-entropy alloy. The transition is irreversible, and our in situ high-temperature synchrotron radiation X-ray diffraction experiments at different pressures of the retained hcp high-entropy alloy reveal that the fcc phase is a stable polymorph at high temperatures, while the hcp structure is more thermodynamically favourable at lower temperatures. As pressure is increased, the critical temperature for the hcp-to-fcc transformation also rises.

  17. [Connective tissue dysplasia, magnesium, and nucleotide polymorphisms].

    PubMed

    Torshin, I Iu; Gromova, O A

    2008-01-01

    Undifferentiated connective tissue dysplasia (UCTD) is one of most common diseases of the connective tissue. High frequency of UCTD in population along with the fact that it can provoke a number of other diseases make UCTD an important object of the modern biomedical research in the areas of cardiology, neurology, rheumatology and pulmonology. Modern diagnostics and determination of the predisposition to UCTD allow elaboration of personalized therapy. In particular, Mg-containing supplements and medications can be effectively used in the therapy of UCTD. In one of our previous works we have analyzed possible molecular mechanisms of UCTD etiology as well as therapeutic action of magnesium. The use of data on nucleotide polymorphisms as complementation of standard medical diagnostics is one of perspective trends of the post-genomic medical research. The present work suggest a number of nucleotide polymorphisms that can be used in genetic association analyses of the UCTD as of well as therapeutic efficiency of magnesium treatment. Selection and analysis of the polymorphisms was done on the base of molecular mechanisms we had proposed earlier, comprehensive analysis of published data and also with the use of an integral approach to analysis of the functional effects of the nucleotide polymorphisms and corresponding amino acid substitutions.

  18. [Cyclooxigenase-1 gene polymorphism and aspirin resistance].

    PubMed

    Bondar', T N; Kravchenko, N A

    2012-01-01

    The literature data concerning structure of cyclo-oxigenase-1--the key enzyme in prostaglandin biosynthesis and the main target of anti-platelet therapy with the use of acetylsalicilic acid are presented in the review. The data on cyclooxigenase-1 gene polymorphism, distribution of the revealed variants in various populations and their possible correlation with biochemical and functional aspirin resistance are presented.

  19. The Effect of Polymorphism on Surface Energetics of D-Mannitol Polymorphs.

    PubMed

    Smith, Robert R; Shah, Umang V; Parambil, Jose V; Burnett, Daniel J; Thielmann, Frank; Heng, Jerry Y Y

    2017-01-01

    The aim of this work was to assess the effect of different crystalline polymorphism on surface energetics of D-mannitol using finite dilution inverse gas chromatography (FD-IGC). Pure α, β and δ polymorphs were prepared via solution crystallisation and characterised by powder X-ray diffraction (P-XRD). The dispersive surface energies were found to range from 43 to 34 mJ/m(2), 50 to 41 mJ/m(2), and 48 to 38 mJ/m(2), for α, β, and δ, respectively, for surface coverage ranging from 0.006 to 0.095. A deconvolution modelling approach was employed to establish their energy sites. The primary sites corresponded to maxima in the dispersive surface energy of 37.1 and 33.5; 43.3 and 39.5; and 38.6, 38.4 and 33.0; for α, β, and δ, respectively. This methodology was also extended to an α-β polymorph mixture to estimate the amount of the constituent α and β components present in the sample. The dispersive surface energies of the α-β mixture were found to be in the range of 48 to 37 mJ/m(2) with 40.0, 42.4, 38.4 and 33.1 mJ/m(2) sites. The deconvolution modelling method extracted the energy contribution of each of the polymorphs from data for the polymorphic mixture. The mixture was found to have a β-polymorph surface content of ∼19%. This work shows the influence of polymorphism on surface energetics and demonstrates that FD-IGC coupled with a simple modelling approach to be a powerful tool for assessing the specific nature of this energetic distribution including the quantification of polymorphic content on the surface.

  20. Vibrational spectroscopic study of polymorphism and polymorphic transformation of the anti-viral drug lamivudine.

    PubMed

    Du, Yong; Zhang, Huili; Xue, Jiadan; Tang, Wenjian; Fang, Hongxia; Zhang, Qi; Li, Yafang; Hong, Zhi

    2015-02-25

    Vibrational spectra of hydrated and anhydrous lamivudines, and also the dynamic process of polymorphic transformation have been characterized by Fourier transform infrared (FT-IR) and Raman spectroscopic techniques. The vibrational modes of both polymorphic lamivudines are assigned. FT-IR and Raman spectral results show that the interaction between crystalline water and lamivudine molecular has an important effect on the molecular vibration motions of polymorphic lamivudines. The two characteristic Raman peaks at 783 and 798 cm(-1) represent hydrated and anhydrous lamivudine respectively. The relationship between changes of two characteristic peak normalized areas and heating time could be fitted with single exponential functions, and the dynamic information of polymorphic transformation of lamivudine drug is obtained. The decay rate of characteristic peak for hydrated lamivudine and the growth rate of that for anhydrous lamivudine are consistent during dehydration transformation process. The reported results provide us important benchmark for qualitatively monitoring different polymorphic drugs and also establishing the corresponding model for the polymorphic transformation of drugs in related pharmaceutical research fields.

  1. Vibrational spectroscopic study of polymorphism and polymorphic transformation of the anti-viral drug lamivudine

    NASA Astrophysics Data System (ADS)

    Du, Yong; Zhang, Huili; Xue, Jiadan; Tang, Wenjian; Fang, Hongxia; Zhang, Qi; Li, Yafang; Hong, Zhi

    2015-02-01

    Vibrational spectra of hydrated and anhydrous lamivudines, and also the dynamic process of polymorphic transformation have been characterized by Fourier transform infrared (FT-IR) and Raman spectroscopic techniques. The vibrational modes of both polymorphic lamivudines are assigned. FT-IR and Raman spectral results show that the interaction between crystalline water and lamivudine molecular has an important effect on the molecular vibration motions of polymorphic lamivudines. The two characteristic Raman peaks at 783 and 798 cm-1 represent hydrated and anhydrous lamivudine respectively. The relationship between changes of two characteristic peak normalized areas and heating time could be fitted with single exponential functions, and the dynamic information of polymorphic transformation of lamivudine drug is obtained. The decay rate of characteristic peak for hydrated lamivudine and the growth rate of that for anhydrous lamivudine are consistent during dehydration transformation process. The reported results provide us important benchmark for qualitatively monitoring different polymorphic drugs and also establishing the corresponding model for the polymorphic transformation of drugs in related pharmaceutical research fields.

  2. Polymorphism Control in Nanostructured Metal Oxides

    NASA Astrophysics Data System (ADS)

    Sood, Shantanu

    Polymorphic phase transformations are common to all nanocrystalline binary metal oxides. The polymorphic nature of such metal oxides makes available a large number of phases with differing crystal structures, each stable under certain conditions of temperature, pressure, and/or particle size. These different crystal structures translate to unique physical and chemical properties for each structural class of polymorphs. Thus predicting when polymorphic phase transitions are likely to occur becomes important to the synthesis of stable functional materials with desired properties. Theoretical calculations using a heuristic approach have resulted in an accurate estimation of the critical particle size predicting metastable to stable phase transitions. This formula is applied to different case studies: for anatase to rutile titania; gamma-Alumina to alpha-Alumina; and tetragonal to monoclinic zirconia. The theoretical values calculated have been seen to be very close to the experimental results from the literature. Manifestation of the effect of phase transitions in nanostructured metal oxides was provided in the study of metastable to stable phase transitions in WO3. Nanowires of tungsten trioxide have been synthesized in-situ inside an electron microscope. Such structure of tungsten trioxide result due to a metastable to stable phase transformation, from the cubic to the monoclinic phase. The transformation is massive and complete. The structures formed are unique one-dimensional nanowires. Such a method can be scaled inside any equipment equipped with an electron gun, for example lithography systems either using STEM or E-beam lithography. Another study on nanowire formation in binary metal oxides involved the synthesis of stable orthorhombic MoO3 by means of blend electrospinning. Both a traditional single jet electrospinning set up and a novel high-throughput process to get high aspect ratio nanowires. The latter is a jet-controlled and flow controlled

  3. Polymorphic hydroxylation of perhexiline maleate in man.

    PubMed Central

    Cooper, R G; Evans, D A; Whibley, E J

    1984-01-01

    Long term perhexiline maleate therapy causes peripheral neuropathy and hepatic damage in certain subjects. An association between these adverse reactions and a genetically determined relative inability to hydroxylate debrisoquine has been described. This association could indicate either that the effects of perhexiline impair debrisoquine oxidation thus producing a phenocopy, or that perhexiline is polymorphically hydroxylated and that the polymorphism is controlled by the same alleles as control the debrisoquine polymorphism. To test the second possibility, a study investigating the hydroxylation status of a population of healthy volunteer subjects has been performed using perhexiline maleate. Hydroxylation phenotyping was performed on 50 normal volunteers. A standard oral dose was given and plasma and urinary perhexiline, 4-monohydroxyperhexiline (MI metabolite), and 4'monohydroxyperhexiline (MIII metabolite) was measured. The 24-hour plasma perhexiline concentration, the 24-hour plasma MI metabolite concentration, and 12 to 24-hour urinary MI metabolite excretion were clearly bimodal, suggesting the existence of a polymorphism for perhexiline hydroxylation. Poor metabolisers represent 6% of the population studied. Known poor metabolisers of debrisoquine are also poor metabolisers of perhexiline, while known extensive metabolisers of debrisoquine are also extensive metabolisers of perhexiline, indicating that in white British subjects the hydroxylation polymorphism is under identical genetic control for both compounds. The poor metaboliser sub-group exhibited the highest plasma perhexiline levels. Perhexiline phenotyping separates the poor and extensive metaboliser phenotypes much more clearly than other tests and defines a sub-group at risk from perhexiline toxicity. Pretreatment phenotyping using this test, followed by exclusion of poor metabolisers from perhexiline therapy, should substantially reduce the incidence of major adverse effects. PMID:6694182

  4. Wnt antagonist gene polymorphisms and renal cancer

    PubMed Central

    Hirata, Hiroshi; Hinoda, Yuji; Nakajima, Koichi; Kikuno, Nobuyuki; Yamamura, Soichiro; Kawakami, Kazumori; Suehiro, Yutaka; Tabatabai, Z. Laura; Ishii, Nobuhisa; Dahiya, Rajvir

    2014-01-01

    Purpose Epigenetic silencing of several Wnt pathway related genes has been reported in renal cancer. Except for the TCF4 gene, there are no reports regarding Wnt pathway gene polymorphisms in renal cancer. Therefore, we hypothesized that the polymorphisms in Wnt signaling genes may be risk factors for renal cancer. Experimental Design A total of 210 patients (145 male and 65 female) with pathologically confirmed renal cell carcinoma (RCC), and 200 age- and sex-matched control individuals were enrolled in this study. We genotyped 14 SNPs in six genes including DKK2 (rs17037102, rs419558, rs447372), DKK3 (rs3206824, rs11022095, rs1472189, rs7396187, rs2291599), DKK4 (rs2073664), sFRP4 (rs1802073, rs1802074), SMAD7 (rs12953717), DAAM2 (rs6937133, rs2504106) using PCR-RFLP and direct sequencing in RCC and age-matched healthy subjects. We also tested the relationship between these polymorphisms and clinicopathologic data including gender, grade, tumor stage, lymph-node involvement, distant metastasis, and overall survival. Results A significant decrease in the frequency of the G/A+A/A genotypes in the DKK3 codon335 rs3206824 was observed in RCC patients compared with controls. The frequency of the rs3206824 (G/A) A- rs7396187 (G/C) C haplotype was significantly lower in RCC compared with other haplotypes. We also found that DKK3 rs1472189 C/T is associated with distant metastasis and furthermore, DKK2 rs17037102 G homozygous patients had a decreased risk for death by multivariate Cox regression analysis. Conclusions This is the first report documenting that DKK3 polymorphisms are associated with RCC and that the DKK2 rs17037102 polymorphism may be a predictor for survival in RCC patients after radical nephrectomy. PMID:19562778

  5. Computerized polymorphic marker identification: Experimental validation and a predicted human polymorphism catalog

    PubMed Central

    Fondon, John W.; Mele, Gina M.; Brezinschek, Ruth I.; Cummings, Donna; Pande, Ashwini; Wren, Jonathan; O’Brien, Kevin M.; Kupfer, Kenneth C.; Wei, Ming-Hui; Lerman, Michael; Minna, John D.; Garner, Harold R.

    1998-01-01

    A computational system for the prediction of polymorphic loci directly and efficiently from human genomic sequence was developed and verified. A suite of programs, collectively called pompous (polymorphic marker prediction of ubiquitous simple sequences) detects tandem repeats ranging from dinucleotides up to 250 mers, scores them according to predicted level of polymorphism, and designs appropriate flanking primers for PCR amplification. This approach was validated on an approximately 750-kilobase region of human chromosome 3p21.3, involved in lung and breast carcinoma homozygous deletions. Target DNA from 36 paired B lymphoblastoid and lung cancer lines was amplified and allelotyped for 33 loci predicted by pompous to be variable in repeat size. We found that among those 36 predominately Caucasian individuals 22 of the 33 (67%) predicted loci were polymorphic with an average heterozygosity of 0.42. Allele loss in this region was found in 27/36 (75%) of the tumor lines using these markers. pompous provides the genetic researcher with an additional tool for the rapid and efficient identification of polymorphic markers, and through a World Wide Web site, investigators can use pompous to identify polymorphic markers for their research. A catalog of 13,261 potential polymorphic markers and associated primer sets has been created from the analysis of 141,779,504 base pairs of human genomic sequence in GenBank. This data is available on our Web site (pompous.swmed.edu) and will be updated periodically as GenBank is expanded and algorithm accuracy is improved. PMID:9636181

  6. Hyphenated spectroscopy as a polymorph screening tool.

    PubMed

    Aaltonen, Jaakko; Strachan, Clare J; Pöllänen, Kati; Yliruusi, Jouko; Rantanen, Jukka

    2007-06-28

    Polymorph screening of a model compound (nitrofurantoin) was performed. Nitrofurantoin was crystallized from acetone-water mixtures with varying process parameters. Two anhydrate forms (alpha and beta) and one monohydrate form (II) were crystallized in the polymorph screen. The solid forms were analyzed with three complementary spectroscopic techniques: near-infrared (NIR) spectroscopy, Raman spectroscopy and terahertz pulsed spectroscopy (TPS), and the results of the solid phase analysis were verified with X-ray powder diffraction (XRPD). NIR and Raman spectroscopy were coupled to achieve a rapid and comprehensive method of solid phase analysis. The hyphenated NIR/Raman spectroscopic data were analyzed with a multivariate method, principal component analysis (PCA). The combination was found effective in screening solid forms due to the complementary characteristics of the methods. NIR spectroscopy is powerful in differentiating between anhydrate and hydrate forms and intermolecular features, whereas Raman spectroscopy is sensitive to intramolecular alterations in the molecular backbone.

  7. Gene polymorphisms, apoptotic capacity and cancer risk.

    PubMed

    Imyanitov, Evgeny N

    2009-04-01

    Programmed cell death has been implicated in various aspects of cancer development. Apoptotic capacity is a subject of significant interindividual variations, which are largely attributed to hereditary traits. Single nucleotide polymorphisms (SNPs) located within cell death genes may influence cancer risk in various ways. Low activity of apoptosis may favor cancer development because of the failure to eliminate cellular clones carrying DNA damage and propensity to inflammation, but may also protect against malignancy due to preservation of antitumor immune cells. Phenotyping studies assessing cell death rate in cancer patients versus healthy controls are limited in number and produced controversial results. TP53 R72P polymorphism is the only SNP whose functional impact on apoptotic response has been replicated in independent investigations. Intriguingly, meta-analysis of TP53 genotyping studies has provided evidence for the association between apoptosis-deficient TP53 genotype and tumor susceptibility. Systematic analysis of cancer-predisposing relevance of other apoptotic gene SNPs remains to be done.

  8. IPD—the Immuno Polymorphism Database

    PubMed Central

    Robinson, James; Mistry, Kavita; McWilliam, Hamish; Lopez, Rodrigo; Marsh, Steven G. E.

    2010-01-01

    The Immuno Polymorphism Database (IPD) (http://www.ebi.ac.uk/ipd/) is a set of specialist databases related to the study of polymorphic genes in the immune system. The IPD project works with specialist groups or nomenclature committees who provide and curate individual sections before they are submitted to IPD for online publication. The IPD project stores all the data in a set of related databases. IPD currently consists of four databases: IPD-KIR, contains the allelic sequences of Killer-cell Immunoglobulin-like Receptors, IPD-MHC, is a database of sequences of the Major Histocompatibility Complex of different species; IPD-human platelet antigens, alloantigens expressed only on platelets and IPD-ESTDAB, which provides access to the European Searchable Tumour cell-line database, a cell bank of immunologically characterised melanoma cell lines. The data is currently available online from the website and ftp directory. PMID:19875415

  9. IPD--the Immuno Polymorphism Database.

    PubMed

    Robinson, James; Mistry, Kavita; McWilliam, Hamish; Lopez, Rodrigo; Marsh, Steven G E

    2010-01-01

    The Immuno Polymorphism Database (IPD) (http://www.ebi.ac.uk/ipd/) is a set of specialist databases related to the study of polymorphic genes in the immune system. The IPD project works with specialist groups or nomenclature committees who provide and curate individual sections before they are submitted to IPD for online publication. The IPD project stores all the data in a set of related databases. IPD currently consists of four databases: IPD-KIR, contains the allelic sequences of Killer-cell Immunoglobulin-like Receptors, IPD-MHC, is a database of sequences of the Major Histocompatibility Complex of different species; IPD-human platelet antigens, alloantigens expressed only on platelets and IPD-ESTDAB, which provides access to the European Searchable Tumour cell-line database, a cell bank of immunologically characterised melanoma cell lines. The data is currently available online from the website and ftp directory.

  10. IPD--the Immuno Polymorphism Database.

    PubMed

    Robinson, James; Halliwell, Jason A; McWilliam, Hamish; Lopez, Rodrigo; Marsh, Steven G E

    2013-01-01

    The Immuno Polymorphism Database (IPD), http://www.ebi.ac.uk/ipd/ is a set of specialist databases related to the study of polymorphic genes in the immune system. The IPD project works with specialist groups or nomenclature committees who provide and curate individual sections before they are submitted to IPD for online publication. The IPD project stores all the data in a set of related databases. IPD currently consists of four databases: IPD-KIR, contains the allelic sequences of killer-cell immunoglobulin-like receptors, IPD-MHC, a database of sequences of the major histocompatibility complex of different species; IPD-HPA, alloantigens expressed only on platelets; and IPD-ESTDAB, which provides access to the European Searchable Tumour Cell-Line Database, a cell bank of immunologically characterized melanoma cell lines. The data is currently available online from the website and FTP directory. This article describes the latest updates and additional tools added to the IPD project.

  11. Kinetics versus Thermodynamics in Virus Capsid Polymorphism.

    PubMed

    Moerman, Pepijn; van der Schoot, Paul; Kegel, Willem

    2016-07-07

    Virus coat proteins spontaneously self-assemble into empty shells in aqueous solution under the appropriate physicochemical conditions, driven by an interaction free energy per bond on the order of 2-5 times the thermal energy kBT. For this seemingly modest interaction strength, each protein building block nonetheless gains a very large binding free energy, between 10 and 20 kBT. Because of this, there is debate about whether the assembly process is reversible or irreversible. Here we discuss capsid polymorphism observed in in vitro experiments from the perspective of nucleation theory and of the thermodynamics of mass action. We specifically consider the potential contribution of a curvature free energy term to the effective interaction potential between the proteins. From these models, we propose experiments that may conclusively reveal whether virus capsid assembly into a mixture of polymorphs is a reversible or an irreversible process.

  12. APOE gene polymorphisms and diabetic peripheral neuropathy.

    PubMed

    Monastiriotis, Christodoulos; Papanas, Nikolaos; Veletza, Stavroula; Maltezos, Efstratios

    2012-09-08

    Genetic factors may influence the natural course of diabetic peripheral neuropathy and explain some of its variability. The aim of this review was to examine the association between apolipoprotein E (apoE) gene polymorphisms and diabetic peripheral neuropathy. Four relevant studies were identified. The two earlier works provided evidence that the ɛ4 allele is a risk factor for this complication, while the two more recent studies were negative. Important differences in the methodology used and in the populations included are obvious, rendering difficult the comparison between studies. In conclusion, the association between APOE gene polymorphisms and diabetic peripheral neuropathy is still unclear. Available evidence is rather limited and results have so far been contradictory. Future studies should employ more robust methodology, adjusting for potential confounders and for the prevalence of neuropathy in the general population with diabetes.

  13. Carbon nitride frameworks and dense crystalline polymorphs

    NASA Astrophysics Data System (ADS)

    Pickard, Chris J.; Salamat, Ashkan; Bojdys, Michael J.; Needs, Richard J.; McMillan, Paul F.

    2016-09-01

    We used ab initio random structure searching (AIRSS) to investigate polymorphism in C3N4 carbon nitride as a function of pressure. Our calculations reveal new framework structures, including a particularly stable chiral polymorph of space group P 43212 containing mixed s p2 and s p3 bonding, that we have produced experimentally and recovered to ambient conditions. As pressure is increased a sequence of structures with fully s p3 -bonded C atoms and three-fold-coordinated N atoms is predicted, culminating in a dense P n m a phase above 250 GPa. Beyond 650 GPa we find that C3N4 becomes unstable to decomposition into diamond and pyrite-structured CN2.

  14. Calorimetric determinations and theoretical calculations of polymorphs of thalidomide

    NASA Astrophysics Data System (ADS)

    Lara-Ochoa, F.; Pérez, G. Espinosa; Mijangos-Santiago, F.

    2007-09-01

    The analysis of the thermograms of thalidomide obtained for the two reported polymorphs α and β by differential scanning calorimetry (DSC) shows some inconsistencies that are discussed in the present work. The conception of a new polymorph form, named β ∗, allowed us to explain the observed thermal behavior more satisfactorily. This new polymorph shows enantiotropy with both α and β polymorphs, reflected in the unique endotherm obtained in the DSC-thermograms, when a heating rate of 10 °C/min is applied. Several additional experiments, such as re-melting of both polymorph forms, showed that there is indeed a new polymorph with an endotherm located between the endotherms of α and β. IR, Raman, and powder X-ray permit us to characterize the isolated compound, resulting from the re-melting of both polymorph forms. Mechanical calculations were performed to elucidate the conformations of each polymorph, and ab initio quantum chemical calculations were performed to determine the energy of the more stable conformers and the spatial cell energy for both polymorphs α and β. These results suggested a possible conformation for the newly discovered polymorph β ∗.

  15. Innate Immune Gene Polymorphisms in Tuberculosis

    PubMed Central

    Sadee, Wolfgang

    2012-01-01

    Tuberculosis (TB) is a leading cause worldwide of human mortality attributable to a single infectious agent. Recent studies targeting candidate genes and “case-control” association have revealed numerous polymorphisms implicated in host susceptibility to TB. Here, we review current progress in the understanding of causative polymorphisms in host innate immune genes associated with TB pathogenesis. We discuss genes encoding several types of proteins: macrophage receptors, such as the mannose receptor (MR, CD206), dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN, CD209), Dectin-1, Toll-like receptors (TLRs), complement receptor 3 (CR3, CD11b/CD18), nucleotide oligomerization domain 1 (NOD1) and NOD2, CD14, P2X7, and the vitamin D nuclear receptor (VDR); soluble C-type lectins, such as surfactant protein-A (SP-A), SP-D, and mannose-binding lectin (MBL); phagocyte cytokines, such as tumor necrosis factor (TNF), interleukin-1β (IL-1β), IL-6, IL-10, IL-12, and IL-18; chemokines, such as IL-8, monocyte chemoattractant protein 1 (MCP-1), RANTES, and CXCL10; and other important innate immune molecules, such as inducible nitric oxide synthase (iNOS) and solute carrier protein 11A1 (SLC11A1). Polymorphisms in these genes have been variably associated with susceptibility to TB among different populations. This apparent variability is probably accounted for by evolutionary selection pressure as a result of long-term host-pathogen interactions in certain regions or populations and, in part, by lack of proper study design and limited knowledge of molecular and functional effects of the implicated genetic variants. Finally, we discuss genomic technologies that hold promise for resolving questions regarding the evolutionary paths of the human genome, functional effects of polymorphisms, and corollary impacts of adaptation on human health, ultimately leading to novel approaches to controlling TB. PMID:22825450

  16. Bimodal expression level polymorphisms in Arabidopsis thaliana

    PubMed Central

    Nagano, Atsushi J.; Tsuchimatsu, Takashi; Okuyama, Yudai; Hara-Nishimura, Ikuko

    2012-01-01

    Differences in gene expression are termed expression level polymorphisms (ELPs). Here, we propose a new ELP class, bimodal ELPs (bELPs), as a criterion to screen for genes that are responsible for natural phenotypic variation and/or that are targeted by balancing selection. bELP genes are characterized by two expression level modes. Genomic scans based on nucleotide sequences are not ideal for identifying genes targeted for selection. A critical concern is that several genes can be present in the selection-targeted regions identified by such scans. This situation indicates the importance of integrating genomic sequence data and other information, such as gene expression data. Comparative transcriptomics is useful for determining evolutionarily and ecologically important polymorphisms. In a genome-wide expression screen of 34 accessions, we identified 344 Arabidopsis thaliana genes exhibiting bELPs. Population genetic analysis revealed that bELP genes had high nucleotide diversities and long linkage disequilibriums. The highest nucleotide diversity (11-fold greater than the genomic mean) was found in the At1g23780 gene, which encodes a putative F-box protein. We observed a clear association between the expression mode and sequence type of the At1g23780 gene. Our results suggest that bELPs will be useful for the screening and functional analysis of genes responsible for phenotypic polymorphisms. Such a “multi-omics” approach has the potential to facilitate the scanning of genes relevant to balanced polymorphisms not only in A. thaliana, but also in other model and non-model organisms. PMID:22751308

  17. An orthorhombic polymorph of mulinic acid.

    PubMed

    Brito, Iván; Bórquez, Jorge; Loyola, Luis Alberto; López-Rodríguez, Matías; Cárdenas, Alejandro

    2010-01-09

    THE TITLE COMPOUND [SYSTEMATIC NAME: (3S,3aS,10bR)-3-isopropyl-5a,8-dimethyl-2,3,4,5,5a,6,7,10,10a,10b-deca-hydro-endo-epidioxy-cyclo-hepta-[e]indene-3a(1H)-carboxylic acid], C(20)H(30)O(4), is a polymorphic form of a previously reported structure [Loyola et al. (1990 ▶). Tetra-hedron, 46, 5413-5420]. The newly found ortho-rhom-bic polymorph crystallizes in P2(1)2(1)2(1) with two mol-ecules in the asymmetric unit. The mol-ecules are linked into discrete D(2) chains by simple O-H⋯O inter-actions. There are only slight variations in the mol-ecular geometry and supra-molecular organization in the crystal structures of the two polymorphs. The densities are 1.145 (monoclinic, P2(1)) and 1.155 Mg m(-3) (ortho-rhom-bic, P2(1)2(1)2(1)).

  18. Polymorphisms within inflammatory genes and colorectal cancer

    PubMed Central

    Landi, Stefano; Gemignani, Federica; Bottari, Fabio; Gioia-Patricola, Lydie; Guino, Elisabet; Cambray, María; Biondo, Sebastiano; Capella, Gabriel; Boldrini, Laura; Canzian, Federico; Moreno, Victor

    2006-01-01

    Background Chronic inflammation is a risk factor for colorectal cancer and polymorphisms in the inflammatory genes could modulate the levels of inflammation. We have investigated ten single nucleotide polymorphisms (SNPs) in the following inflammation-related genes: TLR4 (Asp299Gly), CD14 (-260 T>C), MCP1 (-2518 A>G), IL12A (+7506 A>T, +8707 A>G, +9177 T>A, +9508 G>A), NOS2A (+524T>C), TNF (-857C>T), and PTGS1 (V444I) in 377 colorectal (CRC) cancer cases and 326 controls from Barcelona (Spain). Results There was no statistically significant association between the SNPs investigated and colorectal cancer risk. Conclusion The lack of association may show that the inflammatory genes selected for this study are not involved in the carcinogenic process of colorectum. Alternatively, the negative results may derive from no particular biological effect of the analysed polymorphisms in relation to CRC. Otherwise, the eventual biological effect is so little to go undetected, unless analysing a much larger sample size. PMID:17062130

  19. Introgressive hybridization in a trophically polymorphic cichlid.

    PubMed

    Hulsey, C Darrin; García-de-León, Francisco J

    2013-11-01

    Trophically polymorphic species could represent lineages that are rapidly diverging along an ecological axis or could phenotypically mark the collapse of species through introgressive hybridization. We investigated patterns of introgression between the trophically polymorphic cichlid fish Herichthys minckleyi and its relative H. cyanoguttatus using a combination of population genetics and species tree analyses. We first examined the distribution of mitochondrial haplotypes within the alternative H. minckleyi pharyngeal jaw morphotypes that are endemic to the small desert valley of Cuatro Ciénegas. We recovered two clusters of mitochondrial haplotypes. The first contained a number of slightly differentiated cytochrome b (cytb) haplotypes that showed some phylogeographic signal and were present in both jaw morphotypes. The other haplotype was monomorphic, highly differentiated from the other cluster, present in equal frequencies in the morphotypes, and identical to H. cyanoguttatus haplotypes found outside Cuatro Ciénegas. Then, we investigated whether H. minckleyi individuals with the H. cyanoguttatus cytb were more evolutionarily similar to H. cyanoguttatus or other H. minckleyi using a species tree analysis of 84 nuclear loci. Both H. minckleyi pharyngeal morphotypes, regardless of their cytb haplotype, were quite distinct from H. cyanoguttatus. However, hybridization could be blurring subdivision within H. minckleyi as the alternative jaw morphotypes were not genetically distinct from one another. Accounting for introgression from H. cyanoguttatus will be essential to understand the evolution of the trophically polymorphic cichlid H. minckleyi.

  20. Introgressive hybridization in a trophically polymorphic cichlid

    PubMed Central

    Hulsey, C Darrin; García-de-León, Francisco J

    2013-01-01

    Trophically polymorphic species could represent lineages that are rapidly diverging along an ecological axis or could phenotypically mark the collapse of species through introgressive hybridization. We investigated patterns of introgression between the trophically polymorphic cichlid fish Herichthys minckleyi and its relative H. cyanoguttatus using a combination of population genetics and species tree analyses. We first examined the distribution of mitochondrial haplotypes within the alternative H. minckleyi pharyngeal jaw morphotypes that are endemic to the small desert valley of Cuatro Ciénegas. We recovered two clusters of mitochondrial haplotypes. The first contained a number of slightly differentiated cytochrome b (cytb) haplotypes that showed some phylogeographic signal and were present in both jaw morphotypes. The other haplotype was monomorphic, highly differentiated from the other cluster, present in equal frequencies in the morphotypes, and identical to H. cyanoguttatus haplotypes found outside Cuatro Ciénegas. Then, we investigated whether H. minckleyi individuals with the H. cyanoguttatus cytb were more evolutionarily similar to H. cyanoguttatus or other H. minckleyi using a species tree analysis of 84 nuclear loci. Both H. minckleyi pharyngeal morphotypes, regardless of their cytb haplotype, were quite distinct from H. cyanoguttatus. However, hybridization could be blurring subdivision within H. minckleyi as the alternative jaw morphotypes were not genetically distinct from one another. Accounting for introgression from H. cyanoguttatus will be essential to understand the evolution of the trophically polymorphic cichlid H. minckleyi. PMID:24340193

  1. Single nucleotide polymorphisms and suicidal behaviour.

    PubMed

    Pregelj, Peter

    2012-09-01

    The World Health Organization estimates that almost one million deaths each year are attributable to suicide, and suicide attempt is close to 10 times more common than suicide completion. Suicidal behaviour has multiple causes that are broadly divided into proximal stressors or triggers and predisposition such as genetic. It is also known that single nucleotide polymorphisms (SNPs) occur throughout a human DNA influencing the structure, quantity and the function of proteins and other molecules. Abnormalities of the serotonergic system were observed in suicide victims. Beside 5-HT1A and other serotonin receptors most studied are the serotonin transporter 5' functional promoter variant, and monoamine oxidase A and the tryptophan-hydroxylase 1 and 2 (TPH) polymorphisms. It seems that especially genes regulating serotoninergic system and neuronal systems involved in stress response are associated with suicidal behaviour. Most genetic studies on suicidal behaviour have considered a small set of functional polymorphisms relevant mostly to monoaminergic neurotransmission. However, genes involved in regulation of other factors such as brain-derived neurotropic factor seems to be even more relevant for further research.

  2. Genetic polymorphisms linked to susceptibility to malaria.

    PubMed

    Driss, Adel; Hibbert, Jacqueline M; Wilson, Nana O; Iqbal, Shareen A; Adamkiewicz, Thomas V; Stiles, Jonathan K

    2011-09-19

    The influence of host genetics on susceptibility to Plasmodium falciparum malaria has been extensively studied over the past twenty years. It is now clear that malaria parasites have imposed strong selective forces on the human genome in endemic regions. Different genes have been identified that are associated with different malaria related phenotypes. Factors that promote severity of malaria include parasitaemia, parasite induced inflammation, anaemia and sequestration of parasitized erythrocytes in brain microvasculature.Recent advances in human genome research technologies such as genome-wide association studies (GWAS) and fine genotyping tools have enabled the discovery of several genetic polymorphisms and biomarkers that warrant further study in host-parasite interactions. This review describes and discusses human gene polymorphisms identified thus far that have been shown to be associated with susceptibility or resistance to P. falciparum malaria. Although some polymorphisms play significant roles in susceptibility to malaria, several findings are inconclusive and contradictory and must be considered with caution. The discovery of genetic markers associated with different malaria phenotypes will help elucidate the pathophysiology of malaria and enable development of interventions or cures. Diversity in human populations as well as environmental effects can influence the clinical heterogeneity of malaria, thus warranting further investigations with a goal of developing new interventions, therapies and better management against malaria.

  3. Polymorphic growth rates in myrmecophilous insects.

    PubMed

    Schönrogge, K; Wardlaw, J C; Thomas, J A; Elmes, G W

    2000-04-22

    A polymorphism in growth rates was recently described affecting the larval development of the myrmecophilous butterfly Maculinea rebeli, spanning different years in a single insect population. The close integration of M. rebeli into the host ant colonies, facilitated by adaptations in behaviour and chemical mimicry, make extended larval development a successful strategy. Here we present additional data for M. rebeli and new data for Maculinea alcon (another cuckoo-feeding lycaenid) and the two myrmecophilous predators Maculinea arion and Microdon mutabilis (Diptera: Syrphidae). As predicted, M. alcon shows the same growth pattern as M. rebeli with a proportion of caterpillars developing in one year and the remainder over two years. This pattern holds in both northern and southern European populations, where M. alcon exploits different species of host. Against expectation, the same bimodal distribution of pre-pupation body weights, indicating one and two year developers, was found for the larvae of M. arion and M. mutabilis. As predators, both species are less closely integrated in their host ant colonies, suggesting that the polymorphism in growth rates is a more general adaptation to a myrmecophilous life style, arrived at by convergent evolution between the Maculinea and Microdon species. For predatory species we suggest that biennialism is an adaptation to the migratory behaviour of the host made possible by the predators' ability to fast over extended periods. We also hypothesize that M. arion represents an ancestral strategy in Maculinea butterflies and that the growth polymorphism might have become genetically fixed in the cuckoo-feeding species.

  4. Colour Polymorphism Protects Prey Individuals and Populations Against Predation

    PubMed Central

    Karpestam, Einat; Merilaita, Sami; Forsman, Anders

    2016-01-01

    Colour pattern polymorphism in animals can influence and be influenced by interactions between predators and prey. However, few studies have examined whether polymorphism is adaptive, and there is no evidence that the co-occurrence of two or more natural prey colour variants can increase survival of populations. Here we show that visual predators that exploit polymorphic prey suffer from reduced performance, and further provide rare evidence in support of the hypothesis that prey colour polymorphism may afford protection against predators for both individuals and populations. This protective effect provides a probable explanation for the longstanding, evolutionary puzzle of the existence of colour polymorphisms. We also propose that this protective effect can provide an adaptive explanation for search image formation in predators rather than search image formation explaining polymorphism. PMID:26902799

  5. Colour Polymorphism Protects Prey Individuals and Populations Against Predation.

    PubMed

    Karpestam, Einat; Merilaita, Sami; Forsman, Anders

    2016-02-23

    Colour pattern polymorphism in animals can influence and be influenced by interactions between predators and prey. However, few studies have examined whether polymorphism is adaptive, and there is no evidence that the co-occurrence of two or more natural prey colour variants can increase survival of populations. Here we show that visual predators that exploit polymorphic prey suffer from reduced performance, and further provide rare evidence in support of the hypothesis that prey colour polymorphism may afford protection against predators for both individuals and populations. This protective effect provides a probable explanation for the longstanding, evolutionary puzzle of the existence of colour polymorphisms. We also propose that this protective effect can provide an adaptive explanation for search image formation in predators rather than search image formation explaining polymorphism.

  6. Genetic Polymorphisms, Hormone Levels, and Hot Flashes in Midlife Women

    PubMed Central

    Schilling, Chrissy; Gallicchio, Lisa; Miller, Susan R.; Langenberg, Patricia; Zacur, Howard; Flaws, Jodi A.

    2007-01-01

    Objective Hot flashes disrupt the lives of millions of women each year. Although hot flashes are a public health concern, little is known about risk factors that predispose women to hot flashes. Thus, the objective of this study was to examine whether sex steroid hormone levels and genetic polymorphisms in hormone biosynthesis and degradation enzymes are associated with the risk of hot flashes. Methods In a cross-sectional study design, midlife women aged 45 to 54 years (n=639) were recruited from Baltimore and its surrounding counties. Participants completed a questionnaire and donated a blood sample for steroid hormone analysis and genotyping. The associations between genetic polymorphisms and hormone levels, as well as the associations between genetic polymorphisms, hormone levels, and hot flashes were examined using statistical models. Results A polymorphism in CYP1B1 was associated with lower dehydroepiandrosterone-sulfate (DHEA-S) and progesterone levels, while a polymorphism in CYP19 (aromatase) was associated with higher testosterone and DHEA-S levels. Lower progesterone and sex hormone binding globulin levels, lower free estradiol index, and a higher ratio of total androgens to total estrogens were associated with the experiencing of hot flashes. A polymorphism in CYP1B1 and a polymorphism in 3βHSD were both associated with hot flashes. Conclusion Some genetic polymorphisms may be associated with altered levels of hormones in midlife women. Further, selected genetic polymorphisms and altered hormone levels may be associated with the risk of hot flashes in midlife women. PMID:17187946

  7. 2-Quinolinecarboxaldehyde: Polymorphic behavior of a small rigid molecule

    NASA Astrophysics Data System (ADS)

    Maria, Teresa M. R.; Ermelinda S. Eusébio, M.; Almeida e Silva, J.; Sobral, Abílio J. F. N.; Cardoso, C.; Paixão, J. A.; Ramos Silva, M.

    2012-12-01

    This work reports an investigation on the polymorphism of 2-quinolinecarboxaldehyde, a quinoline derivative, frequently used as a ligand in the synthesis of metal complexes. 2-Quinolinecarboxaldehyde lacks both molecular flexibility and the ability to form strong hydrogen bonds, two characteristics often seen as driving forces for the occurrence of polymorphism. Nevertheless, a rich polymorphic behavior was found for this substance. Polymorphic forms were generated by crystallization from solutions, and by melt cooling. Four polymorphic forms could be clearly identified by thermal analysis investigation and the crystalline structures of forms I and III were solved by single-crystal X-ray diffraction, at room temperature. In polymorph I, molecules are joined by π-π and weak C-H⋯O interactions while in polymorph III helicoidal chiral chains are formed and very weak C-H⋯O intermolecular interactions can be identified. Neither of these intermolecular interactions involves the formyl hydrogen atom. Concomitant polymorph crystallization from the melt was often observed. XRPD diffractograms which showed similarities to that of polymorph I but presented striking differences were obtained in some experiments. In certain cases the discrepancies may be ascribed to effects of preferential orientation. However, the existence of multiple but slightly different structures with small differences seems to be a better explanation for these experimental observations.

  8. Persistence of neutral polymorphisms in Lake Victoria cichlid fish

    PubMed Central

    Nagl, Sandra; Tichy, Herbert; Mayer, Werner E.; Takahata, Naoyuki; Klein, Jan

    1998-01-01

    Phylogenetic trees for groups of closely related species often have different topologies, depending on the genes used. One explanation for the discordant topologies is the persistence of polymorphisms through the speciation phase, followed by differential fixation of alleles in the resulting species. The existence of transspecies polymorphisms has been documented for alleles maintained by balancing selection but not for neutral alleles. In the present study, transspecific persistence of neutral polymorphisms was tested in the endemic haplochromine species flock of Lake Victoria cichlid fish. Putative noncoding region polymorphisms were identified at four randomly selected nuclear loci and tested on a collection of 12 Lake Victoria species and their putative riverine ancestors. At all loci, the same polymorphism was found to be present in nearly all the tested species, both lacustrine and riverine. Different polymorphisms at these loci were found in cichlids of other East African lakes (Malawi and Tanganyika). The Lake Victoria polymorphisms must have therefore arisen after the flocks now inhabiting the three great lakes diverged from one another, but before the riverine ancestors of the Lake Victoria flock colonized the Lake. Calculations based on the mtDNA clock suggest that the polymorphisms have persisted for about 1.4 million years. To maintain neutral polymorphisms for such a long time, the population size must have remained large throughout the entire period. PMID:9826684

  9. Persistence of neutral polymorphisms in Lake Victoria cichlid fish.

    PubMed

    Nagl, S; Tichy, H; Mayer, W E; Takahata, N; Klein, J

    1998-11-24

    Phylogenetic trees for groups of closely related species often have different topologies, depending on the genes used. One explanation for the discordant topologies is the persistence of polymorphisms through the speciation phase, followed by differential fixation of alleles in the resulting species. The existence of transspecies polymorphisms has been documented for alleles maintained by balancing selection but not for neutral alleles. In the present study, transspecific persistence of neutral polymorphisms was tested in the endemic haplochromine species flock of Lake Victoria cichlid fish. Putative noncoding region polymorphisms were identified at four randomly selected nuclear loci and tested on a collection of 12 Lake Victoria species and their putative riverine ancestors. At all loci, the same polymorphism was found to be present in nearly all the tested species, both lacustrine and riverine. Different polymorphisms at these loci were found in cichlids of other East African lakes (Malawi and Tanganyika). The Lake Victoria polymorphisms must have therefore arisen after the flocks now inhabiting the three great lakes diverged from one another, but before the riverine ancestors of the Lake Victoria flock colonized the Lake. Calculations based on the mtDNA clock suggest that the polymorphisms have persisted for about 1.4 million years. To maintain neutral polymorphisms for such a long time, the population size must have remained large throughout the entire period.

  10. Single-nucleotide polymorphism discovery by targeted DNA photocleavage.

    PubMed

    Hart, Jonathan R; Johnson, Martin D; Barton, Jacqueline K

    2004-09-28

    Single-nucleotide polymorphisms are the largest source of genetic variation in humans. We report a method for the discovery of single-nucleotide polymorphisms within genomic DNA. Pooled genomic samples are amplified, denatured, and annealed to generate mismatches at polymorphic DNA sites. Upon photoactivation, these DNA mismatches are then cleaved site-specifically by using a small molecular probe, a bulky metallointercalator, Rhchrysi or Rhphzi. Fluorescent labeling of the cleaved products and separation by capillary electrophoresis permits rapid identification with single-base resolution of the single-nucleotide polymorphism site. This method is remarkably sensitive and minor allele frequencies as low as 5% can be readily detected.

  11. Apparent scarcity of low-density polymorphs of inorganic solids.

    PubMed

    Zwijnenburg, Martijn A; Illas, Francesc; Bromley, Stefan T

    2010-04-30

    For most inorganic solids, very few dense polymorphs and no low-density polymorphs are observed. Taking a wide range of tetrahedrally-coordinated binary solids (e.g., ZnO, GaN) as a prototypical system, we show that the apparent scarcity of low- density polymorphs is not due to significant structural or energetic limitations. Using databases of periodic networks as sources of novel crystal structures, followed by ab initio energy minimization, we predict a dense spectrum of low-density low-energy polymorphs. The diverse range of materials considered indicates that this is likely to be a general phenomenon.

  12. Novel Processing of Ceramics with Polymorphic Control

    NASA Astrophysics Data System (ADS)

    Jodhani, Gagan

    Polymorphism is an important phenomenon exhibited by many materials, including ceramic oxides. The availability of multiple structural configurations for the same chemical composition opens the pathway to a large number of phases with distinct properties. The formation of the crystal structures can be directly correlated to the processing temperature and/or pressure as well as the particle size for nanomaterials. This work focuses on the tailored synthesis of the desired polymorphs of binary and ternary metal oxides through nanoscale processes with emphasis on flame spray pyrolysis. Flame spray pyrolysis (FSP) is a scalable nano-manufacturing process used for the synthesis of oxide based ceramics. The advantage of this process lies in ease of operation and inexpensive processing as well as the uniformity in the particle size distribution of the products. It is a rapid solidification process involving the atomization of precursor using high temperature gradients and low residence times in the flame. Thus, metastable polymorphs have successfully been synthesized by FSP. Although a wide variety of studies have been conducted on the synthesis and applications of ceramics via FSP there has been scarce knowledge on the actual dynamics of crystal structure formation during the process. Various solution parameters were studied to understand the particle and crystal structure formation for the FSP powders. The process parameters were kept the same; 1.5 slm methane and 3.0 slm O2 was used as fuel for the flame, 5slm oxygen was used as dispersion gas and the precursor was fed at 5ml/min. MoO3 was synthesized using different concentrations of precursor and the particle sizes obtained were correlated to the materials parameters such as solution concentration and amount of organic precursor solvent. Another study was conducted on formation of WO3 polymorphs using organic precursor salts dissolved in organic solvent. The solution was prepared to obtain low particle sizes and to

  13. Surface Accuracy Measurement Sensor for Deployable Reflector Antennas (SAMS DRA)

    NASA Technical Reports Server (NTRS)

    Neiswander, R. S.

    1980-01-01

    Specifications, system configurations, and concept tests for surface measurement sensors for deployable reflector antennas are presented. Two approaches toward the optical measurement of remote target displacements are discussed: optical ranging, in which the basic measurement is target-to-sensor range; and in particular, optical angular sensing, in which the principle measurements are of target angular displacements lateral to the line of sight. Four representative space antennas are examined.

  14. Polymorphism in phenobarbital: discovery of a new polymorph and crystal structure of elusive form V.

    PubMed

    Roy, Saikat; Goud, N Rajesh; Matzger, Adam J

    2016-03-21

    This report highlights the discovery of a new polymorph of the anticonvulsant drug phenobarbital (PB) using polymer-induced heteronucleation (PIHn) and unravelling the crystal structure of the elusive form V. Both forms are characterized by structural, thermal and VT-Raman spectroscopy methods to elucidate phase transformation behavior and shed light on stability relationships.

  15. Polymorphism in silicate-postperovskite reviewed (Invited)

    NASA Astrophysics Data System (ADS)

    Tschauner, O. D.

    2010-12-01

    Early on in the examination of postperovskite(ppv)-type magnesium metasilicate it had been debated if this potential deep mantle mineral can be subject to further structural transformation as function of composition, pressure, and temperature within the range of conditions in the lower mantle. MgSiO3-perovskite accommodates minor elements through local lattice distortions by tilt of the corner-sharing octahedral framework. The CaIrO3-type ppv structure does not seem to possess a similar mechanism of local relaxation of lattice strain. Instead minor elements may rather be accommodated by periodic kinks in this layered structure (1). This kinking-mechanism allows for generating a plethora of polymorphs similar in structure and free energy (1,2). However, the elastic properties of ppv may be strongly affected by this type of structural modification. While structural analogues of silicate-ppv exhibit this type of polymorphism (3,4) previous attempts to examine polymorphism in silicate-ppv remained suggestive (2,5). This is mostly owed to the severe constraints imposed on powder diffraction studies conducted under the extreme conditions of stability of MgSiO3-ppv. Here I present new results on silicate-ppv based on different experimental strategies which shed more light on this complex yet important issue of structural modifications in minor-element bearing silicate-ppv. (1) Oganov et al. Nature 438, 1142 (2005);(2) Tschauner et al. Am. Min. 93, 533 (2008); (3) Shirako et al. Phys. Chem. Min. 36, 455 (2009); Yakovlev et al. J. Sol. Stat. Chem. 182, 1545 (2009) Work supported through NNSA Cooperative Agreement DOE-FC88-01NV14049

  16. MICA polymorphism: biology and importance in cancer.

    PubMed

    Chen, Dan; Gyllensten, Ulf

    2014-12-01

    The major histocompatibility complex class I polypeptide-related sequence A gene (MICA) encodes a membrane-bound protein acting as a ligand to stimulate an activating receptor, NKG2D, expressed on the surface of essentially all human natural killer (NK), γδ T and CD8(+) αβ T cells. MICA protein is absent from most cells but can be induced by infections and oncogenic transformation and is frequently expressed in epithelial tumors. Upon binding to MICA, NKG2D activates cytolytic responses of NK and γδ T cells against infected and tumor cells expressing MICA. Therefore, membrane-bound MICA acts as a signal during the early immune response against infection or spontaneously arising tumors. On the other hand, human tumor cells spontaneously release a soluble form of MICA, causing the downregulation of NKG2D and in turn severe impairment of the antitumor immune response of NK and CD8(+) T cells. This is considered to promote tumor immune evasion and also to compromise host resistance to infections. MICA is the most polymorphic non-classical class I gene. A possible association of MICA polymorphism with genetic predisposition to different cancer types has been investigated in candidate gene-based studies. Two genome-wide association studies have identified loci in MICA that influence susceptibility to cervical neoplasia and hepatitis C virus-induced hepatocellular carcinoma, respectively. Given the current level of interest in the field of MICA gene, we discuss the genetics and biology of the MICA gene and the role of its polymorphism in cancer. Gaps in our understanding and future research needs are also discussed. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Adrenergic Polymorphism and the Human Stress Response

    PubMed Central

    Rao, Fangwen; Zhang, Lian; Wessel, Jennifer; Zhang, Kuixing; Wen, Gen; Kennedy, Brian P.; Rana, Brinda K.; Das, Madhusudan; Rodriguez-Flores, Juan L.; Smith, Douglas W.; Cadman, Peter E.; Salem, Rany M.; Mahata, Sushil K.; Schork, Nicholas J.; Taupenot, Laurent; Ziegler, Michael G.; O’Connor, Daniel T.

    2009-01-01

    Tyrosine hydroxylase (TH) is the rate-limiting enzyme in catecholamine biosynthesis. Does common genetic variation at human TH alter autonomic activity and predispose to cardiovascular disease? We undertook systematic polymorphism discovery at the TH locus, and then tested variants for contributions to sympathetic function and blood pressure. We resequenced 80 ethnically diverse individuals across the TH locus. One hundred seventy-two twin pairs were evaluated for sympathetic traits, including catecholamine production and environmental (cold) stress responses. To evaluate hypertension, we genotyped subjects selected from the most extreme diastolic blood pressure percentiles in the population. Human TH promoter haplotype/reporter plasmids were transfected into chromaffin cells. Forty-nine single nucleotide polymorphisms (SNPs) and one tetranucleotide repeat were discovered, but coding region polymorphism did not account for common phenotypic variation. A block of linkage disequilibrium spanned four common variants in the proximal promoter. Catecholamine secretory traits were significantly heritable, as were stress-induced blood pressure changes. In the TH promoter, significant associations were found for urinary catecholamine excretion, as well as blood pressure response to stress. TH promoter haplotype #2 (TGGG) showed pleiotropy, increasing both norepinephrine excretion and blood pressure during stress. In hypertension, a case–control study (1266 subjects, 53% women) established the effect of C-824T in determination of blood pressure. We conclude that human catecholamine secretory traits are heritable, displaying joint genetic determination (pleiotropy) with autonomic activity and finally with blood pressure in the population. Catecholamine secretion is influenced by genetic variation in the adrenergic pathway encoding catecholamine synthesis, especially at the classically rate-limiting step, TH. The results suggest novel pathophysiological links between a key

  18. Placental glucose dehydrogenase polymorphism in Koreans.

    PubMed

    Kim, Y J; Paik, S G; Park, H Y

    1994-12-01

    The genetic polymorphism of placental glucose dehydrogenase (GDH) was investigated in 300 Korean placentae using horizontal starch gel electrophoresis. The allele frequencies for GDH1, GDH2 and GDH3 were 0.537, 0.440 and 0.005, respectively, which were similar to those in Japanese. We also observed an anodal allele which was similar to the GDH4 originally reported in Chinese populations at a low frequency of 0.015. An additional new cathodal allele (named GDH6) was observed in the present study with a very low frequency of 0.003.

  19. [HLA-B27 polymorphism and spondyloarthropathies].

    PubMed

    Peixoto, M J; Gonzales, T; Spinola, H; Couto, A R; Mora, M Gantes; Brehm, A; Santos, M R; Garrett, F; Armas, J Bruges

    2005-01-01

    The association of HLA-B27 with ankylosing spondylitis (AS), and other spondyloarthropathies (SpA), remains as one of the strongest between HLA molecules and human disease. Since it was reported, in 1973, it has been extensively studied in order to understand the underlying pathogenic mechanism. The objective of this article is to review the current knowledge on the structure and polymorphism of HLA-B27 molecule, as well as describe the main pathogenic hypotheses trying to explain its association with AS.

  20. Cardiac and skeletal muscle myosin polymorphism.

    PubMed

    Lowey, S

    1986-06-01

    Skeletal muscles, unlike cardiac tissue, express several myosin isozymes during development which differ in primary structure from adult myosin. Monoclonal antibodies have shown the presence of at least two embryonic myosins, followed by a post-hatch myosin that persists until the appearance of adult myosin in chicken pectoralis muscle. Although the two major cardiac isozymes differ in enzymatic activity, the avian skeletal myosin isozymes all share the same high level of ATPase activity found for adult pectoralis myosin. The functional basis for the extensive myosin polymorphism in skeletal muscles thus remains to be determined.

  1. [Polymorphous photodermatosis--photobiologic diagnosis and therapy].

    PubMed

    Hönigsmann, H; Ortel, B

    1988-08-15

    Polymorphous light eruption is an acquired photodermatosis, whose causal factors have not yet been identified. The diagnosis is based on the clinical picture and on histology. During the symptomless periods, photo-testing is the most important technique to confirm the diagnosis, since there are no specific laboratory parameters. Regarding our own patients, typical lesions could be provoked by UVA in 50%, by UVB in 20% and by both in 30%. The majority of the patients can be protected during the summer season by intermittent preventive photo(chemo)therapy.

  2. What Determines the Ice Polymorph in Clouds?

    PubMed

    Hudait, Arpa; Molinero, Valeria

    2016-07-20

    Ice crystals in the atmosphere nucleate from supercooled liquid water and grow by vapor uptake. The structure of the ice polymorph grown has strong impact on the morphology and light scattering of the ice crystals, modulates the amount of water vapor in ice clouds, and can impact the molecular uptake and reactivity of atmospheric aerosols. Experiments and molecular simulations indicate that ice nucleated and grown from deeply supercooled liquid water is metastable stacking disordered ice. The ice polymorph grown from vapor has not yet been determined. Here we use large-scale molecular simulations to determine the structure of ice that grows as a result of uptake of water vapor in the temperature range relevant to cirrus and mixed-phase clouds, elucidate the molecular mechanism of the formation of ice at the vapor interface, and compute the free energy difference between cubic and hexagonal ice interfaces with vapor. We find that vapor deposition results in growth of stacking disordered ice only under conditions of extreme supersaturation, for which a nonequilibrium liquid layer completely wets the surface of ice. Such extreme conditions have been used to produce stacking disordered frost ice in experiments and may be plausible in the summer polar mesosphere. Growth of ice from vapor at moderate supersaturations in the temperature range relevant to cirrus and mixed-phase clouds, from 200 to 260 K, produces exclusively the stable hexagonal ice polymorph. Cubic ice is disfavored with respect to hexagonal ice not only by a small penalty in the bulk free energy (3.6 ± 1.5 J mol(-1) at 260 K) but also by a large free energy penalty at the ice-vapor interface (89.7 ± 12.8 J mol(-1) at 260 K). The latter originates in higher vibrational entropy of the hexagonal-terminated ice-vapor interface. We predict that the free energy penalty against the cubic ice interface should decrease strongly with temperature, resulting in some degree of stacking disorder in ice grown from

  3. Genetic salivary protein polymorphism in Mexican population.

    PubMed

    Banderas Tarabay, J A; González Begné, M

    1996-01-01

    Genetic polymorphism is the major contributor that affects human salivary composition. In order to determine the molecular phenotypes in saliva, it is important to know the distribution of proteins with specific functions which allows the clinical diagnosis of specific diseases. Unstimulated human whole saliva samples from 120 subjects were subjected to sodium dodecyl sulfate polyacrylamide slab gel electrophoresis (SDS-PAGE). The phenotype distribution of several molecules including MG1, MG2, alpha-Amylase, PRP-I and cystatins were similar. Qualitative and quantitative characteristics were specific in each subject.

  4. A Simplified Account of Polymorphic References. Revised

    DTIC Science & Technology

    1993-06-01

    CloseA(rl) generalizes t, whereas (’loseA,(r, ) does not. (This observation is due to Foite . who also goes on to provide a counterexample to the theorem [I...thettir ’tomintt’lts and’ Suiggest ions. References [11 Andrew W. Appel attd David B. MacQueen. Standard ML of New Je’rsey. In .1. Malitszvttski antI M...Type inference for polymorphic references. Information and Computation. 89:1--3.1. Noveni- ber 1990. [121 Andrew Wright. Typing references by effect

  5. RADB: a database of rheumatoid arthritis-related polymorphisms

    PubMed Central

    Zhang, Ruijie; Luan, Meiwei; Shang, Zhenwei; Duan, Lian; Tang, Guoping; Shi, Miao; Lv, Wenhua; Zhu, Hongjie; Li, Jin; Lv, Hongchao; Zhang, Mingming; Liu, Guiyou; Chen, He; Jiang, Yongshuai

    2014-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease that has a complex genetic basis. Therefore, it is important to explore the genetic background of RA. The extensive recent application of polymorphic genetic markers, especially single nucleotide polymorphisms, has presented us with a large quantity of genetic data. In this study, we developed the Database of Rheumatoid Arthritis-related Polymorphisms (RADB), to integrate all the RA-related genetic polymorphisms and provide a useful resource for researchers. We manually extracted the RA-related polymorphisms from 686 published reports, including RA susceptibility loci, polymorphisms associated with particular clinical features of RA, polymorphisms associated with drug response in RA and polymorphisms associated with a higher risk of cardiovascular disease in RA. Currently, RADB V1.0 contains 3235 polymorphisms that are associated with 636 genes and refer to 68 countries. The detailed information extracted from the literature includes basic information about the articles (e.g. PubMed ID, title and abstract), population information (e.g. country, geographic area and sample size) and polymorphism information (e.g. polymorphism name, gene, genotype, odds ratio and 95% confidence interval, P-value and risk allele). Meanwhile, useful annotations, such as hyperlinks to dbSNP, GenBank, UCSC, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway, are included. In addition, a tool for meta-analysis was developed to summarize the results of multiple studies. The database is freely available at http://www.bioapp.org/RADB. Database URL: http://www.bioapp.org/RADB. PMID:25228593

  6. Association between Tryptophan Hydroxylase 2 Gene Polymorphism and Completed Suicide

    ERIC Educational Resources Information Center

    Fudalej, Sylwia; Ilgen, Mark; Fudalej, Marcin; Kostrzewa, Grazyna; Barry, Kristen; Wojnar, Marcin; Krajewski, Pawel; Blow, Frederic; Ploski, Rafal

    2010-01-01

    The association between suicide and a single nucleotide polymorphism (rs1386483) was examined in the recently identified tryptophan hydroxylase 2 (TPH2) gene. Blood samples of 143 suicide victims and 162 age- and sex-matched controls were examined. The frequency of the TT genotype in the TPH2 polymorphism was higher in suicide victims than in…

  7. Effects of human SAMHD1 polymorphisms on HIV-1 susceptibility

    SciTech Connect

    White, Tommy E.; Brandariz-Nuñez, Alberto; Valle-Casuso, Jose Carlos; Knowlton, Caitlin; Kim, Baek; Sawyer, Sara L.; Diaz-Griffero, Felipe

    2014-07-15

    SAMHD1 is a human restriction factor that prevents efficient infection of macrophages, dendritic cells and resting CD4+ T cells by HIV-1. Here we explored the antiviral activity and biochemical properties of human SAMHD1 polymorphisms. Our studies focused on human SAMHD1 polymorphisms that were previously identified as evolving under positive selection for rapid amino acid replacement during primate speciation. The different human SAMHD1 polymorphisms were tested for their ability to block HIV-1, HIV-2 and equine infectious anemia virus (EIAV). All studied SAMHD1 variants block HIV-1, HIV-2 and EIAV infection when compared to wild type. We found that these variants did not lose their ability to oligomerize or to bind RNA. Furthermore, all tested variants were susceptible to degradation by Vpx, and localized to the nuclear compartment. We tested the ability of human SAMHD1 polymorphisms to decrease the dNTP cellular levels. In agreement, none of the different SAMHD1 variants lost their ability to reduce cellular levels of dNTPs. Finally, we found that none of the tested human SAMHD1 polymorphisms affected the ability of the protein to block LINE-1 retrotransposition. - Highlights: • Human SAMHD1 single-nucleotide polymorphisms block HIV-1 and HIV-2 infection. • SAMHD1 polymorphisms do not affect its ability to block LINE-1 retrotransposition. • SAMHD1 polymorphisms decrease the cellular levels of dNTPs.

  8. Microhabitat variation and sexual selection can maintain male color polymorphisms.

    PubMed

    Chunco, Amanda J; McKinnon, Jeffrey S; Servedio, Maria R

    2007-11-01

    Male color polymorphism may be an important precursor to sympatric speciation by sexual selection, but the processes maintaining such polymorphisms are not well understood. Here, we develop a formal model of the hypothesis that male color polymorphisms may be maintained by variation in the sensory environment resulting in microhabitat-specific selection pressures. We analyze the evolution of two male color morphs when color perception (by females and predators) is dependent on the microhabitat in which natural and sexual selection occur. We find that an environment of heterogeneous microhabitats can lead to the maintenance of color polymorphism despite asymmetries in the strengths of natural and sexual selection and in microhabitat proportions. We show that sexual selection alone is sufficient for polymorphism maintenance over a wide range of parameter space, even when female preferences are weak. Polymorphisms can also be maintained by natural selection acting alone, but the conditions for polymorphism maintenance by natural selection will usually be unrealistic for the case of microhabitat variation. Microhabitat variation and sexual selection for conspicuous males may thus provide a situation particularly favorable to the maintenance of male color polymorphisms. These results are important both because of the general insight they provide into a little appreciated mechanism for the maintenance of variation in natural populations and because such variation is an important prerequisite for sympatric speciation.

  9. Polymorphisms in Autophagy Genes and Susceptibility to Tuberculosis

    PubMed Central

    Alisjahbana, Bachti; Sahiratmadja, Edhyana; Parwati, Ida; Oosting, Marije; Plantinga, Theo S.; Joosten, Leo A. B.; Netea, Mihai G.; Ottenhoff, Tom H. M.; van de Vosse, Esther; van Crevel, Reinout

    2012-01-01

    Recent data suggest that autophagy is important for intracellular killing of Mycobacterium tuberculosis, and polymorphisms in the autophagy gene IRGM have been linked with susceptibility to tuberculosis (TB) among African-Americans, and with TB caused by particular M. tuberculosis genotypes in Ghana. We compared 22 polymorphisms of 14 autophagy genes between 1022 Indonesian TB patients and 952 matched controls, and between patients infected with different M. tuberculosis genotypes, as determined by spoligotyping. The same autophagy polymorphisms were studied in correlation with ex-vivo production of TNF, IL-1β, IL-6, IL-8, IFN-γ and IL-17 in healthy volunteers. No association was found between TB and polymorphisms in the genes ATG10, ATG16L2, ATG2B, ATG5, ATG9B, IRGM, LAMP1, LAMP3, P2RX7, WIPI1, MTOR and ATG4C. Associations were found between polymorphisms in LAMP1 (p = 0.02) and MTOR (p = 0.02) and infection with the successful M. tuberculosis Beijing genotype. The polymorphisms examined were not associated with M. tuberculosis induced cytokines, except for a polymorphism in ATG10, which was linked with IL-8 production (p = 0.04). All associations found lost statistical significance after correction for multiple testing. This first examination of a broad set of polymorphisms in autophagy genes fails to show a clear association with TB, with M. tuberculosis Beijing genotype infection or with ex-vivo pro-inflammatory cytokine production. PMID:22879892

  10. Association between Tryptophan Hydroxylase 2 Gene Polymorphism and Completed Suicide

    ERIC Educational Resources Information Center

    Fudalej, Sylwia; Ilgen, Mark; Fudalej, Marcin; Kostrzewa, Grazyna; Barry, Kristen; Wojnar, Marcin; Krajewski, Pawel; Blow, Frederic; Ploski, Rafal

    2010-01-01

    The association between suicide and a single nucleotide polymorphism (rs1386483) was examined in the recently identified tryptophan hydroxylase 2 (TPH2) gene. Blood samples of 143 suicide victims and 162 age- and sex-matched controls were examined. The frequency of the TT genotype in the TPH2 polymorphism was higher in suicide victims than in…

  11. Microsatellite markers and polymorphism in cheatgrass (Bromus tectorum L.)

    Treesearch

    Alisa P. Ramakrishnan; Craig E. Coleman; Susan E. Meyer; Daniel J. Fairbanks

    2001-01-01

    Cheatgrass (Bromus tectorum) individuals were genetically characterized using polymorphic microsatellite markers. Through analysis of alleles of five polymorphic loci, genotypes were constructed of individuals from four populations in Utah and Nevada. There were 15 different genotypes: Whiterocks, UT, had nine genotypes, Hobble Creek, UT, had seven genotypes,...

  12. Impact of host genetic polymorphisms on vaccine induced antibody response

    PubMed Central

    Linnik, Janina E.; Egli, Adrian

    2016-01-01

    ABSTRACT Many host- and vaccine-specific factors modulate an antibody response. Host genetic polymorphisms, in particular, modulate the immune response in multiple ways on different scales. This review article describes how information on host genetic polymorphisms and corresponding immune cascades may be used to generate personalized vaccine strategies to optimize the antibody response. PMID:26809773

  13. Human lymphocyte polymorphisms detected by quantitative two-dimensional electrophoresis

    SciTech Connect

    Goldman, D.; Merril, C.R.

    1983-09-01

    A survey of 186 soluble lymphocyte proteins for genetic polymorphism was carried out utilizing two-dimensional electrophoresis of /sup 14/C-labeled phytohemagglutinin (PHA)-stimulated human lymphocyte proteins. Nineteen of these proteins exhibited positional variation consistent with independent genetic polymorphism in a primary sample of 28 individuals. Each of these polymorphisms was characterized by quantitative gene-dosage dependence insofar as the heterozygous phenotype expressed approximately 50% of each allelic gene product as was seen in homozygotes. Patterns observed were also identical in monozygotic twins, replicate samples, and replicate gels. The three expected phenotypes (two homozygotes and a heterozygote) were observed in each of 10 of these polymorphisms while the remaining nine had one of the homozygous classes absent. The presence of the three phenotypes, the demonstration of gene-dosage dependence, and our own and previous pedigree analysis of certain of these polymorphisms supports the genetic basis of these variants. Based on this data, the frequency of polymorphic loci for man is: P . 19/186 . .102, and the average heterozygosity is .024. This estimate is approximately 1/3 to 1/2 the rate of polymorphism previously estimated for man in other studies using one-dimensional electrophoresis of isozyme loci. The newly described polymorphisms and others which should be detectable in larger protein surveys with two-dimensional electrophoresis hold promise as genetic markers of the human genome for use in gene mapping and pedigree analyses.

  14. Effects of functional polymorphisms on beef carcass merit

    USDA-ARS?s Scientific Manuscript database

    To develop a resource to identify polymorphisms present in common beef cattle breeds, and relate those polymorphisms to phenotypic differences, low-coverage genomic sequence was obtained on 186 purebred bulls from 15 predominant breeds in the United States, and 84 crossbred sons of these bulls. The...

  15. Bitter taste receptor polymorphisms and human aging.

    PubMed

    Campa, Daniele; De Rango, Francesco; Carrai, Maura; Crocco, Paolina; Montesanto, Alberto; Canzian, Federico; Rose, Giuseppina; Rizzato, Cosmeri; Passarino, Giuseppe; Barale, Roberto

    2012-01-01

    Several studies have shown that genetic factors account for 25% of the variation in human life span. On the basis of published molecular, genetic and epidemiological data, we hypothesized that genetic polymorphisms of taste receptors, which modulate food preferences but are also expressed in a number of organs and regulate food absorption processing and metabolism, could modulate the aging process. Using a tagging approach, we investigated the possible associations between longevity and the common genetic variation at the three bitter taste receptor gene clusters on chromosomes 5, 7 and 12 in a population of 941 individuals ranging in age from 20 to 106 years from the South of Italy. We found that one polymorphism, rs978739, situated 212 bp upstream of the TAS2R16 gene, shows a statistically significant association (p = 0.001) with longevity. In particular, the frequency of A/A homozygotes increases gradually from 35% in subjects aged 20 to 70 up to 55% in centenarians. These data provide suggestive evidence on the possible correlation between human longevity and taste genetics.

  16. IPD—the Immuno Polymorphism Database

    PubMed Central

    Robinson, James; Halliwell, Jason A.; McWilliam, Hamish; Lopez, Rodrigo; Marsh, Steven G. E.

    2013-01-01

    The Immuno Polymorphism Database (IPD), http://www.ebi.ac.uk/ipd/ is a set of specialist databases related to the study of polymorphic genes in the immune system. The IPD project works with specialist groups or nomenclature committees who provide and curate individual sections before they are submitted to IPD for online publication. The IPD project stores all the data in a set of related databases. IPD currently consists of four databases: IPD-KIR, contains the allelic sequences of killer-cell immunoglobulin-like receptors, IPD-MHC, a database of sequences of the major histocompatibility complex of different species; IPD-HPA, alloantigens expressed only on platelets; and IPD-ESTDAB, which provides access to the European Searchable Tumour Cell-Line Database, a cell bank of immunologically characterized melanoma cell lines. The data is currently available online from the website and FTP directory. This article describes the latest updates and additional tools added to the IPD project. PMID:23180793

  17. Plumage polymorphism and fitness in Swainson's hawks.

    PubMed

    Briggs, C W; Collopy, M W; Woodbridge, B

    2011-10-01

    We examine the maintenance of a plumage polymorphism, variation in plumages among the same age and sex class within a population, in a population of Swainson's Hawks. We take advantage of 32 years of data to examine two prevalent hypotheses used to explain the persistence of morphs: apostatic selection and heterozygous advantage. We investigate differences in fitness among three morph classes of a melanistic trait in Swainson's Hawks: light (7% of the local breeding population), intermediate (57%) and dark (36%). Specifically, we examined morph differences in adult apparent survival, breeding success, annual number of fledglings produced, probability of offspring recruitment into the breeding population and lifetime reproductive success (LRS). If apostatic selection were a factor in maintaining morphs, we would expect that individuals with the least frequent morph would perform best in one or more of these fitness categories. Alternatively, if heterozygous advantage played a role in the maintenance of this polymorphism, we would expect heterozygotes (i.e. intermediate morphs) to have one or more increased rates in these categories. We found no difference in adult apparent survival between morph classes. Similarly, there were no differences in breeding success, nest productivity, LRS or probability of recruitment of offspring between parental morph. We conclude that neither apostatic selection nor heterozygous advantage appear to play a role in maintaining morphs in this population. © 2011 The Authors. Journal of Evolutionary Biology © 2011 European Society For Evolutionary Biology.

  18. Dynamically Alterable Arrays of Polymorphic Data Types

    NASA Technical Reports Server (NTRS)

    James, Mark

    2006-01-01

    An application library package was developed that represents data packets for Deep Space Network (DSN) message packets as dynamically alterable arrays composed of arbitrary polymorphic data types. The software was to address a limitation of the present state of the practice for having an array directly composed of a single monomorphic data type. This is a severe limitation when one is dealing with science data in that the types of objects one is dealing with are typically not known in advance and, therefore, are dynamic in nature. The unique feature of this approach is that it enables one to define at run-time the dynamic shape of the matrix with the ability to store polymorphic data types in each of its indices. Existing languages such as C and C++ have the restriction that the shape of the array must be known in advance and each of its elements be a monomorphic data type that is strictly defined at compile-time. This program can be executed on a variety of platforms. It can be distributed in either source code or binary code form. It must be run in conjunction with any one of a number of Lisp compilers that are available commercially or as shareware.

  19. Polymorphic phase transition mechanism of compressed coesite.

    PubMed

    Hu, Q Y; Shu, J-F; Cadien, A; Meng, Y; Yang, W G; Sheng, H W; Mao, H-K

    2015-03-20

    Silicon dioxide is one of the most abundant natural compounds. Polymorphs of SiO₂ and their phase transitions have long been a focus of great interest and intense theoretical and experimental pursuits. Here, compressing single-crystal coesite SiO₂ under hydrostatic pressures of 26-53 GPa at room temperature, we discover a new polymorphic phase transition mechanism of coesite to post-stishovite, by means of single-crystal synchrotron X-ray diffraction experiment and first-principles computational modelling. The transition features the formation of multiple previously unknown triclinic phases of SiO₂ on the transition pathway as structural intermediates. Coexistence of the low-symmetry phases results in extensive splitting of the original coesite X-ray diffraction peaks that appear as dramatic peak broadening and weakening, resembling an amorphous material. This work sheds light on the long-debated pressure-induced amorphization phenomenon of SiO₂, but also provides new insights into the densification mechanism of tetrahedrally bonded structures common in nature.

  20. Polymorphic phase transition mechanism of compressed coesite

    NASA Astrophysics Data System (ADS)

    Hu, Q. Y.; Shu, J.-F.; Cadien, A.; Meng, Y.; Yang, W. G.; Sheng, H. W.; Mao, H.-K.

    2015-03-01

    Silicon dioxide is one of the most abundant natural compounds. Polymorphs of SiO2 and their phase transitions have long been a focus of great interest and intense theoretical and experimental pursuits. Here, compressing single-crystal coesite SiO2 under hydrostatic pressures of 26-53 GPa at room temperature, we discover a new polymorphic phase transition mechanism of coesite to post-stishovite, by means of single-crystal synchrotron X-ray diffraction experiment and first-principles computational modelling. The transition features the formation of multiple previously unknown triclinic phases of SiO2 on the transition pathway as structural intermediates. Coexistence of the low-symmetry phases results in extensive splitting of the original coesite X-ray diffraction peaks that appear as dramatic peak broadening and weakening, resembling an amorphous material. This work sheds light on the long-debated pressure-induced amorphization phenomenon of SiO2, but also provides new insights into the densification mechanism of tetrahedrally bonded structures common in nature.

  1. TNFA promoter polymorphism and susceptibility to brucellosis.

    PubMed

    Caballero, A; Bravo, M J; Nieto, A; Colmenero, J D; Alonso, A; Martín, J

    2000-09-01

    The aim of this study was to investigate the possible influence of the tumor necrosis factor alpha (TNFA) gene promoter polymorphisms and HLA class II genes on the susceptibility to or development of human brucellosis. TNFA genotypes (at positions -308 and -238) were determined in 59 patients with brucellosis and 160 healthy controls by polymerase chain reaction-restriction fragment length polymorphism. There were no significant differences between the patients and the controls for the TNFA-238 genotypes. However, when the overall TNFA-308 genotype distribution of the brucella patients was compared with that of the control subjects, a significant skewing was observed (P = 0.02). The TNFA-308.1/2 genotype was present at significantly higher frequency in the total patient as a whole compared with control subjects (30% versus 15%; P = 0.01, odds ratio (OR) 2.49, 95% confidence interval (CI) 1.16-5.33). No statistically significant differences in the distribution of HLA-DRB1 or DQB1 alleles were observed between brucella patients and control subjects. Stratification to correct for interdependence of TNFA-308.2 and HLA-DR3 alleles confirmed that, in spite of their strong linkage disequilibrium, the association of TNFA-308.2 with brucellosis was independent of HLA-DR3.

  2. IPD--the Immuno Polymorphism Database.

    PubMed

    Robinson, James; Waller, Matthew J; Stoehr, Peter; Marsh, Steven G E

    2005-01-01

    The Immuno Polymorphism Database (IPD) (http://www.ebi.ac.uk/ipd/) is a set of specialist databases related to the study of polymorphic genes in the immune system. IPD currently consists of four databases: IPD-KIR, contains the allelic sequences of Killer-cell Immunoglobulin-like Receptors; IPD-MHC, a database of sequences of the Major Histocompatibility Complex of different species; IPD-HPA, alloantigens expressed only on platelets; and IPD-ESTAB, which provides access to the European Searchable Tumour Cell-Line Database, a cell bank of immunologically characterized melanoma cell lines. The IPD project works with specialist groups or nomenclature committees who provide and curate individual sections before they are submitted to IPD for online publication. The IPD project stores all the data in a set of related databases. Those sections with similar data, such as IPD-KIR and IPD-MHC share the same database structure. The sharing of a common database structure makes it easier to implement common tools for data submission and retrieval. The data are currently available online from the website and ftp directory; files will also be made available in different formats to download from the website and ftp server. The data will also be included in SRS, BLAST and FASTA search engines at the European Bioinformatics Institute.

  3. Polymorphic collaboration in the global grid

    NASA Astrophysics Data System (ADS)

    McQuay, William K.

    2006-05-01

    Next generation collaborative systems must be able to represent the same information in different forms on a broad spectrum of devices and resources from low end personal digital assistants (PDA) to high performance computers (HPC). Users might be on a desktop then switch to a laptop and then to a PDA while accessing the global grid. The user preference profile for a collaboration session should be capable of moving with them as well as be automatically adjusted for the device type. Collaborative systems must be capable of representing the same information in many forms for different domains and on many devices and thus be polymorphic. Polymorphic collaboration will provide an ability for multiple heterogeneous resources (human to human, human to machine and machine to machine) to share information and activities, as well as the ability to regulate collaborative sessions based on client characteristics and needs; reuse user profiles, tool category choices, and settings in future collaboration session by same or different users; use intelligent agents to assist collaborative systems in learning user/resource preferences and behaviors, and autonomously derive optimal information to provide to users and decision makers. This paper discusses ongoing research in next generation collaborative environments with the goal of making electronic collaboration as easy to use as the telephone - collaboration at the touch of the screen.

  4. Functional relevance of human adh polymorphism.

    PubMed

    Eriksson, C J; Fukunaga, T; Sarkola, T; Chen, W J; Chen, C C; Ju, J M; Cheng, A T; Yamamoto, H; Kohlenberg-Müller, K; Kimura, M; Murayama, M; Matsushita, S; Kashima, H; Higuchi, S; Carr, L; Viljoen, D; Brooke, L; Stewart, T; Foroud, T; Su, J; Li, T K; Whitfield, J B

    2001-05-01

    This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were C. J. Peter Eriksson and Tatsushige Fukunaga. The presentations were (1) 4-Methylpyrazole as a tool in the investigation of the role of ADH in the actions of alcohol in humans, by Taisto Sarkola and C. J. Peter Eriksson; (2) ADH2 polymorphism and flushing in Asian populations, by Wei J. Chen, C. C. Chen, J. M. Ju, and Andrew T. A. Cheng; (3) Role of ADH3 genotypes in the acute effects of alcohol in a Finnish population, by Hidetaka Yamamoto, Kathrin Kohlenberg-Müller, and C. J. Peter Eriksson; (4) Clinical characteristics and disease course of alcoholics with different ADH2 genotypes, by Mitsuru Kimura, Masanobu Murayama, Sachio Matsushita, Haruo Kashima, and Susumu Higuchi; (5) ADH2 polymorphism, alcohol drinking, and birth defects, by Lucinda Carr, D. Viljoen, L. Brooke, T. Stewart, T. Foroud, J. Su, and Ting-Kai Li; and (6) ADH genotypes and alcohol use in Europeans, by John B. Whitfield.

  5. Counterintuitive compaction behavior of clopidogrel bisulfate polymorphs.

    PubMed

    Khomane, Kailas S; More, Parth K; Bansal, Arvind K

    2012-07-01

    Being a density violator, clopidogrel bisulfate (CLP) polymorphic system (forms I and II) allows us to study individually the impact of molecular packing (true density) and thermodynamic properties such as heat of fusion on the compaction behavior. These two polymorphs of CLP were investigated for in-die and out-of-die compaction behavior using CTC profile, Heckel, and Walker equations. Compaction studies were performed on a fully instrumented rotary tabletting machine. Detailed examinations of the molecular packing of each form revealed that arrangement of the sulfate anion differs significantly in both crystal forms, thus conferring different compaction behavior to two forms. Close cluster packing of molecules in form I offers a rigid structure, which has poor compressibility and hence resists deformation under compaction pressure. This results into lower densification, higher yield strength, and mean yield pressure, as compared with form II at a given pressure. However, by virtue of higher bonding strength, form I showed superior tabletability, despite its poor compressibility and deformation behavior. Form I, having higher true density and lower heat of fusion showed higher bonding strength. Hence, true density and not heat of fusion can be considered predictor of bonding strength of the pharmaceutical powders.

  6. Bitter Taste Receptor Polymorphisms and Human Aging

    PubMed Central

    Carrai, Maura; Crocco, Paolina; Montesanto, Alberto; Canzian, Federico; Rose, Giuseppina; Rizzato, Cosmeri

    2012-01-01

    Several studies have shown that genetic factors account for 25% of the variation in human life span. On the basis of published molecular, genetic and epidemiological data, we hypothesized that genetic polymorphisms of taste receptors, which modulate food preferences but are also expressed in a number of organs and regulate food absorption processing and metabolism, could modulate the aging process. Using a tagging approach, we investigated the possible associations between longevity and the common genetic variation at the three bitter taste receptor gene clusters on chromosomes 5, 7 and 12 in a population of 941 individuals ranging in age from 20 to 106 years from the South of Italy. We found that one polymorphism, rs978739, situated 212 bp upstream of the TAS2R16 gene, shows a statistically significant association (p = 0.001) with longevity. In particular, the frequency of A/A homozygotes increases gradually from 35% in subjects aged 20 to 70 up to 55% in centenarians. These data provide suggestive evidence on the possible correlation between human longevity and taste genetics. PMID:23133589

  7. A gene feature enumeration approach for describing HLA allele polymorphism.

    PubMed

    Mack, Steven J

    2015-12-01

    HLA genotyping via next generation sequencing (NGS) poses challenges for the use of HLA allele names to analyze and discuss sequence polymorphism. NGS will identify many new synonymous and non-coding HLA sequence variants. Allele names identify the types of nucleotide polymorphism that define an allele (non-synonymous, synonymous and non-coding changes), but do not describe how polymorphism is distributed among the individual features (the flanking untranslated regions, exons and introns) of a gene. Further, HLA alleles cannot be named in the absence of antigen-recognition domain (ARD) encoding exons. Here, a system for describing HLA polymorphism in terms of HLA gene features (GFs) is proposed. This system enumerates the unique nucleotide sequences for each GF in an HLA gene, and records these in a GF enumeration notation that allows both more granular dissection of allele-level HLA polymorphism and the discussion and analysis of GFs in the absence of ARD-encoding exon sequences.

  8. Special considerations in prognostic research in cancer involving genetic polymorphisms

    PubMed Central

    2013-01-01

    Analysis of genetic polymorphisms may help identify putative prognostic markers and determine the biological basis of variable prognosis in patients. However, in contrast to other variables commonly used in the prognostic studies, there are special considerations when studying genetic polymorphisms. For example, variable inheritance patterns (recessive, dominant, codominant, and additive genetic models) need to be explored to identify the specific genotypes associated with the outcome. In addition, several characteristics of genetic polymorphisms, such as their minor allele frequency and linkage disequilibrium among multiple polymorphisms, and the population substructure of the cohort investigated need to be accounted for in the analyses. In addition, in cancer research due to the genomic differences between the tumor and non-tumor DNA, differences in the genetic information obtained using these tissues need to be carefully assessed in prognostic studies. In this article, we review these and other considerations specific to genetic polymorphism by focusing on genetic prognostic studies in cancer. PMID:23773794

  9. Polymorphism of the IGF-I System and Sports Performance.

    PubMed

    Ben-Zaken, Sigal; Meckel, Yoav; Nemet, Dan; Dror, Nitzan; Eliakim, Alon

    2016-06-01

    The potential use genetic polymorphism, and in particularly polymorphism of hormone genes, as tool to predict athletic performance is currently very challenging. Recent studies suggest that single nucleotide polymorphisms in IGF-I and myostatin may be beneficial for endurance and short distance running, and may even be associated with elite performance. Polymorphism in IGF-I receptor may differentiate between the two edges of the endurance-power athletic performance running spectrum suggesting beneficial effects for endurance and prevent from success in power events. In contrast, and despite similar metabolic demands, the myostatin-IGF-I-IGF-IR system seems not to play an important role in swimming excellence. This suggests that combining different sport disciplines for sports genetic research purposes should be done with extreme caution. Finally, since any phenotype reflects a complex relationship between genes, environment, epigenetic factors, and the interactions between them, consulting the young athlete regarding future success cannot be based solely on genetic polymorphism.

  10. Water ice polymorphs and their significance on planetary surfaces

    NASA Technical Reports Server (NTRS)

    Gaffney, E. S.; Matson, E. L.

    1980-01-01

    Impacts into an icy surface could produce significant amounts of high pressure forms of water ice. Due to the relatively low ambient surface temperatures on satellites in the outer solar system and the modest temperature rises accompanying the impact pressures required for water ice metamorphism, high-pressure polymorphs will be created by and may remain after large cratering events. If so, those high-pressure ices should be ubiquitous. Low-pressure cubic ice may be abundant as well. Impacts into an icy regolith may both produce high-pressure polymorphs from ice I and destroy high-pressure polymorphs already present. The result will be an (unknown) equilibrium concentration of high pressure polymorphs in the regolith. Polymorphs may be detectable and mappable by reflection spectroscopy at vacuum ultraviolet and mid-infrared wavelengths.

  11. Assortative mating counteracts the evolution of dispersal polymorphisms.

    PubMed

    Fronhofer, Emanuel A; Kubisch, Alexander; Hovestadt, Thomas; Poethke, Hans-Joachim

    2011-09-01

    Polymorphic dispersal strategies are found in many plant and animal species. An important question is how the genetic variation underlying such polymorphisms is maintained. Numerous mechanisms have been discussed, including kin competition or frequency-dependent selection. In the context of sympatric speciation events, genetic and phenotypic variation is often assumed to be preserved by assortative mating. Thus, recently, this has been advocated as a possible mechanism leading to the evolution of dispersal polymorphisms. Here, we examine the role of assortative mating for the evolution of trade-off-driven dispersal polymorphisms by modeling univoltine insect species in a metapopulation. We show that assortative mating does not favor the evolution of polymorphisms. On the contrary, assortative mating favors the evolution of an intermediate dispersal type and a uni-modal distribution of traits within populations. As an alternative, mechanism dominance may explain the occurrence of two discrete morphs. © 2011 The Author(s).

  12. Inheritance of restriction fragment length polymorphisms, random amplified polymorphic DNAs and isozymes in coastal Douglas-fir

    Treesearch

    K.D. Jermstad; A.M. Reem; J.R. Henifin; N.C. Wheeler; D.B Neale

    1994-01-01

    A total of 225 new genetic loci [151 restriction fragment length polymorphisms (RFLP) and 74 random amplified polymorphic DNAs (RAPD)] in coastal Douglas- fir [Pseudotsuga menziesii (Mirb.) Franco var. menziesii] have been identified using a three-generation outbred pedigree. The Mendelian inheritance of 16 RFLP loci and 29...

  13. Polymorphisms in metabolic genes, their combination and interaction with tobacco smoke and alcohol consumption and risk of gastric cancer: a case-control study in an Italian population

    PubMed Central

    Boccia, Stefania; Sayed-Tabatabaei, Fakhredin A; Persiani, Roberto; Gianfagna, Francesco; Rausei, Stefano; Arzani, Dario; La Greca, Antonio; D'Ugo, Domenico; La Torre, Giuseppe; van Duijn, Cornelia M; Ricciardi, Gualtiero

    2007-01-01

    Background The distribution and the potential gene-gene and gene-environment interaction of selected metabolic genetic polymorphisms was investigated in relation to gastric cancer risk in an Italian population. Methods One hundred and seven cases and 254 hospital controls, matched by age and gender, were genotyped for CYP1A1, CYP2E1, mEH, GSTM1, GSTT1, NAT2 and SULT1A1 polymorphisms. Haplotype analysis was performed for EPHX1 exons 3 and 4, as well as CYP2E1 RsaI (*5 alleles) and CYP2E1 DraI (*5A or *6 alleles). The effect modification by alcohol and cigarette smoking was tested with the heterogeneity test, while the attributable proportion (AP) was used to measure the biological interaction from the gene-gene interaction analysis. Results Gastric cancer risk was found to be associated with the inheritance of GSTT1 null genotype (OR = 2.10, 95%CI: 1.27–3.44) and the SULT1A1 His/His genotype (OR = 2.46, 95%CI: 1.03–5.90). No differences were observed for the haplotype distributions among cases and controls. For the first time an increased risk was detected among individuals carrying the *6 variant allele of CYP2E1 if ever-drinkers (OR = 3.70; 95%CI: 1.45–9.37) with respect to never-drinkers (OR = 0.18; 95% CI: 0.22–1.46) (p value of heterogeneity among the two estimates = 0.001). Similarly, the effect of SULT1A1 variant genotype resulted restricted to ever-smokers, with an OR of 2.58 (95%CI: 1.27–5.25) for the carriers of His allele among smokers, and an OR of 0.86 (95%CI: 0.45–1.64) among never-smokers (p value of heterogeneity among the two estimates = 0.03). The gene-gene interaction analyses demonstrated that individuals with combined GSTT1 null and NAT2 slow acetylators had an additional increased risk of gastric cancer, with an OR of 3.00 (95%CI: 1.52–5.93) and an AP of 52%. Conclusion GSTT1, SULT1A1 and NAT2 polymorphisms appear to modulate individual's susceptibility to gastric cancer in this Italian population, particularly when more than one

  14. CO2 packing polymorphism under pressure: Mechanism and thermodynamics of the I-III polymorphic transition

    NASA Astrophysics Data System (ADS)

    Gimondi, Ilaria; Salvalaglio, Matteo

    2017-09-01

    In this work, we describe the thermodynamics and mechanism of CO2 polymorphic transitions under pressure from form I to form III combining standard molecular dynamics, well-tempered metadynamics, and committor analysis. We find that the phase transformation takes place through a concerted rearrangement of CO2 molecules, which unfolds via an anisotropic expansion of the CO2 supercell. Furthermore, at high pressures, we find that defected form I configurations are thermodynamically more stable with respect to form I without structural defects. Our computational approach shows the capability of simultaneously providing an extensive sampling of the configurational space, estimates of the thermodynamic stability, and a suitable description of a complex, collective polymorphic transition mechanism.

  15. CO2 packing polymorphism under pressure: Mechanism and thermodynamics of the I-III polymorphic transition.

    PubMed

    Gimondi, Ilaria; Salvalaglio, Matteo

    2017-09-21

    In this work, we describe the thermodynamics and mechanism of CO2 polymorphic transitions under pressure from form I to form III combining standard molecular dynamics, well-tempered metadynamics, and committor analysis. We find that the phase transformation takes place through a concerted rearrangement of CO2 molecules, which unfolds via an anisotropic expansion of the CO2 supercell. Furthermore, at high pressures, we find that defected form I configurations are thermodynamically more stable with respect to form I without structural defects. Our computational approach shows the capability of simultaneously providing an extensive sampling of the configurational space, estimates of the thermodynamic stability, and a suitable description of a complex, collective polymorphic transition mechanism.

  16. H pylori seropositivity and cytokine gene polymorphisms

    PubMed Central

    Saijo, Yasuaki; Yoshioka, Eiji; Fukui, Tomonori; Kawaharada, Mariko; Sata, Fumihiro; Sato, Hirokazu; Kishi, Reiko

    2007-01-01

    AIM: To investigate whether the pro- and anti-inflammatory cytokine gene polymorphisms, IL1B-511C/T, IL1B-31C/T, IL6-634C/G, TNF-1031T/C, TNF-857C/T, and IL10-1082A/G, interact with smoking and drinking habits to influence infection with H pylori. METHODS: The subjects were 410 Japanese transit company employees. C-reactive protein and conventional cardiovascular risk factors were evaluated. Serum anti-H pylori antibodies were measured. The genotypes of IL1B-511C/T, IL1B-31C/T, IL6-634C/G, TNF-1031T/C, TNF-857C/T, and IL10-1082A/G polymorphisms were determined by allelic discrimination using fluorogenic probes and a 5´nuclease assay. RESULTS: In gender- and age-adjusted logistic analyses, the subjects with TNF-857T/T had a significantly lower odds ratio (OR) for H pylori seropositivity (reference -857C/C; OR = 0.15, 95%CI: 0.03-0.59, P = 0.007). After stratification according to smoking and drinking status, among never-smokers, the subjects with IL1B-511C/T had a significantly lower OR (reference -511C/C; OR = 0.30, 95%CI: 0.10-0.90, P = 0.032). Among drinkers in the 1-5 times/wk category, the subjects with IL1B-511T/T had a significantly lower OR (reference C/C; OR = 0.38, 95%CI: 0.16-0.95, P = 0.039), and the subjects with IL1B-31C/T and T/T had a significantly higher OR (reference C/C; C/T: OR = 2.59, 95%CI, P = 0.042: 1.04-6.47; C/C: OR = 3.17, 95%CI: 1.23-8.14, P = 0.017). Among current smokers, the subjects with IL6-634C/G had a significantly higher OR (reference C/C; OR = 2.28, 95%CI: 1.13-4.58, P = 0.021). However, the interactions terms between the aforementioned genotypes and lifestyles were not statistically significant. CONCLUSION: Contrary to previous findings, the results herein suggest that the TNF-857T/T genotype may be protective against chronic infection with H pylori. Drinking and smoking habits may influence the effect of cytokine gene polymorphisms. Further studies are required to clarify the effects of the pro- and anti-inflammatory cytokine

  17. Association of Reelin gene polymorphisms with autism.

    PubMed

    Serajee, Fatema J; Zhong, Hailang; Mahbubul Huq, A H M

    2006-01-01

    Genome scans indicate a linkage of autism to the chromosome 7q21-q36 region. Recent studies suggest that the Reelin gene may be one of the loci contributing to the positive linkage between chromosome 7q and autism. However, these studies were relatively small scale, using a few markers in the gene. We investigated 34 single nucleotide polymorphisms (SNPs) in the Reelin gene with an average spacing between the SNPs of 15 kb for evidence of association with autism. There were significant differences in the transmission of the alleles of exon 22 and intron 59 SNP to autistic subjects. Our findings support a role for the Reelin gene in the susceptibility to autism.

  18. Polymorphic Alu insertions among Mayan populations.

    PubMed

    Herrera, R J; Rojas, D P; Terreros, M C

    2007-01-01

    The Mayan homeland within Mesoamerica spans five countries: Belize, El Salvador, Guatemala, Honduras and Mexico. There are indications that the people we call the Maya migrated from the north to the highlands of Guatemala as early as 4000 B.C. Their existence was village-based and agricultural. The culture of these Preclassic Mayans owes much to the earlier Olmec civilization, which flourished in the southern portion of North America. In this study, four different Mayan groups were examined to assess their genetic variability. Ten polymorphic Alu insertion (PAI) loci were employed to ascertain the genetic affinities among these Mayan groups. North American, African, European and Asian populations were also examined as reference populations. Our results suggest that the Mayan groups examined in this study are not genetically homogeneous.

  19. Two polymorphs of 1,8-dichloroanthracene.

    PubMed

    Müller, Peter; Fronczek, Frank R; Smith, Stacey J; Mako, Teresa; Levine, Mindy

    2013-02-01

    A second, monoclinic, polymorph of the title compound, C(14)H(8)Cl(2), has been found. In addition to the structure of this monoclinic form, the structure of the previously described orthorhombic form [Desvergne, Chekpo & Bouas-Laurent (1978). J. Chem. Soc. Perkin Trans. 2, pp. 84-87; Benites, Maverick & Fronczek (1996). Acta Cryst. C52, 647-648] has been redetermined at low temperature and using modern methods. The low-temperature structure of the orthorhombic form is of significantly higher quality than the previously published structure and additional details can be derived. A comparison of the crystal packing of the two forms with a focus on weak intermolecular C-H···Cl interactions shows the monoclinic structure to have one such interaction linking the molecules into infinite ribbons, while two crystallographically independent C-H···Cl interactions give rise to an interesting infinite three-dimensional network in the orthorhombic crystal form.

  20. Tubulin bistability and polymorphic dynamics of microtubules.

    PubMed

    Mohrbach, Hervé; Johner, Albert; Kulić, Igor M

    2010-12-31

    Based on the hypothesis that the GDP-tubulin dimer is a conformationally bistable molecule-rapidly fluctuating between a discrete curved and a straight state-we develop a model for polymorphic dynamics of the microtubule lattice. We show that GDP-tubulin bistability consistently explains unusual dynamic fluctuations, the apparent length-stiffness relation of grafted taxol-stabilized microtubules, and the curved-helical appearance of microtubules in general. When clamped by one end the microtubules undergo an unusual zero energy motion-in its effect reminiscent of a limited rotational hinge. We conclude that microtubules exist in highly cooperative energy-degenerate helical states and discuss possible implications in vivo.

  1. Androgen receptor gene mutation, rearrangement, polymorphism

    PubMed Central

    Eisermann, Kurtis; Wang, Dan; Jing, Yifeng; Pascal, Laura E.

    2013-01-01

    Genetic aberrations of the androgen receptor (AR) caused by mutations, rearrangements, and polymorphisms result in a mutant receptor that has varied functions compared to wild type AR. To date, over 1,000 mutations have been reported in the AR with most of these being associated with androgen insensitivity syndrome (AIS). While mutations of AR associated with prostate cancer occur less often in early stage localized disease, mutations in castration-resistant prostate cancer (CRPC) patients treated with anti-androgens occur more frequently with 10-30% of these patients having some form of mutation in the AR. Resistance to anti-androgen therapy usually results from gain-of-function mutations in the LBD such as is seen with bicalutamide and more recently with enzalutamide (MDV3100). Thus, it is crucial to investigate these new AR mutations arising from drug resistance to anti-androgens and other small molecule pharmacological agents. PMID:25045626

  2. Gene Polymorphisms and Pharmacogenetics in Rheumatoid Arthritis

    PubMed Central

    Rego-Pérez, Ignacio; Fernández-Moreno, Mercedes; Blanco, Francisco J

    2008-01-01

    Rheumatoid arthritis (RA) is a systemic, chronic and inflammatory disease of unknown etiology with genetic predisposition. The advent of new biological agents, as well as the more traditional disease-modifying antirheumatic drugs, has resulted in highly efficient therapies for reducing the symptoms and signs of RA; however, not all patients show the same level of response in disease progression to these therapies. These variations suggest that RA patients may have different genetic regulatory mechanisms. The extensive polymorphisms revealed in non-coding gene-regulatory regions in the immune system, as well as genetic variations in drug-metabolizing enzymes, suggest that this type of variation is of functional and evolutionary importance and may provide clues for developing new therapeutic strategies. Pharmacogenetics is a rapidly advancing area of research that holds the promise that therapies will soon be tailored to an individual patient’s genetic profile. PMID:19506728

  3. Tubulin Bistability and Polymorphic Dynamics of Microtubules

    NASA Astrophysics Data System (ADS)

    Mohrbach, Hervé; Johner, Albert; Kulić, Igor M.

    2010-12-01

    Based on the hypothesis that the GDP-tubulin dimer is a conformationally bistable molecule—rapidly fluctuating between a discrete curved and a straight state—we develop a model for polymorphic dynamics of the microtubule lattice. We show that GDP-tubulin bistability consistently explains unusual dynamic fluctuations, the apparent length-stiffness relation of grafted taxol-stabilized microtubules, and the curved-helical appearance of microtubules in general. When clamped by one end the microtubules undergo an unusual zero energy motion—in its effect reminiscent of a limited rotational hinge. We conclude that microtubules exist in highly cooperative energy-degenerate helical states and discuss possible implications in vivo.

  4. Diosgenone: a second P21 polymorph

    PubMed Central

    Hernández Linares, María-Guadalupe; Guerrero-Luna, Gabriel; Bernès, Sylvain; Flores-Alamo, Marcos; Fernández-Herrera, María A.

    2012-01-01

    Diosgenone [(20S,22R,25R)-spirost-4-en-3-one, C27H40O3] has been proposed as a new therapeutic alternative for the treatment of malaria. The first X-ray structure report for diosgenone was by Piro et al. [(2002). Z. Naturforsch. Teil C, 57, 947–950] in the space group P21 (Z′ = 2). We now report a new polymorph in the same space group, with two mol­ecules in the asymmetric unit. Both mol­ecules have similar conformations, characterized by a skewed envelope A ring, which contains the C=C bond conjugated with the ketone functionality at C3. The dimorphism results from a modification of the relative orientation of the mol­ecules in the asymmetric unit: two independent mol­ecules were arranged anti­parallel in the Piro report, while they are parallel in the present determination. PMID:22904824

  5. Single nucleotide polymorphism for animal fibre identification.

    PubMed

    Subramanian, Selvi; Karthik, T; Vijayaraaghavan, N N

    2005-03-16

    Animal fibres are highly valuable industrial products often adulterated during marketing. Currently, there is no precise method available to identify and differentiate the fibres. In this study, a PCR-RFLP technique was exploited to differentiate cashmere and wool fibres derived from goat and sheep, respectively. The presence of DNA in animal hair shafts has enabled the isolation of DNA from scoured cashmere and wool fibres. The mitochondrial cytochrome b sequences of both species were amplified by PCR using primers designed from conserved regions. The polymorphism observed between the two species was detected by restricting the amplified product by endonucleases viz., BamH1 and Ssp1. The RFLP profile clearly distinguishes the cashmere and wool fibres and this technique can also be exploited to test adulteration in animal fibres qualitatively.

  6. Polymorphism of starch pathway genes in cassava.

    PubMed

    Vasconcelos, L M; Brito, A C; Carmo, C D; Oliveira, E J

    2016-12-02

    The distribution and frequency of single nucleotide polymorphisms (SNPs) can help to understand changes associated with characteristics of interest. We aimed to evaluate nucleotide diversity in six genes involved in starch biosynthesis in cassava using a panel of 96 unrelated accessions. The genes were sequenced, aligned, and used to obtain values for nucleotide diversity (π), segregating sites (θ), Tajima's D test, and neighbor-joining (NJ) clustering. On average, one SNP per 147 and 171 bp was identified in exon and intron regions, respectively. Thirteen heterozygous loci were found. Three of seven SNPs in the exon region resulted in non-synonymous replacement or four synonymous substitutions. However, no associations were noted between SNPs and root dry-matter content. The parameter π ranged from 0.0001 (granule bound starch synthase I) to 0.0033 (α-amylase), averaging 0.0011, while θ ranged from 0.00014 (starch branching enzyme) to 0.00584 (starch synthase I), averaging 0.002353. The θ diversity value was typically double that of the π. Results of the D test did not suggest any evidence of deviance of neutrality in these genes. Among the evaluated accession, 82/96 were clustered using the NJ method but without a clear separation of the root dry-matter content, root pulp coloration, and classification of the cyanogenic compound content. High variation in genes of the starch biosynthetic pathway can be used to identify associations with the functional properties of starch for the use of polymorphisms for selection purposes.

  7. Ecological separation in a polymorphic terrestrial salamander.

    PubMed

    Anthony, Carl D; Venesky, Matthew D; Hickerson, Cari-Ann M

    2008-07-01

    1. When studying speciation, researchers commonly examine reproductive isolation in recently diverged populations. Polymorphic species provide an opportunity to examine the role of reproductive isolation in populations that may be in the process of divergence. 2. We examined a polymorphic population of Plethodon cinereus (red-backed salamanders) for evidence of sympatric ecological separation by colour morphology. Recent studies have correlated temperature and climate with colour morphology in this species, but no studies have looked at differences in diet or mate choice between colour morphs. We used artificial cover objects to assess salamander diet, mating preference and surface activity over a 2-year period at a field site in north-eastern Ohio. 3. We detected differences in diet between two colour morphs, striped and unstriped. The diets of striped individuals were significantly more diverse and were made up of more profitable prey than the diets of unstriped salamanders. 4. Opposite sex pairs were made up of individuals of the same colour morph and striped males were found more often with larger females than were unstriped males. 5. We corroborate findings of earlier studies suggesting that the unstriped form is adapted to warmer conditions. Unstriped individuals were the first to withdraw from the forest floor as temperatures fell in the late fall. We found no evidence that the colour morphs responded differently to abiotic factors such as soil moisture and relative humidity, and responses to surface temperatures were also equivocal. 6. We conclude that the two colour morphs exhibit some degree of ecological separation and tend to mate assortatively, but are unlikely to be undergoing divergence given the observed frequency of intermorph pairings.

  8. Consequences of POR mutations and polymorphisms

    PubMed Central

    Miller, Walter L.; Agrawal, Vishal; Sandee, Duanpen; Tee, Meng Kian; Huang, Ningwu; Choi, Ji Ha; Morrissey, Kari; Giacomini, Kathleen M.

    2015-01-01

    P450 oxidoreductase (POR) transports electrons from NADPH to all microsomal cytochrome P450 enzymes, including steroidogenic P450c17, P450c21 and P450aro. Severe POR mutations A287P (in Europeans) and R457H (in Japanese) cause the Antley-Bixler skeletal malformation syndrome (ABS) plus impaired steroidogenesis (causing genital anomalies), but the basis of ABS is unclear. We have characterized the activities of ~40 POR variants, showing that assays based on P450c17 activities, but not cytochrome c assays, correlate with the clinical phenotype. The human POR gene is highly polymorphic: the A503V sequence variant, which decreases P450c17 activities to ~60%, is found on ~28% of human alleles. A promoter polymorphism (~8% of Asians and ~13% of Caucasians) at −152 reduces transcriptional activity by half. Screening of 35 POR variants showed that most mutants lacking activity with P450c17 or cytochrome c also lacked activity to support CYP1A2 and CYP2C19 metabolism of EOMCC (a fluorogenic non-drug substrate), although there were some remarkable differences: Q153R causes ABS and has ~30% of wild-type activity with P450c17 but had 144% of WT activity with CYP1A2 and 284% with CYP2C19. The effects of POR variants on CYP3A4, which metabolizes nearly 50% of clinically used drugs, was examined with multiple, clinically-relevant drug substrates, showing that A287P and R457H dramatically reduce drug metabolism, and that A503V variably impairs drug metabolism. The degree of activity can vary with the drug substrate assayed, as the drugs can influence the conformation of the P450. POR is probably an important contributor to genetic variation in both steroidogenesis and drug metabolism. PMID:21070833

  9. Consequences of POR mutations and polymorphisms.

    PubMed

    Miller, Walter L; Agrawal, Vishal; Sandee, Duanpen; Tee, Meng Kian; Huang, Ningwu; Choi, Ji Ha; Morrissey, Kari; Giacomini, Kathleen M

    2011-04-10

    P450 oxidoreductase (POR) transports electrons from NADPH to all microsomal cytochrome P450 enzymes, including steroidogenic P450c17, P450c21 and P450aro. Severe POR mutations A287P (in Europeans) and R457H (in Japanese) cause the Antley-Bixler skeletal malformation syndrome (ABS) plus impaired steroidogenesis (causing genital anomalies), but the basis of ABS is unclear. We have characterized the activities of ∼40 POR variants, showing that assays based on P450c17 activities, but not cytochrome c assays, correlate with the clinical phenotype. The human POR gene is highly polymorphic: the A503V sequence variant, which decreases P450c17 activities to ∼60%, is found on ∼28% of human alleles. A promoter polymorphism (∼8% of Asians and ∼13% of Caucasians) at -152 reduces transcriptional activity by half. Screening of 35 POR variants showed that most mutants lacking activity with P450c17 or cytochrome c also lacked activity to support CYP1A2 and CYP2C19 metabolism of EOMCC (a fluorogenic non-drug substrate), although there were some remarkable differences: Q153R causes ABS and has ∼30% of wild-type activity with P450c17 but had 144% of WT activity with CYP1A2 and 284% with CYP2C19. The effects of POR variants on CYP3A4, which metabolizes nearly 50% of clinically used drugs, was examined with multiple, clinically relevant drug substrates, showing that A287P and R457H dramatically reduce drug metabolism, and that A503V variably impairs drug metabolism. The degree of activity can vary with the drug substrate assayed, as the drugs can influence the conformation of the P450. POR is probably an important contributor to genetic variation in both steroidogenesis and drug metabolism. Copyright © 2010. Published by Elsevier Ireland Ltd.

  10. KCNN2 polymorphisms and cardiac tachyarrhythmias.

    PubMed

    Yu, Chih-Chieh; Chia-Ti, Tsai; Chen, Pei-Lung; Wu, Cho-Kai; Chiu, Fu-Chun; Chiang, Fu-Tien; Chen, Peng-Sheng; Chen, Chi-Ling; Lin, Lian-Yu; Juang, Jyh-Ming; Ho, Li-Ting; Lai, Ling-Ping; Yang, Wei-Shiung; Lin, Jiunn-Lee

    2016-07-01

    Potassium calcium-activated channel subfamily N member 2 (KCNN2) encodes an integral membrane protein that forms small-conductance calcium-activated potassium (SK) channels. Recent studies in animal models show that SK channels are important in atrial and ventricular repolarization and arrhythmogenesis. However, the importance of SK channels in human arrhythmia remains unclear. The purpose of the present study was to test the association between genetic polymorphism of the SK2 channel and the occurrence of cardiac tachyarrhythmias in humans. We enrolled 327 Han Chinese, including 72 with clinically significant ventricular tachyarrhythmias (VTa) who had a history of aborted sudden cardiac death (SCD) or unexplained syncope, 98 with a history of atrial fibrillation (AF), and 144 normal controls. We genotyped 12 representative tag single nucleotide polymorphisms (SNPs) across a 141-kb genetic region containing the KCNN2 gene; these captured the full haplotype information. The rs13184658 and rs10076582 variants of KCNN2 were associated with VTa in both the additive and dominant models (odds ratio [OR] 2.89, 95% confidence interval [CI] = 1.505-5.545, P = 0.001; and OR 2.55, 95% CI = 1.428-4.566, P = 0.002, respectively). After adjustment for potential risk factors, the association remained significant. The population attributable risks of these 2 variants of VTa were 17.3% and 10.6%, respectively. One variant (rs13184658) showed weak but significant association with AF in a dominant model (OR 1.91, CI = 1.025-3.570], P = 0.042). There was a significant association between the KCNN2 variants and clinically significant VTa. These findings suggest an association between KCNN2 and VTa; it also appears that KCNN2 variants may be adjunctive markers for risk stratification in patients susceptible to SCD.

  11. APOE gene polymorphism analysis in Barranquilla, Colombia.

    PubMed

    Ruiz, Martha; Arias, Isis; Rolón, Gloria; Hernández, Enio; Garavito, Pilar; Silvera-Redondo, Carlos

    2016-03-03

    The genetic variability present in the APOE gene polymorphism is considered an important factor associated with predisposition to diseases affecting lipid metabolism, as well as heart diseases and Alzheimer's disease, among others. Understanding it as a risk factor in different populations and ethnic groups is a useful tool.  To analyze the APOE gene polymorphism and determine allelic and genotypic frequencies of a representative sample of population from Barranquilla, Colombia.  We performed a descriptive and comparative study. The sample size was 227 unrelated individuals from Barranquilla, Colombia.  The most frequent allele was the ε3, with 85%, followed by the ε4 allele (13%) and ε2 (1.8%). The genotypes found were: ε3/ε3: 71.8%, ε3/ε4: 24.2%, ε2/ε3: 2.2%, ε2/ε4: 1.3% and ε4/ε4: 0.4%. The ε2/ε2 genotype was not found in this study. The sample exhibited the Hardy-Weinberg equilibrium.  The frequency of the ε3 allele and the ε3/ε3 genotype was similar to that reported in the literature in countries like Brazil, Mexico, Colombia, and in some Colombian Amerindian ethnic groups. The ε2/ε2 genotype was absent. This result is consistent with those found in other population groups worldwide. The frequency of the ε4 allele and the genotypes associated in this population could be related to the presence of diseases such as hypercholesterolemia, myocardial infarction and Alzheimer.

  12. KCNN2 polymorphisms and cardiac tachyarrhythmias

    PubMed Central

    Yu, Chih-Chieh; Chia-Ti, Tsai; Chen, Pei-Lung; Wu, Cho-Kai; Chiu, Fu-Chun; Chiang, Fu-Tien; Chen, Peng-Sheng; Chen, Chi-Ling; Lin, Lian-Yu; Juang, Jyh-Ming; Ho, Li-Ting; Lai, Ling-Ping; Yang, Wei-Shiung; Lin, Jiunn-Lee

    2016-01-01

    Abstract Potassium calcium-activated channel subfamily N member 2 (KCNN2) encodes an integral membrane protein that forms small-conductance calcium-activated potassium (SK) channels. Recent studies in animal models show that SK channels are important in atrial and ventricular repolarization and arrhythmogenesis. However, the importance of SK channels in human arrhythmia remains unclear. The purpose of the present study was to test the association between genetic polymorphism of the SK2 channel and the occurrence of cardiac tachyarrhythmias in humans. We enrolled 327 Han Chinese, including 72 with clinically significant ventricular tachyarrhythmias (VTa) who had a history of aborted sudden cardiac death (SCD) or unexplained syncope, 98 with a history of atrial fibrillation (AF), and 144 normal controls. We genotyped 12 representative tag single nucleotide polymorphisms (SNPs) across a 141-kb genetic region containing the KCNN2 gene; these captured the full haplotype information. The rs13184658 and rs10076582 variants of KCNN2 were associated with VTa in both the additive and dominant models (odds ratio [OR] 2.89, 95% confidence interval [CI] = 1.505–5.545, P = 0.001; and OR 2.55, 95% CI = 1.428–4.566, P = 0.002, respectively). After adjustment for potential risk factors, the association remained significant. The population attributable risks of these 2 variants of VTa were 17.3% and 10.6%, respectively. One variant (rs13184658) showed weak but significant association with AF in a dominant model (OR 1.91, CI = 1.025–3.570], P = 0.042). There was a significant association between the KCNN2 variants and clinically significant VTa. These findings suggest an association between KCNN2 and VTa; it also appears that KCNN2 variants may be adjunctive markers for risk stratification in patients susceptible to SCD. PMID:27442679

  13. Identification of polymorphism in ethylone hydrochloride: synthesis and characterization.

    PubMed

    Maheux, Chad R; Alarcon, Idralyn Q; Copeland, Catherine R; Cameron, T Stanley; Linden, Anthony; Grossert, J Stuart

    2016-08-01

    Ethylone, a synthetic cathinone with psychoactive properties, is a designer drug which has appeared on the recreational drug market in recent years. Since 2012, illicit shipments of ethylone hydrochloride have been intercepted with increasing frequency at the Canadian border. Analysis has revealed that ethylone hydrochloride exists as two distinct polymorphs. In addition, several minor impurities were detected in some seized exhibits. In this study, the two conformational polymorphs of ethylone hydrochloride have been synthesized and fully characterized by FTIR, FT-Raman, powder XRD, GC-MS, ESI-MS/MS and NMR ((13) C CPMAS, (1) H, (13) C). The two polymorphs can be distinguished by vibrational spectroscopy, solid-state nuclear magnetic resonance spectroscopy and X-ray diffraction. The FTIR data are applied to the identification of both polymorphs of ethylone hydrochloride (mixed with methylone hydrochloride) in a laboratory submission labelled as 'Ocean Snow Ultra'. The data presented in this study will assist forensic scientists in the differentiation of the two ethylone hydrochloride polymorphs. This report, alongside our recent article on the single crystal X-ray structure of a second polymorph of this synthetic cathinone, is the first to confirm polymorphism in ethylone hydrochloride. © 2015 Canada Border Services Agency. Drug Testing and Analysis published by John Wiley & Sons, Ltd. © 2015 Canada Border Services Agency. Drug Testing and Analysis published by John Wiley & Sons, Ltd.

  14. Identification of polymorphism in ethylone hydrochloride: synthesis and characterization

    PubMed Central

    Alarcon, Idralyn Q.; Copeland, Catherine R.; Cameron, T. Stanley; Linden, Anthony; Grossert, J. Stuart

    2015-01-01

    Ethylone, a synthetic cathinone with psychoactive properties, is a designer drug which has appeared on the recreational drug market in recent years. Since 2012, illicit shipments of ethylone hydrochloride have been intercepted with increasing frequency at the Canadian border. Analysis has revealed that ethylone hydrochloride exists as two distinct polymorphs. In addition, several minor impurities were detected in some seized exhibits. In this study, the two conformational polymorphs of ethylone hydrochloride have been synthesized and fully characterized by FTIR, FT‐Raman, powder XRD, GC‐MS, ESI‐MS/MS and NMR (13C CPMAS, 1H, 13C). The two polymorphs can be distinguished by vibrational spectroscopy, solid‐state nuclear magnetic resonance spectroscopy and X‐ray diffraction. The FTIR data are applied to the identification of both polymorphs of ethylone hydrochloride (mixed with methylone hydrochloride) in a laboratory submission labelled as 'Ocean Snow Ultra’. The data presented in this study will assist forensic scientists in the differentiation of the two ethylone hydrochloride polymorphs. This report, alongside our recent article on the single crystal X‐ray structure of a second polymorph of this synthetic cathinone, is the first to confirm polymorphism in ethylone hydrochloride. © 2015 Canada Border Services Agency. Drug Testing and Analysis published by John Wiley & Sons, Ltd. © 2015 Canada Border Services Agency. Drug Testing and Analysis published by John Wiley & Sons, Ltd. PMID:26344849

  15. Sexual selection and genetic colour polymorphisms in animals.

    PubMed

    Wellenreuther, Maren; Svensson, Erik I; Hansson, Bengt

    2014-11-01

    Genetic colour polymorphisms are widespread across animals and often subjected to complex selection regimes. Traditionally, colour morphs were used as simple visual markers to measure allele frequency changes in nature, selection, population divergence and speciation. With advances in sequencing technology and analysis methods, several model systems are emerging where the molecular targets of selection are being described. Here, we discuss recent studies on the genetics of sexually selected colour polymorphisms, aiming at (i) reviewing the evidence of sexual selection on colour polymorphisms, (ii) highlighting the genetic architecture, molecular and developmental basis underlying phenotypic colour diversification and (iii) discuss how the maintenance of such polymorphisms might be facilitated or constrained by these. Studies of the genetic architecture of colour polymorphism point towards the importance of tight clustering of colour loci with other trait loci, such as in the case of inversions and supergene structures. Other interesting findings include linkage between colour loci and mate preferences or sex determination, and the role of introgression and regulatory variation in fuelling polymorphisms. We highlight that more studies are needed that explicitly integrate fitness consequences of sexual selection on colour with the underlying molecular targets of colour to gain insights into the evolutionary consequences of sexual selection on polymorphism maintenance. © 2014 John Wiley & Sons Ltd.

  16. Zoledronic acid: monoclinic and triclinic polymorphs from powder diffraction data.

    PubMed

    Chernyshev, Vladimir V; Shkavrov, Sergey V; Paseshnichenko, Ksenia A; Puryaeva, Tamara P; Velikodny, Yurii A

    2013-03-01

    The crystal structures of the monoclinic and triclinic polymorphs of zoledronic acid, C5H10N2O7P2, have been established from laboratory powder X-ray diffraction data. The molecules in both polymorphs are described as zwitterions, namely 1-(2-hydroxy-2-phosphonato-2-phosphonoethyl)-1H-imidazol-3-ium. Strong intermolecular hydrogen bonds (with donor-acceptor distances of 2.60 Å or less) link the molecules into layers, parallel to the (100) plane in the monoclinic polymorph and to the (1-10) plane in the triclinic polymorph. The phosphonic acid groups form the inner side of each layer, while the imidazolium groups lie to the outside of the layer, protruding in opposite directions. In both polymorphs, layers related by translation along [100] interact through weak hydrogen bonds (with donor-acceptor distances greater than 2.70 Å), forming three-dimensional layered structures. In the monoclinic polymorph, there are hydrogen-bonded centrosymmetric dimers linked by four strong O-H...O hydrogen bonds, which are not present in the triclinic polymorph.

  17. Does colour polymorphism enhance survival of prey populations?

    PubMed Central

    Wennersten, Lena; Forsman, Anders

    2009-01-01

    That colour polymorphism may protect prey populations from predation is an old but rarely tested hypothesis. We examine whether colour polymorphic populations of prey exposed to avian predators in an ecologically valid visual context were exposed to increased extinction risk compared with monomorphic populations. We made 2976 artificial pastry prey, resembling Lepidoptera larvae, in four different colours and presented them in 124 monomorphic and 124 tetramorphic populations on tree trunks and branches such that they would be exposed to predation by free-living birds, and monitored their ‘survival’. Among monomorphic populations, there was a significant effect of prey coloration on survival, confirming that coloration influenced susceptibility to visually oriented predators. Survival of polymorphic populations was inferior to that of monomorphic green populations, but did not differ significantly from monomorphic brown, yellow or red populations. Differences in survival within polymorphic populations paralleled those seen among monomorphic populations; the red morph most frequently went extinct first and the green morph most frequently survived the longest. Our findings do not support the traditional protective polymorphism hypothesis and are in conflict with those of earlier studies. As a possible explanation to our findings, we offer a competing ‘giveaway cue’ hypothesis: that polymorphic populations may include one morph that attracts the attention of predators and that polymorphic populations therefore may suffer increased predation compared with some monomorphic populations. PMID:19324729

  18. Does colour polymorphism enhance survival of prey populations?

    PubMed

    Wennersten, Lena; Forsman, Anders

    2009-06-22

    That colour polymorphism may protect prey populations from predation is an old but rarely tested hypothesis. We examine whether colour polymorphic populations of prey exposed to avian predators in an ecologically valid visual context were exposed to increased extinction risk compared with monomorphic populations. We made 2976 artificial pastry prey, resembling Lepidoptera larvae, in four different colours and presented them in 124 monomorphic and 124 tetramorphic populations on tree trunks and branches such that they would be exposed to predation by free-living birds, and monitored their 'survival'. Among monomorphic populations, there was a significant effect of prey coloration on survival, confirming that coloration influenced susceptibility to visually oriented predators. Survival of polymorphic populations was inferior to that of monomorphic green populations, but did not differ significantly from monomorphic brown, yellow or red populations. Differences in survival within polymorphic populations paralleled those seen among monomorphic populations; the red morph most frequently went extinct first and the green morph most frequently survived the longest. Our findings do not support the traditional protective polymorphism hypothesis and are in conflict with those of earlier studies. As a possible explanation to our findings, we offer a competing 'giveaway cue' hypothesis: that polymorphic populations may include one morph that attracts the attention of predators and that polymorphic populations therefore may suffer increased predation compared with some monomorphic populations.

  19. Alzheimer's Disease and Paraoxonase 1 (PON1) Gene Polymorphisms.

    PubMed

    Saeidi, Mohsen; Shakeri, Raheleh; Marjani, Abdoljalal; Khajeniazi, Safoura

    2017-01-01

    Some studies have indicated that human paraoxonase 1 (PON1) activity shows a polymorphic distribution. The aim of this study was to determine the distribution of PON1 polymorphism in patients with Alzheimer's disease in Gorgan and compare it with a healthy control group. The study included 100 healthy individuals and 50 patients. Enzyme activity and genetic polymorphism of PON1 were determined. There were significant differences in distribution of genotypes and alleles among patients and control group. The most common genotype was CT in patients and control group, while the most frequent alleles were T and C in patients and controls, respectively. There was a statistically significant variation between serum PON1 activity and -108C> T polymorphism. The highest PON1 enzyme activities in the patients and controls were found in CC, while lower enzyme activities were seen in CT and TT genotypes in both genders and age groups. Onset of Alzheimer's disease may depend on different polymorphisms of the PON1 enzyme. Late or early-onset of Alzheimer's disease may also depend on age and gender distribution, especially for arylesterase enzyme. Further studies on polymorphism of the enzyme are necessary for interpretation of possible polymorphic effects of enzyme on PON1 activity in humans.

  20. Neotame anhydrate polymorphs. II: Quantitation and relative physical stability.

    PubMed

    Dong, Zedong; Munson, Eric J; Schroeder, Steve A; Prakash, Indra; Grant, David J W

    2002-09-01

    To study the relative thermodynamic and kinetic stabilities of neotame anhydrate polymorphs A, D, F, and G, and to develop a quantitative method for analyzing polymorphic mixtures of A and G by powder X-ray diffractometry (PXRD). Based on the melting points, heats of fusion, and densities of the four polymorphs, thermodynamic rules were applied to study their thermodynamic relationships. The phase transition temperature of Forms A and G was estimated from their heats of solution and intrinsic dissolution rates (J) in 2-propanol. Using PXRD, a method for the quantitative analysis of polymorphic mixtures of Forms A and G was developed. Binary polymorphic mixtures of Forms A, D, F, or G were stored under zero relative humidity at 23 or 70 degrees C, and their compositions were monitored by PXRD. The endothermic enthalpy of solution of A, D, F, and G follows the rank order: G (29.71 +/- 0.82 kJ/mol, n = 4) > A (28.48 +/- 0.51 kJ/mol, n = 4) > D (20.43 +/- 0.45 kJ/mol, n = 4) > F (18.77 +/- 0.31 kJ/mol, n = 4). The van't Hoff plots of ln(J) against 1/T for A and G show good linearity between 25 degrees C and 32 degrees C. At 23 degrees C polymorphic mixtures remain unchanged for 4 months. However, at 70 degrees C the phase transition is fast and the relative stability of the four polymorphs follows the rank order: G > D > F and G > A. PXRD provides a reliable and accurate technique for the quantitative analysis of polymorphic mixtures of Forms A and G. Among the four polymorphs, A-G and A-D are enantiotropic pairs, whereas D-F, D-G, F-G are monotropic pairs. The phase transition temperature between A and G lies within the range 35-70 degrees C.

  1. Methylenetetrahydrofolate Reductase gene polymorphism in children with allergic rhinitis.

    PubMed

    Dogru, M; Aydin, H; Aktas, A; Cırık, A A

    2015-01-01

    Methylenetetrahydrofolate Reductase (MTHFR) polymorphisms by impairing folate metabolism may influence the development of allergic diseases. The results of studies evaluating the relationship between MTHFR polymorphisms and atopic disease are controversial. The aim of this study was to investigate the association between the polymorphisms of C677T and A1298C for MTHFR gene and allergic rhinitis (AR) in children. Ninety patients followed up with diagnosis of allergic rhinitis in our clinic and 30 children with no allergic diseases were included in the study. All participants were genotyped for the MTHFR (C677T) and (A1298C) polymorphisms. Vitamin b12, folate and homocysteine levels were measured. The mean age of patients was 9.2±2.9 years; 66.7% of the patients were male. There was no significant difference between patient and control groups regarding gender, age and atopy history of the family (p>0.05). The frequency of homozygotes for MTHFR C677T polymorphism in the patient and control groups was 3.3% and 10%, respectively. The frequency of homozygotes for MTHFR A1298C polymorphism among groups was 26.7% and 16.7%, respectively. The association between allergic rhinitis and polymorphisms of C677T and A1298C for MTHFR gene was not statistically significant in patients compared with controls (p>0.05). There were no statistically significant differences between the patients and the control group in terms of serum vitamin b12, folate and homocysteine levels (p>0.05). We found no evidence for an association between allergic rhinitis and polymorphisms of C677T and A1298C for MTHFR gene in children. Further studies investigating the relationship between MTHFR polymorphism and AR are required. Copyright © 2014 SEICAP. Published by Elsevier Espana. All rights reserved.

  2. Fast identification of rubrene polymorphs by lattice phonon Raman microscopy

    NASA Astrophysics Data System (ADS)

    Socci, Joseph; Salzillo, Tommaso; Della Valle, Raffaele Guido; Venuti, Elisabetta; Brillante, Aldo

    2017-09-01

    Confocal Raman microscopy in the lattice phonon region has been used to study the polymorphism of the organic semiconductor 5,6,11,12-tetraphenyl-tetracene (rubrene). Following literature guidelines, crystals of rubrene have been prepared using a number of solution growth and vapour deposition methods, obtaining samples of different morphologies which could be related to the various polymorphs of this compound. The technique has enabled us an easy and non invasive identification of the three known polymorphs and of their phase homogeneity with a lateral spatial resolution below 1 μm.

  3. Prenatal diagnosis of polymorphic ventricular tachycardia using 64-channel magnetocardiography.

    PubMed

    Fukushima, Akimune; Nakai, Kenji; Matsumoto, Atsushi; Strasburger, Janette; Sugiyama, Toru

    2010-05-01

    We describe polymorphic ventricular tachycardia (VT) diagnosed using fetal magnetocardiography (FMCG). The fetus of a 33-year-old Japanese female at 24 weeks of pregnancy was diagnosed as bradycardia (60 beats/min) by fetal cardiotocography (CTG). Ultrasound findings indicated a diagnosis of an atrioventricular (AV) block involving extrasystole, but FMCG revealed a polymorphic VT followed by ventricular asystole. Standard ECG immediately after cesarean section at 37 weeks of pregnancy confirmed long QT syndrome followed by nonsustained polymorphic VT and an advanced AV block with wide QRS. Echocardiography demonstrated moderate left ventricular dysfunction in the neonate requiring implantation with a permanent pacemaker.

  4. CD24 Ala/Val polymorphism and multiple sclerosis.

    PubMed

    Goris, An; Maranian, Melanie; Walton, Amie; Yeo, Tai Wai; Ban, Maria; Gray, Julia; Dubois, Bénédicte; Compston, Alastair; Sawcer, Stephen

    2006-06-01

    CD24 is expressed on a broad range of cells in the immune and central nervous systems and appears to be required for development of experimental autoimmune encephalomyelitis in mice. Association of a CD24 Ala/Val coding polymorphism with susceptibility to and progression of multiple sclerosis was recently reported. We typed this coding polymorphism in a combined cohort of 1,180 cases and 1,168 unrelated and family-based controls from Belgium and the UK, but were unable to confirm either association. Since the CD24 gene is part of a segmental duplication, special care is required for the identification and genotyping of single nucleotide polymorphisms.

  5. Endometriosis and RAS system gene polymorphisms: the association of ACE A2350G polymorphism with endometriosis in Polish individuals.

    PubMed

    Kowalczyńska, Liliana J; Ferenc, Tomasz; Wojciechowski, Michał; Mordalska, Anna; Pogoda, Krzysztof; Malinowski, Andrzej

    2014-05-01

    To analyze the polymorphisms of angiotensin I converting enzyme (ACE) gene (insertion/deletion [I/D], A2350G) and angiotensin II type 1 receptor gene (A1166C) in women with endometriosis and to determine the correlation of the identified genotypes with the severity of the disease. Additionally, to estimate the prognostic value of the polymorphisms in patients with endometriosis treated due to infertility. The study group included 241 women, the control group (without endometriosis)-127. The molecular analysis was performed by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism technique. For I/D ACE and A1166C AT1 polymorphisms no significant differences were observed between the study and control groups and between the severity grades of the disease (p>0.05). For A2350G ACE polymorphism the frequency of genotypes for the study and control groups respectively was the following: AA-31.54%, AG-54.36%, GG-14.11% and AA-55.12%, AG-36.22%, GG-8.66% (x(2)=19.36, p<0.0001). Statistically significant differences were found between the frequency of A and G alleles between both groups (x(2)=15.16, p=0.0001), but not when individual grades of the disease severity were compared. There was no association between the investigated polymorphisms and the effect of infertility treatment. A2350G polymorphism (allele G, AG genotype) of ACE gene seems to be associated with the development of endometriosis.

  6. [Advances in the Association between Apolipoprotein (a) Gene Polymorphisms and Coronary Heart Disease].

    PubMed

    Zhu, Li; L, Zhan; Song, Yong-yan

    2015-08-01

    Human apolipoprotein (a) (LPA) gene is highly polymorphic, and the polymorphic loci on this gene include the Kringle 4 subtype 2(KIV-2) repeat polymorphism, the pentanucleotide repeat (TTTTA)n polymorphism, and a number of single nucleotide polymorphisms. KIV-2 repeat polymorphism was found to be significantly associated with coronary heart disease(CHD), and the reducing number of KIV-2 repeats is a risk factor for CHD. Both the increase and decrease of the pentanucleotide repeat(TTTTA)n polymorphism repeats are possibly associated with CHD risk. In single nucleotide polymorphisms loci, the rs10455872 and rs3798220 loci were widely reported to be associated with CHD, while other loci were less reported. The association between LPA polymorphisms and CHD may be mediated by either the elevation of plasma LPA level or the change of LPA subtypes. This article reviews the association between the LPA polymorphisms and CHD and the underlying mechanisms.

  7. Polymorphic microsatellite loci for the razor clam, Sinonovacula constricta.

    PubMed

    Ma, H-T; Jiang, H-B; Liu, X-Q; Wu, X-P; Wei, X-M

    2015-01-15

    The razor clam, Sinonovacula constricta, is an important commercial bivalve and a popular mollusca food in China. Twelve polymorphic microsatellite markers were isolated from the razor clam using a partial genomic library enriched for tandem repeat sequences of (CA)16, (GA)16. Polymorphisms of these loci were evaluated in a wild population of 30 individuals. The allele number of these polymorphic markers ranged from 5-15 per locus with an average of 9.333. Observed and expected heterozygosity values ranged from 0.192-1.000 and 0.219-0.906. Polymorphism information content ranged from 0.209-0.892 with an average of 0.704. Three loci significantly deviated from Hardy-Weinberg equilibrium after Bonferroni correction. No significant linkage disequilibrium was detected between these loci. This set of microsatellite loci are useful for genetic studies in S. constricta.

  8. Mitochondrial DNA polymorphisms/haplogroups in hereditary spastic paraplegia.

    PubMed

    Sánchez-Ferrero, Elena; Coto, Eliecer; Corao, Ana I; Díaz, Marta; Gámez, Josep; Esteban, Jesús; Gonzalo, Juan F; Pascual-Pascual, Samuel I; López De Munaín, Adolfo; Morís, Germán; Infante, Jon; Del Castillo, Emilia; Márquez, Celedonio; Alvarez, Victoria

    2012-02-01

    Mitochondrial dysfunction could contribute to the development of spastic paraplegia. Among others, two of the genes implicated in hereditary spastic paraplegia encoded mitochondrial proteins and some of the clinical features frequently found in these patients resemble those observed in patients with mitochondrial DNA (mtDNA) mutations. We investigated the association between common mtDNA polymorphisms and spastic paraplegia. The ten mtDNA polymorphisms that defined the common European haplogroups were determined in 424 patients, 19% with a complicated phenotype. A rare haplogroup was associated with the disease in patients without a SPG3A, SPG4, or SPG7 mutation. Allele 10398G was more frequent among patients with a pure versus complicated phenotype. This mtDNA polymorphism was previously associated with the risk of developing other neurodegenerative diseases. In conclusion, some mtDNA polymorphisms could contribute to the development of spastic paraplegia or act as modifiers of the phenotype.

  9. Lowest enthalpy polymorph of cold-compressed graphite phase.

    PubMed

    Li, Da; Bao, Kuo; Tian, Fubo; Zeng, Zhenwu; He, Zhi; Liu, Bingbing; Cui, Tian

    2012-04-07

    Based on an ab initio evolutionary algorithm, a novel carbon polymorph with an orthorhombic Cmcm symmetry is predicted, named as C carbon, which has the lowest enthalpy among the previously proposed cold-compressed graphite phases.

  10. Polymorphs of Serpentine: Identification by Means of Raman Spectroscopy

    NASA Astrophysics Data System (ADS)

    Petriglieri, J. R.; Bersani, D.; Salvioli-Mariani, E.; Mantovani, L.; Tribaudino, M.; Lottici, P. P.; Laporte-Magoni, C.

    2014-06-01

    Raman micro-mapping, based on the OH stretching bands, was successfully employed to identify the four main polymorphs of serpentine directly on cross-sections of rocks coming from the Koniambo massif (New Caledonia).

  11. [Blood polymorphism in the study of isolated communities].

    PubMed

    Fujiki, N; Hirayama, M; Nomura, M; Nakanaga, M; Mano, K

    1988-01-01

    Isolated communities offer a unique opportunity for the study of biological and social consequences of consanguinity and migration. The studies of genetic polymorphisms have contributed greatly, not only to knowledge of the genetic constitution of a given individual and population, but also to clarify either relationship between structure and function of polymorphic traits or the susceptibility to multifactorial diseases, in which interaction between the gene and environment cannot be ignored. For over 25 years, we have investigated the effect of consanguinity and genetic polymorphisms in 9 isolated communities in Western Japan. We reported here different values of gene frequency for each polymorphic trait, compared with the neighboring communities and described how we applied these data to clarification of the genetic constitution of isolated communities as well as of genetic susceptibility to some diseases.

  12. Chromosome Polymorphism in Microtus (Alexandromys) mujanensis (Arvicolinae, Rodentia).

    PubMed

    Lemskaya, Natalya A; Kartavtseva, Irina V; Rubtsova, Nadezhda V; Golenishchev, Fedor N; Sheremetyeva, Irina N; Graphodatsky, Alexander S

    2015-01-01

    The Muya Valley vole (Microtus mujanensis) has a constant diploid chromosome number of 2n = 38, but an unstable karyotype with polymorphic chromosome pairs. Here, we describe 4 karyotypic variants involving 2 polymorphic chromosome pairs, MMUJ8 and MMUJ14, in 6 animals from Buryatia using a combination of GTG-banding and chromosome painting with M. agrestis probes. We suggest that the polymorphic pairs MMUJ8 and MMUJ14 were formed through pericentric inversions that played a major role during karyotype evolution of the species. We also propose that the stable diploid number with some ongoing polymorphism in the number of chromosome arms indicates that this evolutionarily young endemic species of Russian Far East is on the way to karyotype and likely species stabilization.

  13. [Study of Chloroplast DNA Polymorphism in the Sunflower (Helianthus L.)].

    PubMed

    Markina, N V; Usatov, A V; Logacheva, M D; Azarin, K V; Gorbachenko, C F; Kornienko, I V; Gavrilova, V A; Tihobaeva, V E

    2015-08-01

    The polymorphism of microsatellite loci of chloroplast genome in six Helianthus species and 46 lines of cultivated sunflower H. annuus (17 CMS lines and 29 Rf-lines) were studied. The differences between species are confined to four SSR loci. Within cultivated forms of the sunflower H. annuus, the polymorphism is absent. A comparative analysis was performed on sequences of the cpDNA inbred line 3629, line 398941 of the wild sunflower, and the American line HA383 H. annuus. As a result, 52 polymorphic loci represented by 27 SSR and 25 SNP were found; they can be used for genotyping of H. annuus samples, including cultural varieties: twelve polymorphic positions, of which eight are SSR and four are SNP.

  14. Diabat Interpolation for Polymorph Free-Energy Differences.

    PubMed

    Kamat, Kartik; Peters, Baron

    2017-02-02

    Existing methods to compute free-energy differences between polymorphs use harmonic approximations, advanced non-Boltzmann bias sampling techniques, and/or multistage free-energy perturbations. This work demonstrates how Bennett's diabat interpolation method ( J. Comput. Phys. 1976, 22, 245 ) can be combined with energy gaps from lattice-switch Monte Carlo techniques ( Phys. Rev. E 2000, 61, 906 ) to swiftly estimate polymorph free-energy differences. The new method requires only two unbiased molecular dynamics simulations, one for each polymorph. To illustrate the new method, we compute the free-energy difference between face-centered cubic and body-centered cubic polymorphs for a Gaussian core solid. We discuss the justification for parabolic models of the free-energy diabats and similarities to methods that have been used in studies of electron transfer.

  15. No association between apolipoprotein E polymorphisms and recurrent pregnancy loss.

    PubMed

    Bianca, Sebastiano; Barrano, Barbara; Cutuli, Nunzio; Indaco, Lara; Cataliotti, Antonella; Milana, Gabriella; Barone, Chiara; Ettore, Giuseppe

    2010-01-01

    Our study does not support the reported association between APOE and recurrent pregnancy loss (RPL) than the clinical management of these patients should not be influenced by the presence or not of APO E polymorphisms.

  16. Mineralogy of Silica Polymorphs in Basaltic Clasts in Eucrites

    NASA Astrophysics Data System (ADS)

    Ono, H.; Takenouchi, A.; Mikouchi, T.

    2016-08-01

    We analyzed silica polymorphs in basaltic clasts in Y-75011, Pasamonte and Stannern eucrites. Cristobalite and quartz have been found, which suggests wide occurrence of hydrothermal activity throughout the crust of Vesta.