Identification of 55,000 Replicated DNA Methylation QTL

DNA methylation plays an important role in the regulation of transcription. Genetic control of DNA methylation is a potential candidate for explaining the many identified SNP associations with disease that are not found in coding regions. We replicated 52,916 cis and 2,025 trans DNA methylation quantitative trait loci (mQTL) using methylation from whole blood measured on Illumina HumanMethylation450 arrays in the Brisbane Systems Genetics Study (n = 614 from 177 families) and the Lothian Birth Cohorts of 1921 and 1936 (combined n = 1366). The trans mQTL SNPs were found to be over-represented in 1 Mbp subtelomeric regions, and on chromosomes 16 and 19. There was a significant increase in trans mQTL DNA methylation sites in upstream and 5' UTR regions. The genetic heritability of a number of complex traits and diseases was partitioned into components due to mQTL and the remainder of the genome. Significant enrichment was observed for height (p = 2.1 × 10), ulcerative colitis (p = 2 × 10), Crohn's disease (p = 6 × 10) and coronary artery disease (p = 5.5 × 10) when compared to a random sample of SNPs with matched minor allele frequency, although this enrichment is explained by the genomic location of the mQTL SNPs

Provasopressin expression by breast cancer cells: implications for growth and novel treatment strategies

The arginine vasopressin (AVP) gene is expressed in certain cancers such as breast cancer, where it is believed to act as an autocrine growth factor. However, little is known about the regulation of the AVP protein precursor (proAVP) or AVP-mediated signaling in breast cancer and this study was undertaken to address some of the basic issues. The cultured cell lines examined (Mcf7, Skbr3, BT474, ZR75, Mcf10a) and human breast cancer tissue extract were found to express proAVP mRNA. Western analysis revealed multiple forms of proAVP protein were present in cell lysates, corresponding to those detected in human hypothalamus extracts. Monoclonal antibodies directed against different regions of proAVP bound to intact live Mcf7 and Skbr3 cells. Dexamethasone increased the amount of proAVP-associated glycopeptide (VAG) secreted by Skbr3 cells and a combination of dexamethasone, IBMX and 8br-cAMP increased cellular levels of VAG. Exogenous AVP (1, 10, and 100 nM) elevated phospho-ERK1/2 levels, and increased cell proliferation was observed in the presence of 10 nM AVP. Concurrent treatment with the V1a receptor antagonist SR49059 reduced the effects of AVP on proliferation in Mcf7 cells, and abolished it in Skbr3 cells. Results here show that proAVP components are found at the surface of Skbr3 and Mcf7 cells and are also secreted from these cells. In addition, they show that AVP promotes cancer cell growth, apparently through a V1-type receptor-mediated pathway and subsequent ERK1/2 activation. Thus, strategies for targeting proAVP should be examined for their effectiveness in diagnosing and treating breast cancer

Polychaete richness and abundance enhanced in anthropogenically modified estuaries despite high concentrations of toxic contaminants

Ecological communities are increasingly exposed to multiple chemical and physical stressors, but distinguishing anthropogenic impacts from other environmental drivers remains challenging. Rarely are multiple stressors investigated in replicated studies over large spatial scales (\u3e1000 kms) or supported with manipulations that are necessary to interpret ecological patterns. We measured the composition of sediment infaunal communities in relation to anthropogenic and natural stressors at multiple sites within seven estuaries. We observed increases in the richness and abundance of polychaete worms in heavily modified estuaries with severe metal contamination, but no changes in the diversity or abundance of other taxa. Estuaries in which toxic contaminants were elevated also showed evidence of organic enrichment. We hypothesised that the observed response of polychaetes was not a ‘positive’ response to toxic contamination or a reduction in biotic competition, but due to high levels of nutrients in heavily modified estuaries driving productivity in the water column and enriching the sediment over large spatial scales. We deployed defaunated field-collected sediments from the surveyed estuaries in a small scale experiment, but observed no effects of sediment characteristics (toxic or enriching). Furthermore, invertebrate recruitment instead reflected the low diversity and abundance observed during field surveys of this relatively ‘pristine’ estuary. This suggests that differences observed in the survey are not a direct consequence of sediment characteristics (even severe metal contamination) but are related to parameters that covary with estuary modification such as enhanced productivity from nutrient inputs and the diversity of the local species pool. This has implications for the interpretation of diversity measures in large-scale monitoring studies in which the observed patterns may be strongly influenced by many factors that covary with anthropogenic modification

Is embolism resistance in plant xylem associated with quantity and characteristics of lignin?

The appearance of lignin during plant evolution was of defining importance in the colonization of the terrestrial environment. Among several evolutionary advantages, lignin deposition in the xylem increased mechanical support allowing plants to become tall, enabled more efficient water transport, and made the conduits strong enough to transport water under tension. Greater lignin content in the xylem may also improve resistance to embolism induced by drought. In this review we suggest, based on 91 species (54 angiosperms and 37 gymnosperms) data available for lignin content and Ψ50 (the water potential when 50% of conductivity in the xylem is lost), a limiting constraint of lignin content to embolism resistance across various groups of seed plants. For a Ψ50 reduction of approximately −0.3 MPa, plants allocate at least one percent of extra lignin to their wood. Species with low lignin content seem to be more vulnerable to embolism, whereas species with higher content show considerable variation in embolism resistance. Lignin content may play an indirect role in embolism resistance, since higher total lignin content is related to thicker cell walls. We also discuss the vulnerability to embolism regarding the different composition of lignin between gymnosperms and angiosperms and the performance of transgenic plants with modified lignin content and composition

International Social Survey Programme: Religion I-III - ISSP 1991-1998-2008

Die Kumulation der ISSP-Studien aus den Jahren 1991, 1998 und 2008besteht aus zwei Datensätzen: ZA5070 und ZA5071. Die vorliegendeStudienbeschreibung bezieht sich auf den Datensatz ZA5070. Er enthältalle kumulierten inhaltlichen sowie Demographievariablen. DerZusatzdatensatz ZA5071 enthält dagegen jene, meist länderspezifischenVariablen, die aus den verschiedensten Gründen nicht kumulierbar waren.Diese Variablen können jedoch, wenn nötig, sehr leicht in denHauptdatensatz integriert werden. Einen umfassenden Überblick über denAufbau der Kumulation, die Variablen und die wichtigstenKodierungsentscheidungen bietet das nachfolgende pdf-Dokument: Guide for the ISSP ´Religion´ cumulation of the years 1991, 1998 and 2008 Einstellung zur religiösen Praxis. Themen: Einschätzung des persönlichen Glücksgefühls; Verantwortung desStaates für die Bereitstellung von Arbeitsplätzen und den Abbau vonUnterschieden zwischen Reich und Arm; Einstellung zu vorehelichemGeschlechtsverkehr und zu außerehelichem Geschlechtsverkehr (Ehebruch);Einstellung zu homosexuellen Beziehungen zwischen Erwachsenen;Einstellung zu Abtreibung im Falle von Behinderung oder Krankheit desBabys und im Falle geringen Einkommens der Familie; Rollenverständnisin der Ehe; Einstellung zum Steuerbetrug und zur Angabe falscherInformationen zum Erhalt staatlicher Sozialleistungen;Institutionenvertrauen (Parlament, Unternehmen und Industrie, Kircheund religiöse Organisationen, Gerichte und Rechtssystem, Schulen undBildungssystem); Einstellung zum Einfluss von religiösen Führern aufWähler und Regierung; Beurteilung der Macht von Kirchen und religiösenOrganisationen im Lande; Zweifel oder fester Glaube an Gott (SkalaDeismus); Glaube an: ein Leben nach dem Tod, Himmel, Hölle, Wunder;Einstellung zur Bibel; Einstellung zu einer höheren Wahrheit und zumSinn des Lebens (Gott kümmert sich um jeden Menschen persönlich, nurwenig persönlicher Einfluss auf das Leben möglich (Fatalismus), Lebenhat nur einen Sinn aufgrund der Existenz Gottes, Leben dient keinemZweck, eigenes Tun verleiht dem Leben Sinn); jeder gestaltet seinSchicksal selbst; Bekehrung zum Glauben nach einem Schlüsselerlebnis;Religion der Mutter, des Vaters und des Ehepartners bzw. Partners;Religion, mit der der Befragte aufgewachsen ist; Kirchgangshäufigkeitdes Vaters und der Mutter in der Kindheit des Befragten; persönlicheKirchgangshäufigkeit in der Jugend; Häufigkeit des Betens und derTeilnahme an religiösen Aktivitäten; Selbsteinschätzung derReligiosität und Spiritualität; Glaube an Glücksbringer, Wahrsager,Gesundbeter und Horoskope; Erlebnis von Wiedergeburt; Konzept von Gott(semantisches Differential: Mutter/Vater, Herr und Meister/Ehepartner,Richter/Liebender, Freund/König); Weltimage: Schlechtes versus Gutes,der Mensch ist gut versus korrupt; Personenvertrauen; Einstellung zuWissenschaft und Religion (Skala: moderne Wissenschaft bringt mehrSchaden als Nutzen, zu viel Vertrauen in die Wissenschaft und zu wenigreligiöses Vertrauen, Religionen bringen mehr Konflikte als Frieden,Intoleranz von Menschen mit starken religiösen Überzeugungen); Wahrheitin einer oder in allen Religionen; demokratische oder göttliche Gesetzeals Grundlage für Entscheidungen zwischen richtig und falsch. Demographie: Geschlecht; Alter; Familienstand; Zusammenleben mit einemPartner; Jahre der Schulbildung, höchster Bildungsabschluss;derzeitiger Beschäftigungsstatus des Befragten und seines Partners;Wochenarbeitszeit; Beruf (ISCO-88) des Befragten und seines Partners;Vorgesetztenfunktion; Beschäftigung im privaten oder öffentlichenDienst oder Selbständigkeit; Selbständige wurden gefragt: Anzahl derBeschäftigten; Gewerkschaftsmitgliedschaft; Haushaltsgröße;Haushaltszusammensetzung; Parteipräferenz (links-rechts),länderspezifische Parteipräferenz; Wahlbeteiligung bei der letztenWahl; Kirchgangshäufigkeit; Konfession (länderspezifisch); Selbsteinstufung auf einer Oben-Unten-Skala; Region (länderspezifisch). Zusätzlich verkodet wurde: Gewichtungsfaktoren

International Social Survey Programme: Religion I-III ADD ON - ISSP 1991-1998-2008

The release of the cumulated ISSP ´Religion´ modules for the years 1991, 1998 and 2008 consists of two separate datasets: ZA5070 and ZA5071. This documentation deals with the supplementary dataset ZA5071. It contains all those, mainly national-specific background variables that belong to the current ISSP standard, but could not be cumulated for various reasons. The variables, however, can be matched easily to the cumulated file if necessary. A comprehensive overview on the contents, the structure and basic coding rules of both data files can be found in the following guide: Guide for the ISSP ´Religion´ cumulation of the years 1991, 1998 and 2008 Religion - (non-cumulated background variables of the individual modules) Variables for all countries and modules if available: country-specific education and degree; country-specific occupation (respondent as well as partner); earnings of respondent (country specific); family income (country-specific); country-specific party affiliation; size of community (country-specific); country of origin or ethnic group affiliation (country-specific); type of community: urban-rural area. Single variables: spouse’s working for private or public sector or self-employed 2008; self-placement on a top-bottom scale 2008, administrative mode of data-collection 2008, case substitution flag 2008