Zimmermann P.,European Academy Bozen Bolzano EURAC |
Tasser E.,European Academy Bozen Bolzano EURAC |
Leitinger G.,European Academy Bozen Bolzano EURAC |
Leitinger G.,University of Innsbruck |
And 2 more authors.
Agriculture, Ecosystems and Environment | Year: 2010
This study aims at (1) detecting the main agricultural land-use/land-cover (LULC) trends that have occurred across the Alps since the 19th century and (2) assessing how landscape-scale biodiversity is affected by spatiotemporal LULC patterns. In a representative analysis, 35 municipalities covering the principal types of environmental, agro-economic and political conditions in the Alps were investigated. Based on historical maps and aerial photographs the LULC trends were determined using a hierarchical cluster analysis. Data on the plant species richness of the occurring LULC classes were derived from phytosociological literature. Finally, land-cover and floristic data were used to calculate indicators for the three aspects of α-, β- and γ-diversity.Five main LULC trends could be found. Areas with grassland farming either experienced (1) the abandonment of grassland or (2) continuous grassland use. Areas with mixed agriculture either underwent (3) a specialisation in grassland farming, (4) a specialisation in vine and fruit cultures or (5) the continuous use of arable fields. Vine and fruit farming along with land abandonment and urban sprawl had the most negative impact on all aspects of landscape-scale biodiversity. © 2010 Elsevier B.V.
Allebrandt K.V.,Ludwig Maximilians University of Munich |
Amin N.,Erasmus University Rotterdam |
Muller-Myhsok B.,Max Planck Institute of Psychiatry |
Esko T.,University of Tartu |
And 27 more authors.
Molecular Psychiatry | Year: 2013
Humans sleep approximately a third of their lifetime. The observation that individuals with either long or short sleep duration show associations with metabolic syndrome and psychiatric disorders suggests that the length of sleep is adaptive. Although sleep duration can be influenced by photoperiod (season) and phase of entrainment (chronotype), human familial sleep disorders indicate that there is a strong genetic modulation of sleep. Therefore, we conducted high-density genome-wide association studies for sleep duration in seven European populations (N4251). We identified an intronic variant (rs11046205; P3.99 × 10 8) in the ABCC9 gene that explains 5% of the variation in sleep duration. An influence of season and chronotype on sleep duration was solely observed in the replication sample (N5949). Meta-analysis of the associations found in a subgroup of the replication sample, chosen for season of entry and chronotype, together with the discovery results showed genome-wide significance. RNA interference knockdown experiments of the conserved ABCC9 homologue in Drosophila neurons renders flies sleepless during the first 3 h of the night. ABCC9 encodes an ATP-sensitive potassium channel subunit (SUR2), serving as a sensor of intracellular energy metabolism. © 2013 Macmillan Publishers Limited.
PubMed | New York University, University of Tartu, Cedars Sinai Medical Center, University of Washington and 29 more.
Type: Journal Article | Journal: Aging cell | Year: 2016
The growth hormone/insulin-like growth factor (IGF) axis can be manipulated in animal models to promote longevity, and IGF-related proteins including IGF-I and IGF-binding protein-3 (IGFBP-3) have also been implicated in risk of human diseases including cardiovascular diseases, diabetes, and cancer. Through genomewide association study of up to 30884 adults of European ancestry from 21 studies, we confirmed and extended the list of previously identified loci associated with circulating IGF-I and IGFBP-3 concentrations (IGF1, IGFBP3, GCKR, TNS3, GHSR, FOXO3, ASXL2, NUBP2/IGFALS, SORCS2, and CELSR2). Significant sex interactions, which were characterized by different genotype-phenotype associations between men and women, were found only for associations of IGFBP-3 concentrations with SNPs at the loci IGFBP3 and SORCS2. Analyses of SNPs, gene expression, and protein levels suggested that interplay between IGFBP3 and genes within the NUBP2 locus (IGFALS and HAGH) may affect circulating IGF-I and IGFBP-3 concentrations. The IGF-I-decreasing allele of SNP rs934073, which is an eQTL of ASXL2, was associated with lower adiposity and higher likelihood of survival beyond 90years. The known longevity-associated variant rs2153960 (FOXO3) was observed to be a genomewide significant SNP for IGF-I concentrations. Bioinformatics analysis suggested enrichment of putative regulatory elements among these IGF-I- and IGFBP-3-associated loci, particularly of rs646776 at CELSR2. In conclusion, this study identified several loci associated with circulating IGF-I and IGFBP-3 concentrations and provides clues to the potential role of the IGF axis in mediating effects of known (FOXO3) and novel (ASXL2) longevity-associated loci.
PubMed | Fred Hutchinson Cancer Research Center, Centro Cardiologico Monzino IRCCS, University of Milan Bicocca, Goethe University Frankfurt and 7 more.
Type: | Journal: Journal of molecular and cellular cardiology | Year: 2015
Communication between cardiomyocytes depends upon gap junctions (GJ). Previous studies have demonstrated that electrical stimulation induces GJ remodeling and modifies histone acetylase (HAT) and deacetylase (HDAC) activities, although these two results have not been linked. The aim of this work was to establish whether electrical stimulation modulates GJ-mediated cardiac cell-cell communication by acetylation-dependent mechanisms. Field stimulation of HL-1 cardiomyocytes at 0.5 Hz for 24 h significantly reduced connexin43 (Cx43) expression and cell-cell communication. HDAC activity was down-regulated whereas HAT activity was not modified resulting in increased acetylation of Cx43. Consistent with a post-translational mechanism, we did not observe a reduction in Cx43 mRNA in electrically stimulated cells, while the proteasomal inhibitor MG132 maintained Cx43 expression. Further, the treatment of paced cells with the HAT inhibitor Anacardic Acid maintained both the levels of Cx43 and cell-cell communication. Finally, we observed increased acetylation of Cx43 in the left ventricles of dogs subjected to chronic tachypacing as a model of abnormal ventricular activation. In conclusion, our findings suggest that altered electrical activity can regulate cardiomyocyte communication by influencing the acetylation status of Cx43.
Poenisch M.,University of Heidelberg |
Metz P.,University of Heidelberg |
Blankenburg H.,Max Planck Institute for Informatics |
Ruggieri A.,University of Heidelberg |
And 11 more authors.
PLoS pathogens | Year: 2015
Hepatitis C virus (HCV) is a major cause of chronic liver disease affecting around 130 million people worldwide. While great progress has been made to define the principle steps of the viral life cycle, detailed knowledge how HCV interacts with its host cells is still limited. To overcome this limitation we conducted a comprehensive whole-virus RNA interference-based screen and identified 40 host dependency and 16 host restriction factors involved in HCV entry/replication or assembly/release. Of these factors, heterogeneous nuclear ribonucleoprotein K (HNRNPK) was found to suppress HCV particle production without affecting viral RNA replication. This suppression of virus production was specific to HCV, independent from assembly competence and genotype, and not found with the related Dengue virus. By using a knock-down rescue approach we identified the domains within HNRNPK required for suppression of HCV particle production. Importantly, HNRNPK was found to interact specifically with HCV RNA and this interaction was impaired by mutations that also reduced the ability to suppress HCV particle production. Finally, we found that in HCV-infected cells, subcellular distribution of HNRNPK was altered; the protein was recruited to sites in close proximity of lipid droplets and colocalized with core protein as well as HCV plus-strand RNA, which was not the case with HNRNPK variants unable to suppress HCV virion formation. These results suggest that HNRNPK might determine efficiency of HCV particle production by limiting the availability of viral RNA for incorporation into virions. This study adds a new function to HNRNPK that acts as central hub in the replication cycle of multiple other viruses.
Poenisch M.,University of Heidelberg |
Metz P.,University of Heidelberg |
Blankenburg H.,Max Planck Institute for Informatics |
Blankenburg H.,European Academy Bozen Bolzano EURAC |
And 13 more authors.
PLoS Pathogens | Year: 2015
Hepatitis C virus (HCV) is a major cause of chronic liver disease affecting around 130 million people worldwide. While great progress has been made to define the principle steps of the viral life cycle, detailed knowledge how HCV interacts with its host cells is still limited. To overcome this limitation we conducted a comprehensive whole-virus RNA interference-based screen and identified 40 host dependency and 16 host restriction factors involved in HCV entry/replication or assembly/release. Of these factors, heterogeneous nuclear ribonucleoprotein K (HNRNPK) was found to suppress HCV particle production without affecting viral RNA replication. This suppression of virus production was specific to HCV, independent from assembly competence and genotype, and not found with the related Dengue virus. By using a knock-down rescue approach we identified the domains within HNRNPK required for suppression of HCV particle production. Importantly, HNRNPK was found to interact specifically with HCV RNA and this interaction was impaired by mutations that also reduced the ability to suppress HCV particle production. Finally, we found that in HCV-infected cells, subcellular distribution of HNRNPK was altered; the protein was recruited to sites in close proximity of lipid droplets and colocalized with core protein as well as HCV plus-strand RNA, which was not the case with HNRNPK variants unable to suppress HCV virion formation. These results suggest that HNRNPK might determine efficiency of HCV particle production by limiting the availability of viral RNA for incorporation into virions. This study adds a new function to HNRNPK that acts as central hub in the replication cycle of multiple other viruses. © 2015 Poenisch et al.
Schwienbacher C.,European Academy Bozen Bolzano EURAC |
Schwienbacher C.,University of Lübeck
BMC research notes | Year: 2014
BACKGROUND: Research on microRNAs (miRNAs) is becoming an increasingly attractive field, as these small RNA molecules are involved in several physiological functions and diseases. To date, only few studies have assessed the expression of blood miRNAs related to Parkinson's disease (PD) using microarray and quantitative real-time PCR (qRT-PCR). Measuring miRNA expression involves normalization of qRT-PCR data using endogenous reference genes for calibration, but their choice remains a delicate problem with serious impact on the resulting expression levels. The aim of the present study was to evaluate the suitability of a set of commonly used small RNAs as normalizers and to identify which of these miRNAs might be considered reliable reference genes in qRT-PCR expression analyses on PD blood samples.RESULTS: Commonly used reference genes snoRNA RNU24, snRNA RNU6B, snoRNA Z30 and miR-103a-3p were selected from the literature. We then analyzed the effect of using these genes as reference, alone or in any possible combination, on the measured expression levels of the target genes miR-30b-5p and miR-29a-3p, which have been previously reported to be deregulated in PD blood samples.CONCLUSIONS: We identified RNU24 and Z30 as a reliable and stable pair of reference genes in PD blood samples.
Arnold M.,Helmholtz Center for Environmental Research |
Ellwanger D.C.,Helmholtz Center for Environmental Research |
Ellwanger D.C.,TU Munich |
Hartsperger M.L.,Helmholtz Center for Environmental Research |
And 5 more authors.
PLoS ONE | Year: 2012
Genome-wide association studies (GWAS) have become an effective tool to map genes and regions contributing to multifactorial human diseases and traits. A comparably small number of variants identified by GWAS are known to have a direct effect on protein structure whereas the majority of variants is thought to exert their moderate influences on the phenotype through regulatory changes in mRNA expression. MicroRNAs (miRNAs) have been identified as powerful posttranscriptional regulators of mRNAs. Binding to their target sites, which are mostly located within the 3′-untranslated region (3′-UTR) of mRNA transcripts, they modulate mRNA expression and stability. Until today almost all human mRNA transcripts are known to harbor at least one miRNA target site with an average of over 20 miRNA target sites per transcript. Among 5,101 GWAS-identified sentinel single nucleotide polymorphisms (SNPs) that correspond to 18,884 SNPs in linkage disequilibrium (LD) with the sentinels (r2 ≥ 0.8) we identified a significant overrepresentation of SNPs that affect the 3′-UTR of genes (OR = 2.33, 95% CI = 2.12-2.57, P < 10-52). This effect was even stronger considering all SNPs in one LD bin a single signal (OR = 4.27, 95% CI = 3.84-4.74, P < 10-114). Based on crosslinking immunoprecipitation data we identified four mechanisms affecting miRNA regulation by 3′-UTR mutations: (i) deletion or (ii) creation of miRNA recognition elements within validated RNA-induced silencing complex binding sites, (iii) alteration of 3′-UTR splicing leading to a loss of binding sites, and (iv) change of binding affinity due to modifications of 3′-UTR folding. We annotated 53 SNPs of a total of 288 trait-associated 3′-UTR SNPs as mediating at least one of these mechanisms. Using a qualitative systems biology approach, we demonstrate how our findings can be used to support biological interpretation of GWAS results as well as to provide new experimentally testable hypotheses. © 2012 Arnold et al.
Salvadori U.,Bolzano Hospital |
Minelli C.,European Academy Bozen Bolzano EURAC |
Graziotin B.,Bolzano Hospital |
Gentilini I.,Bolzano Hospital
Blood Transfusion | Year: 2014
Background. The Haemonetics MCS®+ cell separator is a device dedicated to the collection of leucoreduced single-donor platelets. The new Universal Platelet protocol has been introduced to improve the efficiency of apheresis and increase flexibility in the collection of leucoreduced platelets in combination with red blood cells and plasma. In this study we compared its performance with that of the previous Concentrated Single Donor Platelet protocol. Materials and methods. This observational study had a within-subject design and involved 135 donors who underwent plateletapheresis with both protocols. The primary end-point was collection efficiency; secondary end-points were other performance indices, such as procedure time and collection rate. A satisfaction questionnaire was also administered to the 135 donors to evaluate opinions on duration, comfort and side-effects of donations with the two protocols. For each parameter of interest, we tested the difference between the two protocols within donors, using a one-sample t-test or exact McNemar's test as appropriate. Results. The collection efficiency of the Universal Platelet protocol was significantly higher than that of the Concentrated Single Donor Platelet protocol (58% vs 47%; p<0.0001). The Universal Platelet Protocol collected more platelets in less time, leading to a higher collection rate (6.5 vs 5.0×109/min; p<0.0001). In general, donors found apheresis with the Universal Platelet protocol of equal duration or faster, of similar or greater comfort and with an equal number or fewer side effects, compared with the Concentrated Single Donor Platelet protocol. Discussion. Our study endorses the use of the new Universal Platelet protocol in daily transfusion practice since it substantially improves collection efficiency in leucoreduced platelet procedures compared with the Concentrated Single Donor Platelet protocol. This technical improvement seems to be accompanied by equal or greater comfort for the donor. © SIMTI Servizi Srl.
Mascalzoni D.,European Academy Bozen Bolzano EURAC |
Janssens A.C.J.,Rotterdam University |
Stewart A.,PHG Foundation |
Pramstaller P.,European Academy Bozen Bolzano EURAC |
And 7 more authors.
European Journal of Human Genetics | Year: 2010
Family-based research in genetically isolated populations is an effective approach for identifying loci influencing variation in disease traits. In common with all studies in humans, those in genetically isolated populations need ethical approval; however, existing ethical frameworks may be inadequate to protect participant privacy and confidentiality and to address participants information needs in such populations. Using the ethical-legal guidelines of the Council for International Organizations of Medical Sciences (CIOMS) as a template, we compared the participant information leaflets and consent forms of studies in five European genetically isolated populations to identify additional information that should be incorporated into information leaflets and consent forms to guarantee satisfactorily informed consent. We highlight the additional information that participants require on the research purpose and the reasons why their population was chosen; on the potential risks and benefits of participation; on the opportunities for benefit sharing; on privacy; on the withdrawal of consent and on the disclosure of genetic data. This research raises some important issues that should be addressed properly and identifies relevant types of information that should be incorporated into information leaflets for this type of study. © 2010 Macmillan Publishers Limited All rights reserved.