| 1. |
- Carninci, P, et al.
(author)
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The transcriptional landscape of the mammalian genome
- 2005
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In: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 309:5740, s. 1559-1563
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Journal article (peer-reviewed)abstract
- This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5′ and 3′ boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.
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| 2. |
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| 3. |
- Jeppesen, H. B., et al.
(author)
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Multi-quasiparticle states in (256)Rf
- 2009
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In: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 79:3, s. 031303-
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Journal article (peer-reviewed)abstract
- Excited states in (256)Rf were populated via the Pb-208(Ti-50,2n) fusion-evaporation reaction. Delayed gamma-ray and electron decay spectroscopy was performed and three isomeric states in (256)Rf have been identified. A fourth low-energy nonyrast state was identified from the gamma-ray decay of one of the higher lying isomers. The states are interpreted as multi-quasiparticle excitations.
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| 4. |
- Fridner, Ann, et al.
(author)
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The research collaboration HOUPE: Health and Organisation among University Hospital Physcians in four European countries: Sweden, Norway, Iceland and Italy
- 2008
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In: BMA – AMA – CMA International conference on Doctors Health, London, 18-20th of November 2008.
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Conference paper (peer-reviewed)abstract
- Background: Hospital statistics show increased pre-pensioning and sickness absence among physicians in Sweden. In addition, female physicians experience unconstructive work conditions, inequality of pay, and less career advancement than their male counterparts in university hospitals despite increased share of women in medical education. Signs of ill-health among physicians might have severe consequences for people involved, patients, hospital economy and for health service provided. HOUPE is a research collaboration between four University Hospitals in Europe; Karolinska University Hospital, Stockholm, Landspitali University Hospital, Reykjavik, St Olavs University Hospital, Trondheim and University Hospital Azienda Ospedaliera, Padova.Objective: In 2002 national research groups anchored at four University Hospitals in Sweden, Norway, Iceland and Italy started a comprehensive research program abbreviated: The HOUPE project intended to provide a systematic comparison of university hospitals in Europe and how the structure and organization of these hospitals affected the research activity, work load, work satisfaction, gender equality, career advancement, health, and wellbeing of physicians. Next phase in our longitudinal design will include the university hospital in Budapest, Hungary.Funding: Medical Association in Iceland and Sweden, SLS - Swedish Physician Society, NorFA, Vinnova, Stockholm City Council, the four University Hospitals.Method: Three level of data collection were executed: Document analysis concerning national frameworks, register data/hospital statistics and a cross sectional survey in 2005/2006 (N = 2095/3867) among permanently employed university hospital physicians in each country.Results: Numerous research projects are scheduled in each country based on these data in different national research project. Preliminary results will be presented based on these ongoing analyzes on differences in the prevalence of harassment level, suicide ideation, hospitals emphasize of clinical research, and the tension between work load and interaction between career and role as caregivers at home, inequality of pay between men and women, and between medical and academic position.Intervention and prevention: Survey feedback seminars (Fridner & Pingel, 2006) with physicians in each clinic and Occupational Stress Index (OSI) for physicians (Belkic, 2003).Conclusions: The lack of studies that address organisational and psychosocial work conditions for physicians in Iceland and Italy makes HOUPE data important for this purpose. Numerous research projects were scheduled in each country based on these data. In addition, HOUPE data will be able to identify existing practices in management systems of university hospitals and trough comparison between the university hospitals highlight best practice.
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| 5. |
- Pavan, C., et al.
(author)
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Generation of the iPSC line FINi002-A from a male Parkinson's disease patient carrying compound heterozygous mutations in the PRKN gene
- 2023
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In: Stem Cell Research. - 1873-5061. ; 73
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Journal article (peer-reviewed)abstract
- The most common cause of autosomal recessive familial Parkinson's disease (PD) are mutations in the PRKN/PARK2 gene encoding an E3 ubiquitin protein-ligase PARKIN. We report the generation of an iPSC cell line from the fibroblasts of a male PD patient carrying a common missense variant in exon 7 (p.Arg275Trp), and a 133 kb deletion encompassing exon 8, using transiently-present Sendai virus. The established line displays typical human primed iPSC morphology and expression of pluripotency-associated markers, normal karyotype without SNP array-detectable copy number variations and can give rise to derivatives of all three embryonic germ layers. We envisage the usefulness of this iPSC line, carrying a common and well-studied missense mutation in the RING1 domain of the PARKIN protein, for the elucidation of PARKIN-dependent mechanisms of PD using in vitro and in vivo models.
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| 6. |
- de Angelis, G., et al.
(author)
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Coherent proton-neutron contribution to octupole correlations in the neutron-deficient Xe-114 nucleus
- 2002
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In: Physics Letters B. - 0370-2693 .- 1873-2445. ; 535:04-jan, s. 93-102
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Journal article (peer-reviewed)abstract
- Gamma ray linear polarization and picosecond lifetimes have been measured for levels in the neutron deficient nucleus Xe-114 using the EUROBALL IV spectrometer and the Cologne plunger device. The EUCLIDES Si-ball was used to improve the reaction channel selectivity. The linear polarization results have, for the first time, unambiguously determined the electromagnetic character of the dipole transitions de-exciting the negative parity level sequence, providing clear evidence for enhanced octupole collectivity. The discovery of two E3 transitions and the measurement of the lifetimes of the states depopulated by these transitions have allowed a quantitative determination of the octupole collectivity in the A approximate to 112 mass region. The large measured B(E3) values, close to approximate to 70 W.u., are among the strongest observed hitherto and indicate a coherent proton-neutron contribution to the octupole moment.
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| 7. |
- Gadea, A., et al.
(author)
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Observation of Ni-54 : Cross-conjugate symmetry in f(7/2) mirror energy differences
- 2006
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In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 97:15, s. 152501-
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Journal article (peer-reviewed)abstract
- Gamma decays from excited states up to J(pi)=6(+) in the N=Z-2 nucleus Ni-54 have been identified for the first time. Level energies are compared with those of the isobars Co-54 and Fe-54 and of the cross-conjugate nuclei of mass A=42. The good but puzzling f(7/2) cross-conjugate symmetry in mirror and triplet energy differences is analyzed. Shell model calculations reproduce the new data but the necessary nuclear charge-dependent phenomenology is not fully explained by modern nucleon-nucleon potentials.
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| 8. |
- Gadea, A., et al.
(author)
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Spectroscopy at N=Z with EUROBALL III
- 1999
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In: AIP Conference Proceedings. - : AIP. - 1551-7616 .- 0094-243X. ; 495, s. 195-198
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Conference paper (peer-reviewed)abstract
- A complete study of the nuclear structure by means of gamma spectroscopy requires, in addition to the high resolution gamma measurement and accurate DCO's or angular distributions, the information concerning the Electric or Magnetic character of the transition. This information for transitions in nuclei far from stability valley is now reachable in the new generation of Ge-arrays based in composite detectors. EUROBALL III is a good example with the high polarization sensitivity of the 90 degrees ring of Clovers. The Polarization correlations PCO's measured in coincidence with the Cluster detectors permits to investigate transitions in weakly populated nuclei. In this contribution we present results on medium mass N=Z nuclei measured with EUROBALL III coupled with light particle ancillary detectors.
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| 9. |
- Lona-Durazo, Frida, et al.
(author)
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Meta-analysis of GWA studies provides new insights on the genetic architecture of skin pigmentation in recently admixed populations
- 2019
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In: BMC Genetics. - : BMC. - 1471-2156. ; 20
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Journal article (peer-reviewed)abstract
- Background: Association studies in recently admixed populations are extremely useful to identify the genetic architecture of pigmentation, due to their high genotypic and phenotypic variation. However, to date only four Genome-Wide Association Studies (GWAS) have been carried out in these populations.Results: We present a GWAS of skin pigmentation in an admixed sample from Cuba (N=762). Additionally, we conducted a meta-analysis including the Cuban sample, and admixed samples from Cape Verde, Puerto Rico and African-Americans from San Francisco. This meta-analysis is one of the largest efforts so far to characterize the genetic basis of skin pigmentation in admixed populations (N=2,104). We identified five genome-wide significant regions in the meta-analysis, and explored if the markers observed in these regions are associated with the expression of relevant pigmentary genes in human melanocyte cultures. In three of the regions identified in the meta-analysis (SLC24A5, SLC45A2, and GRM5/TYR), the association seems to be driven by non-synonymous variants (rs1426654, rs16891982, and rs1042602, respectively). The rs16891982 polymorphism is strongly associated with the expression of the SLC45A2 gene. In the GRM5/TYR region, in addition to the rs1042602 non-synonymous SNP located on the TYR gene, variants located in the nearby GRM5 gene have an independent effect on pigmentation, possibly through regulation of gene expression of the TYR gene. We also replicated an association recently described near the MFSD12 gene on chromosome 19 (lead variant rs112332856). Additionally, our analyses support the presence of multiple signals in the OCA2/HERC2/APBA2 region on chromosome 15. A clear causal candidate is the HERC2 intronic variant rs12913832, which has a profound influence on OCA2 expression. This variant has pleiotropic effects on eye, hair, and skin pigmentation. However, conditional and haplotype-based analyses indicate the presence of other variants with independent effects on melanin levels in OCA2 and APBA2. Finally, a follow-up of genome-wide signals identified in a recent GWAS for tanning response indicates that there is a substantial overlap in the genetic factors influencing skin pigmentation and tanning response.Conclusions: Our meta-analysis of skin pigmentation GWAS in recently admixed populations provides new insights about the genetic architecture of this complex trait.
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| 10. |
- Pavan, Chiara, et al.
(author)
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DNase Treatment Prevents Cerebrospinal Fluid Block in Early Experimental Pneumococcal Meningitis
- 2021
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In: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 90:4, s. 653-669
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Journal article (peer-reviewed)abstract
- Objective: Streptococcus pneumoniae is the most common cause of bacterial meningitis, a disease that, despite treatment with antibiotics, still is associated with high mortality and morbidity worldwide. Diffuse brain swelling is a leading cause of morbidity in S pneumoniae meningitis. We hypothesized that neutrophil extracellular traps (NETs) disrupt cerebrospinal fluid (CSF) transport by the glymphatic system and contribute to edema formation in S pneumoniae meningitis. Methods: We used DNase I treatment to disrupt NETs and then assessed glymphatic function by cisterna magna injections of CSF tracers in a rat model of S pneumoniae meningitis. Results: Our analysis showed that CSF influx into the brain parenchyma, as well as CSF drainage to the cervical lymph nodes, was significantly reduced in the rat model of S pneumoniae meningitis. Degrading NETs by DNase treatment restored glymphatic transport and eliminated the increase in brain weight in the rats. In contrast, first-line antibiotic treatment had no such effect on restoring fluid dynamics. Interpretation: This study suggests that CSF accumulation is responsible for cerebral edema formation and identifies the glymphatic system and NETs as possible new treatment targets in S pneumoniae meningitis. ANN NEUROL 2021.
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| 11. |
- Ramos, Marta, et al.
(author)
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Cisterna Magna Injection in Rats to Study Glymphatic Function
- 2019
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In: Methods in molecular biology (Clifton, N.J.). - New York, NY : Springer New York. - 1940-6029. ; 1938, s. 97-104
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Journal article (peer-reviewed)abstract
- The recently discovered glymphatic system, which supports brain-wide clearance of metabolic waste, has become the subject of intense research within the past few years. Its nomenclature arose due to its functionally analogous nature to the lymphatic system in combination with glial cells that are part of its anatomical boundaries. The influx of cerebrospinal fluid (CSF) from perivascular spaces into the brain interstitium acts to clear intraparenchymal solutes. CSF is produced by the choroid plexus and flows from the ventricles to the subarachnoid space via the cisterna magna, and as such the injection of tracer molecules into any one of these spaces could be used for studying CSF movement through the glymphatic system. Of these options, the cisterna magna is most favorable as it offers a route of entry that does not involve craniotomy. Herein we describe the cisterna magna (CM) injection procedure carried out in rats, essential for studying glymphatic influx and efflux dynamics.
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| 12. |
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| 13. |
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| 14. |
- Zhang, Tongwu, et al.
(author)
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Cell-type-specific eQTL of primary melanocytes facilitates identification of melanoma susceptibility genes
- 2018
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In: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 28:11, s. 1621-1635
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Journal article (peer-reviewed)abstract
- Most expression quantitative trait locus (eQTL) studies to date have been performed in heterogeneous tissues as opposed to specific cell types. To better understand the cell-type-specific regulatory landscape of human melanocytes, which give rise to melanoma but account for <5% of typical human skin biopsies, we performed an eQTL analysis in primary melanocyte cultures from 106 newborn males. We identified 597,335 cis-eQTL SNPs prior to linkage disequilibrium (LD) pruning and 4997 eGenes (FDR < 0.05). Melanocyte eQTLs differed considerably from those identified in the 44 GTEx tissue types, including skin. Over a third of melanocyte eGenes, including key genes in melanin synthesis pathways, were unique to melanocytes compared to those of GTEx skin tissues or TCGA melanomas. The melanocyte data set also identified trans-eQTLs, including those connecting a pigmentation-associated functional SNP with four genes, likely through cis-regulation of IRF4. Melanocyte eQTLs are enriched in cis-regulatory signatures found in melanocytes as well as in melanoma-associated variants identified through genome-wide association studies. Melanocyte eQTLs also colocalized with melanoma GWAS variants in five known loci. Finally, a transcriptome-wide association study using melanocyte eQTLs uncovered four novel susceptibility loci, where imputed expression levels of five genes (ZFP90, HEBP1, MSC, CBWD1, and RP11-383H13.1) were associated with melanoma at genome-wide significant P-values. Our data highlight the utility of lineage-specific eQTL resources for annotating GWAS findings, and present a robust database for genomic research of melanoma risk and melanocyte biology.
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| 15. |
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