Odin observations of H2O in the Galactic Centre

The Odin satellite has been used to detect emission and absorption in the 557-GHz H2O line in the Galactic Centre towards the Sgr A* Circumnuclear Disk (CND), and the Sgr A +20 km/s and +50 km/s molecular clouds. Strong broad H2O emission lines have been detected in all three objects. Narrow H2O absorption lines are present at all three positions and originate along the lines of sight in the 3-kpc Spiral Arm, the -30 km/s Spiral Arm and the Local Sgr Spiral Arm. Broad H2O absorption lines near -130 km/s are also observed, originating in the Expanding Molecular Ring. A new molecular feature (the ``High Positive Velocity Gas'' - HPVG) has been identified in the positive velocity range of ~ +120 to +220 km/s, seen definitely in absorption against the stronger dust continuum emission from the +20 km/s and +50 km/s clouds and possibly in emission towards the position of Sgr A* CND. The 548-GHz H2_18O isotope line towards the CND is not detected at the 0.02 K (rms) level.Comment: 5 pages, 3 figures, accepted by A&A, special Odin Letters issu

Sources of increase in lowermost stratospheric sulphurous and carbonaceous aerosol background concentrations during 1999–2008 derived from CARIBIC flights

This study focuses on sulphurous and carbonaceous aerosol, the major constituents of particulate matter in the lowermost stratosphere (LMS), based on in situ measurements from 1999 to 2008. Aerosol particles in the size range of 0.08–2 µm were collected monthly during intercontinental flights with the CARIBIC passenger aircraft, presenting the first long-term study on carbonaceous aerosol in the LMS. Elemental concentrations were derived via subsequent laboratory-based ion beam analysis. The stoichiometry indicates that the sulphurous fraction is sulphate, while an O/C ratio of 0.2 indicates that the carbonaceous aerosol is organic. The concentration of the carbonaceous component corresponded on average to approximately 25% of that of the sulphurous, and could not be explained by forest fires or biomass burning, since the average mass ratio of Fe to K was 16 times higher than typical ratios in effluents from biomass burning. The data reveal increasing concentrations of particulate sulphur and carbon with a doubling of particulate sulphur from 1999 to 2008 in the northern hemisphere LMS. Periods of elevated concentrations of particulate sulphur in the LMS are linked to downward transport of aerosol from higher altitudes, using ozone as a tracer for stratospheric air. Tropical volcanic eruptions penetrating the tropical tropopause are identified as the likely cause of the particulate sulphur and carbon increase in the LMS, where entrainment of lower tropospheric air into volcanic jets and plumes could be the cause of the carbon increase

Glioblastoma—a moving target

The slow development of effective treatment of glioblastoma is contrasted by the rapidly advancing research on the molecular mechanisms underlying the disease. Amplification and overexpression of receptor tyrosine kinases, particularly EGFR and PDGFRA, are complemented by mutations in the PI3K, RB1, and p53 signaling pathways. In addition to finding effective means to target these pathways, we may take advantage of the recent understanding of the hierarchical structure of tumor cell populations, where the progressive expansion of the tumor relies on a minor subpopulation of glioma stem cells, or glioma-initiating cells. Finding ways to reprogram these cells and block their self-renewal is one of the most important topics for future research

A DNA Sequence Directed Mutual Transcription Regulation of HSF1 and NFIX Involves Novel Heat Sensitive Protein Interactions

BACKGROUND: Though the Nuclear factor 1 family member NFIX has been strongly implicated in PDGFB-induced glioblastoma, its molecular mechanisms of action remain unknown. HSF1, a heat shock-related transcription factor is also a powerful modifier of carcinogenesis by several factors, including PDGFB. How HSF1 transcription is controlled has remained largely elusive. METHODOLOGY/PRINCIPAL FINDINGS: By combining microarray expression profiling and a yeast-two-hybrid screen, we identified that NFIX and its interactions with CGGBP1 and HMGN1 regulate expression of HSF1. We found that CGGBP1 organizes a bifunctional transcriptional complex at small CGG repeats in the HSF1 promoter. Under chronic heat shock, NFIX uses CGGBP1 and HMGN1 to get recruited to this promoter and in turn affects their binding to DNA. Results show that the interactions of NFIX with CGGBP1 and HMGN1 in the soluble fraction are heat shock sensitive due to preferential localization of CGGBP1 to heterochromatin after heat shock. HSF1 in turn was found to bind to the NFIX promoter and repress its expression in a heat shock sensitive manner. CONCLUSIONS/SIGNIFICANCE: NFIX and HSF1 exert a mutual transcriptional repressive effect on each other which requires CGG repeat in HSF1 promoter and HSF1 binding site in NFIX promoter. We unravel a unique mechanism of heat shock sensitive DNA sequence-directed reciprocal transcriptional regulation between NFIX and HSF1. Our findings provide new insights into mechanisms of transcription regulation under stress

Review of journal of cardiovascular magnetic resonance 2010

There were 75 articles published in the Journal of Cardiovascular Magnetic Resonance (JCMR) in 2010, which is a 34% increase in the number of articles since 2009. The quality of the submissions continues to increase, and the editors were delighted with the recent announcement of the JCMR Impact Factor of 4.33 which showed a 90% increase since last year. Our acceptance rate is approximately 30%, but has been falling as the number of articles being submitted has been increasing. In accordance with Open-Access publishing, the JCMR articles go on-line as they are accepted with no collating of the articles into sections or special thematic issues. Last year for the first time, the Editors summarized the papers for the readership into broad areas of interest or theme, which we felt would be useful to practitioners of cardiovascular magnetic resonance (CMR) so that you could review areas of interest from the previous year in a single article in relation to each other and other recent JCMR articles [1]. This experiment proved very popular with a very high rate of downloading, and therefore we intend to continue this review annually. The papers are presented in themes and comparison is drawn with previously published JCMR papers to identify the continuity of thought and publication in the journal. We hope that you find the open-access system increases wider reading and citation of your papers, and that you will continue to send your quality manuscripts to JCMR for publication

Формирование эмоциональной культуры как компонента инновационной культуры студентов

Homozygosity has long been associated with rare, often devastating, Mendelian disorders1 and Darwin was one of the first to recognise that inbreeding reduces evolutionary fitness2. However, the effect of the more distant parental relatedness common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity, ROH), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power3,4. Here we use ROH to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts and find statistically significant associations between summed runs of homozygosity (SROH) and four complex traits: height, forced expiratory lung volume in 1 second (FEV1), general cognitive ability (g) and educational attainment (nominal p<1 × 10−300, 2.1 × 10−6, 2.5 × 10−10, 1.8 × 10−10). In each case increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing convincing evidence for the first time that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples5,6, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein (LDL) cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection7, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Betong i arkitekturen. Gestaltning och teknik 1930-1980

Bengt J O Johansson: Betong i arkitekturen. Gestaltning och teknik 1930–1980 (Concrete in Architecture. Design and Technology 1930–1980). G\uf6teborg 2008.Written in Swedish with an English summary.This is a study of the interaction between design and technology for buildings of concrete construction during 1930-1980. Its aim is to describe the design and constructional development during the different stages of style change throughout this period, and how design and technology have influenced each other. Knowledge about building technology utilising concrete is essential for understanding the building heritage of our own era.The study encompasses architecture and construction technology. The sources are literature and drawings, and the buildings themselves.The study begins with an account of the development of concrete building technology during the period in question. Construction technology provides the basis for the analysis of the interaction with architecture. This interaction is described in three thematically sectioned chapters and summarised and analysed in a concluding chapter. These thematic chapters deal with concrete as ’the material for modernism’, as ‘the material for design’ and as ‘the material for rationalism’.Concrete construction was at the beginning of the 1930s an ideal in the creation of functionalist (modernistic) architecture, even if the structures were initially mostly of traditional character. During this decennium, however, concrete became the most commonly used material for construction in buildings.From the 1950s onwards, on-site concrete constructions were utilised in the creation of buildings of character. The textured surface of the concrete, often derived by carefully shaped casts or through finishing processes made a vital contribution to the design. Concrete formed load-bearing elements and constructions gave design to interiors, exte-riors, and even complete volumes. Architects adopted concrete construction technology and at the same time freed themselves from traditional architecture with historical roots. This resulted in painstakingly designed concrete buildings.Parallel with this, from the 1960s onwards, industrialised construction with precast concrete modular sections for entire building structures and fa\ue7ades were developed. Here the construction process and prefabrication technology became design-oriented motives, often finding expression through their large-scale, repetition, and duplication of identical modular units in the individual building and the repetition of identical buildings. The concrete surfaces of the fa\ue7ades’ sectional units were produced rationally; they formed and accentuated this industrialised construction

Betong och arkitektur. Betongens utveckling i husbyggandet 1880-1940 med G\uf6teborg som exempel

This is a study of development of concrete and concrete structures, and its architectural influences in Sweden during the period 1880-1940