46 research outputs found
Depressive symptoms and mortality-findings from Helsinki birth cohort study
Background:Â Individuals with depression and depressive symptoms have a higher mortality rate than non-depressed individuals. The increased comorbidity and mortality associated with depression has remained largely unexplained. The underlying pathophysiological differences between depressive subtypes, melancholic and non-melancholic, may provide some explanation to this phenomenon.Methods:Â One thousand nine hundred and ninety five participants (mean age 61 years) from the Helsinki Birth Cohort Study were recruited for this prospective study and followed up for a mean of 14.1 years. Information regarding medical history, lifestyle, and biochemical parameters were obtained. Depressive symptoms were assessed using the Beck Depression Inventory. Standardized mortality ratios were calculated.Results:Â Participants were followed up for a total of 28,044 person-years. The melancholic depressive group had an increased adjusted risk of mortality [HR 1.49 (95% CI: 1.02-2.20)] when compared to the non-depressive group. Comparing mortality to the whole population of Finland using standardized mortality ratios (SMR) both the non-melancholic [1.11 (95% CI: 0.85-1.44)] and melancholic depressive [1.26 (95% CI: 0.87-1.81)] groups had higher mortality than the non-depressive group [0.82 (95% CI: 0.73-0.93)].Conclusions:Â Melancholic depressive symptoms are most strongly related to a higher mortality risk.</p
A data preparation and migration framework for implementing modular product structures in PLM
This paper reports the research on the complex process of implementing modular product structures in a Product Lifecycle Management (PLM) system. There are many challenges in implementing the system. One main challenge is organising or mapping existing product data and migrating it to the new PLM system. Companies often use a PLM tool for management of CAD files, documents and drawings, but they do not take advantage of the full potential of the PLM system to support the development activities of modular products. Product data management tools are used mainly for product CAD data management and PLM systems support by automating and managing some of the operational complexity of modular product design. The aim of this research is to propose a data model that can be used for implementing modular product structures in a PLM system and a tool that can formalise the existing data so as to migrate it into the PLM system
c-Kit-Mediated Functional Positioning of Stem Cells to Their Niches Is Essential for Maintenance and Regeneration of Adult Hematopoiesis
The mechanism by which hematopoietic stem and progenitor cells (HSPCs) through interaction with their niches maintain and reconstitute adult hematopoietic cells is unknown. To functionally and genetically track localization of HSPCs with their niches, we employed novel mutant loxPs, lox66 and lox71 and Cre-recombinase technology to conditionally delete c-Kit in adult mice, while simultaneously enabling GFP expression in the c-Kit-deficient cells. Conditional deletion of c-Kit resulted in hematopoietic failure and splenic atrophy both at steady state and after marrow ablation leading to the demise of the treated adult mice. Within the marrow, the c-Kit-expressing GFP+ cells were positioned to Kit ligand (KL)-expressing niche cells. This c-Kit-mediated cellular adhesion was essential for long-term maintenance and expansion of HSPCs. These results lay the foundation for delivering KL within specific niches to maintain and restore hematopoiesis
Disproportionate cardiac hypertrophy during early postnatal development in infants born preterm.
Background Adults born very preterm have increased cardiac mass and reduced function. We investigated whether a hypertrophic phenomenon occurs in later preterm infants and when this occurs during early development.
Methods Cardiac ultrasound was performed on 392 infants (33% preterm at mean gestation 34±2 weeks). Scans were performed during fetal development in 137, at birth and 3 months of postnatal age in 200, and during both fetal and postnatal development in 55. Cardiac morphology and function was quantified and computational models created to identify geometric changes.
Results At birth, preterm offspring had reduced cardiac mass and volume relative to body size with a more globular heart. By 3 months, ventricular shape had normalized but both left and right ventricular mass relative to body size were significantly higher than expected for postmenstrual age (left 57.8±41.9 vs. 27.3±29.4%, P<0.001; right 39.3±38.1 vs. 16.6±40.8, P=0.002). Greater changes were associated with lower gestational age at birth (left P<0.001; right P=0.001).
Conclusion Preterm offspring, including those born in late gestation, have a disproportionate increase in ventricular mass from birth up to 3 months of postnatal age. These differences were not present before birth. Early postnatal development may provide a window for interventions relevant to long-term cardiovascular health
3T3 Cell Lines Stably Expressing Pax6 or Pax6(5a) – A New Tool Used for Identification of Common and Isoform Specific Target Genes
Pax6 and Pax6(5a) are two isoforms of the evolutionary conserved Pax6 gene often co-expressed in specific stochiometric relationship in the brain and the eye during development. The Pax6(5a) protein differs from Pax6 by having a 14 amino acid insert in the paired domain, causing the two proteins to have different DNA binding specificities. Difference in functions during development is proven by the fact that mutations in the 14 amino acid insertion for Pax6(5a) give a slightly different eye phenotype than the one described for Pax6. Whereas quite many Pax6 target genes have been published during the last years, few Pax6(5a) specific target genes have been reported on. However, target genes identified by Pax6 knockout studies can probably be Pax6(5a) targets as well, since this isoform also will be affected by the knockout. In order to identify new Pax6 target genes, and to try to distinguish between genes regulated by Pax6 and Pax6(5a), we generated FlpIn-3T3 cell lines stably expressing Pax6 or Pax6(5a). RNA was harvested from these cell lines and used in gene expression microarrays where we identified a number of genes differentially regulated by Pax6 and Pax6(5a). A majority of these were associated with the extracellular region. By qPCR we verified that Ncam1, Ngef, Sphk1, Dkk3 and Crtap are Pax6(5a) specific target genes, while Tgfbi, Vegfa, EphB2, Klk8 and Edn1 were confirmed as Pax6 specific target genes. Nbl1, Ngfb and seven genes encoding different glycosyl transferases appeared to be regulated by both. Direct binding to the promoters of Crtap, Ctgf, Edn1, Dkk3, Pdgfb and Ngef was verified by ChIP. Furthermore, a change in morphology of the stably transfected Pax6 and Pax6(5a) cells was observed, and the Pax6 expressing cells were shown to have increased proliferation and migration capacities
Functional Redundancy of Two Pax-Like Proteins in Transcriptional Activation of Cyst Wall Protein Genes in Giardia lamblia
The protozoan Giardia lamblia differentiates from a pathogenic trophozoite into an infectious cyst to survive outside of the host. During encystation, genes encoding cyst wall proteins (CWPs) are coordinately induced. Pax family transcription factors are involved in a variety of developmental processes in animals. Nine Pax proteins have been found to play an important role in tissue and organ development in humans. To understand the progression from primitive to more complex eukaryotic cells, we tried to identify putative pax genes in the G. lamblia genome and found two genes, pax1 and pax2, with limited similarity. We found that Pax1 may transactivate the encystation-induced cwp genes and interact with AT-rich initiatior elements that are essential for promoter activity and transcription start site selection. In this study, we further characterized Pax2 and found that, like Pax1, Pax2 was present in Giardia nuclei and it may specifically bind to the AT-rich initiator elements of the encystation-induced cwp1-3 and myb2 genes. Interestingly, overexpression of Pax2 increased the cwp1-3 and myb2 gene expression and cyst formation. Deletion of the C-terminal paired domain or mutation of the basic amino acids of the paired domain resulted in a decrease of nuclear localization, DNA-binding activity, and transactivation activity of Pax2. These results are similar to those found in the previous Pax1 study. In addition, the profiles of gene expression in the Pax2 and Pax1 overexpressing cells significantly overlap in the same direction and ERK1 associated complexes may phosphorylate Pax2 and Pax1, suggesting that Pax2 and Pax1 may be downstream components of a MAPK/ERK1 signaling pathway. Our results reveal functional redundancy between Pax2 and Pax1 in up-regulation of the key encystation-induced genes. These results illustrate functional redundancy of a gene family can occur in order to increase maintenance of important gene function in the protozoan organism G. lamblia
CCN2/Connective Tissue Growth Factor Is Essential for Pericyte Adhesion and Endothelial Basement Membrane Formation during Angiogenesis
CCN2/Connective Tissue Growth Factor (CTGF) is a matricellular protein that regulates cell adhesion, migration, and survival. CCN2 is best known for its ability to promote fibrosis by mediating the ability of transforming growth factor β (TGFβ) to induce excess extracellular matrix production. In addition to its role in pathological processes, CCN2 is required for chondrogenesis. CCN2 is also highly expressed during development in endothelial cells, suggesting a role in angiogenesis. The potential role of CCN2 in angiogenesis is unclear, however, as both pro- and anti-angiogenic effects have been reported. Here, through analysis of Ccn2-deficient mice, we show that CCN2 is required for stable association and retention of pericytes by endothelial cells. PDGF signaling and the establishment of the endothelial basement membrane are required for pericytes recruitment and retention. CCN2 induced PDGF-B expression in endothelial cells, and potentiated PDGF-B-mediated Akt signaling in mural (vascular smooth muscle/pericyte) cells. In addition, CCN2 induced the production of endothelial basement membrane components in vitro, and was required for their expression in vivo. Overall, these results highlight CCN2 as an essential mediator of vascular remodeling by regulating endothelial-pericyte interactions. Although most studies of CCN2 function have focused on effects of CCN2 overexpression on the interstitial extracellular matrix, the results presented here show that CCN2 is required for the normal production of vascular basement membranes
Relativistic Dynamics and Extreme Mass Ratio Inspirals
It is now well-established that a dark, compact object (DCO), very likely a
massive black hole (MBH) of around four million solar masses is lurking at the
centre of the Milky Way. While a consensus is emerging about the origin and
growth of supermassive black holes (with masses larger than a billion solar
masses), MBHs with smaller masses, such as the one in our galactic centre,
remain understudied and enigmatic. The key to understanding these holes - how
some of them grow by orders of magnitude in mass - lies in understanding the
dynamics of the stars in the galactic neighbourhood. Stars interact with the
central MBH primarily through their gradual inspiral due to the emission of
gravitational radiation. Also stars produce gases which will subsequently be
accreted by the MBH through collisions and disruptions brought about by the
strong central tidal field. Such processes can contribute significantly to the
mass of the MBH and progress in understanding them requires theoretical work in
preparation for future gravitational radiation millihertz missions and X-ray
observatories. In particular, a unique probe of these regions is the
gravitational radiation that is emitted by some compact stars very close to the
black holes and which could be surveyed by a millihertz gravitational wave
interferometer scrutinizing the range of masses fundamental to understanding
the origin and growth of supermassive black holes. By extracting the
information carried by the gravitational radiation, we can determine the mass
and spin of the central MBH with unprecedented precision and we can determine
how the holes "eat" stars that happen to be near them.Comment: Update from the first version, 151 pages, accepted for publication @
Living Reviews in Relativit
Relativistic Binaries in Globular Clusters
Galactic globular clusters are old, dense star systems typically containing
10\super{4}--10\super{7} stars. As an old population of stars, globular
clusters contain many collapsed and degenerate objects. As a dense population
of stars, globular clusters are the scene of many interesting close dynamical
interactions between stars. These dynamical interactions can alter the
evolution of individual stars and can produce tight binary systems containing
one or two compact objects. In this review, we discuss theoretical models of
globular cluster evolution and binary evolution, techniques for simulating this
evolution that leads to relativistic binaries, and current and possible future
observational evidence for this population. Our discussion of globular cluster
evolution will focus on the processes that boost the production of hard binary
systems and the subsequent interaction of these binaries that can alter the
properties of both bodies and can lead to exotic objects. Direct {\it N}-body
integrations and Fokker--Planck simulations of the evolution of globular
clusters that incorporate tidal interactions and lead to predictions of
relativistic binary populations are also discussed. We discuss the current
observational evidence for cataclysmic variables, millisecond pulsars, and
low-mass X-ray binaries as well as possible future detection of relativistic
binaries with gravitational radiation.Comment: 88 pages, 13 figures. Submitted update of Living Reviews articl