971 research outputs found
Defects of steroidogenesis
In the biosynthesis of steroid hormones the neutral lipid cholesterol, a normal constituent of lipid bilayers is transformed via a series of hydroxylation, oxidation, and reduction steps into a vast array of biologically active compounds: mineralocorticoids, glucocorticoids, and sex hormones. Glucocorticoids regulate many aspects of metabolism and immune function, whereas mineralocorticoids help maintain blood volume and control renal excretion of electrolytes. Sex hormones are essential for sex differentiation in male and support reproduction. They include androgens, estrogens, and progestins. A block in the pathway of steroid biosynthesis leads to the lack of hormones downstream and accumulation of the upstream compounds that can activate other members of the steroid receptor family. This review deals with the clinical consequences of these block
New models for PIXE simulation with Geant4
Particle induced X-ray emission (PIXE) is a physical effect that is not yet
adequately modelled in Geant4. The current status as in Geant4 9.2 release is
reviewed and new developments are described. The capabilities of the software
prototype are illustrated in application to the shielding of the X-ray
detectors of the eROSITA telescope on the upcoming Spectrum-X-Gamma space
mission.Comment: To be published in the Proceedings of the CHEP (Computing in High
Energy Physics) 2009 conferenc
The Geant4-DNA project
The Geant4-DNA project proposes to develop an open-source simulation software
based and fully included in the general-purpose Geant4 Monte Carlo simulation
toolkit. The main objective of this software is to simulate biological damages
induced by ionising radiation at the cellular and sub-cellular scale. This
project was originally initiated by the European Space Agency for the
prediction of deleterious effects of radiation that may affect astronauts
during future long duration space exploration missions. In this paper, the
Geant4-DNA collaboration presents an overview of the whole ongoing project,
including its most recent developments already available in the last Geant4
public release (9.3 BETA), as well as an illustration example simulating the
direct irradiation of a chromatin fibre. Expected extensions involving several
research domains, such as particle physics, chemistry and cellular and
molecular biology, within a fully interdiciplinary activity of the Geant4
collaboration are also discussed.Comment: presented by S. Incerti at the ASIA SIMULATION CONFERENCE 2009,
October 7-9, 2009, Ritsumeikan University, Shiga, Japa
Modeling post-fire regeneration patterns under different restoration scenarios to improve forest recovery in degraded ecosystems
The Dlx5 homeodomain gene is essential for normal olfactory development and connectivity in the mouse.
Defects of steroidogenesis
In the biosynthesis of steroid hormones the neutral lipid cholesterol, a normal constituent of lipid bilayers is transformed via a series of hydroxylation, oxidation, and reduction steps into a vast array of biologically active compounds: mineralocorticoids, glucocorticoids, and sex hormones. Glucocorticoids regulate many aspects of metabolism and immune function, whereas mineralocorticoids help maintain blood volume and control renal excretion of electrolytes. Sex hormones are essential for sex differentiation in male and support reproduction. They include androgens, estrogens, and progestins. A block in the pathway of steroid biosynthesis leads to the lack of hormones downstream and accumulation of the upstream compounds that can activate other members of the steroid receptor family. This review deals with the clinical consequences of these blocks
Msx1 and Dlx5 act independently in development of craniofacial skeleton, but converge on the regulation of Bmp signaling in palate formation.
The HLA-B*35 allele modulates ER stress, inflammation and proliferation in PBMCs from Limited Cutaneous Systemic Sclerosis patients
Introduction\ud
HLA-B*35 is associated with increased risk of developing pulmonary hypertension in SSc patients. We previously reported that HLA-B*35 induces endothelial cell dysfunction via activation of ER stress/UPR and upregulation of the inflammatory response. Because PBMCs from lcSSc-PAH patients are also characterized by activation of ER stress/UPR and inflammation, the goal of this study was to assess whether the presence of HLA-B*35 contributes to those characteristics.\ud
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Methods\ud
PBMCs were purified from healthy controls (n = 49 HC) and lcSSc patients, (n = 44 with PAH, n = 53 without PAH). PBMCs from each group were stratified for the presence of HLA-B*35. Global changes in gene expression in response to HLA-B*35, HLA-B*8 or empty lentivirus were investigated by microarray analysis in HC PBMCs. Total RNA was extracted and qPCR was performed to measure gene expression.\ud
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Results\ud
ER stress markers, in particular the chaperones BiP and DNAJB1 were significantly elevated in PBMC samples carrying the HLA-B*35 allele. IL-6 expression was also significantly increased in HLA-B*35 lcSSc PBMCs and positively correlated with ER stress markers. Likewise, HMGB1 was increased in HLA-B*35-positive lcSSc PBMCs. Global gene expression analysis was used to further probe the role of HLA-B*35. Among genes downregulated by HLA-B*35 lentivirus were genes related to complement (C1QB, C1QC), cell cycle (CDNK1A) and apoptosis (Bax, Gadd45). Interestingly, complement genes (C1QC and C1QB) showed elevated expression in lcSSc without PAH, but were expressed at the low levels in lcSSc-PAH. The presence of HLA-B*35 correlated with the decreased expression of the complement genes. Furthermore, HLA-B*35 correlated with decreased expression of cyclin inhibitors (p21, p57) and pro-apoptotic genes (Bax, Gadd45) in lcSSc B35 subjects. FYN, a tyrosine kinase involved in proliferation of immune cells, was among the genes that were positively regulated by HLA-B*35. HLA-B*35 correlated with increased levels of FYN in lcSSc PBMCs.\ud
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Conclusions\ud
Our study demonstrates that HLA-B*35 contributes to the dysregulated expression of selected ER stress, inflammation and proliferation related genes in lcSSc patient PBMCs, as well as healthy individuals, thus supporting a pathogenic role of HLA-B*35 in the development of PAH in SSc patients
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