127 research outputs found
Diminution du taux d'ARNm du collagène VII chez des patients atteints d'une forme sévère d'épidermolyse bulleuse dystrophique
Les épidermolyses bulleuses dystrophiques récessives (EBDR) constituent un groupe de maladies héréditaires caractérisées par une fragilité cutanéo-muqueuse extrême associée à une anomalie des fibres d'ancrage essentiellement constituées de collagène VIL Dans les EBDR elles sont réduites voire complètement absentes. Récemment, une liaison génétique entre le phénotype des EBDR et le gène du collagène VII a été établie. Au cours de ce travail, on a étudié le taux des ARNm du collagène VII chez 7 patients atteints d'EBDR dont 6 sont atteints d'une forme sévère (EBDR mutilante de Rallopeau-Siemens). On a, ainsi, montré une forte diminution de ce taux chez 3 de ces derniers. Ces résultats suggèrent que, chez ces 3 patients, une mutation dans le gène du collagène VII peut être à l'origine d'une diminution du taux des ARN du collagène VII et, par conséquent, de la réduction ou l'absence des fibres d'ancrages responsable du phénotype de la maladie
Gravitational Waves from Gravitational Collapse
Gravitational wave emission from the gravitational collapse of massive stars
has been studied for more than three decades. Current state of the art
numerical investigations of collapse include those that use progenitors with
realistic angular momentum profiles, properly treat microphysics issues,
account for general relativity, and examine non--axisymmetric effects in three
dimensions. Such simulations predict that gravitational waves from various
phenomena associated with gravitational collapse could be detectable with
advanced ground--based and future space--based interferometric observatories.Comment: 68 pages including 13 figures; revised version accepted for
publication in Living Reviews in Relativity (http://www.livingreviews.org
Authentic leading as relational accountability: Facing up to the conflicting expectations of media leaders
Physics, Astrophysics and Cosmology with Gravitational Waves
Gravitational wave detectors are already operating at interesting sensitivity
levels, and they have an upgrade path that should result in secure detections
by 2014. We review the physics of gravitational waves, how they interact with
detectors (bars and interferometers), and how these detectors operate. We study
the most likely sources of gravitational waves and review the data analysis
methods that are used to extract their signals from detector noise. Then we
consider the consequences of gravitational wave detections and observations for
physics, astrophysics, and cosmology.Comment: 137 pages, 16 figures, Published version
<http://www.livingreviews.org/lrr-2009-2
Global continental and marine detrital εNd: An updated compilation for use in understanding marine Nd cycling
Understanding the role of sediment-water interactions in the oceanic cycling of neodymium (Nd) isotopes is essential for its reliable use as a modern and palaeoceanographic tracer of ocean circulation. However, the exact processes that control Nd cycling in the ocean are poorly defined and require an up-to-date knowledge of the sources, sinks and transformation of this tracer to and within the ocean (e.g. as per the GEOTRACES core mission). We propose a considerable improvement of Nd-source identification by providing an extensive and up-to-date compilation of published terrestrial and marine sedimentary Nd isotopic measurements. From this database, we construct high resolution, gridded, global maps that characterise the Nd-isotopic signature of the continental margins and seafloor sediment. Here, we present the database, interpolation methods, and final data products. Consistent with the previous studies that inform our compilation, our global results show unradiogenic detrital Nd isotopic values (εNd ≈ -20) in the North Atlantic, εNd values of ≈ -12 to -7 in the Indian and Southern Ocean, and radiogenic values (εNd ≈ -3 to +4) in the Pacific. The new, high-resolution interpolation is useful for improving conceptual knowledge of Nd sources and sinks and enables the application of isotope-enabled ocean models to understand targeted Nd behaviour in the oceans. Such applications may include: examining the strength and distribution of a possible benthic flux required to reconcile global Nd budgets, establishing the potential use of Nd isotopes as a kinematic tracer of ocean circulation, and a general quantification of the non-conservative sedimentary processes that may contribute to marine Nd cycling
Two novel human cytomegalovirus NK cell evasion functions target MICA for lysosomal degradation
NKG2D plays a major role in controlling immune responses through the regulation of natural killer (NK) cells, αβ and γδ T-cell function. This activating receptor recognizes eight distinct ligands (the MHC Class I polypeptide-related sequences (MIC) A andB, and UL16-binding proteins (ULBP)1–6) induced by cellular stress to promote recognition cells perturbed by malignant transformation or microbial infection. Studies into human cytomegalovirus (HCMV) have aided both the identification and characterization of NKG2D ligands (NKG2DLs). HCMV immediate early (IE) gene up regulates NKGDLs, and we now describe the differential activation of ULBP2 and MICA/B by IE1 and IE2 respectively. Despite activation by IE functions, HCMV effectively suppressed cell surface expression of NKGDLs through both the early and late phases of infection. The immune evasion functions UL16, UL142, and microRNA(miR)-UL112 are known to target NKG2DLs. While infection with a UL16 deletion mutant caused the expected increase in MICB and ULBP2 cell surface expression, deletion of UL142 did not have a similar impact on its target, MICA. We therefore performed a systematic screen of the viral genome to search of addition functions that targeted MICA. US18 and US20 were identified as novel NK cell evasion functions capable of acting independently to promote MICA degradation by lysosomal degradation. The most dramatic effect on MICA expression was achieved when US18 and US20 acted in concert. US18 and US20 are the first members of the US12 gene family to have been assigned a function. The US12 family has 10 members encoded sequentially through US12–US21; a genetic arrangement, which is suggestive of an ‘accordion’ expansion of an ancestral gene in response to a selective pressure. This expansion must have be an ancient event as the whole family is conserved across simian cytomegaloviruses from old world monkeys. The evolutionary benefit bestowed by the combinatorial effect of US18 and US20 on MICA may have contributed to sustaining the US12 gene family
The RIP140 Gene Is a Transcriptional Target of E2F1
RIP140 is a transcriptional coregulator involved in energy homeostasis and ovulation which is controlled at the transcriptional level by several nuclear receptors. We demonstrate here that RIP140 is a novel target gene of the E2F1 transcription factor. Bioinformatics analysis, gel shift assay, and chromatin immunoprecipitation demonstrate that the RIP140 promoter contains bona fide E2F response elements. In transiently transfected MCF-7 breast cancer cells, the RIP140 promoter is transactivated by overexpression of E2F1/DP1. Interestingly, RIP140 mRNA is finely regulated during cell cycle progression (5-fold increase at the G1/S and G2/M transitions). The positive regulation by E2F1 requires sequences located in the proximal region of the promoter (−73/+167), involves Sp1 transcription factors, and undergoes a negative feedback control by RIP140. Finally, we show that E2F1 participates in the induction of RIP140 expression during adipocyte differentiation. Altogether, this work identifies the RIP140 gene as a new transcriptional target of E2F1 which may explain some of the effect of E2F1 in both cancer and metabolic diseases
The Confrontation between General Relativity and Experiment
The status of experimental tests of general relativity and of theoretical
frameworks for analysing them is reviewed. Einstein's equivalence principle
(EEP) is well supported by experiments such as the Eotvos experiment, tests of
special relativity, and the gravitational redshift experiment. Future tests of
EEP and of the inverse square law are searching for new interactions arising
from unification or quantum gravity. Tests of general relativity at the
post-Newtonian level have reached high precision, including the light
deflection, the Shapiro time delay, the perihelion advance of Mercury, and the
Nordtvedt effect in lunar motion. Gravitational-wave damping has been detected
in an amount that agrees with general relativity to better than half a percent
using the Hulse-Taylor binary pulsar, and other binary pulsar systems have
yielded other tests, especially of strong-field effects. When direct
observation of gravitational radiation from astrophysical sources begins, new
tests of general relativity will be possible.Comment: 89 pages, 8 figures; an update of the Living Review article
originally published in 2001; final published version incorporating referees'
suggestion
Lactobacillus plantarum displaying CCL3 chemokine in fusion with HIV-1 Gag derived antigen causes increased recruitment of T cells
Background Chemokines are attractive candidates for vaccine adjuvants due to their ability to recruit the immune cells. Lactic acid bacteria (LAB)-based delivery vehicles have potential to be used as a cheap and safe option for vaccination. Chemokine produced on the surface of LAB may potentially enhance the immune response to an antigen and this approach can be considered in development of future mucosal vaccines.
Results We have constructed strains of Lactobacillus plantarum displaying a chemokine on their surface. L. plantarum was genetically engineered to express and anchor to the surface a protein called CCL3Gag. CCL3Gag is a fusion protein comprising of truncated HIV-1 Gag antigen and the murine chemokine CCL3, also known as MIP-1α. Various surface anchoring strategies were explored: (1) a lipobox-based covalent membrane anchor, (2) sortase-mediated covalent cell wall anchoring, (3) LysM-based non-covalent cell wall anchoring, and (4) an N-terminal signal peptide-based transmembrane anchor. Protein production and correct localization were confirmed using Western blotting, flow cytometry and immunofluorescence microscopy. Using a chemotaxis assay, we demonstrated that CCL3Gag-producing L. plantarum strains are able to recruit immune cells in vitro.
Conclusions The results show the ability of engineered L. plantarum to produce a functional chemotactic protein immobilized on the bacterial surface. We observed that the activity of surface-displayed CCL3Gag differed depending on the type of anchor used. The chemokine which is a part of the bacteria-based vaccine may increase the recruitment of immune cells and, thereby, enhance the reaction of the immune system to the vaccine
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