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  • 1
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    Role of Foxl2 in uterine maturation and function (2015)
    Oxford University Press
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    Publication Date: 2015-05-09
    Description: Foxl2 codes for a forkhead/HNF3 transcription factor essential for follicular maturation and maintenance of ovarian identity. FOXL2 mutations are associated with Blepharophimosis, Ptosis and Epicanthus inversus Syndrome (BPES) characterized by eyelid malformations (types I and II) and premature ovarian insufficiency (type I). We show that Foxl2 is not only expressed by the ovary, but also by other components of the mouse female reproductive tract, including the uterus, the cervix and the oviduct. In the uterus, Foxl2 expression is first observed in the neonatal mesenchyme and, during uterine maturation, persists in the stroma and in the deep inner myometrial layer (IML). In the adult, Foxl2 is expressed in the differentiated stromal layer, but no longer in the myometrium. Conditional deletion of Foxl2 in the postnatal (PN) uterus using Progesterone Receptor-cre ( Pgr cre/+ ) mice results in infertility. During PN uterine maturation Pgr cre/+ ; Foxl2 flox/flox mice present a severely reduced thickness of the stroma layer and an hypertrophic, disorganized IML. In adult Pgr cre/+ ; Foxl2 flox/flox mice a supplementary muscular layer is present at the stroma/myometrium border and vascular smooth muscle cells fail to form a coherent layer around uterine arteries. Wnt signalling pathways play a central role in uterine maturation; in Pgr cre/+ ; Foxl2 flox/flox mice, Wnt genes are deregulated suggesting that Foxl2 acts through these signals. In humans, thickening of the IML (also called "junctional zone") is associated with reduced fertility, endometriosis and adenomyosis. Our data suggest that Foxl2 has a crucial role in PN uterine maturation and could help to understand sub-fertility predisposition in women.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 2
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    Fast radio bursts: the observational case for a Galactic origin (2015)
    Oxford University Press
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    Publication Date: 2015-10-15
    Description: There are by now ten published detections of fast radio bursts (FRBs) – single bright GHz-band millisecond pulses of unknown origin. Proposed explanations cover a broad range from exotic processes at cosmological distances to atmospheric and terrestrial sources. Loeb, Maoz, and Shvartzvald have previously suggested that FRB sources could be nearby flare stars, and pointed out the presence of a W-UMa-type contact binary within the beam of one out of three FRB fields that they examined. To further test the flare-star hypothesis, we use time-domain optical photometry and spectroscopy, and now find possible flare stars in additional FRB fields, with one to three such cases among all eight FRB fields studied. We evaluate the chance probabilities of these possible associations to be in the range ~0.1 per cent to 9 per cent, depending on the input assumptions. Further, we re-analyse the probability that two FRBs recently discovered three years apart within the same radio beam are unrelated. Contrary to other claims, we conclude with 99 per cent confidence that the two events are from the same repeating source. The different dispersion measures between the two bursts then rule out a cosmological intergalactic-medium origin for the dispersion measure, but are consistent with the flare-star scenario with a varying plasma blanket between bursts. Finally, we review some theoretical objections that have been raised against a local flare-star FRB origin, and show that they are incorrect.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 3
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    Repressor activity of the RpoS/{sigma}S-dependent RNA polymerase requires DNA binding (2015)
    Oxford University Press
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    Publication Date: 2015-02-18
    Description: The RpoS/ S sigma subunit of RNA polymerase (RNAP) activates transcription of stationary phase genes in many Gram-negative bacteria and controls adaptive functions, including stress resistance, biofilm formation and virulence. In this study, we address an important but poorly understood aspect of S -dependent control, that of a repressor. Negative regulation by S has been proposed to result largely from competition between S and other factors for binding to a limited amount of core RNAP (E). To assess whether S binding to E alone results in significant downregulation of gene expression by other factors, we characterized an rpoS mutant of Salmonella enterica serovar Typhimurium producing a S protein proficient for E S complex formation but deficient in promoter DNA binding. Genome expression profiling and physiological assays revealed that this mutant was defective for negative regulation, indicating that gene repression by S requires its binding to DNA. Although the mechanisms of repression by S are likely specific to individual genes and environmental conditions, the study of transcription downregulation of the succinate dehydrogenase operon suggests that competition at the promoter DNA level plays an important role in gene repression by E S .
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 4
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    Existence and uniqueness of classifying spaces for fusion systems over discrete p-toral groups (2015)
    Oxford University Press
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    Publication Date: 2015-01-20
    Description: A major question in the theory of $p$ -local finite groups was whether any saturated fusion system over a finite $p$ -group admits an associated centric linking system, and when it does, whether it is unique. Both questions were answered in the affirmative by Chermak, using the theory of partial groups and localities he developed. Using Chermak's ideas combined with the techniques of obstruction theory, Bob Oliver gave a different proof of Chermak's theorem. In this paper, we generalize Oliver's proof to the context of fusion systems over discrete $p$ -toral groups, thus positively resolving the analogous questions in $p$ -local compact group theory.
    Print ISSN: 0024-6107
    Electronic ISSN: 1469-7750
    Topics: Mathematics
    Published by Oxford University Press
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  • 5
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    Dlx5 and Dlx6 control uterine adenogenesis during post-natal maturation: possible consequences for endometriosis (2015)
    Oxford University Press
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    Publication Date: 2015-12-25
    Description: Dlx5 and Dlx6 are two closely associated homeobox genes which code for transcription factors involved in the control of steroidogenesis and reproduction. Inactivation of Dlx5 / 6 in the mouse results in a Leydig cell defect in the male and in ovarian insufficiency in the female. DLX5/6 are also strongly expressed by the human endometrium but their function in the uterus is unknown. The involvement of DLX5/6 in human uterine pathology is suggested by their strong downregulation in endometriotic lesions and upregulation in endometrioïd adenocarcinomas. We first show that Dlx5 / 6 expression begins in Müllerian ducts epithelia and persists then in the uterine luminal and glandular epithelia throughout post-natal maturation and in the adult. We then use a new mouse model in which Dlx5 and Dlx6 can be simultaneously inactivated in the endometrium using a Pgr cre/+ allele. Post-natal inactivation of Dlx5 / 6 in the uterus results in sterility without any obvious ovarian involvement. The uteri of Pgr cre/+ ; Dlx5/6 flox/flox mice present very few uterine glands and numerous abnormally large and branched invaginations of the uterine lumen. In Dlx5/6 mutant uteri, the expression of genes involved in gland formation ( Foxa2 ) and in epithelial remodelling during implantation ( Msx1 ) is significantly reduced. Furthermore, we show that DLX5 is highly expressed in human endometrial glandular epithelium and that its expression is affected in endometriosis. We conclude that Dlx5 and Dlx6 expression determines uterine architecture and adenogenesis and is needed for implantation. Given their importance for female reproduction, DLX5 and DLX6 must be regarded as interesting targets for future clinical research.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 6
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    Skin fibroblasts from pantothenate kinase-associated neurodegeneration patients show altered cellular oxidative status and have defective iron-handling properties (2012)
    Oxford University Press
    Details
    Publication Date: 2012-08-28
    Description: Pantothenate kinase-associated neurodegeneration (PKAN) is a neurodegenerative disease belonging to the group of neurodegeneration with brain iron accumulation disorders. It is characterized by progressive impairments in movement, speech and cognition. The disease is inherited in a recessive manner due to mutations in the Pantothenate Kinase-2 ( PANK2 ) gene that encodes a mitochondrial protein involved in Coenzyme A synthesis. To investigate the link between a PANK2 gene defect and iron accumulation, we analyzed primary skin fibroblasts from three PKAN patients and three unaffected subjects. The oxidative status of the cells and their ability to respond to iron were analyzed in both basal and iron supplementation conditions. In basal conditions, PKAN fibroblasts show an increase in carbonylated proteins and altered expression of antioxidant enzymes with respect to the controls. After iron supplementation, the PKAN fibroblasts had a defective response to the additional iron. Under these conditions, ferritins were up-regulated and Transferrin Receptor 1 (TfR1) was down-regulated to a minor extent in patients compared with the controls. Analysis of iron regulatory proteins (IRPs) reveals that, with respect to the controls, PKAN fibroblasts have a reduced amount of membrane-associated mRNA-bound IRP1, which responds imperfectly to iron. This accounts for the defective expression of ferritin and TfR1 in patients' cells. The inaccurate quantity of these proteins produced a higher bioactive labile iron pool and consequently increased iron-dependent reactive oxygen species formation. Our results suggest that Pank2 deficiency promotes an increased oxidative status that is further enhanced by the addition of iron, potentially causing damage in cells.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 7
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    Genetic prion disease: no role for the immune system in disease pathogenesis? (2014)
    Oxford University Press
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    Publication Date: 2014-10-22
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 8
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    Magnetic fabrics induced by dynamic faulting reveal damage zone sizes in soft rocks, Dead Sea basin (2014)
    Oxford University Press
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    Publication Date: 2014-09-27
    Description: The anisotropy of magnetic susceptibility (AMS) of soft rocks was measured in order to distinguish between the effect of remote and local strain fields, determine the size of the related inelastic damage zone and resolve the fault-plane solutions of past earthquakes. The AMS fabrics were explored next to late Pleistocene syndepositional normal faults (total displacement up to ~3.5 m) that cross soft lacustrine rocks within the seismically active Dead Sea basin. ‘Deposition fabrics’ prevail meters away from the fault planes and are characterized by scattered maximum and intermediate principal AMS axes. ‘Deformation fabrics’ are detected up to tens of centimetres from the fault planes and are characterized by well-grouped AMS axes, in which one of the principal axes is parallel to the strike of the nearby fault. Variations in the AMS fabrics and magnetic lineations define the size of the inelastic damage zone around the faults. The results demonstrate that the deformation-driven magnetic fabrics and the associated inelastic damage zones are compatible with coseismic dynamic faulting and the effects of the local strain field during earthquakes. Most of the AMS fabrics show a conspicuous similarity to that of the fault-plane solutions, i.e., the principal AMS axes and instantaneous strain ellipsoids are coaxial. These results suggest a novel application of the AMS method for defining the shape and size of the damage zones surrounding dynamic faults and determining the full tensor of the local strain field.
    Keywords: Geomagnetism, Rock Magnetism and Palaeomagnetism
    Print ISSN: 0956-540X
    Electronic ISSN: 1365-246X
    Topics: Geosciences
    Published by Oxford University Press on behalf of The Deutsche Geophysikalische Gesellschaft (DGG) and the Royal Astronomical Society (RAS).
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  • 9
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    A Survey on the Development of Security Mechanisms for Body Area Networks (2014)
    Oxford University Press
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    Publication Date: 2014-09-25
    Description: Advances in lightweight, small-sized and low-power sensors led to the development of wearable biosensors, and thus, to the accurate monitoring of human periphery. On top of this, pervasive computing has been improved and technologies have been matured enough to build plug-and-play body area networks (BANs). In a BAN, the main functionality of a node is to effectively and efficiently collect data from vital body parts, share it with the neighbors and make decisions accordingly. Because of the fact that the captured phenomenon is highly sensitive to privacy breaches in addition to being transmitted using the wireless communication medium, BANs require a security infrastructure. However, due to the extreme energy scarcity, bandwidth and storage constraints of the nodes, conventional solutions are inapplicable. In this survey, we present an overview of BANs and provide a detailed investigation into the developed security infrastructures. We examined the literature and combined the corresponding proposals under two major classes: (i) pure-cryptographic security mechanisms and (ii) bio-cryptographic security mechanisms. Pure-cryptographic methods include constructions based on the well-known symmetric or asymmetric cryptography primitives and they are suitable for securing the communication between any two network entities. On the other hand, bio-cryptographic methods benefit from the network's context-awareness and to the best of our knowledge, they have been utilized only for the communication among the biosensors.
    Print ISSN: 0010-4620
    Electronic ISSN: 1460-2067
    Topics: Computer Science
    Published by Oxford University Press
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  • 10
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    Type 1 diabetes affects topoisomerase I activity and GlcNAcylation in rat organs: Kidney, liver and pancreas (2012)
    Oxford University Press
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    Publication Date: 2012-04-05
    Description: Chronic hyperglycemia leads to the development of diabetes-induced organ complications, through changes in gene expression and protein function. We previously showed that in cell lines, topoisomerase I (topo I) is modified by O-GlcNAcylation, which affects its DNA relaxation activity. Since topo I participates in gene expression processes, we assumed that high glucose levels will affect its regulation and activity. Here we examined the effect of hyperglycemia on the regulation, GlcNAcylation and activity of topo I, in various internal rat organs that were subjected to diabetes-induced complications. Type 1 diabetes was induced in female rats by Streptozotocin injection. Topo I activity in nuclear protein extracts derived from diabetic and nondiabetic rat organs and topo I mRNA level were examined. Topo I and O-linked beta-N-acetylglucosamine ( O -GlcNAc) transferase proteins and their O-GlcNAcylation were determined by western blot and immunoprecipitation assays. We show that topo I activity and enzyme protein level decreased in various tissues derived from the diabetic animals, whereas the enzyme mRNA level was not altered. Topo I protein was modified in vivo by O -GlcNAc, and O -GlcNAc transferase was coprecipitated with topo I protein, suggesting a possible interaction between both enzymes. This study demonstrates, for the first time, that topo I activity is regulated by high glucose levels, as a result of the diabetic state and is modified in vivo by O-GlcNAcylation, suggesting that topo I, an essential enzyme for gene expression, is involved in cellular processes which may lead to the pathogenesis of diabetic complications.
    Print ISSN: 0959-6658
    Electronic ISSN: 1460-2423
    Topics: Biology , Medicine
    Published by Oxford University Press
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