4,030 research outputs found
Kiss1 mutant placentas show normal structure and function in the mouse.
INTRODUCTION: Kisspeptins, encoded by the Kiss1 gene, are a set of related neuropeptides that are required for activation of the mammalian reproductive axis at puberty and to maintain fertility. In addition, kisspeptin signaling via the G-protein coupled receptor GPR54 (KISS1R) has been suggested to regulate human placental formation and correlations have been found between altered kisspeptin levels in the maternal blood and the development of pre-eclampsia. METHODS: We have used Kiss1 and Gpr54 mutant mice to investigate the role of kisspeptin signaling in the structure and function of the mouse placenta. RESULTS: Expression of Kiss1 and Gpr54 was confirmed in the mouse placenta but no differences in birth weight were found in mice that had been supported by a mutant placenta during fetal development. Stereological measurements found no differences between Kiss1 mutant and wild-type placentas. Measurement of amino-acid and glucose transport across the Kiss1 mutant placentas at E15.5 days did not reveal any functional defects. DISCUSSION: These data indicate that mouse placentas can develop a normal structure and function without kisspeptin signaling and can support normal fetal development and growth.This work was supported by the BBSRC (Grant number BB/F01936X/1), Alice Herreboudt was supported by a BBSRC CASE studentship in collaboration with Takeda Cambridge.This is the final published version. It first appeared at http://www.sciencedirect.com/science/article/pii/S0143400414008285
Analysis of Parametric Oscillatory Instability in Power Recycled LIGO Interferometer
We present the analysis of a nonlinear effect of parametric oscillatory
instability in power recycled LIGO interferometer with the Fabry-Perot (FP)
cavities in the arms. The basis for this effect is the excitation of the
additional (Stokes) optical mode and the mirror elastic mode, when the optical
energy stored in the main FP cavity main mode exceeds the certain threshold and
the frequencies are related so that sum of frequencies of Stokes and elastic
modes are approximately equal to frequencyof main mode. The presence of
anti-Stokes modes (with frequency approximately equal to sum of frequencies of
main and elastic modes) can depress parametric instability. However, it is very
likely that the anti-Stokes modes will not compensate the parametric
instability completely.Comment: 9 pages, 2 figures. submitted to Physics Letters
Total knee arthroplasty using a hybrid navigation technique
The use of computer navigation is becoming a well-recognized technical alternative to conventional total knee arthroplasty (TKA). However, computer navigation has a substantial learning curve and the use of commercially available navigation systems increases surgical time. In addition, the potential risks associated with the navigation TKA, such as, registration errors, notching of the anterior femoral cortex, oversizing of the femoral component, and overresection must be taken into consideration. On the other hand, conventional techniques are familiar and intuitive to most practicing surgeons, and thus, are easier to perform and are less prone to anterior notching and femoral component oversizing. However, conventional techniques have greater risks of inaccurate and inconsistent component alignment than computer navigation. This paper describes a novel technique that combines computer navigation and conventional TKA
Partial Homology Relations - Satisfiability in terms of Di-Cographs
Directed cographs (di-cographs) play a crucial role in the reconstruction of
evolutionary histories of genes based on homology relations which are binary
relations between genes. A variety of methods based on pairwise sequence
comparisons can be used to infer such homology relations (e.g.\ orthology,
paralogy, xenology). They are \emph{satisfiable} if the relations can be
explained by an event-labeled gene tree, i.e., they can simultaneously co-exist
in an evolutionary history of the underlying genes. Every gene tree is
equivalently interpreted as a so-called cotree that entirely encodes the
structure of a di-cograph. Thus, satisfiable homology relations must
necessarily form a di-cograph. The inferred homology relations might not cover
each pair of genes and thus, provide only partial knowledge on the full set of
homology relations. Moreover, for particular pairs of genes, it might be known
with a high degree of certainty that they are not orthologs (resp.\ paralogs,
xenologs) which yields forbidden pairs of genes. Motivated by this observation,
we characterize (partial) satisfiable homology relations with or without
forbidden gene pairs, provide a quadratic-time algorithm for their recognition
and for the computation of a cotree that explains the given relations
Mindfulness-based stress reduction in Parkinson’s disease: a systematic review
Background:
Mindfulness based stress reduction (MBSR) is increasingly being used to improve outcomes such as stress and depression in a range of long-term conditions (LTCs). While systematic reviews on MBSR have taken place for a number of conditions there remains limited information on its impact on individuals with Parkinson’s disease (PD).
Methods:
Medline, Central, Embase, Amed, CINAHAL were searched in March 2016. These databases were searched using a combination of MeSH subject headings where available and keywords in the title and abstracts. We also searched the reference lists of related reviews. Study quality was assessed based on questions from the Cochrane Collaboration risk of bias tool.
Results:
Two interventions and three papers with a total of 66 participants were included. The interventions were undertaken in Belgium (n = 27) and the USA (n = 39). One study reported significantly increased grey matter density (GMD) in the brains of the MBSR group compared to the usual care group. Significant improvements were reported in one study for a number of outcomes including PD outcomes, depression, mindfulness, and quality of life indicators. Only one intervention was of reasonable quality and both interventions failed to control for potential confounders in the analysis. Adverse events and reasons for drop-outs were not reported. There was also no reporting on the costs/benefits of the intervention or how they affected health service utilisation.
Conclusion:
This systematic review found limited and inconclusive evidence of the effectiveness of MBSR for PD patients. Both of the included interventions claimed positive effects for PD patients but significant outcomes were often contradicted by other results. Further trials with larger sample sizes, control groups and longer follow-ups are needed before the evidence for MBSR in PD can be conclusively judged
Mindfulness-based interventions in epilepsy: a systematic review
Mindfulness based interventions (MBIs) are increasingly used to help patients cope with physical and mental long-term conditions (LTCs). Epilepsy is associated with a range of mental and physical comorbidities that have a detrimental effect on quality of life (QOL), but it is not clear whether MBIs can help. We systematically reviewed the literature to determine the effectiveness of MBIs in people with epilepsy. Medline, Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, Allied and Complimentary Medicine Database, and PsychInfo were searched in March 2016. These databases were searched using a combination of subject headings where available and keywords in the title and abstracts. We also searched the reference lists of related reviews. Study quality was assessed using the Cochrane Collaboration risk of bias tool. Three randomised controlled trials (RCTs) with a total of 231 participants were included. The interventions were tested in the USA (n = 171) and China (Hong Kong) (n = 60). Significant improvements were reported in depression symptoms, quality of life, anxiety, and depression knowledge and skills. Two of the included studies were assessed as being at unclear/high risk of bias - with randomisation and allocation procedures, as well as adverse events and reasons for drop-outs poorly reported. There was no reporting on intervention costs/benefits or how they affected health service utilisation. This systematic review found limited evidence for the effectiveness of MBIs in epilepsy, however preliminary evidence suggests it may lead to some improvement in anxiety, depression and quality of life. Further trials with larger sample sizes, active control groups and longer follow-ups are needed before the evidence for MBIs in epilepsy can be conclusively determined
Eosinophils Are Important for Protection, Immunoregulation and Pathology during Infection with Nematode Microfilariae
Eosinophil responses typify both allergic and parasitic helminth disease. In helminthic disease, the role of eosinophils can be both protective in immune responses and destructive in pathological responses. To investigate whether eosinophils are involved in both protection and pathology during filarial nematode infection, we explored the role of eosinophils and their granule proteins, eosinophil peroxidase (EPO) and major basic protein-1 (MBP-1), during infection with Brugia malayi microfilariae. Using eosinophil-deficient mice (PHIL), we further clarify the role of eosinophils in clearance of microfilariae during primary, but not challenge infection in vivo. Deletion of EPO or MBP-1 alone was insufficient to abrogate parasite clearance suggesting that either these molecules are redundant or eosinophils act indirectly in parasite clearance via augmentation of other protective responses. Absence of eosinophils increased mast cell recruitment, but not other cell types, into the broncho-alveolar lavage fluid during challenge infection. In addition absence of eosinophils or EPO alone, augmented parasite-induced IgE responses, as measured by ELISA, demonstrating that eosinophils are involved in regulation of IgE. Whole body plethysmography indicated that nematode-induced changes in airway physiology were reduced in challenge infection in the absence of eosinophils and also during primary infection in the absence of EPO alone. However lack of eosinophils or MBP-1 actually increased goblet cell mucus production. We did not find any major differences in cytokine responses in the absence of eosinophils, EPO or MBP-1. These results reveal that eosinophils actively participate in regulation of IgE and goblet cell mucus production via granule secretion during nematode-induced pathology and highlight their importance both as effector cells, as damage-inducing cells and as supervisory cells that shape both innate and adaptive immunity
Experimental GHZ Entanglement beyond Qubits
The Greenberger-Horne-Zeilinger (GHZ) argument provides an all-or-nothing
contradiction between quantum mechanics and local-realistic theories. In its
original formulation, GHZ investigated three and four particles entangled in
two dimensions only. Very recently, higher dimensional contradictions
especially in three dimensions and three particles have been discovered but it
has remained unclear how to produce such states. In this article we
experimentally show how to generate a three-dimensional GHZ state from
two-photon orbital-angular-momentum entanglement. The first suggestion for a
setup which generates three-dimensional GHZ entanglement from these entangled
pairs came from using the computer algorithm Melvin. The procedure employs
novel concepts significantly beyond the qubit case. Our experiment opens up the
possibility of a truly high-dimensional test of the GHZ-contradiction which,
interestingly, employs non-Hermitian operators.Comment: 6+6 pages, 8 figure
Cellular origins of adult human islet in vitro dedifferentiation
Cultured human islets can be dedifferentiated to duct-like structures composed mainly of cytokeratin\u207a and nestin\u207a cells. Given that these structures possess the potential to redifferentiate into islet-like structures, we sought to elucidate their specific cellular origins. Adenoviral vectors were engineered for \u3b2-, \u3b1-, \u3b4- or PP-cell-specific GFP expression. A doublestranded system was designed whereby cultures were infected with two vectors: one expressed GFP behind the cumateinducible promoter sequence, and the other expressed the requisite transactivator behind the human insulin, glucagon, somatostatin or pancreatic polypeptide promoter. This system labels hormone\u207a cells in the islet in a cell-specific manner, allowing these cells to be tracked during the course of transformation from islet to duct-like structure. Post-infection, islets were cultured to induce dedifferentiation. Fluorescence microscopy demonstrated that \u3b1-, \u3b4- and PP-cells contributed equally to the cytokeratin\u207a population, with minimal b-cell contribution, whereas the converse was true for nestin\u207a cells. Complementary targeted cell ablation studies, using streptozotocin or similar adenoviral expression of the Bax (Bcl2-associated X protein) toxigene, validated these findings and suggested a redundancy between \u3b1-, \u3b4- and PP-cells with respect to cytokeratin\u207a cell derivation. These results call into question the traditional understanding of islet cells as being terminally differentiated and provide support for the concept of adult islet morphogenetic plasticity.NRC publication: Ye
Antagonism between Gdf6a and retinoic acid pathways controls timing of retinal neurogenesis and growth of the eye in zebrafish.
Maintaining neurogenesis in growing tissues requires a tight balance between progenitor cell proliferation and differentiation. In the zebrafish retina, neuronal differentiation proceeds in two stages with embryonic retinal progenitor cells (RPCs) of the central retina accounting for the first rounds of differentiation, and stem cells from the ciliary marginal zone (CMZ) being responsible for late neurogenesis and growth of the eye. In this study, we analyse two mutants with small eyes that display defects during both early and late phases of retinal neurogenesis. These mutants carry lesions in gdf6a, a gene encoding a BMP family member previously implicated in dorsoventral patterning of the eye. We show that gdf6a mutant eyes exhibit expanded retinoic acid (RA) signalling and demonstrate that exogenous activation of this pathway in wild-type eyes inhibits retinal growth, generating small eyes with a reduced CMZ and fewer proliferating progenitors, similar to gdf6a mutants. We provide evidence that RA regulates the timing of RPC differentiation by promoting cell cycle exit. Furthermore, reducing RA signalling in gdf6a mutants re-establishes appropriate timing of embryonic retinal neurogenesis and restores putative stem and progenitor cell populations in the CMZ. Together, our results support a model in which dorsally expressed gdf6a limits RA pathway activity to control the transition from proliferation to differentiation in the growing eye
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