1,819 research outputs found

    Quantification of three-dimensional folding using fluvial terraces: A case study from the Mushi anticline, northern margin of the Chinese Pamir

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    Fold deformation in three dimensions involves shortening, uplift, and lateral growth. Fluvial terraces represent strain markers that have been widely applied to constrain a fold's shortening and uplift. For the lateral growth, however, the utility of fluvial terraces has been commonly ignored. Situated along northern margin of Chinese Pamir, the Mushi anticline preserves, along its northern flank, flights of passively deformed fluvial terraces that can be used to constrain three-dimensional folding history, especially lateral growth. The Mushi anticline is a geometrically simple fault-tip fold with a total shortening of 740?±?110?m and rock uplift of ~1300?m. Geologic and geomorphic mapping and dGPS surveys reveal that terrace surfaces perpendicular to the fold's strike display increased rotation with age, implying the fold grows by progressive limb rotation. We use a pure-shear fault-tip fold model to estimate a uniform shortening rate of 1.5?+?1.3/?0.5?mm/a and a rock-uplift rate of 2.3?+?2.1/?0.8?mm/a. Parallel to the fold's strike, longitudinal profiles of terrace surfaces also display age-dependent increases in slopes. We present a new model to distinguish lateral growth mechanisms (lateral lengthening and/or rotation above a fixed tip). This model indicates that eastward lengthening of the Mushi anticline ceased by at least ~134?ka and its lateral growth has been dominated by rotation. Our study confirms that terrace deformation along a fold's strike not only can constrain the lateral lengthening rate but can serve to quantify the magnitude and rate of lateral rotation: attributes that are commonly difficult to define when relying on other geomorphic criteria

    DNA methylation-based age prediction and telomere length in white blood cells and cumulus cells of infertile women with normal or poor response to ovarian stimulation.

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    An algorithm assessing the methylation levels of 353 informative CpG sites in the human genome permits accurate prediction of the chronologic age of a subject. Interestingly, when there is discrepancy between the predicted age and chronologic age (age acceleration or AgeAccel ), patients are at risk for morbidity and mortality. Identification of infertile patients at risk for accelerated reproductive senescence may permit preventative action. This study aimed to assess the accuracy of the epigenetic clock concept in reproductive age women undergoing fertility treatment by applying the age prediction algorithm in peripheral (white blood cells [WBCs]) and follicular somatic cells (cumulus cells [CCs]), and to identify whether women with premature reproductive aging (diminished ovarian reserve) were at risk of AgeAccel in their age prediction. Results indicated that the epigenetic algorithm accurately predicts age when applied to WBCs but not to CCs. The age prediction of CCs was substantially younger than chronologic age regardless of the patient\u27s age or response to stimulation. In addition, telomeres of CCs were significantly longer than that of WBCs. Our findings suggest that CCs do not demonstrate changes in methylome-predicted age or telomere-length in association with increasing female age or ovarian response to stimulation

    Expression and cellular localization of cyclooxygenases and prostaglandin E synthases in the hemorrhagic brain

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    <p>Abstract</p> <p>Background</p> <p>Although cyclooxygenases (COX) and prostaglandin E synthases (PGES) have been implicated in ischemic stroke injury, little is known about their role in intracerebral hemorrhage (ICH)-induced brain damage. This study examines the expression and cellular localization of COX-1, COX-2, microsomal PGES-1 (mPGES-1), mPGES-2, and cytosolic PGES (cPGES) in mice that have undergone hemorrhagic brain injury.</p> <p>Methods</p> <p>ICH was induced in C57BL/6 mice by intrastriatal injection of collagenase. Expression and cellular localization of COX-1, COX-2, mPGES-1, mPGES-2, and cPGES were examined by immunofluorescence staining.</p> <p>Results</p> <p>In the hemorrhagic brain, COX-1, mPGES-2, and cPGES were expressed constitutively in neurons; COX-1 was also constitutively expressed in microglia. The immunoreactivity of COX-2 was increased in neurons and astrocytes surrounding blood vessels at 5 h and then tended to decrease in neurons and increase in astrocytes at 1 day. At 3 days after ICH, COX-2 was observed primarily in astrocytes but was absent in neurons. Interestingly, the immunoreactivity of mPGES-1 was increased in neurons in the ipsilateral cortex and astrocytes in the ipsilateral striatum at 1 day post-ICH; the immunoreactivity of astrocytic mPGES-1 further increased at 3 days.</p> <p>Conclusion</p> <p>Our data suggest that microglial COX-1, neuronal COX-2, and astrocytic COX-2 and mPGES-1 may work sequentially to affect ICH outcomes. These findings have implications for efforts to develop anti-inflammatory strategies that target COX/PGES pathways to reduce ICH-induced secondary brain damage.</p

    Multidimensional transition fronts for Fisher–KPP reactions

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    We study entire solutions to homogeneous reaction-diffusion equations in several dimensions with Fisher-KPP reactions. Any entire solution 0 < u < 1 is known to satisfy lim t→−∞ sup|x|≤c|t| u(t,x) = 0 for each c < 2√f′(0), and we consider here those satisfying lim t→−∞ sup|x|≤c|t| u(t,x) = 0 for some c > 2√f′(0). When f is C_2 and concave, our main result provides an almost complete characterization of transition fronts as well as transition solutions with bounded width within this class of solutions

    Use of complementary and alternative medicine in patients with inborn errors of metabolism: A single-center study

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    Background and Objectives: There is a paucity of information on the use of complementary and alternative medicine (CAM) in patients with inborn errors of metabolism (IEM). This study\u27s objective was to evaluate the self-reported use and perceived effectiveness of CAM in adults and children with IEM. Methods: Patients aged 0-70 years and caregivers seen at the London Health Sciences Centre Metabolic Clinic (London, Ontario, Canada) between July 2017 and August 2017 were recruited to complete a questionnaire regarding CAM use to help their IEM diagnosis and perceived effectiveness of these therapies. Survey responses were analyzed using descriptive statistics; age, sex, and education level associations among CAM users were tested using the Pearson χ2 test. Results: Of 50 potential participants, 44 (88%) completed the questionnaire, including 21 adults (6 by caregivers) and 23 children (22 by caregivers). The most common IEM category was Aminoacidopathies and Small Molecule Disorders (50%). Twenty-seven (61%) participants reported CAM use to help their IEM diagnosis. The most common CAM therapies used were chiropractic manipulation, omega-3 fatty acids, probiotics, and aromatherapy/essential oils. Most CAM users and caregivers (74%) perceived their CAM therapies as effective overall. Among CAM users, 40% had not discussed CAM use with a health care professional (HCP). CAM use was similar when comparing age, sex and education level. Conclusions: CAM is commonly used among patients with IEM. The safety and efficacy of CAM therapies for IEM should be further investigated. HCPs and patients should openly discuss CAM use in order to evaluate safety

    Quantification of O-glycosylation stoichiometry and dynamics using resolvable mass tags

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    Mechanistic studies of O-GlcNAc glycosylation have been limited by an inability to monitor the glycosylation stoichiometries of proteins obtained from cells. Here we describe a powerful method to visualize the O-GlcNAc–modified protein subpopulation using resolvable polyethylene glycol mass tags. This approach enables rapid quantification of in vivo glycosylation levels on endogenous proteins without the need for protein purification, advanced instrumentation or expensive radiolabels. In addition, it establishes the glycosylation state (for example, mono-, di-, tri-) of proteins, providing information regarding overall O-GlcNAc site occupancy that cannot be obtained using mass spectrometry. Finally, we apply this strategy to rapidly assess the complex interplay between glycosylation and phosphorylation and discover an unexpected reverse 'yin-yang' relationship on the transcriptional repressor MeCP2 that was undetectable by traditional methods. We anticipate that this mass-tagging strategy will advance our understanding of O-GlcNAc glycosylation, as well as other post-translational modifications and poorly understood glycosylation motifs

    GEMC1 and MCIDAS interactions with SWI/SNF complexes regulate the multiciliated cell-specific transcriptional program

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    Cell signalling; TranscriptionSeñalización celular; TranscripciónSenyalització cel·lular; TranscripcióMulticiliated cells (MCCs) project dozens to hundreds of motile cilia from their apical surface to promote the movement of fluids or gametes in the mammalian brain, airway or reproductive organs. Differentiation of MCCs requires the sequential action of the Geminin family transcriptional activators, GEMC1 and MCIDAS, that both interact with E2F4/5-DP1. How these factors activate transcription and the extent to which they play redundant functions remains poorly understood. Here, we demonstrate that the transcriptional targets and proximal proteomes of GEMC1 and MCIDAS are highly similar. However, we identified distinct interactions with SWI/SNF subcomplexes; GEMC1 interacts primarily with the ARID1A containing BAF complex while MCIDAS interacts primarily with BRD9 containing ncBAF complexes. Treatment with a BRD9 inhibitor impaired MCIDAS-mediated activation of several target genes and compromised the MCC differentiation program in multiple cell based models. Our data suggest that the differential engagement of distinct SWI/SNF subcomplexes by GEMC1 and MCIDAS is required for MCC-specific transcriptional regulation and mediated by their distinct C-terminal domains.We thank F. Guillemot, C. Lynch, M. Serrano, and S. Brody for antibodies, F. Supek for cells and reagents, A. Holland and C. Jewett for DEUP1 antibody and expansion microscopy suggestions, J. St-Germain for data analysis, J. Lüders for help with expansion microscopy, T. Dantas for sharing unpublished data and support from the IRB Functional Genomics and Biostatistics/Bioinformatics, Protein Expression and Mass Spectrometry Core Facilities. ML and BT were funded by Severo Ochoa FPI fellowships from the Ministry of Science, Innovation and Universities (MCIU), PK by an Advanced Postdoc Mobility fellowship from the Swiss National Science Foundation and the Kurt and Senta Herrmann Foundation and I.G.C by an AECC fellowship. THS was funded by the MCIU (PGC2018-095616-B-I00/GINDATA) and by the NIH Intramural Research Program, National Cancer Institute, Center for Cancer Research. X.S. was supported by MINECO (PID2019-110198RB-I00) and the European Research Council (CONCERT, contract number 648201). IRB Barcelona is the recipient of institutional funding from FEDER and the Centres of Excellence Severo Ochoa award to IRB Barcelona from MINECO (Government of Spain). MRM was funded by the National Heart, Lung and Blood Institute of the NIH (R01-HL128370). VC was funded by the Associazione Italiana per la Ricerca sul Cancro (AIRC), the European Research Council (ERC) grant 614541 and the GiovanniArmenise foundation career development award to VC. SR was funded by a Singapore National Medical Research Council (NMRC) Open Fund-Individual Research Grant (OFIRG19nov-0037). HZ was supported by National Cancer Institute (R01 CA220551)
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