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91.
Convergent,incremental, and criterion‐related validity of multi‐informant assessments of adolescents' fears of negative and positive evaluation 下载免费PDF全文
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Chromosome 17q12 duplications: Further delineation of the range of psychiatric and clinical phenotypes 下载免费PDF全文
Arveen Kamath Stefanie C. Linden Ffion M. Evans Jeremy Hall Sian F. Jose Sally A. Spillane Alan D. R. Hardie Sian M. Morgan Daniela T. Pilz 《American journal of medical genetics. Part B, Neuropsychiatric genetics》2018,177(5):520-528
Copy number variants at chromosome 17q12 have been associated with a spectrum of phenotypes. Deletions of 17q12 are well described and associated with maturity onset diabetes of the young type 5 (MODY5) and cystic renal disease (HNF1β) as well as cognitive impairment and seizures. Duplication of 17q12 is emerging as a new genetic syndrome, associated with learning disability, seizures, and behavioral problems. The duplication is often inherited from an apparently unaffected parent. Here, we describe a three‐generation family with multiple individuals carrying a17q12 microduplication with varying clinical features, consistent with variable penetrance. The proband who inherited a 1.8 Mb interstitial 17q12 duplication from his mother presented with developmental delay, behavioral problems, and mild dysmorphism. One of his sisters, his maternal uncle, and his maternal grandmother also carry the 17q12 microduplication. Clinical features of the carriers include renal problems, diabetes mellitus, learning difficulties, epilepsy and mental illness. Cognitive abilities range from normal function to moderate impairment (full‐scale IQ range: 52‐99). In light of recent reports of association of this locus with schizophrenia, we performed a detailed psychiatric assessment and confirmed that one family member has symptoms consistent with a diagnosis of schizophrenia and another has a prodromal syndrome with attenuated positive symptoms of psychosis. This report extends the clinical phenotype associated with the 17q12 microduplication and highlights the phenotypic variability. 相似文献
94.
Matthew B. Jessee J. Grant Mouser Samuel L. Buckner Scott J. Dankel Kevin T. Mattocks Takashi Abe Jeremy P. Loenneke 《The journal of physiological sciences : JPS》2018,68(6):769-779
To determine the effects of load and blood flow restriction (BFR) on muscular responses, we asked 12 participants to perform chest presses under four different conditions [30/0, 30/40, 50/0, and 50/40, presented as percentage one-repetition maximum (1RM)/percentage arterial occlusion pressure (AOP)]. Muscle thickness increased pre- to post-exercise [chest: mean 0.29, 95% confidence interval (CI) 0.21, 0.37 cm; triceps: mean 0.44, 95% CI 0.34, 0.54 cm], remaining elevated for 15 min post-exercise. Electromyography amplitude was greater with 50% 1RM and increased over time for the first three repetitions of each set of chest presses. The last three repetitions differed across time only. AOP increased from pre- to post-exercise, augmented by BFR [30/0: mean 31, 95% CI 18, 44 mmHg; 30/40: mean 39, 95% CI 28, 50 mmHg; 50/0: mean 32, 95% CI 23, 41 mmHg; 50/40: mean 46, 95% CI 32, 59 mmHg). Tranquility decreased and physical exhaustion increased from the pre- to post-condition, with both parameters returning to the baseline 15 min post-exercise level. In conclusion, load and BFR do not elicit meaningful differences in the acute response of chest press exercise taken to failure. 相似文献
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The intestine is a critical site of immune cell development that not only controls intestinal immunity but extra‐intestinal immunity as well. Recent findings have highlighted important roles for gut microbiota in shaping lung inflammation. Here, we discuss interactions between the microbiota and immune system including T cells, protective effects of microbiota on lung infections, the role of diet in shaping the composition of gut microbiota and susceptibility to asthma, epidemiologic evidence implicating antibiotic use and microbiota in asthma and clinical trials investigating probiotics as potential treatments for atopy and asthma. The systemic effects of gut microbiota are partially attributed to their generating metabolites including short chain fatty acids, which can suppress lung inflammation through the activation of G protein‐coupled receptors. Thus, studying the interactions between microbiota and immune cells can lead to the identification of therapeutic targets for chronic lower respiratory diseases. 相似文献
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Joanna J. Kaylor Jeremy D. Cook Jacob Makshanoff Nicholas Bischoff Jennifer Yong Gabriel H. Travis 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(20):7302-7307
Absorption of a photon by a rhodopsin or cone-opsin pigment isomerizes its 11-cis-retinaldehyde (11-cis-RAL) chromophore to all-trans-retinaldehyde (all-trans-RAL), which dissociates after a brief period of activation. Light sensitivity is restored to the resulting apo-opsin when it recombines with another 11-cis-RAL. Conversion of all-trans-RAL to 11-cis-RAL is carried out by an enzyme pathway called the visual cycle in cells of the retinal pigment epithelium. A second visual cycle is present in Müller cells of the retina. The retinol isomerase for this noncanonical pathway is dihydroceramide desaturase (DES1), which catalyzes equilibrium isomerization of retinol. Because 11-cis-retinol (11-cis-ROL) constitutes only a small fraction of total retinols in an equilibrium mixture, a subsequent step involving selective removal of 11-cis-ROL is required to drive synthesis of 11-cis-retinoids for production of visual chromophore. Selective esterification of 11-cis-ROL is one possibility. Crude homogenates of chicken retinas rapidly convert all-trans-ROL to 11-cis-retinyl esters (11-cis-REs) with minimal formation of other retinyl-ester isomers. This enzymatic activity implies the existence of an 11-cis-specific retinyl-ester synthase in Müller cells. Here, we evaluated multifunctional O-acyltransferase (MFAT) as a candidate for this 11-cis-RE-synthase. MFAT exhibited much higher catalytic efficiency as a synthase of 11-cis-REs versus other retinyl-ester isomers. Further, we show that MFAT is expressed in Müller cells. Finally, homogenates of cells coexpressing DES1 and MFAT catalyzed the conversion of all-trans-ROL to 11-cis-RP, similar to what we observed with chicken-retina homogenates. MFAT is therefore an excellent candidate for the retinyl-ester synthase that cooperates with DES1 to drive synthesis of 11-cis-retinoids by mass action.Light perception begins with the absorption of a photon by an opsin pigment in the membranous outer segment (OS) of a rod or cone photoreceptor cell. The light-absorbing chromophore in most vertebrate opsins is 11-cis-retinaldehyde (11-cis-RAL). Photon capture isomerizes the 11-cis-RAL to all-trans-retinaldehyde (all-trans-RAL), inducing conformational changes in the protein that lead to its active meta-II state. After a brief period of signaling through the transduction cascade, meta II decays to yield apo-opsin and free all-trans-RAL. Light sensitivity is restored to the apo-opsin when it combines with 11-cis-RAL to regenerate the pigment. Conversion of all-trans-RAL to 11-cis-RAL is carried out by a multistep enzyme pathway called the visual cycle, located in cells of the retinal pigment epithelium (RPE) (1, 2). The retinoid isomerase in this pathway is Rpe65, which converts an all-trans-retinyl ester (all-trans-RE), such as all-trans-retinyl palmitate (all-trans-RP), to 11-cis-retinol (11-cis-ROL) and a free fatty acid (3–5). Retinyl esters are synthesized in RPE cells by lecithin:retinol acyl transferase (LRAT), which transfers a fatty acid from phosphatidylcholine to retinol (6, 7). LRAT converts both all-trans-ROL and 11-cis-ROL to their cognate esters with similar catalytic efficiency (8).A second visual cycle is present in Müller cells of the retina, providing 11-cis-ROL to cones (9–11). Cones, but not rods, can use 11-cis-ROL as a chromophore precursor to regenerate bleached opsin pigments (10, 12, 13). The isomerase in the noncanonical pathway is dihydroceramide desaturase (DES1) (11). DES1 catalyzes rapid equilibrium isomerization of retinol (11). At equilibrium, 11-cis-ROL is much less abundant than all-trans-ROL, due to the 4.1 kcal/mole difference in free energy between these isomers (14). Accordingly, a secondary source of energy is required to drive the conversion of all-trans-ROL to 11-cis-ROL by DES1. Retinas from cone-dominant species contain 11-cis-retinyl esters (11-cis-REs), whereas retinyl esters are much less abundant in retinas from rod-dominant species (11, 13, 15). Homogenates from cone-dominant chicken and ground-squirrel retinas convert all-trans-ROL predominantly to 11-cis-REs in the presence of palmitoyl CoA (palm CoA) (13, 16, 17). These observations suggest that selective esterification of 11-cis-ROL may be the driving force for 11-cis-retinoid formation. In the current work, we sought to identify the protein responsible for the 11-cis-RE-synthase activity in Müller cells. We evaluated multifunctional O-acyltransferase (MFAT) as a candidate for this synthase. MFAT, also called acyl-CoA wax-alcohol acyltransferase-2 (AWAT2), catalyzes palm CoA-dependent synthesis of triglycerides, wax monoesters, and retinyl esters (18). It is present in the endoplasmic reticulum and predominantly expressed in skin (18). The retinol-isomer specificity of MFAT, and its expression in ocular tissues, has not been studied. 相似文献