Manic episodes are one of the major diagnostic symptoms in a spectrum of neuropsychiatric disorders that include schizophrenia, obsessive-compulsive disorder and bipolar disorder (BD). Despite a ...possible association between BD and the gene encoding phospholipase Cγ1 (PLCG1), its etiological basis remains unclear. Here, we report that mice lacking phospholipase Cγ1 (PLCγ1) in the forebrain (Plcg1
; CaMKII) exhibit hyperactivity, decreased anxiety-like behavior, reduced depressive-related behavior, hyperhedonia, hyperphagia, impaired learning and memory and exaggerated startle responses. Inhibitory transmission in hippocampal pyramidal neurons and striatal dopamine receptor D1-expressing neurons of Plcg1-deficient mice was significantly reduced. The decrease in inhibitory transmission is likely due to a reduced number of γ-aminobutyric acid (GABA)-ergic boutons, which may result from impaired localization and/or stabilization of postsynaptic CaMKII (Ca
/calmodulin-dependent protein kinase II) at inhibitory synapses. Moreover, mutant mice display impaired brain-derived neurotrophic factor-tropomyosin receptor kinase B-dependent synaptic plasticity in the hippocampus, which could account for deficits of spatial memory. Lithium and valproate, the drugs presently used to treat mania associated with BD, rescued the hyperactive phenotypes of Plcg1
; CaMKII mice. These findings provide evidence that PLCγ1 is critical for synaptic function and plasticity and that the loss of PLCγ1 from the forebrain results in manic-like behavior.
Background and purpose
Along with intracranial atherosclerotic disease (ICAD), moyamoya disease (MMD) is the most common cause of middle cerebral artery (MCA) occlusion in Asians. Although they have ...differing vascular wall pathologies, conventional angiographic evaluation methods cannot easily differentiate MMD from ICAD in certain situations, such as in young patients with atherosclerotic risk factors. High resolution magnetic resonance imaging (HR‐MRI) findings for the diseased segments of MCAs in MMD and symptomatic ICAD were compared to further elucidate differences in arterial wall changes.
Methods
Angiographically confirmed patients, 12 MMD and 20 ICAD, who suffered a stroke due to MCA occlusion were recruited and underwent HR‐MRI. The size of the outer diameter and other stenotic vessel wall characteristics revealed by HR‐MRI, including enhancement, eccentricity and other lesion patterns, were analyzed by two independent reviewers in a blind fashion.
Results
MMD patients were younger than ICAD patients (32.92 ± 11.08 years vs. 51.85 ± 11.97 years; mean ± SD) and displayed a smaller outer diameter in the stenotic portion (1.61 ± 0.43 mm for MMD vs. 3.03 ± 0.53 mm for ICAD, P < 0.0001). Eccentric lesions (three of 12 in MMD vs. 19 of 20 in ICAD, P < 0.0001) and focal enhancements in diseased areas (two of seven in MMD vs. 13 of 17 in ICAD, P = 0.061) were less common in MMD cases.
Conclusions
Our HR‐MRI findings show that MMD is associated with smaller, concentric occlusive lesions which are rarely enhanced compared with symptomatic ICAD, consistent with the results of previous pathological reports. HR‐MRI may therefore have utility in differentiating MMD from ICAD.
Duck hepatitis was first reported in 1985 in Korea. The complete nucleotide sequence of two past Korean isolates, DHV-HS and DHV-HSS, isolated in 1994 and 1995, and four recent Korean isolates, ...AP-03337, AP-04009, AP-04114 and AP-04203 isolated in 2003 and 2004, were determined. Phylogenetic analysis using the 3D protein sequence confirmed that the previously characterized duck hepatitis virus type 1 strains and the six Korean isolates described here constitute a monophyletic group and form two clades/genotypes in which all except the four recent Korean isolates form one group (A) and the recent Korean isolates of 2003 and 2004 constitute a second group (B). Phylogenetic analysis of the VP1 protein supported the division into two different groups. Antisera raised against viruses of group A showed significant neutralizing cross-reaction against a member of the same genotype but not to a strain of group B and vice versa. These results demonstrated that the two genotypes also could be regarded as two different serotypes.
We statistically examined the plasmapause location (Lpp) under quiet geomagnetic conditions (Kp ≤ 1) using the electron density inferred from the Time History of Events and Macroscale Interactions ...during Substorms (THEMIS) spacecraft potential for 2 year period (2008 and 2009). Five hundred forty‐three Lpp samples were identified under steady quiet conditions with Kp values ≤ 1 during 12 h prior to the plasmapause crossing. From our large data set, we determined the medians and means of Lpp in L and magnetic local time (MLT). They are located near geosynchronous orbit and nearly circular. The Lpp medians show a slight bulge located in postdusk sector. Comparing with previous models, our median or mean Lpp is extended ∼1–2 L from the Earth than the model Lpp along the local time from 0800 to 2400 MLT. That is, Lpp locations in the previous models are underestimated during quiet geomagnetic conditions.
Key Points
Plasmapause locations under quiet geomagnetic conditions
Plasmaspheric bulge in the dusk sector
Quiet time plasmapause extended toward geosynchronous orbit
The RENO experiment reports more precisely measured values of θ_{13} and |Δm_{ee}^{2}| using ∼2200 live days of data. The amplitude and frequency of reactor electron antineutrino (νover ¯_{e}) ...oscillation are measured by comparing the prompt signal spectra obtained from two identical near and far detectors. In the period between August 2011 and February 2018, the far (near) detector observed 103 212 (850 666) νover ¯_{e} candidate events with a background fraction of 4.8% (2.0%). A clear energy and baseline dependent disappearance of reactor νover ¯_{e} is observed in the deficit of the measured number of νover ¯_{e}. Based on the measured far-to-near ratio of prompt spectra, we obtain sin^{2}2θ_{13}=0.0896±0.0048(stat)±0.0047(syst) and |Δm_{ee}^{2}|=2.68±0.12(stat)±0.07(syst)×10^{-3} eV^{2}.
Substantial empirical evidence has indicated impairment in the cognitive functioning of patients with obsessive-compulsive disorder (OCD) despite inconsistencies. Although several confounding factors ...have been investigated to explain the conflicting results, the findings remain mixed. This study aimed to investigate cognitive dysfunction in patients with OCD using a meta-analytic approach.
The PubMed database was searched between 1980 and October 2012, and reference lists of review papers were examined. A total of 221 studies were identified, of which 88 studies met inclusion criteria. Neuropsychological performance and demographic and clinical variables were extracted from each study.
Patients with OCD were significantly impaired in tasks that measured visuospatial memory, executive function, verbal memory and verbal fluency, whereas auditory attention was preserved in these individuals. The largest effect size was found in the ability to recall complex visual stimuli. Overall effect estimates were in the small to medium ranges for executive function, verbal memory and verbal fluency. The effects of potentially confounding factors including educational level, symptom severity, medication status and co-morbid disorders were not significant.
Patients with OCD appear to have wide-ranging cognitive deficits, although their impairment is not so large in general. The different test forms and methods of testing may have influenced the performance of patients with OCD, indicating the need to select carefully the test forms and methods of testing used in future research. The effects of various confounding variables on cognitive functioning need to be investigated further and to be controlled before a definite conclusion can be made.
ATP-dependent chromatin remodeling complexes such as SWI/SNF (SWItch/Sucrose NonFermentable) have been implicated in DNA double-strand break (DSB) repair and damage responses. However, the regulatory ...mechanisms that control the function of chromatin remodelers in DNA damage response are largely unknown. Here, we show that ataxia telangiectasia mutated (ATM) mediates the phosphorylation of BRG1, the catalytic ATPase of the SWI/SNF complex that contributes to DSB repair by binding γ-H2AX-containing nucleosomes via interaction with acetylated histone H3 and stimulating γ-H2AX formation, at Ser-721 in response to DNA damage. ATM-mediated phosphorylation of BRG1 occurs rapidly and transiently after DNA damage. Phosphorylated BRG1 binds γ-H2AX-containing nucleosomes to form the repair foci. The Ser-721 phosphorylation of BRG1 is critical for binding γ-H2AX-containing nucleosomes and stimulating γ-H2AX formation and DSB repair. BRG1 binds to acetylated H3 peptides much better after phosphorylation at Ser-721 by DNA damage. However, the phosphorylation of Ser-721 does not significantly affect the ATPase and transcriptional activities of BRG1. These results, establishing BRG1 as a novel and functional ATM substrate, suggest that the ATM-mediated phosphorylation of BRG1 facilitates DSB repair by stimulating the association of this remodeler with γ-H2AX nucleosomes via enhancing the affinity to acetylated H3. Our work also suggests that the mechanism of BRG1 stimulation of DNA repair is independent of the remodeler's enzymatic or transcriptional activities.
Classification of endometrial carcinomas (ECs) by morphologic features is inconsistent, and yields limited prognostic and predictive information. A new system for classification based on the ...molecular categories identified in The Cancer Genome Atlas is proposed.
Genomic data from the Cancer Genome Atlas (TCGA) support classification of endometrial carcinomas into four prognostically significant subgroups; we used the TCGA data set to develop surrogate assays that could replicate the TCGA classification, but without the need for the labor-intensive and cost-prohibitive genomic methodology. Combinations of the most relevant assays were carried forward and tested on a new independent cohort of 152 endometrial carcinoma cases, and molecular vs clinical risk group stratification was compared.
Replication of TCGA survival curves was achieved with statistical significance using multiple different molecular classification models (16 total tested). Internal validation supported carrying forward a classifier based on the following components: mismatch repair protein immunohistochemistry, POLE mutational analysis and p53 immunohistochemistry as a surrogate for 'copy-number' status. The proposed molecular classifier was associated with clinical outcomes, as was stage, grade, lymph-vascular space invasion, nodal involvement and adjuvant treatment. In multivariable analysis both molecular classification and clinical risk groups were associated with outcomes, but differed greatly in composition of cases within each category, with half of POLE and mismatch repair loss subgroups residing within the clinically defined 'high-risk' group. Combining the molecular classifier with clinicopathologic features or risk groups provided the highest C-index for discrimination of outcome survival curves.
Molecular classification of ECs can be achieved using clinically applicable methods on formalin-fixed paraffin-embedded samples, and provides independent prognostic information beyond established risk factors. This pragmatic molecular classification tool has potential to be used routinely in guiding treatment for individuals with endometrial carcinoma and in stratifying cases in future clinical trials.
An ultrafast electrochromic display is fabricated based upon well defined nanotube arrays of poly(3,4‐ethylenedioxythiophene), PEDOT (see Figure). The thin nature of the nanotube walls (10 – 20 nm) ...offers a short ion‐diffusion distance, which results in an ultrafast switching rate (color‐switching time < 10 ms). The arrayed long nanotube structure furnishes strong coloration.
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