bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activity‐dependent regulation of release probability at excitatory hippocampal synapses: a crucial role of fragile X mental retardation protein in neurotransmission
Authors: Wang Xiao‐Sheng , Peng Chun‐Zi , Cai Wei‐Jun , Xia Jian , Jin Daozhong , Dai Yuqiao , Luo Xue‐Gang , Klyachko Vitaly A. , Deng Pan‐Yue 
Published: March 2014

AbstractTranscriptional silencing of the Fmr1 gene encoding fragile X mental retardation protein (FMRP) causes fragile X syndrome (FXS), the most common form of inherited intellectual disability and the leading genetic cause of autism. FMRP has been suggested to play important roles in regulating neurotransmission and short‐term synaptic plasticity at excitatory hippocampal and cortical synapses. However, the origins and mechanisms of these FMRP actions remain incompletely understood, and the role of FMRP in regulating synaptic release probability and presynaptic function remains debated. Here we used variance‐mean analysis and peak‐scaled nonstationary variance analysis to examine changes in both presynaptic and postsynaptic parameters during repetitive activity at excitatory CA3–CA1 hippocampal synapses in a mouse model of FXS. Our analyses revealed that loss of FMRP did not affect the basal release probability or basal synaptic transmission, but caused an abnormally elevated release probability specifically during repetitive activity. These abnormalities were not accompanied by changes in excitatory postsynaptic current kinetics, quantal size or postsynaptic α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor conductance. Our results thus indicate that FMRP regulates neurotransmission at excitatory hippocampal synapses specifically during repetitive activity via modulation of release probability in a presynaptic manner. Our study suggests that FMRP function in regulating neurotransmitter release is an activity‐dependent phenomenon that may contribute to the pathophysiology of FXS.
Spike wave location and density disturb sleep slow waves in patients with CSWS (continuous spike waves during sleep)
Authors: Bölsterli Heinzle Bigna K. , Fattinger Sara , Kurth Salomé , LeBourgeois Monique K. , Ringli Maya , Bast Thomas , Critelli Hanne , Schmitt Bernhard , Huber Reto 
Published: March 2014

SummaryObjectiveIn CSWS (continuous spike waves during sleep) activation of spike waves during slow wave sleep has been causally linked to neuropsychological deficits, but the pathophysiologic mechanisms are still unknown. In healthy subjects, the overnight decrease of the slope of slow waves in NREM (non–rapid eye movement) sleep has been linked to brain recovery to regain optimal cognitive performance. Here, we investigated whether the electrophysiologic hallmark of CSWS, the spike waves during sleep, is related to an alteration in the overnight decrease of the slope, and if this alteration is linked to location and density of spike waves.MethodsIn a retrospective study, the slope of slow waves (0.5–2 Hz) in the first hour and last hour of sleep (19 electroencephalography [EEG] electrodes) of 14 patients with CSWS (3.1–13.5 years) was calculated. The spike wave “focus” was determined as the location of highest spike amplitude and the density of spike waves as spike wave index (SWI).ResultsThere was no overnight change of the slope of slow waves in the “focus.” Instead, in “nonfocal” regions, the slope decreased significantly. This difference in the overnight course resulted in a steeper slope in the “focus” compared to “nonfocal” electrodes during the last hour of sleep. Spike wave density was correlated with the impairment of the overnight slope decrease: The higher the SWI, the more hampered the slope decrease.SignificanceLocation and density of spike waves are related to an alteration of the physiologic overnight decrease of the slow wave slope. This overnight decrease of the slope was shown to be closely related to the recovery function of sleep. Such recovery is necessary for optimal cognitive performance during wakefulness. Therefore we propose the impairment of this process by spike waves as a potential mechanism leading to neuropsychological deficits in CSWS.A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Altered thalamocortical functional connectivity in idiopathic generalized epilepsy
Authors: Kim Jung Bin , Suh Sang‐il , Seo Woo‐Keun , Oh Kyungmi , Koh Seong‐Beom , Kim Ji Hyun 
Published: March 2014

SummaryObjectiveAberrant thalamocortical network has been hypothesized to play a crucial role in the fundamental pathogenesis underlying idiopathic generalized epilepsy (IGE). We aimed to investigate alterations of thalamocortical functional network in patients with IGE using thalamic seed‐based functional connectivity (FC) analysis, and their relationships with frontal cognitive functions and clinical characteristics.MethodsForty‐nine IGE patients (31 with juvenile myoclonic epilepsy, 17 with IGE with generalized tonic–clonic seizures only, one with juvenile absence epilepsy) and 42 control subjects were prospectively recruited. Voxel‐based morphometry (VBM) was first performed to detect thalamic region of gray matter (GM) reduction in patients compared to controls. Between‐group comparison of thalamocortical FC was then carried out using resting‐state functional magnetic resonance imaging (MRI) analysis seeding at thalamic region of volume difference. In addition, thalamocortical FC was correlated with frontal cognitive performance and clinical variables.ResultsNeuropsychological assessment revealed that patients with IGE had poorer performance than controls on most of the frontal cognitive functions. VBM detected a reduction in GM in the anteromedial thalamus in patients relative to controls. FC analysis seeding at the anteromedial thalamus revealed a reduction of thalamocortical FC in the bilateral medial prefrontal cortex and precuneus/posterior cingulate cortex in patients with IGE compared to controls. Thalamocortical FC strength of bilateral medial prefrontal cortex correlated negatively with disease duration, but did not correlate with seizure frequency or frontal cognitive functions in patients with IGE.SignificanceOur results indicate that IGE is associated with decreased thalamocortical FC between anteromedial thalamus and medial prefrontal cortex and precuneus/posterior cingulate cortex. Our finding of greater reduction of medial prefrontal FC in relation to increasing disease duration suggests that thalamoprefrontal network abnormality, the proposed pathophysiologic mechanism underlying IGE, may be the consequence of the long‐standing burden of the disease.
Disrupted anatomic white matter network in left mesial temporal lobe epilepsy
Authors: Liu Min , Chen Zhang , Beaulieu Christian , Gross Donald W. 
Published: March 2014

SummaryObjectiveBrain imaging studies have shown widespread structural abnormalities in patients with temporal lobe epilepsy (TLE) within and beyond the affected temporal lobe, suggesting an altered network. Graph theoretical analysis based on white matter tractography has provided a new perspective to evaluate the connectivity of the brain. The alterations in the topologic properties of a whole brain white matter network in patients with TLE remain unknown. The purpose of this study was to examine the white matter network in a cohort of patients with left TLE and mesial temporal sclerosis (mTLE) compared to healthy controls.MethodsAnatomic brain networks of 16 patients with left mTLE were compared to those of 21 healthy controls. A white matter structural network was constructed from diffusion tensor tractography for each participant, and network parameters were compared between the patient and control groups.ResultsPatients with left mTLE exhibited concurrent decreases of global and local efficiencies and widespread reduction of regional efficiency in ipsilateral temporal, bilateral frontal, and bilateral parietal areas. Communication hubs, such as the left precuneus, were also altered in patients with mTLE compared to controls.SignificanceOur results demonstrate white matter network disruption in patients with left mTLE, supporting the notion that mTLE is a systemic brain disorder.A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Understanding molecular recognition of promiscuity of thermophilic methionine adenosyltransferase sMAT from Sulfolobus solfataricus
Authors: Wang Fengbin , Singh Shanteri , Zhang Jianjun , Huber Tyler D. , Helmich Kate E. , Sunkara Manjula , Hurley Katherine A. , Goff Randal D. , Bingman Craig A. , Morris Andrew J. , Thorson Jon S. , Phillips George N. 
Published: March 2014

Methionine adenosyltransferase (MAT) is a family of enzymes that utilizes ATP and methionine to produce S‐adenosylmethionine (AdoMet), the most crucial methyl donor in the biological methylation of biomolecules and bioactive natural products. Here, we report that the MAT from Sulfolobus solfataricus (sMAT), an enzyme from a poorly explored class of the MAT family, has the ability to produce a range of differentially alkylated AdoMet analogs in the presence of non‐native methionine analogs and ATP. To investigate the molecular basis for AdoMet analog production, we have crystallized the sMAT in the AdoMet bound, S‐adenosylethionine (AdoEth) bound and unbound forms. Notably, among these structures, the AdoEth bound form offers the first MAT structure containing a non‐native product, and cumulatively these structures add new structural insight into the MAT family and allow for detailed active site comparison with its homologs in Escherichia coli and human. As a thermostable MAT structure from archaea, the structures herein also provide a basis for future engineering to potentially broaden AdoMet analog production as reagents for methyltransferase‐catalyzed ‘alkylrandomization’ and/or the study of methylation in the context of biological processes.DatabasesPDB IDs: 4HPV, 4L7I, 4K0B and 4L2Z.
EC 2.5.1.6
Structured digital abstract• sMAT and sMAT bind by x-ray crystallography (View interaction)
Recognition of and intent to use gastrostomy or ventilator treatments in older patients with advanced dementia: Differences between laypeople and healthcare professionals in Japan
Authors: Kawasaki Ayako , Matsushima Masato , Miura Yasuhiko , Watanabe Takamasa , Tominaga Tomokazu , Nagata Takuya , Hirayama Yoko , Moriya Akinari , Nomura Kouji 
Published: March 2014

AimWe compared differences between laypeople and healthcare professionals in the recognition of and intent to use gastrostomy and ventilator treatments in older patients with dementia.MethodsBetween November 2011 and January 2012, a questionnaire survey was carried out. People who underwent a general health check‐up at Nomura Hospital Preventive Medical Center were recruited as the laypeople group. Physicians and nurses working in Mitaka, Tokyo, Japan, were recruited as the healthcare professional group. We assessed the recognition rate of ventilator and gastrostomy treatments. Then we provided two scenarios for participants to determine whether these methods represented life‐sustaining treatments that will simply delay an inevitable death. Intentions were compared between cases with and without advance directives.ResultsApproximately 60% of laypeople did not know what gastrostomy is. Healthcare professionals were more likely to recognize a ventilator as a life‐sustaining treatment; in contrast, there were no significant differences in judgments regarding gastrostomy. Both groups were more likely to have intent to use a gastrostomy and a ventilator for family members than themselves. Furthermore, healthcare professionals were more likely to want to use these items for patients than their family members. Advance directive for withholding life‐sustaining treatment reduced the intention to use these treatments.ConclusionIt is necessary to increase our understanding regarding knowledge of end‐of‐life care options of both laypeople and healthcare professionals. Geriatr Gerontol Int 2015; 15: 318–325.
Ion release and mechanical properties of calcium silicate and calcium hydroxide materials used for pulp capping
Authors: Natale L. C. , Rodrigues M. C. , Xavier T. A. , Simões A. , de Souza D. N. , Braga R. R. 
Published: March 2014

AbstractAimTo compare the ion release and mechanical properties of a calcium hydroxide (Dycal) and two calcium silicate (MTAAngelus and Biodentine) cements.MethodologyCalcium and hydroxyl ion release in water from 24‐h set cements were calculated from titration with HCl (n = 3). Calcium release after 7, 14, 21 and 28 days at pH5.5 and 7.0 was measured using ICP‐OES (n = 6). Flexural strength (FS) and modulus (E) were tested after 48‐h storage, and compressive strength (CS) was tested after 48 h and 7 days (n = 10). Ion release and mechanical data were subjected toanova/Tukey and Kruskal–Wallis/Mann–Whitney tests, respectively (α = 0.05).ResultsTitration curves revealed that Dycal released significantly fewer ions in solution than calcium silicates (P < 0.001). Calcium release remained constant at pH7.0, whilst at pH5.5, it dropped significantly by 24% after 21 days (P < 0.05). At pH5.5, MTA Angelus released significantly more calcium than Dycal (P < 0.01), whilst Biodentine had superior ion release than Dycal at pH7.0 (P < 0.01). Biodentine had superior flexural strength, flexural modulus and compressive strength than the other cements, whilstMTAAngelus had higher modulus than Dycal (P < 0.001).ConclusionsImmediate calcium and hydroxyl ion release in solution was significantly lower for Dycal. In general, all materials released constant calcium levels over 28 days, but release from Dycal was significantly lower than Biodentine andMTAAngelus depending on pHconditions. Biodentine had substantially higher strength and modulus thanMTAAngelus and Dycal, both of which demonstrated low stress‐bearing capabilities.
Divergence of the gene aly in experimentally evolved cytoraces, the members of the nasuta‐albomicans complex of Drosophila
Authors: Radhika P. N. , Ramachandra N. B. 
Published: March 2014

AbstractWe generated cytoraces by crossing the chromosomal races (Drosophila nasuta nasuta and Drosophila nasuta albomicans) of the nasuta subgroup of Drosophila and maintained the offspring over many generations through sibling mating. These cytoraces, along with their parents, are members of the nasuta‐albomicans complex of Drosophila. The gene always early (aly) is one of the rapidly evolving genes in the genus Drosophila and plays a central role in regulating meiosis. Here we examined the rate of molecular evolution of aly in cytoraces of Drosophila and demonstrated that the rate of substitutions amongst cytoraces is around eight times greater than their parents and even amongst species of subgenera. Thus, the presence of positive selection in the laboratory‐derived cytoraces based on the analysis of the synonymous and nonsynonymous substitution rates of aly suggests the rapid evolution in cytoraces.
Chronic lymphocytic leukaemia: could immunological tolerance mechanisms be the origin of lymphoid neoplasms?
Authors: García‐Muñoz Ricardo , Llorente Luis 
Published: March 2014

SummaryImmunological tolerance theory in chronic lymphocytic leukaemia (CLL): we suggest that B cells that express B‐cell receptors (BCR) that recognize their own BCR epitopes are viewed by immune system as ‘dangerous cells’. BCR autonomous signalling may induce constant receptor editing and mistakes in allelic exclusion. The fact that whole BCR recognizes a self‐antigen or foreing antigen may be irrelevant in early B cell development. In early B cells, autonomous signalling induced by recognition of the BCR’s own epitopes simulates an antigen‐antibody engagement. In the bone marrow this interaction is viewed as recognition of self‐molecules and induces receptor editing. In mature B cells autonomous signalling by the BCR may promote ‘reversible anergy’ and also may correct self‐reactivity induced by the somatic hypermutation mechanisms in mutated CLL B cells. However, in unmutated CLL B cells, BCR autonomous signalling in addition to self‐antigen recognition augments B cell activation, proliferation and genomic instability. We suggest that CLL originates from a coordinated normal immunologic tolerance mechanism to destroy self‐reactive B cells. Additional genetic damage induced by tolerance mechanisms may immortalize self‐reactive B cells and transform them into a leukemia.
Distinct B‐cell populations contribute to vaccine antigen‐specific antibody production in a transgenic mouse model
Authors: O Eunju , Ko Eun‐Ju , Kim Min‐Chul , Lee Young‐Tae , Song Jae‐Min , Kwon Young‐Man , Compans Richard W. , Kang Sang‐Moo 
Published: March 2014

SummaryThe generation of memory B cells by vaccination plays a critical role in maintaining antigen‐specific antibodies and producing antibody responses upon re‐exposure to a pathogen. B‐cell populations contributing to antibody production and protection by vaccination remain poorly defined. We used influenza virus‐like particle (VLP) vaccine in a transgenic mouse model that would identify germinal centre‐derived memory B cells with the expression of yellow fluorescent protein (YFP+ cells). Immunization with influenza VLP vaccine did not induce significant increases in YFP+ cells although vaccine antigen‐specific antibodies in sera were found to confer protection against a lethal dose of influenza A virus (A/PR8). In addition, CD43+ B220− populations with low YFP+ cells mainly contributed to the production of vaccine antigen‐specific IgG isotype‐switched antibodies whereas CD43− B220+ populations with high YFP+ cells were able to produce vaccine antigen‐specific IgM antibodies. Challenge infection of immunized transgenic mice with live influenza A virus resulted in significant increases in YFP+ cells in the B220− populations of spleen and bone marrow cells. These results suggest that CD43+ B220− B cells generated by vaccination are important for producing influenza vaccine antigen‐specific antibodies and conferring protection.
Racial variation in sex steroid hormone concentration in black and white men: a meta‐analysis
Authors: Richard A. , Rohrmann S. , Zhang L. , Eichholzer M. , Basaria S. , Selvin E. , Dobs A. S. , Kanarek N. , Menke A. , Nelson W. G. , Platz E. A. 
Published: March 2014

SummarySex steroid hormones are associated with chronic diseases and mortality with risk associations that differ between racial and ethnic groups. However, it is currently unclear whether sex steroid hormone levels differ between black and white men. The aim of this study was to assess racial variation in circulating testosterone, free testosterone, sex hormone‐binding globulin (SHBG) and estradiol levels in men. We searched PubMed for articles comparing circulating hormones in black and white men. A meta‐analysis was performed using weighted mean differences (WMD) to compare hormones levels between black and white men. Fifteen eligible studies were identified; three did not report adjusted means. After age adjustment, free testosterone levels were significantly higher in black than in white men (WMD = 4.07 pg/mL, 95% CI 1.26, 6.88). Depending on the free testosterone concentration in white men, this WMD translates into a racial difference ranging from 2.5 to 4.9%. Total testosterone (WMD = 0.10 ng/mL, 95% CI −0.02, 0.22), estradiol (WMD = 0.67 pg/mL, 95% CI −0.04, 1.38) and SHBG (WMD = −0.45 nmol/L, 95% CI −1.75, 0.85) concentrations did not differ comparing blacks with whites. After adjustment for age, black men have a modestly but significantly 2.5 to 4.9% higher free testosterone level than white men. Based on previous studies on effects of sex steroid hormones on risk of chronic diseases or mortality, this modest difference is unlikely to explain racial differences in disease risk.
The effect of a web‐based education programme (WBEP) on disease severity, quality of life and mothers' self‐efficacy in children with atopic dermatitis
Authors: Son Hae Kyoung , Lim Jiyoung 
Published: March 2014

AbstractAimsTo develop and evaluate the effects of a web‐based education programme in early childhood for children with atopic dermatitis.BackgroundThe prevalence rate of atopic dermatitis is highest in early childhood. A holistic approach is urgently needed for young children with respect to disease severity, quality of life and management, particularly parental knowledge about atopic dermatitis and adherence to treatment.DesignA quasi‐experimental study design was used.MethodsA total of 40 mother–child dyads participated in the study from 1 July–30 November 2011 in Korea. All children were under 3 years of age. The programme was based on the Network‐Based Instructional System Design model, which consists of five phases: analysis, design, development, implementation and evaluation. The experimental group participated in the programme for 2 weeks. Participants took part in a learning session during the first week and then conducted the practice session at home during the second week. Participant knowledge and compliance were evaluated through online quizzes and self‐checklists. Statistical analyses (chi‐square test and t‐test) were performed using the Statistical Analysis System, Version 9.13.Results/findingsThere was a significant improvement in disease severity, quality of life and mothers' self‐efficacy in the experimental group; thus, the web‐based education programme was effective.ConclusionThe web‐based education programme as an advanced intervention may be useful in providing basic data for future atopic dermatitis‐related studies. Moreover, the programme may serve as a nursing educational intervention tool for clinical nursing practices.
EU Co‐Ordination and the Convergence of Domestic Unemployment Protection Schemes
Authors: Paetzold Jörg , Van Vliet Olaf 
Published: March 2014

AbstractThe European Employment Strategy (EES) aims to promote convergence towards higher employment and lower unemployment by soft law instruments. Previous studies in the Europeanization literature on the impact of the EES are mainly focused on active labour market policies. This article explains cross‐national variation in national passive labour market policies. Building on new pooled time‐series data, the empirical findings reveal the presence of a convergence process among the most advanced economies regarding passive labour market policy efforts, with the EES fostering this trend even further. Furthermore, the findings support the argument that the EES creates pressure on governments to reform domestic labour market policies, but this pressure varies across countries and over time. The findings provide new insights into the relationship between Europeanization and convergence, which may be relevant for EU co‐ordination more generally – for example, for the EU 2020 strategy.