Current quark mass dependence of nucleon magnetic moments and radii

A calculation of the current-quark-mass-dependence of nucleon static electromagnetic properties is necessary in order to use observational data as a means to place constraints on the variation of Nature's fundamental parameters. A Poincare' covariant Faddeev equation, which describes baryons as composites of confined-quarks and -nonpointlike-diquarks, is used to calculate this dependence The results indicate that, like observables dependent on the nucleons' magnetic moments, quantities sensitive to their magnetic and charge radii, such as the energy levels and transition frequencies in Hydrogen and Deuterium, might also provide a tool with which to place limits on the allowed variation in Nature's constants.Comment: 23 pages, 2 figures, 4 tables, 4 appendice

Resequencing PNMT in European hypertensive and normotensive individuals: no common susceptibilily variants for hypertension and purifying selection on intron 1

<p>Abstract</p> <p>Background</p> <p>Human linkage and animal QTL studies have indicated the contribution of genes on Chr17 into blood pressure regulation. One candidate gene is <it>PNMT</it>, coding for phenylethanolamine-N-methyltransferase, catalyzing the synthesis of epinephrine from norepinephrine.</p> <p>Methods</p> <p>Fine-scale variation of <it>PNMT </it>was screened by resequencing hypertensive (n = 50) and normotensive (n = 50) individuals from two European populations (Estonians and Czechs). The resulting polymorphism data were analyzed by statistical genetics methods using Genepop 3.4, PHASE 2.1 and DnaSP 4.0 software programs. <it>In silico </it>prediction of transcription factor binding sites for intron 1 was performed with MatInspector 2.2 software.</p> <p>Results</p> <p><it>PNMT </it>was characterized by minimum variation and excess of rare SNPs in both normo- and hypertensive individuals. None of the SNPs showed significant differences in allelic frequencies among population samples, as well as between screened hypertensives and normotensives. In the joint case-control analysis of the Estonian and the Czech samples, hypertension patients had a significant excess of heterozygotes for two promoter region polymorphisms (SNP-184; SNP-390). The identified variation pattern of <it>PNMT </it>reflects the effect of purifying selection consistent with an important role of PNMT-synthesized epinephrine in the regulation of cardiovascular and metabolic functions, and as a CNS neurotransmitter. A striking feature is the lack of intronic variation. <it>In silico </it>analysis of <it>PNMT </it>intron 1 confirmed the presence of a human-specific putative Glucocorticoid Responsive Element (GRE), inserted by <it>Alu</it>-mediated transfer. Further analysis of intron 1 supported the possible existence of a full Glucocorticoid Responsive Unit (GRU) predicted to consist of multiple gene regulatory elements known to cooperate with GRE in driving transcription. The role of these elements in regulating <it>PNMT </it>expression patterns and thus determining the dynamics of the synthesis of epinephrine is still to be studied.</p> <p>Conclusion</p> <p>We suggest that the differences in PNMT expression between normotensives and hypertensives are not determined by the polymorphisms in this gene, but rather by the interplay of gene expression regulators, which may vary among individuals. Understanding the determinants of PNMT expression may assist in developing PNMT inhibitors as potential novel therapeutics.</p

Psychiatric disorders and clinical correlates of suicidal patients admitted to a psychiatric hospital in Tokyo

<p>Abstract</p> <p>Background</p> <p>Patients admitted to a psychiatric hospital with suicidal behavior (SB) are considered to be especially at high risk of suicide. However, the number of studies that have addressed this patient population remains insufficient compared to that of studies on suicidal patients in emergency or medical settings. The purpose of this study is to seek features of a sample of newly admitted suicidal psychiatric patients in a metropolitan area of Japan.</p> <p>Method</p> <p>155 suicidal patients consecutively admitted to a large psychiatric center during a 20-month period, admission styles of whom were mostly involuntary, were assessed using Structured Clinical Interviews for DSM-IV Axis I and II Disorders (SCID-I CV and SCID-II) and SB-related psychiatric measures. Associations of the psychiatric diagnoses and SB-related characteristics with gender and age were examined.</p> <p>Results</p> <p>The common DSM-IV axis I diagnoses were affective disorders 62%, anxiety disorders 56% and substance-related disorders 38%. 56% of the subjects were diagnosed as having borderline PD, and 87% of them, at least one type of personality disorder (PD). SB methods used prior to admission were self-cutting 41%, overdosing 32%, self-strangulation 15%, jumping from a height 12% and attempting traffic death 10%, the first two of which were frequent among young females. The median (range) of the total number of SBs in the lifetime history was 7 (1-141). Severity of depressive symptomatology, suicidal intent and other symptoms, proportions of the subjects who reported SB-preceding life events and life problems, and childhood and adolescent abuse were comparable to those of the previous studies conducted in medical or emergency service settings. Gender and age-relevant life-problems and life events were identified.</p> <p>Conclusions</p> <p>Features of the studied sample were the high prevalence of affective disorders, anxiety disorders and borderline PD, a variety of SB methods used prior to admission and frequent SB repetition in the lifetime history. Gender and age appeared to have an influence on SB method selection and SB-preceding processes. The findings have important implications for assessment and treatment of psychiatric suicidal patients.</p

RASSF1A hypermethylation in pretreatment serum DNA of neuroblastoma patients: a prognostic marker

The tumour suppressor gene RASSF1A is known to be frequently silenced by promoter hypermethylation in neuroblastoma tumours. Here we explored the possible prognostic significance of aberrant promoter hypermethylation of RASSF1A in serum DNA samples of patients with neuroblastoma as a surrogate marker for circulating tumour cells. We analysed the methylation status of the RASSF1A gene in matched tumour and pretreatment serum DNA obtained from 68 neuroblastoma patients. Hypermethylation of RASSF1A in tumour samples was found in 64 patients (94%). In contrast, serum methylation of RASSF1A was observed in 17 patients (25%). Serum methylation of RASSF1A was found to be statistically associated with age ⩾12 months at diagnosis (P=0.002), stage 4 (P<0.001) and MYCN amplification (P<0.001). The influence of serum RASSF1A methylation on prognosis was found to be comparable with that of the currently most reliable marker, MYCN amplification on univariate analysis (hazard ratio, 9.2; 95% confidence interval (CI), 2.8–30.1; P<0.001). In multivariate analysis of survival, methylation of RASSF1A in serum had a hazard ratio of 2.4 (95% CI, 0.6–9.2), although this association did not reach statistical significance (P=0.194). These findings show that the methylation status of RASSF1A in the serum of patients with neuroblastoma has the potential to become a prognostic predictor of outcome

Synthetic Lethal Screen Identifies NF-κB as a Target for Combination Therapy with Topotecan for patients with Neuroblastoma

<p>Abstract</p> <p>Background</p> <p>Despite aggressive multimodal treatments the overall survival of patients with high-risk neuroblastoma remains poor. The aim of this study was to identify novel combination chemotherapy to improve survival rate in patients with high-risk neuroblastoma.</p> <p>Methods</p> <p>We took a synthetic lethal approach using a siRNA library targeting 418 apoptosis-related genes and identified genes and pathways whose inhibition synergized with topotecan. Microarray analyses of cells treated with topotecan were performed to identify if the same genes or pathways were altered by the drug. An inhibitor of this pathway was used in combination with topotecan to confirm synergism by <it>in vitro </it>and <it>in vivo </it>studies.</p> <p>Results</p> <p>We found that there were nine genes whose suppression synergized with topotecan to enhance cell death, and the NF-κB signaling pathway was significantly enriched. Microarray analysis of cells treated with topotecan revealed a significant enrichment of NF-κB target genes among the differentially altered genes, suggesting that NF-κB pathway was activated in the treated cells. Combination of topotecan and known NF-κB inhibitors (NSC 676914 or bortezomib) significantly reduced cell growth and induced caspase 3 activity <it>in vitro</it>. Furthermore, in a neuroblastoma xenograft mouse model, combined treatment of topotecan and bortezomib significantly delayed tumor formation compared to single-drug treatments.</p> <p>Conclusions</p> <p>Synthetic lethal screening provides a rational approach for selecting drugs for use in combination therapy and warrants clinical evaluation of the efficacy of the combination of topotecan and bortezomib or other NF-κB inhibitors in patients with high risk neuroblastoma.</p

Electrophysiological dynamics of Chinese phonology during visual word recognition in Chinese-English bilinguals

Silent word reading leads to the activation of orthographic (spelling), meaning, as well as phonological (sound) information. For bilinguals, native language information can also be activated automatically when they read words in their second language. For example, when Chinese-English bilinguals read words in their second language (English), the phonology of the Chinese translations is automatically activated. Chinese phonology, however, consists of consonants and vowels (segmental) and tonal information. To what extent these two aspects of Chinese phonology are activated is yet unclear. Here, we used behavioural measures, event-related potentials and oscillatory EEG to investigate Chinese segmental and tonal activation during word recognition. Evidence of Chinese segmental activation was found when bilinguals read English words (faster responses, reduced N400, gamma-band power reduction) and when they read Chinese words (increased LPC, gamma-band power reduction). In contrast, evidence for Chinese tonal activation was only found when bilinguals read Chinese words (gamma-band power increase). Together, our converging behavioural and electrophysiological evidence indicates that Chinese segmental information is activated during English word reading, whereas both segmental and tonal information are activated during Chinese word reading. Importantly, gamma-band oscillations are modulated differently by tonal and segmental activation, suggesting independent processing of Chinese tones and segments