119 research outputs found
西准噶尔紫苏花岗岩成因岩石学研究
Charnockites occur as giant enclaves or pendants(?) in the Miaoergou Batholith, Western Junggar region. These rocks are composed of ortho- and clinopyroxenes, fayalite, perthite, antiperthite, and quartz, and are characterized by positive εNd values (+4.8+5.9). Mineral assemblage, texture and field occurrence indicate an igneous origin for the charnockites.Temperature and pressure estimations give700800 ℃and 45 kb crystallization conditions.The charnockites enclose small surmicaceous enclaves and large banded angular xenoliths. The former are considered as restites, while the latter are equivalent to the country pyroclastic rocks. The positive but lowerεNd values (+2.6+3.5) for the restites require that the juvenile lower crust was the dominant source for charnockitic magma, and parental magma of the charnockites from this source was mixed with some melt from depleted mantle, before crystallization. The voluminous alkaline granites in the region were probably from the same magma source, but crystallized at upper crust depth.紫苏花岗岩呈岩体形式侵入于石炭纪地层中,又为碱长花岗岩侵入.紫苏花岗岩由斜方辉石、单斜辉石、铁橄榄石、条纹长石、石英组成,以正εNd 为特征(εNd=+4.8~+5.8).矿物组成、结构和野外产状表明:这些紫苏花岗岩是火成成因的.温压计算估测其结晶条件是T=700~800 ℃, P=420~575 kPa.紫苏花岗岩中有小的富云母包体和巨大的条带状捕虏体.前者被认为是残留体,后者与其围岩-火山碎屑岩相当.残留体中较低的εNd 正值(εNd=+2.6~+3.5)要求新生的下部地壳是紫苏花岗岩的主要源岩:来自这些源岩的紫苏花岗岩的母岩浆在结晶前与一些来自于亏损地幔中的融体混合.该地区体积巨大的碱性花岗岩可能也来自相同的岩浆源,只不过它是在较浅的地壳深度上结晶的.关键词:新疆;西准噶尔;紫苏花岗岩;富云母包体;碱性花岗岩紫苏花岗岩呈岩体形式侵入于石炭纪地层中,又为碱长花岗岩侵入.紫苏花岗岩由斜方辉石、单斜辉石、铁橄榄石、条纹长石、石英组成,以正εNd 为特征(εNd=+4.8~+5.8).矿物组成、结构和野外产状表明:这些紫苏花岗岩是火成成因的.温压计算估测其结晶条件是T=700~800 ℃, P=420~575 kPa.紫苏花岗岩中有小的富云母包体和巨大的条带状捕虏体.前者被认为是残留体,后者与其围岩-火山碎屑岩相当.残留体中较低的εNd 正值(εNd=+2.6~+3.5)要求新生的下部地壳是紫苏花岗岩的主要源岩:来自这些源岩的紫苏花岗岩的母岩浆在结晶前与一些来自于亏损地幔中的融体混合.该地区体积巨大的碱性花岗岩可能也来自相同的岩浆源,只不过它是在较浅的地壳深度上结晶的.published_or_final_versio
Accurate Prediction of Protein Structural Class
Because of the increasing gap between the data from sequencing and structural genomics, the accurate prediction of the structural class of a protein domain solely from the primary sequence has remained a challenging problem in structural biology. Traditional sequence-based predictors generally select several sequence features and then feed them directly into a classification program to identify the structural class. The current best sequence-based predictor achieved an overall accuracy of 74.1% when tested on a widely used, non-homologous benchmark dataset 25PDB. In the present work, we built a multiple linear regression (MLR) model to convert the 440-dimensional (440D) sequence feature vector extracted from the Position Specific Scoring Matrix (PSSM) of a protein domain to a 4-dimensinal (4D) structural feature vector, which could then be used to predict the four major structural classes. We performed 10-fold cross-validation and jackknife tests of the method on a large non-homologous dataset containing 8,244 domains distributed among the four major classes. The performance of our approach outperformed all of the existing sequence-based methods and had an overall accuracy of 83.1%, which is even higher than the results of those predicted secondary structure-based methods
Metabolic labeling of RNA uncovers principles of RNA production and degradation dynamics in mammalian cells
available in PMC 2011 November 01.Cellular RNA levels are determined by the interplay of RNA production, processing and degradation. However, because most studies of RNA regulation do not distinguish the separate contributions of these processes, little is known about how they are temporally integrated. Here we combine metabolic labeling of RNA at high temporal resolution with advanced RNA quantification and computational modeling to estimate RNA transcription and degradation rates during the response of mouse dendritic cells to lipopolysaccharide. We find that changes in transcription rates determine the majority of temporal changes in RNA levels, but that changes in degradation rates are important for shaping sharp 'peaked' responses. We used sequencing of the newly transcribed RNA population to estimate temporally constant RNA processing and degradation rates genome wide. Degradation rates vary significantly between genes and contribute to the observed differences in the dynamic response. Certain transcripts, including those encoding cytokines and transcription factors, mature faster. Our study provides a quantitative approach to study the integrative process of RNA regulation.Human Frontier Science Program (Strasbourg, France)Howard Hughes Medical InstituteBurroughs Wellcome Fund (Career Award at the Scientific Interface
A Phospholipidomic Analysis of All Defined Human Plasma Lipoproteins
Since plasma lipoproteins contain both protein and phospholipid components, either may be involved in processes such as atherosclerosis. In this study the identification of plasma lipoprotein-associated phospholipids, which is essential for understanding these processes at the molecular level, are performed. LC-ESI/MS, LC-ESI-MS/MS and High Performance Thin Layer Chromatography (HPTLC) analysis of different lipoprotein fractions collected from pooled plasma revealed the presence of phosphatidylethanolamine (PE), phosphatidylinositol (PI), and sphingomyeline (SM) only on lipoproteins and phosphatidylcholine (PC), Lyso-PC on both lipoproteins and plasma lipoprotein free fraction (PLFF). Cardiolipin, phosphatidylglycerol (PG) and Phosphatidylserine (PS) were observed neither in the lipoprotein fractions nor in PLFF. All three approaches led to the same results regarding phospholipids occurrence in plasma lipoproteins and PLFF. A high abundancy of PE and SM was observed in VLDL and LDL fractions respectively. This study provides for the first time the knowledge about the phospholipid composition of all defined plasma lipoproteins
Adult Romantic Attachment, Negative Emotionality, and Depressive Symptoms in Middle Aged Men: A Multivariate Genetic Analysis
Adult romantic attachment styles reflect ways of relating in close relationships and are associated with depression and negative emotionality. We estimated the extent to which dimensions of romantic attachment and negative emotionality share genetic or environmental risk factors in 1,237 middle-aged men in the Vietnam Era Twin Study of Aging (VETSA). A common genetic factor largely explained the covariance between attachment-related anxiety, attachment-related avoidance, depressive symptoms, and two measures of negative emotionality: Stress-Reaction (anxiety), and Alienation. Multivariate results supported genetic and environmental differences in attachment. Attachment-related anxiety and attachment-related avoidance were each influenced by additional genetic factors not shared with other measures; the genetic correlation between the attachment measure-specific genetic factors was 0.41, indicating some, but not complete overlap of genetic factors. Genetically informative longitudinal studies on attachment relationship dimensions can help to illuminate the role of relationship-based risk factors in healthy aging
Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals
Copy number variants (CNV) are established risk factors for neurodevelopmental disorders with seizures or epilepsy. With the hypothesis that seizure
disorders share genetic risk factors, we pooled CNV data from 10,590 individuals with seizure disorders, 16,109 individuals with clinically validated epilepsy, and 492,324 population controls and identified 25 genome-wide
significant loci, 22 of which are novel for seizure disorders, such as deletions at
1p36.33, 1q44, 2p21-p16.3, 3q29, 8p23.3-p23.2, 9p24.3, 10q26.3, 15q11.2, 15q12-
q13.1, 16p12.2, 17q21.31, duplications at 2q13, 9q34.3, 16p13.3, 17q12, 19p13.3,
20q13.33, and reciprocal CNVs at 16p11.2, and 22q11.21. Using genetic data
from additional 248,751 individuals with 23 neuropsychiatric phenotypes, we
explored the pleiotropy of these 25 loci. Finally, in a subset of individuals with
epilepsy and detailed clinical data available, we performed phenome-wide
association analyses between individual CNVs and clinical annotations categorized through the Human Phenotype Ontology (HPO). For six CNVs, we
identified 19 significant associations with specific HPO terms and generated,
for all CNVs, phenotype signatures across 17 clinical categories relevant for
epileptologists. This is the most comprehensive investigation of CNVs in epilepsy and related seizure disorders, with potential implications for clinical
practice
Protocol for investigating genetic determinants of posttraumatic stress disorder in women from the Nurses' Health Study II
<p>Abstract</p> <p>Background</p> <p>One in nine American women will meet criteria for the diagnosis of posttraumatic stress disorder (PTSD) in their lifetime. Although twin studies suggest genetic influences account for substantial variance in PTSD risk, little progress has been made in identifying variants in specific genes that influence liability to this common, debilitating disorder.</p> <p>Methods and design</p> <p>We are using the unique resource of the Nurses Health Study II, a prospective epidemiologic cohort of 68,518 women, to conduct what promises to be the largest candidate gene association study of PTSD to date. The entire cohort will be screened for trauma exposure and PTSD; 3,000 women will be selected for PTSD diagnostic interviews based on the screening data. Our nested case-control study will genotype1000 women who developed PTSD following a history of trauma exposure; 1000 controls will be selected from women who experienced similar traumas but did not develop PTSD.</p> <p>The primary aim of this study is to detect genetic variants that predict the development of PTSD following trauma. We posit inherited vulnerability to PTSD is mediated by genetic variation in three specific neurobiological systems whose alterations are implicated in PTSD etiology: the hypothalamic-pituitary-adrenal axis, the locus coeruleus/noradrenergic system, and the limbic-frontal neuro-circuitry of fear. The secondary, exploratory aim of this study is to dissect genetic influences on PTSD in the broader genetic and environmental context for the candidate genes that show significant association with PTSD in detection analyses. This will involve: conducting conditional tests to identify the causal genetic variant among multiple correlated signals; testing whether the effect of PTSD genetic risk variants is moderated by age of first trauma, trauma type, and trauma severity; and exploring gene-gene interactions using a novel gene-based statistical approach.</p> <p>Discussion</p> <p>Identification of liability genes for PTSD would represent a major advance in understanding the pathophysiology of the disorder. Such understanding could advance the development of new pharmacological agents for PTSD treatment and prevention. Moreover, the addition of PTSD assessment data will make the NHSII cohort an unparalleled resource for future genetic studies of PTSD as well as provide the unique opportunity for the prospective examination of PTSD-disease associations.</p
Anti-angiogenic therapy for cancer: Current progress, unresolved questions and future directions
Tumours require a vascular supply to grow and can achieve this via the expression of pro-angiogenic growth factors, including members of the vascular endothelial growth factor (VEGF) family of ligands. Since one or more of the VEGF ligand family is overexpressed in most solid cancers, there was great optimism that inhibition of the VEGF pathway would represent an effective anti-angiogenic therapy for most tumour types. Encouragingly, VEGF pathway targeted drugs such as bevacizumab, sunitinib and aflibercept have shown activity in certain settings. However, inhibition of VEGF signalling is not effective in all cancers, prompting the need to further understand how the vasculature can be effectively targeted in tumours. Here we present a succinct review of the progress with VEGF-targeted therapy and the unresolved questions that exist in the field: including its use in different disease stages (metastatic, adjuvant, neoadjuvant), interactions with chemotherapy, duration and scheduling of therapy, potential predictive biomarkers and proposed mechanisms of resistance, including paradoxical effects such as enhanced tumour aggressiveness. In terms of future directions, we discuss the need to delineate further the complexities of tumour vascularisation if we are to develop more effective and personalised anti-angiogenic therapies. © 2014 The Author(s)
What Do We Know About Neuropsychological Aspects Of Schizophrenia?
Application of a neuropsychological perspective to the study of schizophrenia has established a number of important facts about this disorder. Some of the key findings from the existing literature are that, while neurocognitive impairment is present in most, if not all, persons with schizophrenia, there is both substantial interpatient heterogeneity and remarkable within-patient stability of cognitive function over the long-term course of the illness. Such findings have contributed to the firm establishment of neurobiologic models of schizophrenia, and thereby help to reduce the social stigma that was sometimes associated with purely psychogenic models popular during parts of the 20th century. Neuropsychological studies in recent decades have established the primacy of cognitive functions over psychopathologic symptoms as determinants of functional capacity and independence in everyday functioning. Although the cognitive benefits of both conventional and even second generation antipsychotic medications appear marginal at best, recognition of the primacy of cognitive deficits as determinants of functional disability in schizophrenia has catalyzed recent efforts to develop targeted treatments for the cognitive deficits of this disorder. Despite these accomplishments, however, some issues remain to be resolved. Efforts to firmly establish the specific neurocognitive/neuropathologic systems responsible for schizophrenia remain elusive, as do efforts to definitively demonstrate the specific cognitive deficits underlying specific forms of functional impairment. Further progress may be fostered by recent initiatives to integrate neuropsychological studies with experimental neuroscience, perhaps leading to measures of deficits in cognitive processes more clearly associated with specific, identifiable brain systems
Seizure prediction : ready for a new era
Acknowledgements: The authors acknowledge colleagues in the international seizure prediction group for valuable discussions. L.K. acknowledges funding support from the National Health and Medical Research Council (APP1130468) and the James S. McDonnell Foundation (220020419) and acknowledges the contribution of Dean R. Freestone at the University of Melbourne, Australia, to the creation of Fig. 3.Peer reviewedPostprin
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