Nuclear pore assembly proceeds by an inside-out extrusion of the nuclear envelope

The nuclear pore complex (NPC) mediates nucleocytoplasmic transport through the nuclear envelope. How the NPC assembles into this double membrane boundary has remained enigmatic. Here, we captured temporally staged assembly intermediates by correlating live cell imaging with high-resolution electron tomography and super-resolution microscopy. Intermediates were dome-shaped evaginations of the inner nuclear membrane (INM), that grew in diameter and depth until they fused with the flat outer nuclear membrane. Live and super-resolved fluorescence microscopy revealed the molecular maturation of the intermediates, which initially contained the nuclear and cytoplasmic ring component Nup107, and only later the cytoplasmic filament component Nup358. EM particle averaging showed that the evagination base was surrounded by an 8-fold rotationally symmetric ring structure from the beginning and that a growing mushroomshaped density was continuously associated with the deforming membrane. Quantitative structural analysis revealed that interphase NPC assembly proceeds by an asymmetric inside-out extrusion of the INM

A four-gene LincRNA expression signature predicts risk in multiple cohorts of acute myeloid leukemia patients.

Prognostic gene expression signatures have been proposed as clinical tools to clarify therapeutic options in acute myeloid leukemia (AML). However, these signatures rely on measuring large numbers of genes and often perform poorly when applied to independent cohorts or those with older patients. Long intergenic non-coding RNAs (lincRNAs) are emerging as important regulators of cell identity and oncogenesis, but knowledge of their utility as prognostic markers in AML is limited. Here we analyze transcriptomic data from multiple cohorts of clinically annotated AML patients and report that (i) microarrays designed for coding gene expression can be repurposed to yield robust lincRNA expression data, (ii) some lincRNA genes are located in close proximity to hematopoietic coding genes and show strong expression correlations in AML, (iii) lincRNA gene expression patterns distinguish cytogenetic and molecular subtypes of AML, (iv) lincRNA signatures composed of three or four genes are independent predictors of clinical outcome and further dichotomize survival in European Leukemia Net (ELN) risk groups and (v) an analytical tool based on logistic regression analysis of quantitative PCR measurement of four lincRNA genes (LINC4) can be used to determine risk in AML

Inter-hemispheric EEG coherence analysis in Parkinson's disease : Assessing brain activity during emotion processing

Parkinson’s disease (PD) is not only characterized by its prominent motor symptoms but also associated with disturbances in cognitive and emotional functioning. The objective of the present study was to investigate the influence of emotion processing on inter-hemispheric electroencephalography (EEG) coherence in PD. Multimodal emotional stimuli (happiness, sadness, fear, anger, surprise, and disgust) were presented to 20 PD patients and 30 age-, education level-, and gender-matched healthy controls (HC) while EEG was recorded. Inter-hemispheric coherence was computed from seven homologous EEG electrode pairs (AF3–AF4, F7–F8, F3–F4, FC5–FC6, T7–T8, P7–P8, and O1–O2) for delta, theta, alpha, beta, and gamma frequency bands. In addition, subjective ratings were obtained for a representative of emotional stimuli. Interhemispherically, PD patients showed significantly lower coherence in theta, alpha, beta, and gamma frequency bands than HC during emotion processing. No significant changes were found in the delta frequency band coherence. We also found that PD patients were more impaired in recognizing negative emotions (sadness, fear, anger, and disgust) than relatively positive emotions (happiness and surprise). Behaviorally, PD patients did not show impairment in emotion recognition as measured by subjective ratings. These findings suggest that PD patients may have an impairment of inter-hemispheric functional connectivity (i.e., a decline in cortical connectivity) during emotion processing. This study may increase the awareness of EEG emotional response studies in clinical practice to uncover potential neurophysiologic abnormalities

A new family of diprotodontian marsupials from the latest Oligocene of Australia and the evolution of wombats, koalas, and their relatives (Vombatiformes)

We describe the partial cranium and skeleton of a new diprotodontian marsupial from the late Oligocene (~26–25 Ma) Namba Formation of South Australia. This is one of the oldest Australian marsupial fossils known from an associated skeleton and it reveals previously unsuspected morphological diversity within Vombatiformes, the clade that includes wombats (Vombatidae), koalas (Phascolarctidae) and several extinct families. Several aspects of the skull and teeth of the new taxon, which we refer to a new family, are intermediate between members of the fossil family Wynyardiidae and wombats. Its postcranial skeleton exhibits features associated with scratch-digging, but it is unlikely to have been a true burrower. Body mass estimates based on postcranial dimensions range between 143 and 171 kg, suggesting that it was ~5 times larger than living wombats. Phylogenetic analysis based on 79 craniodental and 20 postcranial characters places the new taxon as sister to vombatids, with which it forms the superfamily Vombatoidea as defined here. It suggests that the highly derived vombatids evolved from wynyardiid-like ancestors, and that scratch-digging adaptations evolved in vombatoids prior to the appearance of the ever-growing (hypselodont) molars that are a characteristic feature of all post-Miocene vombatids. Ancestral state reconstructions on our preferred phylogeny suggest that bunolophodont molars are plesiomorphic for vombatiforms, with full lophodonty (characteristic of diprotodontoids) evolving from a selenodont morphology that was retained by phascolarctids and ilariids, and wynyardiids and vombatoids retaining an intermediate selenolophodont condition. There appear to have been at least six independent acquisitions of very large (>100 kg) body size within Vombatiformes, several having already occurred by the late Oligocene

An exploratory study of the relationship between parental attitudes and behaviour and young people's consumption of alcohol

Background Concern is growing regarding frequent and excessive misuse of alcohol by young people. The average age at which young people in Europe start to drink is twelve and a half, and during the last decade, the quantity of alcohol consumed by younger adolescents in the UK has increased. Families are known to play an important role in shaping young people's alcohol misuse, although family risk and protective factors associated with misuse in a UK context are in need of further investigation. Methods The study used a cross-sectional design, involving secondary analyses of self-completion questionnaire responses from 6,628 secondary school children (i.e. aged 11-16 years), from 12 schools within an urban location in Wales. Items relating to family functioning and perceived parental attitudes were first subjected to factor analysis. Associations of family closeness and conflict, parental monitoring and attitudes and family history of substance misuse with children's self reported alcohol consumption were examined using logistic regression analyses. Results Approximately three quarters of respondents reported having tried alcohol, most of whom had first tried alcohol aged 12 or under. Parental monitoring and family closeness were positively correlated with one another and were both associated with significantly lower levels of drinking behaviours. Family violence and conflict, more liberal parental attitudes towards substance use and towards alcohol and petty crime, and family history of substance misuse were positively correlated with one another and with higher levels of drinking behaviours. Parental monitoring was identified as the family functioning factor most consistently associated with drinking behaviour in multivariate analyses. Conclusions Significant relationships were found between young people's drinking behaviours and perceptions of risk and protective factors in the family environment. Parental monitoring was strongly associated with family closeness and appeared to form one part of a parenting style of more general communication and regulation of children's behaviour. Findings support the need for alcohol misuse prevention interventions which address risk and protective factors within the family setting. Timing of such prevention work should be related both to the development of family relationships and the age at which young people begin drinking alcohol

Finite-element-method (FEM) model generation of time-resolved 3D echocardiographic geometry data for mitral-valve volumetry

INTRODUCTION: Mitral Valve (MV) 3D structural data can be easily obtained using standard transesophageal echocardiography (TEE) devices but quantitative pre- and intraoperative volume analysis of the MV is presently not feasible in the cardiac operation room (OR). Finite element method (FEM) modelling is necessary to carry out precise and individual volume analysis and in the future will form the basis for simulation of cardiac interventions. METHOD: With the present retrospective pilot study we describe a method to transfer MV geometric data to 3D Slicer 2 software, an open-source medical visualization and analysis software package. A newly developed software program (ROIExtract) allowed selection of a region-of-interest (ROI) from the TEE data and data transformation for use in 3D Slicer. FEM models for quantitative volumetric studies were generated. RESULTS: ROI selection permitted the visualization and calculations required to create a sequence of volume rendered models of the MV allowing time-based visualization of regional deformation. Quantitation of tissue volume, especially important in myxomatous degeneration can be carried out. Rendered volumes are shown in 3D as well as in time-resolved 4D animations. CONCLUSION: The visualization of the segmented MV may significantly enhance clinical interpretation. This method provides an infrastructure for the study of image guided assessment of clinical findings and surgical planning. For complete pre- and intraoperative 3D MV FEM analysis, three input elements are necessary: 1. time-gated, reality-based structural information, 2. continuous MV pressure and 3. instantaneous tissue elastance. The present process makes the first of these elements available. Volume defect analysis is essential to fully understand functional and geometrical dysfunction of but not limited to the valve. 3D Slicer was used for semi-automatic valve border detection and volume-rendering of clinical 3D echocardiographic data. FEM based models were also calculated. METHOD: A Philips/HP Sonos 5500 ultrasound device stores volume data as time-resolved 4D volume data sets. Data sets for three subjects were used. Since 3D Slicer does not process time-resolved data sets, we employed a standard movie maker to animate the individual time-based models and visualizations. Calculation time and model size were minimized. Pressures were also easily available. We speculate that calculation of instantaneous elastance may be possible using instantaneous pressure values and tissue deformation data derived from the animated FEM

How important is the context of an adolescent's first alcoholic drink? Evidence that parental provision may reduce later heavy episodic drinking

Objective: This study examined the extent to which a retrospective measure of parental provision of the first alcoholic beverage was related to current heavy episodic drinking and current responsible drinking practices. Sample: 608 14- to 17-year-olds from the 2007 Australian National Drug Strategy Household Survey. Measures: Source of first alcoholic beverage (friends/parents/others), source of current alcohol, age of onset of alcohol use, current responsible drinking practices, and proportion of current friends who drink. Results: Binary logistic and multiple regression procedures revealed that parental provision of an adolescent's first alcoholic beverage predicted lower current heavy episodic drinking, and responsible drinking mediated this association. Discussion: The results suggested that for adolescents who become alcohol users, parental provision of the first drink may reduce subsequent alcohol-related risks compared to introduction to alcohol by friends and other sources. Alcohol-related risks remain significant for adolescents who consume alcohol, independent of who is the provider. Copyright (C) 2012 S. Karger AG, Base

Feasibility studies of the time-like proton electromagnetic form factor measurements with PANDA at FAIR

The possibility of measuring the proton electromagnetic form factors in the time-like region at FAIR with the \PANDA detector is discussed. Detailed simulations on signal efficiency for the annihilation of $\bar p +p$ into a lepton pair as well as for the most important background channels have been performed. It is shown that precision measurements of the differential cross section of the reaction $\bar p +p \to e^++ e^-$ can be obtained in a wide angular and kinematical range. The individual determination of the moduli of the electric and magnetic proton form factors will be possible up to a value of momentum transfer squared of $q^2\simeq 14$ (GeV/c)$^2$. The total $\bar p +p\to e^++e^-$ cross section will be measured up to $q^2\simeq 28$ (GeV/c)$^2$. The results obtained from simulated events are compared to the existing data. Sensitivity to the two photons exchange mechanism is also investigated.Comment: 12 pages, 4 tables, 8 figures Revised, added details on simulations, 4 tables, 9 figure

Microsurgical and tractographic anatomical study of insular and transsylvian transinsular approach

This study is to define the operative anatomy of the insula with emphasis on the transsylvian transinsular approach. The anatomy was studied in 15 brain specimens, among five were dissected by use of fiber dissection technique; diffusion tensor imaging of 10 healthy volunteers was obtained with a 1.5-T MR system. The temporal stem consists mainly of the uncinate fasciculus, inferior occipitofrontal fasciculus, Meyer’s loop of the optic radiation and anterior commissure. The transinsular approach requires an incision of the inferior limiting sulcus. In this procedure, the fibers of the temporal stem can be interrupted to various degrees. The fiber dissection technique is a very relevant and reliable method for neurosurgeons to study the details of brain anatomic features. The DTI fiber tracking technique can identify the fiber tracts of the temporal stem. Moreover, it will also help further functional study of human insula