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Functions of idh1 and its mutation in the regulation of developmental hematopoiesis in zebrafish

BLOOD 2015年第19期125卷 2974-2984页

作者： Shi, Xiangguo He, Bai-Liang Ma, Alvin C. H. Guo, Yuhan Chi, Yali Man, Cheuk Him Zhang, Wenqing Zhang, Yiyue Wen, Zilong Cheng, Tao Leung, Anskar Y. H. Univ Hong Kong Li Ka Shing Fac Med Div Haematol Dept Med Pokfulam Hong Kong Peoples R China Southern Med Univ Dept Cell Biol Guangzhou Guangdong Peoples R China Hong Kong Univ Sci & Technol Div Life Sci State Key Lab Mol Neurosci Kowloon Hong Kong Peoples R China Chinese Acad Med Sci Inst Hematol State Key Lab Expt Hematol Tianjin Peoples R China Chinese Acad Med Sci Blood Dis Hosp Tianjin Peoples R China Peking Union Med Coll Tianjin Peoples R China Chinese Acad Med Sci Ctr Stem Cell Med Beijing 100730 Peoples R China

Isocitrate dehydrogenase 1 mutation (IDH1-R132H) was recently identified in acute myeloid leukemia with normal cytogenetics. The mutant enzyme is thought to convert a-ketoglutarate to the pathogenic 2-hydroxyglutarate (2-HG) that affects DNA methylation via inhibition of ten-eleven translocation 2. However, the role of wild-type IDH1 in normal hematopoiesis and its relevance to acute myeloid leukemia is unknown. Here we showed that zebrafish idh1 (zidh1) knockdown by morpholino and targeted mutagenesis by transcription activator-like effector nuclease might induce blockade in myeloid differentiation, as evident by an increase in pu.1 and decrease in mpo, l-plastin, and mpeg1 expression, and significantly reduce definitive hematopoiesis. Morpholino knockdown of zidh2 also induced a blockade in myeloid differentiation but definitive hematopoiesis was not affected. The hematopoietic phenotype of zidh1 knock down was not rescuable by zidh2 messenger RNA, suggesting nonredundant functions. Overexpression of human IDH1-R132H or its zebrafish ortholog resulted in 2-HG elevation and expansion of myelopoiesis in zebrafish embryos. A human IDH1-R132H-specific inhibitor (AGI-5198) significantly ameliorated both hematopoietic and 2-HG responses in human but not zebrafish IDH1 mutant expression. The results provided important insights to the role of zidh1 in myelopoiesis and definitive hematopoiesis and of IDH1-R132H in leukemogenesis.

关键词： Animals Animals, Genetically Modified Animals, Genetically Modified Benzeneacetamides/pharmacology Blotting, Western Blotting, Western Cells, Cultured Embryo, Nonmammalian/cytology Embryo, Nonmammalian/drug effects Embryo, Nonmammalian/metabolism Enzyme-Linked Immunosorbent Assay Enzyme-Linked Immunosorbent Assay Flow Cytometry Flow Cytometry Gas Chromatography-Mass Spectrometry Glutarates/metabolism Hematopoiesis/physiology Humans image processing, computer-assisted Imidazoles/pharmacology Immunoenzyme Techniques Immunoenzyme Techniques Isocitrate Dehydrogenase/antagonists & inhibitors Isocitrate Dehydrogenase/antagonists & inhibitors Isocitrate Dehydrogenase/genetics Isocitrate Dehydrogenase/genetics Isocitrate Dehydrogenase/metabolism Isocitrate Dehydrogenase/metabolism Mutagenesis, Site-Directed Mutation/genetics Myelopoiesis/physiology Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger/genetics Zebrafish/genetics Zebrafish/growth & development Zebrafish/metabolism

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Usefulness of Low-dose Nonenhanced Computed Tomography With Iterative Reconstruction for Evaluation of Urolithiasis: Diagnostic Performance and Agreement between the Urologist and the Radiologist

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UROLOGY 2015年第3期85卷 531-538页

作者： Kwon, Jong Kyou Chang, In Ho Moon, Young Tae Lee, Jong Beum Park, Hyun Jeong Park, Sung Bin Chung Ang Univ Coll Med Chung Ang Univ Hosp Dept Urol Seoul 156756 South Korea Chung Ang Univ Coll Med Chung Ang Univ Hosp Dept Radiol Seoul 156756 South Korea

OBJECTIVE To evaluate the efficacy of low-dose nonenhanced computed tomography (LDCT) with iterative reconstruction (IR) technique for urologists to detect urolithiasis by comparing diagnostic performance and interobserver agreement between the urologist and the uroradiologist. PATIENTS AND METHODS We evaluated the 116 patients with urinary stones (n = 197) using both conventional-dose nonenhanced computed tomography (CT) using filtered back projection (CDCT-FBP) and LDCT-IR. Scans were interpreted for stone characteristics, objective image noise, and subjective image assessment. Diagnostic performance and interobserver agreement of LDCT-IR were assessed between 1 urologist and 1 radiologist. RESULTS There were no significant differences in all stones. The average effective dose (mSV) in the all size groups was 5.92 (CDCT-FBP) and 1.39 (LDCT-IR), respectively (P < .001). The average effective dose reduction rate was 76.6%, allowing minimal additional radiation exposure from simultaneous CT. Objective image noise was higher in LDCT-IR (20.0-26.2;P < .01), but there was no significant difference in the Hounsfield unit between both CT protocols (52.3 and 56.7;P = .103). There were no cases of any unacceptable images in subjective image assessment. The sensitivity and specificity of LDCT-IR were 99.1%-100.0% with a diagnostic accuracy of 99.1%-100% for stones >= 3 mm. Diagnostic performance was similar between the urologist and the radiologist. Interobserver agreement of LDCT-IR between the 2 reviewers was high with kappa values (0.901-1.000). CONCLUSION LDCT-IR provided an excellent diagnostic performance and interobserver agreement between the urologist and the uroradiologist, reducing radiation exposure significantly;in real settings, the urologist should consider replacing LDCT-IR as the standard examination for detecting urolithiasis. (C) 2015 Elsevier Inc.

关键词： Humans image processing, computer-assisted Kidney Calculi/radiography Observer Variation Prospective Studies Radiation Dosage Radiation Dosage Radiology/statistics & numerical data Tomography, X-Ray Computed/methods Ureteral Calculi/radiography Urolithiasis/radiography Urology/statistics & numerical data

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Pharyngeal electrical stimulation can modulate swallowing in cortical processing and behavior - Magnetoencephalographic evidence

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NEUROimage 2015年 104卷 117-124页

作者： Suntrup, Sonja Teismann, Inga Wollbrink, Andreas Winkels, Martin Warnecke, Tobias Pantev, Christo Dziewas, Rainer Univ Munster Dept Neurol D-48149 Munster Germany Univ Munster Inst Biomagnetism & Biosignalanal D-48149 Munster Germany

Background: The act of swallowing is a complex neuromuscular function that is processed in a distributed network involving cortical, subcortical and brainstem structures. Difficulty in swallowing arises from a variety of neurologic diseases for which therapeutic options are currently limited. Pharyngeal electrical stimulation (PES) is a novel intervention designed to promote plastic changes in the pharyngeal motor cortex to aid dysphagia rehabilitation. In the present study we evaluate the effect of PES on cortical swallowing network activity and associated changes in swallowing performance. Methods: In a randomized, crossover study design 10 min of real (0.2-ms pulses, 5Hz, 280 V, stimulation intensity at 75% of maximum tolerated threshold) or sham PES were delivered to 14 healthy volunteers in two separate sessions. Stimulation was delivered via a pair of bipolar ring electrodes mounted on an intraluminal catheter positioned in the pharynx. Before and after each intervention swallowing capacity (ml/s) was tested using a 150 ml-water swallowing stress test. Event-related desynchronization (ERD) of cortical oscillatory activity during volitional swallowing was recorded applying whole-head magnetoencephalography before, immediately after and 45 min past the intervention. Results: A prominent reduction of ERD in sensorimotor brain areas occurred in the alpha and beta frequency ranges immediately after real PES but not after sham stimulation (p < 0.05) and had faded after 45 min. Volume per swallow and swallowing capacity significantly increased following real stimulation only. Conclusion: Attenuation of ERD following PES reflects stimulation-induced increased swallowing processing efficiency, which is associated with subtle changes in swallowing function in healthy subjects. Our data contribute evidence that swallowing network organization and behavior can effectively be modulated by PES. (C) 2014 Elsevier Inc. All rights reserved.

关键词： Adult Behavior/physiology Cross-Over Studies Deglutition/physiology Electric Stimulation Electromyography Evoked Potentials/physiology Female Humans image processing, computer-assisted Magnetoencephalography Magnetoencephalography Male Motor Cortex/physiology Pharynx/physiology

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High resolution whole brain diffusion imaging at 7 T for the Human Connectome Project

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NEUROimage 2015年 122卷 318-331页

作者： Vu, A. T. Auerbach, E. Lenglet, C. Moeller, S. Sotiropoulos, S. N. Jbabdi, S. Andersson, J. Yacoub, E. Ugurbil, K. Univ Minnesota Ctr Magnet Resonance Res Minneapolis MN 55455 USA Univ Oxford Ctr Funct Magnet Resonance Imaging Brain FMRIB Oxford OX1 2JD England

Mapping structural connectivity in healthy adults for the Human Connectome Project (HCP) benefits from high quality, high resolution, multiband (MB)-accelerated whole brain diffusion MRI (dMRI). Acquiring such data at ultrahigh fields (7 T and above) can improve intrinsic signal-to-noise ratio (SNR), but suffers from shorter T-2 and T-2. relaxation times, increased B-1(+) inhomogeneity (resulting in signal loss in cerebellar and temporal lobe regions), and increased power deposition (i.e. specific absorption rate (SAR)), thereby limiting our ability to reduce the repetition time (TR). Here, we present recent developments and optimizations in 7 T image acquisitions for the HCP that allow us to efficiently obtain high quality, high resolution whole brain in-vivo dMRI data at 7 T. These data show spatial details typically seen only in ex-vivo studies and complement already very high quality 3 T HCP data in the same subjects. The advances are the result of intensive pilot studies aimed at mitigating the limitations of dMRI at 7 T. The data quality and methods described here are representative of the datasets that will be made freely available to the community in 2015. (C) 2015 Elsevier Inc. All rights reserved.

关键词： Artifacts Brain/anatomy & histology Connectome/methods Diffusion Magnetic Resonance Imaging/methods Humans image processing, computer-assisted Signal processing, computer-assisted Signal-To-Noise Ratio

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Precision and neuronal dynamics in the human posterior parietal cortex during evidence accumulation

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NEUROimage 2015年 107卷 219-228页

作者： FitzGerald, Thomas H. B. Moran, Rosalyn J. Friston, Karl J. Dolan, Raymond J. Wellcome Trust Ctr Neuroimaging London WC1N 3BG England Virginia Tech Caril Res Inst Roanoke VA USA Bradley Dept Elect & Comp Engn Roanoke VA USA

Primate studies show slow ramping activity in posterior parietal cortex (PPC) neurons during perceptual decision-making. These findings have inspired a rich theoretical literature to account for this activity. These accounts are largely unrelated to Bayesian theories of perception and predictive coding, a related formulation of perceptual inference in the cortical hierarchy. Here, we tested a key prediction of such hierarchical inference, namely that the estimated precision (reliability) of information ascending the cortical hierarchy plays a key role in determining both the speed of decision-making and the rate of increase of PPC activity. Using dynamic causal modelling of magnetoencephalographic (MEG) evoked responses, recorded during a simple perceptual decision-making task, we recover ramping-activity from an anatomically and functionally plausible network of regions, including early visual cortex, the middle temporal area (MT) and PPC. Precision, as reflected by the gain on pyramidal cell activity, was strongly correlated with both the speed of decision making and the slope of PPC ramping activity. Our findings indicate that the dynamics of neuronal activity in the human PPC during perceptual decision-making recapitulate those observed in the macaque, and in so doing we link observations from primate electrophysiology and human choice behaviour. Moreover, the synaptic gain control modulating these dynamics is consistent with predictive coding formulations of evidence accumulation. (C) 2014 The Authors. Published by Elsevier Inc.

关键词： Adult Decision Making/physiology Discrimination (Psychology)/physiology Female Humans image processing, computer-assisted Magnetoencephalography Magnetoencephalography Male Neurons/physiology Parietal Lobe/cytology Parietal Lobe/physiology Photic Stimulation Psychomotor Performance/physiology Pyramidal Cells/physiology Reaction Time/physiology Temporal Lobe/physiology Visual Cortex/physiology Visual Perception/physiology Young Adult

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Anatomy of the Femoral Footprint of the Posterior Cruciate Ligament: A Systematic Review

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ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY 2015年第2期31卷 345-354页

作者： Narvy, Steven J. Pearl, Matthew Vrla, Michael Yi, Anthony Hatch, George F. Rick, III Univ So Calif Keck Sch Med Dept Orthopaed Surg Los Angeles CA 90089 USA

Purpose: The purpose of this study was to summarize the past 10 years of orthopaedic literature to better delineate the femoral origin of the posterior cruciate ligament (PCL). Methods: A PubMed search was conducted by 2 independent reviewers (M.P., M.V.) using the search terms "posterior cruciate ligament"or "PCL," "femur" or "femoral," and "anatomy" or "origin" or "footprint."Cadaveric and radiographic studies performed between January 1, 2003, and November 30, 2013, were analyzed. Results: Aggregate data from radiographic parameters indicate that the anatomic origin of the anterolateral bundle lies 40% of the distance from the anterior articular surface of the femur and 14.5% of the tangent distance from the Blumensaat line toward the intercondylar notch. The origin of the posteromedial bundle lies 56% from the anterior surface and 36.5% of the tangent distance toward the notch. On the basis of cadaveric data, the center of the anterolateral bundle is 8 mm from the anterior surface (27.5% of the Blumensaat line), 4.7 mm tangent from the Blumensaat line toward the notch (22.5% of the tangent distance), and 3.6 mm from the medial intercondylar ridge;the center of the posteromedial bundle is 11.9 mm from the anterior articular surface (42.5%), 10.9 mm along the tangent line (57.5%), and 3.1 mm from the medial intercondylar ridge. Conclusions: We were able to precisely delineate the femoral origin of the PCL through our systematic review. Clinical Relevance: Our systematic review may assist arthroscopic knee surgeons in placing anatomic tunnels during reconstruction of the PCL.

关键词： Body Weights and Measures Cadaver Dissection Dissection Femur/anatomy & histology Femur/radiography Femur/surgery Humans image processing, computer-assisted Knee Joint/anatomy & histology Knee Joint/radiography Knee Joint/surgery Posterior Cruciate Ligament/anatomy & histology Posterior Cruciate Ligament/radiography Posterior Cruciate Ligament/surgery

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Journal Club: Real-Time Magnetic Resonance-Guided Stereotactic Laser Amygdalohippocampotomy for Mesial Temporal Lobe Epilepsy

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NEUROSURGERY 2015年第2期77卷 307-309页

作者： Meng, Ying Suppiah, Suganth Mansouri, Alireza Univ Toronto Div Neurosurg Toronto ON Canada Univ Hlth Network Toronto Western Hosp Toronto ON Canada McMaster Univ Dept Clin Epidemiol & Biostat Hamilton ON Canada

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Ceiba: scalable visualization of phylogenies and 2D/3D image collections

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BIOINFORMATICS 2014年第17期30卷 2506-2507页

作者： Sanderson, Michael J. Univ Arizona Dept Ecol & Evolutionary Biol Tucson AZ 85721 USA

A Summary: Phylogenetic trees with hundreds of thousands of leaves are now being inferred from sequence data, posing significant challenges for visualization and exploratory analysis. image data supplying valuable context for species in trees (and cues for exploring them) are becoming increasingly available in biodiversity databases and elsewhere but have rarely been built into tree visualization software in a scalable way. Ceiba lets the user explore large trees and inspect image collection arrays (sets of 'homologous' images) comprising mixtures of 2D and 3D image objects. Ceiba exploits recent improvements in graphics hardware, OpenGL toolkits and many standard high-performance computer graphics strategies, such as texture compression, level of detail control, culling, animations and image caching. Its tree layouts can be tuned by user-provided phylogenetic definitions of subtrees. The code has been extensively tested on phylogenies of up to 55 000 leaves and images.

关键词： computer Graphics image processing, computer-assisted Imaging, Three-Dimensional Phylogeny Phylogeny Software User-computer Interface

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Laser Scanning Microscopy and Quantitative image Analysis of Neuronal Tissue 1

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丛书名： Neuromethods 87

2014年

作者： Lidia Bakota Roland Brandt (eds.)

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The salience network is responsible for switching between the default mode network and the central executive network: Replication from DCM

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NEUROimage 2014年 99卷 180-190页

作者： Goulden, Nia Khusnulina, Aygul Davis, Nicholas J. Bracewell, Robert M. Bokde, Arun L. McNulty, Jonathan P. Mullins, Paul G. Bangor Univ Bangor Gwynedd Wales Swansea Univ Swansea W Glam Wales Univ Dublin Trinity Coll Dublin 2 Ireland Univ Coll Dublin Dublin 2 Ireland

With the advent of new analysis methods in neuroimaging that involve independent component analysis (ICA) and dynamic causal modelling (DCM), investigations have focused on measuring both the activity and connectivity of specific brain networks. In this study we combined DCM with spatial ICA to investigate network switching in the brain. Using time courses determined by ICA in our dynamic causal models, we focused on the dynamics of switching between the default mode network (DMN), the network which is active when the brain is not engaging in a specific task, and the central executive network (CEN), which is active when the brain is engaging in a task requiring attention: Previous work using Granger causality methods has shown that regions of the brain which respond to the degree of subjective salience of a stimulus, the salience network, are responsible for switching between the DMN and the CEN (Sridharan et al., 2008). In this work we apply DCM to ICA time courses representing these networks in resting state data. In order to test the repeatability of our work we applied this to two independent datasets. This work confirms that the salience network drives the switching between default mode and central executive networks and that our novel technique is repeatable. Crown Copyright (C) 2014 Published by Elsevier Inc All rights reserved.

关键词： Adult Bayes Theorem Brain Mapping/methods Brain Mapping/methods Data Interpretation, Statistical Executive Function/physiology Female Humans image processing, computer-assisted Magnetic Resonance Imaging/methods Male Models, Neurological Nerve Net/physiology Rest/physiology Stochastic Processes

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