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Bubblegrams Reveal the Inner Body of Bacteriophage φKZ

SCIENCE 2012年第6065期335卷 182-182页

作者： Wu, Weimin Thomas, Julie A. Cheng, Naiqian Black, Lindsay W. Steven, Alasdair C. Natl Inst Arthrit & Musculoskeletal & Skin Dis NI Struct Biol Lab NIH Bethesda MD 20892 USA Univ Maryland Sch Med Dept Biochem & Mol Biol Baltimore MD 21201 USA

Dense packing of macromolecules in cellular compartments and higher-order assemblies makes it difficult to pick out even quite large components in electron micrographs, despite nominally high resolution. Immunogold labeling and histochemical procedures offer ways to map certain components but are limited in their applicability. Here, we present a differential mapping procedure, based on the physical principle of protein’s greater sensitivity to radiation damage compared with that of nucleic acid.

关键词： Capsid/ultrastructure Cryoelectron Microscopy DNA, Viral image processing, computer-assisted Nucleocapsid/ultrastructure Pseudomonas Phages/chemistry Pseudomonas Phages/radiation effects Pseudomonas Phages/ultrastructure Viral Proteins/analysis

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Biomedical Signal and image processing

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IEEE PULSE 2011年第3期2卷 41-54页

作者： Cerutti, Sergio Baselli, Giuseppe Bianchi, Anna Maria Caiani, Enrico Contini, Davide Cubeddu, Rinaldo Dercole, Fabio Di Rienzo, Luca Liberati, Diego Mainardi, Luca Ravazzani, Paolo Rinaldi, Sergio Signorini, Maria Gabriella Torricelli, Alessandro Politecn Milan Dipartimento Bioingn I-20133 Milan Italy Politecn Milan Dipartimento Fis I-20133 Milan Italy Politecn Milan Dipartimento Elettron & Informaz I-20133 Milan Italy Politecn Milan Dipartimento Elettrotecn I-20133 Milan Italy CNR Ist Elettron & Ingn Informaz & Telecomunicaz I-20133 Milan Italy Ist Nazl Fis Nucl I-20133 Milan Italy CNR Ist Ingn Biomed I-20133 Milan Italy

Generally, physiological modeling and biomedical signal processing constitute two important paradigms of biomedical engineering (BME): their fundamental concepts are taught starting from undergraduate studies and are more completely dealt with in the last years of graduate curricula, as well as in Ph.D. courses. Traditionally, these two cultural aspects were separated, with the first one more oriented to physiological issues and how to model them and the second one more dedicated to the development of processing tools or algorithms to enhance useful information from clinical data. A practical consequence was that those who did models did not do signal processing and vice versa. However, in recent years,the need for closer integration between signal processing and modeling of the relevant biological systems emerged very clearly [1], [2]. This is not only true for training purposes(i.e., to properly prepare the new professional members of BME) but also for the development of newly conceived research projects in which the integration between biomedical signal and image processing (BSIP) and modeling plays a crucial role. Just to give simple examples, topics such as brain–computer machine or interfaces,neuroengineering, nonlinear dynamical analysis of the cardiovascular (CV) system,integration of sensory-motor characteristics aimed at the building of advanced prostheses and rehabilitation tools, and wearable devices for vital sign monitoring and others do require an intelligent fusion of modeling and signal processing competences that are certainly peculiar of our discipline of BME.

关键词： Algorithms Biomedical Engineering Diagnostic Imaging Electrodiagnosis Humans image Interpretation, computer-assisted image processing, computer-assisted Models, Biological Signal processing, computer-assisted

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A comparison of high definition-image enhanced colonoscopy and standard white-light colonoscopy for colorectal polyp detection

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ENDOSCOPY 2011年第12期43卷 1045-1051页

作者： Gross, S. A. Buchner, A. M. Crook, J. E. Cangemi, J. R. Picco, M. F. Wolfsen, H. C. DeVault, K. R. Loeb, D. S. Raimondo, M. Woodward, T. A. Wallace, M. B. Mayo Clin Div Gastroenterol & Hepatol Jacksonville FL 32224 USA Mayo Clin Biostat Unit Jacksonville FL 32224 USA

Background and study aims: Colonoscopy is widely used to detect and remove precancerous polyps, but fails to detect some polyps. Recent studies evaluating different image-enhanced methods have revealed conflicting results. The efficacy of colonoscopy imaging with simultaneous use of commercially available improvements, including high definition narrow band imaging (HD-NBI), and monochromatic charge-coupled device (CCD) video, was compared with a widely used standard definition white light (SDWL) colonoscopy system for detecting colorectal polyps. The primary aim was to determine whether the combination of image-enhanced colonoscopy systems resulted in fewer missed polyps compared with conventional colonoscopy. Patients and methods: In a randomized controlled trial (***. study number NCT00825292) patients having routine screening and surveillance underwent tandem colonoscopies with SDWL and image-enhanced (HD-NBI) colonoscopy. The main outcome measurement was the per-polyp false-negative ("miss") rate. Secondary outcomes were adenoma miss rate, and per-patient polyp and adenoma miss rates. Results: 100 patients were randomized and 96 were included in the analysis. In total, 177 polyps were detected;of these, 72 (41 %) were adenomatous. Polyp and adenoma miss rates for SDWL colonoscopy were 57% (60/105) and 49% (19/39);those for image-enhanced colonoscopy were 31% (22/72) and 27% (9/33) (P = 0.005 and P = 0.036 for polyps and adenomas, respectively). image-enhanced and SDWL approaches had similar per-patient miss rates for polyps (6/35 vs. 9/32, P = 0.27) and adenomas (4/22 vs. 8/20, P = 0.11). Conclusions: Utilization of multiple recent improvements in image-enhanced colonoscopy was associated with a reduced miss rate for all polyps and for adenomatous polyps. It is not known which individual feature or combination of image-enhancement features led to the improvement.

关键词： Aged Colonic Polyps/diagnosis Colonoscopy/methods Female Humans image Enhancement image processing, computer-assisted Male Middle Aged Precancerous Conditions/diagnosis

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Making a Tool of an Artifact: The Application of Photoinduced Lo Domains in Giant Unilamellar Vesicles to the Study of Lo/Ld Phase Spinodal Decomposition and Its Modulation by the Ganglioside GM1

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LANGMUIR 2011年第24期27卷 15074-15082页

作者： Staneva, Galya Seigneuret, Michel Conjeaud, Helene Puff', Nicolas Angeova, Miglena I. Univ Paris Diderot UMR 7057 Paris France CNRS Paris France Bulgarian Acad Sci Inst Biophys & Biomed Engn Sofia Bulgaria Univ Paris 06 UPMC Dept Phys UFR 925 Paris France

Electroformed giant unilamellar vesicles containing liquid-ordered Lo domains are important tools for the modeling of the physicochemical properties and biological functions of lipid rafts. Lo domains are usually imaged using fluorescence microscopy of differentially phase-partionioning membrane-embedded probes. Recently, it has been shown that these probes also have a photosensitizing effect that leads to lipid chemical modification during the fluorescence microscopy experiments. Moreover, the lipid reaction products are able as such to promote Lo microdomain formation, leading to potential artifacts. We show here that this photoinduced effect can also purposely be used as a new approach to study Lo microdomain formation in giant unilamellar vesicles. Photosensitized lipid modification can promote Lo microdomain appearance and growth uniformly and on a faster time scale, thereby yielding new information on such processes. For instance, in egg phosphatidylcholine/egg sphingomyelin/cholesterol 50:30:20 (mol/mol) giant unilamellar vesicles, photoinduced Lo microdomain formation appears to occur by the rarely observed spinodal decomposition process rather than by the common nucleation process usually observed for Lo domain formation in bilayers. Moreover, temperature and the presence of the ganglioside GM1 have a profound effect on the morphological outcome of the photoinduced phase separation, eventually leading to features such as bicontinuous phases, phase percolation inversions, and patterns evoking double phase separations. GM1 also has the effect of destabilizing Lo microdomains. These properties may have consequences for Lo nanodomains stability and therefore for raft dynamics in biomembranes. Our data show that photoinduced Lo microdomains can be used to obtain new data on fast raft-mimicking processes in giant unilamellar vesicles.

关键词： Animals Artifacts Biomimetics/methods Chickens Cholesterol/chemistry Cholesterol/metabolism G(M1) Ganglioside/chemistry G(M1) Ganglioside/pharmacology image processing, computer-assisted Kinetics Light Light Lipid Bilayers/chemistry Lipid Bilayers/metabolism Membrane Microdomains/chemistry Membrane Microdomains/drug effects Membrane Microdomains/metabolism Membrane Microdomains/radiation effects Microscopy, Fluorescence Microscopy, Video Phosphatidylcholines/chemistry Phosphatidylcholines/metabolism Photochemical Processes/radiation effects Sphingomyelins/chemistry Sphingomyelins/metabolism Temperature Time Factors Unilamellar Liposomes/chemistry Unilamellar Liposomes/metabolism

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Key role of glycoprotein Ib/V/IX and von Willebrand factor in platelet activation-dependent fibrin formation at low shear flow

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BLOOD 2011年第2期117卷 651-660页

作者： Cosemans, Judith M. E. M. Schols, Saskia E. M. Stefanini, Lucia de Witt, Susanne Feijge, Marion A. H. Hamulyak, Karly Deckmyn, Hans Bergmeier, Wolfgang Heemskerk, Johan W. M. Maastricht Univ Cardiovasc Res Inst Maastricht Dept Biochem NL-6200 MD Maastricht Netherlands Maastricht Univ Cardiovasc Res Inst Maastricht Dept Internal Med NL-6200 MD Maastricht Netherlands Maastricht Univ Med Ctr NL-6200 MD Maastricht Netherlands Thomas Jefferson Univ Dept Med Div Hematol Philadelphia PA 19107 USA Thomas Jefferson Univ Cardeza Fdn Hematol Res Philadelphia PA 19107 USA Lab Thrombosis Res Kortrijk Belgium

A microscopic method was developed to study the role of platelets in fibrin formation. Perfusion of adhered platelets with plasma under coagulating conditions at a low shear rate (250(-1)) resulted in the assembly of a star-like fibrin network at the platelet surface. The focal fibrin formation on platelets was preceded by rises in cytosolic Ca2+, morphologic changes, and phosphatidylserine exposure. Fibrin formation was slightly affected by alpha(IIb)beta(3) blockage, but it was greatly delayed and reduced by the following: inhibition of thrombin or platelet activation;interference in the binding of von Willebrand factor (VWF) to glycoprotein Ib/V/IX (GpIb-V-IX);plasma or blood from patients with type 1 von Willebrand disease;and plasma from mice deficient in VWF or the extracellular domain of GpIb alpha. In this process, the GpIb-binding A1 domain of VWF was similarly effective as full-length VWF. Prestimulation of platelets enhanced the formation of fibrin, which was abrogated by blockage of phosphatidylserine. Together, these results show that, in the presence of thrombin and low shear flow, VWF-induced activation of GpIb-V-IX triggers platelet procoagulant activity and anchorage of a star-like fibrin network. This process can be relevant in hemostasis and the manifestation of von Willebrand disease. (Blood. 2011;117(2):651-660)

关键词： Animals Blood Coagulation/physiology Blood Platelets/metabolism Fibrin/biosynthesis Humans image processing, computer-assisted Mice Mice, Transgenic Mice, Transgenic Microscopy, Confocal Platelet Activation/physiology Platelet Glycoprotein GPIb-IX Complex/metabolism Shear Strength von Willebrand Diseases/metabolism von Willebrand Diseases/physiopathology von Willebrand Factor/metabolism

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Regional brain atrophy in children with multiple sclerosis

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NEUROimage 2011年第2期58卷 409-415页

作者： Aubert-Broche, B. Fonov, V. Ghassemi, R. Narayanan, S. Arnold, D. L. Banwell, B. Sled, J. G. Collins, D. L. McGill Univ Montreal Neurol Inst McConnell Brain Imaging Ctr Montreal PQ Canada Univ Toronto Hosp Sick Children Div Neurol Toronto ON M5G 1X8 Canada Univ Toronto Hosp Sick Children Ctr Phenogenom Toronto ON M5G 1X8 Canada

We used cross-sectional tensor-based morphometry to visualize reduced volume in the whole brains of pediatric patients with multiple sclerosis, relative to healthy controls. As a marker of local volume difference, we used the Jacobian determinant of the deformation field that maps each subject to a standard space. To properly assess abnormal differences in volume in this age group, it is necessary to account for the normal, age-related differences in brain volume. This was accomplished by computing normalized z-score Jacobian determinant values at each voxel to represent the local volume difference (in standard deviations) between an individual subject and an age- and sex-matched healthy normal population. Compared with healthy controls, pediatric patients with multiple sclerosis exhibited significantly reduced volumes within the thalamus and the splenium of the corpus callosum and significant expansions in the ventricles. While T2-weighted lesion volume was correlated with reduced splenium volume, no correlation was found between T2-weighted lesion volume and reduced thalamic volume. Reduced volumes of the optic pathways, including that of the optic tracts and optic radiations, correlated with disease duration. Our results suggest that focal inflammatory lesions may play an important role in tract degeneration, including transsynaptic degeneration. Crown Copyright (C) 2011 Published by Elsevier Inc. All rights reserved.

关键词： Adolescent Algorithms Anatomy, Cross-Sectional Atrophy Brain/pathology Brain Mapping Brain Mapping Child Cluster Analysis Diffusion Tensor Imaging Diffusion Tensor Imaging Female Humans image processing, computer-assisted Male Multiple Sclerosis, Relapsing-Remitting/pathology Nerve Degeneration/pathology Probability Regression Analysis

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Subclinical Lung Disease, Macrocytosis, and Premature Graying in Kindreds With Telomerase (TERT) Mutations

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CHEST 2011年第3期140卷 753-763页

作者： de Leon, Alberto Diaz Cronkhite, Jennifer T. Yilmaz, Cuneyt Brewington, Cecelia Wang, Richard Xing, Chao Hsia, Connie C. W. Garcia, Christine Kim Univ Texas SW Med Ctr Dallas McDermott Ctr Human Growth & Dev Dallas TX 75390 USA Univ Texas SW Med Ctr Dallas Dept Internal Med Div Pulm & Crit Care Med Dallas TX 75390 USA Univ Texas SW Med Ctr Dallas Dept Radiol Dallas TX 75390 USA Univ Texas SW Med Ctr Dallas Dept Dermatol Dallas TX 75390 USA

Background: Mutations in the human gene encoding the protein component of telomerase (TERT) are the most common genetic defect in patients with familial idiopathic pulmonary fibrosis (IPF). The subclinical phenotypes of asymptomatic members of these families have not been evaluated with respect to TERT mutation status or telomere length. Methods: We measured a variety of pulmonary, blood, skin, and bone parameters for 20 subjects with heterozygous TERT mutations (carriers) and 20 family members who had not inherited a TERT mutation (noncarriers) to identify the spectrum of phenotypes associated with mutations in this gene. The two groups were matched for sex, age, and cigarette smoking. Three TERT mutation carriers had IPF (IPF carriers). The rest of the carriers were apparently healthy (asymptomatic carriers) and were compared with the noncarriers. Results: Asymptomatic carriers exhibited significantly lower diffusing capacity of lung for carbon monoxide (DLCO), impaired recruitment of DLCO with exercise, radiographic signs of lung fibrosis, and increased fractional lung tissue volume quantified by high-resolution chest CT scan than noncarriers. RBC and platelet counts were significantly lower, and the mean corpuscular volume and mean corpuscular hemoglobin concentration were significantly higher in carriers than in noncarriers. Carriers reported significantly earlier graying of hair than noncarriers. TERT mutation status is more accurately predicted by short telomere lengths than any of these measured phenotypes. Conclusions: TERT mutation carriers exhibit early preclinical signs of lung fibrosis, bone marrow dysfunction, and premature graying. These clinical features and short telomere lengths characterize patients with germline TERT mutations. CHEST 2011;140(3):753-763

关键词： Adult Aging, Premature/genetics Bone Density Erythrocyte Count Erythrocyte Count Exercise Test Female Germ-Line Mutation Hair Color/genetics Heterozygote Humans Idiopathic Pulmonary Fibrosis/blood Idiopathic Pulmonary Fibrosis/genetics Idiopathic Pulmonary Fibrosis/radiography image processing, computer-assisted Male Middle Aged Phenotype Prospective Studies Pulmonary Diffusing Capacity Respiratory Function Tests Telomerase/genetics Telomere/genetics Telomere/pathology Tomography, X-Ray Computed

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Cognitive state and connectivity effects of the genome-wide significant psychosis variant in ZNF804A

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NEUROimage 2011年第3期54卷 2514-2523页

作者： Esslinger, Christine Kirsch, Peter Haddad, Leila Mier, Daniela Sauer, Carina Erk, Susanne Schnell, Knut Arnold, Claudia Witt, Stephanie H. Rietschel, Marcella Cichon, Sven Walter, Henrik Meyer-Lindenberg, Andreas Heidelberg Univ Dept Psychiat & Psychotherapy Cent Inst Mental Hlth D-68159 Mannheim Germany Charite Dept Psychiat & Psychotherapy Div Mind & Brain Res D-13353 Berlin Germany Univ Bonn Div Med Psychol Dept Psychiat & Psychotherapy D-53105 Bonn Germany Heidelberg Univ Dept Genet Epidemiol Psychiat Cent Inst Mental Hlth D-68159 Mannheim Germany Univ Bonn Dept Genom Life & Brain Ctr D-53105 Bonn Germany Univ Bonn Inst Human Genet D-53105 Bonn Germany

Alterations of connectivity are central to the systems-level pathophysiology of schizophrenia. One of the best-established genome-wide significant risk variants for this highly heritable disorder, the rs1344706 single nucleotide polymorphism in ZNF804A, was recently shown to modulate connectivity in healthy carriers during working memory (WM) in a pattern mirroring that which was found in overt disease. However, it was unclear whether this finding is specific to WM or if it is present regardless of cognitive state. Therefore, we examined genotype effects on connectivity in healthy carriers during rest and an emotion processing task without WM component. 111 healthy German subjects performed a battery of functional imaging tasks. Functional connectivity with the right dorsolateral prefrontal cortex during rest and an implicit emotion recognition task was determined using the seed voxel method and compared to results during WM. During rest and during the emotional task, a pattern of reduced interhemispheric prefrontal connectivity with increasing number of rs1344706 risk alleles could be seen that was close to identical to that during WM, suggesting a state-independent influence of the genetic variant on interhemispheric processing, possibly through structural effects. By contrast, the abnormal prefronto-hippocampal connectivity was only seen during the WM task, indicating a degree of task specificity in agreement with prior results in patients with schizophrenia. Our findings confirm a key role for disturbed functional connectivity in the genetic risk architecture of schizophrenia and identify cognitive state-dependent and independent components with regard to WM function. (C) 2010 Elsevier Inc. All rights reserved.

关键词： Cognition/physiology DNA/genetics Emotions/physiology Genome-Wide Association Study Genotype Germany Heterozygote image processing, computer-assisted Kruppel-Like Transcription Factors/genetics Magnetic Resonance Imaging Memory, Short-Term/physiology Neural Pathways/physiology Oxygen/blood Polymorphism, Single Nucleotide Prefrontal Cortex/physiology Psychotic Disorders/genetics Psychotic Disorders/psychology Schizophrenia/genetics Schizophrenic Psychology Social Perception

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Interpretation-mediated changes in neural activity during language comprehension

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NEUROimage 2011年第3期55卷 1314-1323页

作者： Cooper, Emily A. Hasson, Uri Small, Steven L. Univ Calif Berkeley Banks Lab Helen Wills Neurosci Inst Berkeley CA 94720 USA Univ Trento Ctr Mind Brain Sci Trento Italy Univ Trento Fac Cognit Sci Trento Italy Univ Chicago Dept Psychol Chicago IL 60637 USA Univ Chicago Dept Neurol Chicago IL 60637 USA

Using functional magnetic resonance imaging (fMRI), we identified cortical regions mediating interpretive processes that take place during language comprehension. We manipulated participants' interpretation of texts by asking them to focus on action-, space-, or time-related features while listening to identical short stories. We identify several cortical regions where activity varied significantly in response to this attention manipulation, even though the content being processed was exactly the same. Activity in the posterior and anterior sections of the left inferior frontal gyrus (IFG), which are thought to have different sensitivities to high-level language processing, was modulated by the listeners' attentional focus, but in ways that were quite different. The posterior left IFG (Pars Opercularis) showed different activity levels for the three conditions. However, a population coding analysis demonstrated similar distributions of activity across conditions. This suggests that while the gain of the response in the Pars Opercularis was modulated, its core organization was relatively invariant across the experimental conditions. In the anterior left IFG (Pars Triangularis), the analysis of population codes revealed different activity patterns between conditions: there was little similarity between activity during time-attention and action- and space-attention, however there were similar activity patterns while attending to space and action information. In addition, both the left superior temporal gyrus and sulcus showed greater activity in the space and action attention conditions when contrasted with time attention. We discuss these findings in light of work on the role of left IFG in processing semantic information in language, and in light of theories suggesting that temporal information in language is processed in the brain using similar mechanisms as spatial information. Our findings suggest that a substantial source of variance in neural activity during lan

关键词： Acoustic Stimulation Attention/physiology Brain/physiology Brain Mapping Brain Mapping Comprehension/physiology Data Interpretation, Statistical Female Functional Laterality/physiology Humans image processing, computer-assisted Language Magnetic Resonance Imaging Male Narration Oxygen/blood Semantics Space Perception/physiology Young Adult

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Effects of transcranial direct current stimulation (tDCS) on human regional cerebral blood flow

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NEUROimage 2011年第1期58卷 26-33页

作者： Zheng, Xin Alsop, David C. Schlaug, Gottfried Beth Israel Deaconess Med Ctr Dept Neurol Neuroimaging & Stroke Recovery Labs Boston MA 02215 USA Harvard Univ Sch Med Boston MA USA Beth Israel Deaconess Med Ctr Dept Radiol Div MRI Res Boston MA 02215 USA

Transcranial direct current stimulation (tDCS) can up- and down-regulate cortical excitability depending on current direction, however our abilities to measure brain-tissue effects of the stimulation and its after-effects have been limited so far. We used regional cerebral blood flow (rCBF), a surrogate measure of brain activity, to examine regional brain-tissue and brain-network effects during and after tDCS. We varied the polarity (anodal and cathodal) as well as the current strength (0.8 to 2.0 mA) of the stimulation. Fourteen healthy subjects were randomized into receiving either anodal or cathodal stimulation (two subjects received both, one week apart) while undergoing Arterial Spin Labeling (ASL) in the MRI scanner with an alternating off-on sampling paradigm. The stimulating, MRI-compatible electrode was placed over the right motor region and the reference electrode over the contralateral supra-orbital region. SPM5 was used to process and extract the rCBF data using a 10 mm spherical volume of interest (VOI) placed in the motor cortex directly underneath the stimulating scalp electrode. Anodal stimulation induced a large increase (17.1%) in rCBF during stimulation, which retumed to baseline after the current was turned off, but exhibited an increase in rCBF again in the post-stimulation period. Cathodal stimulation induced a smaller increase (5.6%) during stimulation, a significant decrease compared to baseline (-6.5%) after cessation, and a continued decrease in the post-stimulation period. These changes in rCBF were all significant when compared to the pre-stimulation baseline or to a control region. Furthermore, for anodal stimulation, there was a significant correlation between current strength and the increase in rCBF in the on-period relative to the pre-stimulation baseline. The differential rCBF after-effects of anodal (increase in resting state rCBF) and cathodal (decrease in resting state rCBF) tDCS support findings of behavioral and cognitive after

关键词： Adult Brain Chemistry/physiology Cerebrovascular Circulation/physiology Electric Stimulation/instrumentation Electric Stimulation/methods Electrodes Female Humans image processing, computer-assisted Magnetic Resonance Imaging Male Receptors, N-Methyl-D-Aspartate/metabolism Receptors, N-Methyl-D-Aspartate/metabolism Safety Young Adult

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