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Author Amorim, K.N.S.; Chagas, D.C.G.; Sulczewski, F.B.; Boscardin, S.B. file  url
openurl 
  Title Dendritic Cells and Their Multiple Roles during Malaria Infection Type Journal Article
  Year 2016 Publication Journal of Immunology Research Abbreviated Journal J Immunol Res  
  Volume 2016 Issue Pages (down) 2926436  
  Keywords Antigen Presentation; Dendritic Cells/*immunology; Humans; Immunologic Tests; Life Cycle Stages; Malaria/*immunology/parasitology; Plasmodium/growth & development/immunology; T-Lymphocytes/immunology  
  Abstract Dendritic cells (DCs) play a central role in the initiation of adaptive immune responses, efficiently presenting antigens to T cells. This ability relies on the presence of numerous surface and intracellular receptors capable of sensing microbial components as well as inflammation and on a very efficient machinery for antigen presentation. In this way, DCs sense the presence of a myriad of pathogens, including Plasmodium spp., the causative agent of malaria. Despite many efforts to control this infection, malaria is still responsible for high rates of morbidity and mortality. Different groups have shown that DCs act during Plasmodium infection, and data suggest that the phenotypically distinct DCs subsets are key factors in the regulation of immunity during infection. In this review, we will discuss the importance of DCs for the induction of immunity against the different stages of Plasmodium, the outcomes of DCs activation, and also what is currently known about Plasmodium components that trigger such activation.  
  Call Number Serial 1687  
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Author Yogev, O.; Yogev, O.; Singer, E.; Shaulian, E.; Goldberg, M.; Fox, T.D.; Pines, O. file  url
openurl 
  Title Fumarase: a mitochondrial metabolic enzyme and a cytosolic/nuclear component of the DNA damage response Type Journal Article
  Year 2010 Publication PLoS Biology Abbreviated Journal PLoS Biol  
  Volume 8 Issue 3 Pages (down) e1000328  
  Keywords Cell Nucleus/*metabolism; Cytosol/*metabolism; *DNA Damage; Fumarate Hydratase/genetics/*metabolism; Fumarates/metabolism; Gene Knockdown Techniques; HeLa Cells; Histones/genetics/metabolism; Humans; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism; Isoenzymes/genetics/*metabolism; Kidney Neoplasms/enzymology/genetics; Leiomyomatosis/enzymology/genetics; Mitochondria/*enzymology; Saccharomyces cerevisiae/enzymology/genetics; Saccharomyces cerevisiae Proteins/genetics/metabolism; Tumor Suppressor Proteins/genetics/metabolism  
  Abstract In eukaryotes, fumarase (FH in human) is a well-known tricarboxylic-acid-cycle enzyme in the mitochondrial matrix. However, conserved from yeast to humans is a cytosolic isoenzyme of fumarase whose function in this compartment remains obscure. A few years ago, FH was surprisingly shown to underlie a tumor susceptibility syndrome, Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC). A biallelic inactivation of FH has been detected in almost all HLRCC tumors, and therefore FH was suggested to function as a tumor suppressor. Recently it was suggested that FH inhibition leads to elevated intracellular fumarate, which in turn acts as a competitive inhibitor of HPH (HIF prolyl hydroxylase), thereby causing stabilization of HIF (Hypoxia-inducible factor) by preventing proteasomal degradation. The transcription factor HIF increases the expression of angiogenesis regulated genes, such as VEGF, which can lead to high microvessel density and tumorigenesis. Yet this mechanism does not fully explain the large cytosolic population of fumarase molecules. We constructed a yeast strain in which fumarase is localized exclusively to mitochondria. This led to the discovery that the yeast cytosolic fumarase plays a key role in the protection of cells from DNA damage, particularly from DNA double-strand breaks. We show that the cytosolic fumarase is a member of the DNA damage response that is recruited from the cytosol to the nucleus upon DNA damage induction. This function of fumarase depends on its enzymatic activity, and its absence in cells can be complemented by high concentrations of fumaric acid. Our findings suggest that fumarase and fumaric acid are critical elements of the DNA damage response, which underlies the tumor suppressor role of fumarase in human cells and which is most probably HIF independent. This study shows an exciting crosstalk between primary metabolism and the DNA damage response, thereby providing a scenario for metabolic control of tumor propagation.  
  Call Number Serial 1880  
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Author Yu, C.; Smith, L.B. file  url
openurl 
  Title Joint attention without gaze following: human infants and their parents coordinate visual attention to objects through eye-hand coordination Type Journal Article
  Year 2013 Publication PloS one Abbreviated Journal PLoS One  
  Volume 8 Issue 11 Pages (down) e79659  
  Keywords *Attention; Female; *Fixation, Ocular; Humans; Infant; *Infant Behavior; *Parent-Child Relations; *Parents; Psychomotor Performance  
  Abstract The coordination of visual attention among social partners is central to many components of human behavior and human development. Previous research has focused on one pathway to the coordination of looking behavior by social partners, gaze following. The extant evidence shows that even very young infants follow the direction of another's gaze but they do so only in highly constrained spatial contexts because gaze direction is not a spatially precise cue as to the visual target and not easily used in spatially complex social interactions. Our findings, derived from the moment-to-moment tracking of eye gaze of one-year-olds and their parents as they actively played with toys, provide evidence for an alternative pathway, through the coordination of hands and eyes in goal-directed action. In goal-directed actions, the hands and eyes of the actor are tightly coordinated both temporally and spatially, and thus, in contexts including manual engagement with objects, hand movements and eye movements provide redundant information about where the eyes are looking. Our findings show that one-year-olds rarely look to the parent's face and eyes in these contexts but rather infants and parents coordinate looking behavior without gaze following by attending to objects held by the self or the social partner. This pathway, through eye-hand coupling, leads to coordinated joint switches in visual attention and to an overall high rate of looking at the same object at the same time, and may be the dominant pathway through which physically active toddlers align their looking behavior with a social partner.  
  Call Number Serial 1799  
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Author Yu, C.; Smith, L.B. file  url
openurl 
  Title Joint attention without gaze following: human infants and their parents coordinate visual attention to objects through eye-hand coordination Type Journal Article
  Year 2013 Publication PloS one Abbreviated Journal PLoS One  
  Volume 8 Issue 11 Pages (down) e79659  
  Keywords *Attention; Female; *Fixation, Ocular; Humans; Infant; *Infant Behavior; *Parent-Child Relations; *Parents; Psychomotor Performance  
  Abstract The coordination of visual attention among social partners is central to many components of human behavior and human development. Previous research has focused on one pathway to the coordination of looking behavior by social partners, gaze following. The extant evidence shows that even very young infants follow the direction of another's gaze but they do so only in highly constrained spatial contexts because gaze direction is not a spatially precise cue as to the visual target and not easily used in spatially complex social interactions. Our findings, derived from the moment-to-moment tracking of eye gaze of one-year-olds and their parents as they actively played with toys, provide evidence for an alternative pathway, through the coordination of hands and eyes in goal-directed action. In goal-directed actions, the hands and eyes of the actor are tightly coordinated both temporally and spatially, and thus, in contexts including manual engagement with objects, hand movements and eye movements provide redundant information about where the eyes are looking. Our findings show that one-year-olds rarely look to the parent's face and eyes in these contexts but rather infants and parents coordinate looking behavior without gaze following by attending to objects held by the self or the social partner. This pathway, through eye-hand coupling, leads to coordinated joint switches in visual attention and to an overall high rate of looking at the same object at the same time, and may be the dominant pathway through which physically active toddlers align their looking behavior with a social partner.  
  Call Number Serial 1818  
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Author Galatzer-Levy, I.R.; Ankri, Y.; Freedman, S.; Israeli-Shalev, Y.; Roitman, P.; Gilad, M.; Shalev, A.Y. file  url
openurl 
  Title Early PTSD symptom trajectories: persistence, recovery, and response to treatment: results from the Jerusalem Trauma Outreach and Prevention Study (J-TOPS) Type Journal Article
  Year 2013 Publication PloS one Abbreviated Journal PLoS One  
  Volume 8 Issue 8 Pages (down) e70084  
  Keywords Adolescent; Adult; Aged; Cognitive Therapy/methods; Cohort Studies; Data Interpretation, Statistical; Disease Progression; Female; Humans; Israel; Likelihood Functions; Male; Middle Aged; Models, Statistical; Psychometrics; Stress Disorders, Post-Traumatic/*diagnosis/*therapy; Symptom Assessment; Time Factors; Treatment Outcome  
  Abstract CONTEXT: Uncovering heterogeneities in the progression of early PTSD symptoms can improve our understanding of the disorder's pathogenesis and prophylaxis. OBJECTIVES: To describe discrete symptom trajectories and examine their relevance for preventive interventions. DESIGN: Latent Growth Mixture Modeling (LGMM) of data from a randomized controlled study of early treatment. LGMM identifies latent longitudinal trajectories by exploring discrete mixture distributions underlying observable data. SETTING: Hadassah Hospital unselectively receives trauma survivors from Jerusalem and vicinity. PARTICIPANTS: Adult survivors of potentially traumatic events consecutively admitted to the hospital's emergency department (ED) were assessed ten days and one-, five-, nine- and fifteen months after ED admission. Participants with data at ten days and at least two additional assessments (n = 957) were included; 125 received cognitive behavioral therapy (CBT) between one and nine months. APPROACH: We used LGMM to identify latent parameters of symptom progression and tested the effect of CBT on these parameters. CBT consisted of 12 weekly sessions of either cognitive therapy (n = 41) or prolonged exposure (PE, n = 49), starting 29.8+/-5.7 days after ED admission, or delayed PE (n = 35) starting at 151.8+/-42.4 days. CBT effectively reduced PTSD symptoms in the entire sample. MAIN OUTCOME MEASURE: Latent trajectories of PTSD symptoms; effects of CBT on these trajectories. RESULTS: THREE TRAJECTORIES WERE IDENTIFIED: Rapid Remitting (rapid decrease in symptoms from 1- to 5-months; 56% of the sample), Slow Remitting (progressive decrease in symptoms over 15 months; 27%) and Non-Remitting (persistently elevated symptoms; 17%). CBT accelerated the recovery of the Slow Remitting class but did not affect the other classes. CONCLUSIONS: The early course of PTSD symptoms is characterized by distinct and diverging response patterns that are centrally relevant to understanding the disorder and preventing its occurrence. Studies of the pathogenesis of PTSD may benefit from using clustered symptom trajectories as their dependent variables.  
  Call Number Serial 1307  
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Author Shanks, R.M.Q.; Lahr, R.M.; Stella, N.A.; Arena, K.E.; Brothers, K.M.; Kwak, D.H.; Liu, X.; Kalivoda, E.J. file  url
openurl 
  Title A Serratia marcescens PigP homolog controls prodigiosin biosynthesis, swarming motility and hemolysis and is regulated by cAMP-CRP and HexS Type Journal Article
  Year 2013 Publication PloS one Abbreviated Journal PLoS One  
  Volume 8 Issue 3 Pages (down) e57634  
  Keywords Bacterial Proteins/*genetics/metabolism; Depsipeptides/*biosynthesis/genetics/pharmacology; Erythrocytes/drug effects; *Gene Expression Regulation, Bacterial; Genetic Complementation Test; Hemolysis/drug effects; Hexosyltransferases/genetics/metabolism; Humans; Membrane Proteins/genetics/metabolism; Movement/drug effects; Mutation; Operon; Prodigiosin/*biosynthesis; Sequence Homology, Amino Acid; Serratia marcescens/*genetics/metabolism; Signal Transduction; Transcription Factors/*genetics/metabolism  
  Abstract Swarming motility and hemolysis are virulence-associated determinants for a wide array of pathogenic bacteria. The broad host-range opportunistic pathogen Serratia marcescens produces serratamolide, a small cyclic amino-lipid, that promotes swarming motility and hemolysis. Serratamolide is negatively regulated by the transcription factors HexS and CRP. Positive regulators of serratamolide production are unknown. Similar to serratamolide, the antibiotic pigment, prodigiosin, is regulated by temperature, growth phase, HexS, and CRP. Because of this co-regulation, we tested the hypothesis that a homolog of the PigP transcription factor of the atypical Serratia species ATCC 39006, which positively regulates prodigiosin biosynthesis, is also a positive regulator of serratamolide production in S. marcescens. Mutation of pigP in clinical, environmental, and laboratory strains of S. marcescens conferred pleiotropic phenotypes including the loss of swarming motility, hemolysis, and severely reduced prodigiosin and serratamolide synthesis. Transcriptional analysis and electrophoretic mobility shift assays place PigP in a regulatory pathway with upstream regulators CRP and HexS. The data from this study identifies a positive regulator of serratamolide production, describes novel roles for the PigP transcription factor, shows for the first time that PigP directly regulates the pigment biosynthetic operon, and identifies upstream regulators of pigP. This study suggests that PigP is important for the ability of S. marcescens to compete in the environment.  
  Call Number Serial 1612  
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Author Changeux, J.-P. file  url
openurl 
  Title The concept of allosteric interaction and its consequences for the chemistry of the brain Type Journal Article
  Year 2013 Publication The Journal of Biological Chemistry Abbreviated Journal J Biol Chem  
  Volume 288 Issue 38 Pages (down) 26969-26986  
  Keywords Allosteric Regulation/physiology; Brain Chemistry/*physiology; History, 20th Century; History, 21st Century; Humans; *Models, Biological; *Molecular Dynamics Simulation; Nerve Tissue Proteins/*metabolism; Portraits as Topic; Prokaryotic Cells/physiology; Allosteric Regulation; Membrane Proteins; Neurons; Nicotinic Acetylcholine Receptors; Synaptic Plasticity  
  Abstract Throughout this Reflections article, I have tried to follow up on the genesis in the 1960s and subsequent evolution of the concept of allosteric interaction and to examine its consequences within the past decades, essentially in the field of the neuroscience. The main conclusion is that allosteric mechanisms built on similar structural principles operate in bacterial regulatory enzymes, gene repressors (and the related nuclear receptors), rhodopsin, G-protein-coupled receptors, neurotransmitter receptors, ion channels, and so on from prokaryotes up to the human brain yet with important features of their own. Thus, future research on these basic cybernetic sensors is expected to develop in two major directions: at the elementary level, toward the atomic structure and molecular dynamics of the conformational changes involved in signal recognition and transduction, but also at a higher level of organization, the contribution of allosteric mechanisms to the modulation of brain functions.  
  Call Number Serial 1878  
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Author Changeux, J.-P. file  url
openurl 
  Title The concept of allosteric interaction and its consequences for the chemistry of the brain Type Journal Article
  Year 2013 Publication The Journal of Biological Chemistry Abbreviated Journal J Biol Chem  
  Volume 288 Issue 38 Pages (down) 26969-26986  
  Keywords Allosteric Regulation/physiology; Brain Chemistry/*physiology; History, 20th Century; History, 21st Century; Humans; *Models, Biological; *Molecular Dynamics Simulation; Nerve Tissue Proteins/*metabolism; Portraits as Topic; Prokaryotic Cells/physiology; Allosteric Regulation; Membrane Proteins; Neurons; Nicotinic Acetylcholine Receptors; Synaptic Plasticity  
  Abstract Throughout this Reflections article, I have tried to follow up on the genesis in the 1960s and subsequent evolution of the concept of allosteric interaction and to examine its consequences within the past decades, essentially in the field of the neuroscience. The main conclusion is that allosteric mechanisms built on similar structural principles operate in bacterial regulatory enzymes, gene repressors (and the related nuclear receptors), rhodopsin, G-protein-coupled receptors, neurotransmitter receptors, ion channels, and so on from prokaryotes up to the human brain yet with important features of their own. Thus, future research on these basic cybernetic sensors is expected to develop in two major directions: at the elementary level, toward the atomic structure and molecular dynamics of the conformational changes involved in signal recognition and transduction, but also at a higher level of organization, the contribution of allosteric mechanisms to the modulation of brain functions.  
  Call Number Serial 1888  
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Author Cattaneo, L.; Fabbri-Destro, M.; Boria, S.; Pieraccini, C.; Monti, A.; Cossu, G.; Rizzolatti, G. file  url
doi  openurl
  Title Impairment of actions chains in autism and its possible role in intention understanding Type Journal Article
  Year 2007 Publication Proceedings of the National Academy of Sciences of the United States of America Abbreviated Journal Proc Natl Acad Sci U S A  
  Volume 104 Issue 45 Pages (down) 17825-17830  
  Keywords Autistic Disorder--physiopathology; Child; Child, Preschool; Comprehension--physiology; Electromyography; Female; Humans; Intelligence; Intention; Male; Motor Activity; Perception--physiology; Reference Values  
  Abstract Experiments in monkeys demonstrated that many parietal and premotor neurons coding a specific motor act (e.g., grasping) show a markedly different activation when this act is part of actions that have different goals (e.g., grasping for eating vs. grasping for placing). Many of these “action-constrained” neurons have mirror properties firing selectively to the observation of the initial motor act of the actions to which they belong motorically. By activating a specific action chain from its very outset, this mechanism allows the observers to have an internal copy of the whole action before its execution, thus enabling them to understand directly the agent's intention. Using electromyographic recordings, we show that a similar chained organization exists in typically developing children, whereas it is impaired in children with autism. We propose that, as a consequence of this functional impairment, high-functioning autistic children may understand the intentions of others cognitively but lack the mechanism for understanding them experientially.  
  Call Number Serial 18  
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Author Schiefer, M.; Tan, D.; Sidek, S.M.; Tyler, D.J. file  url
openurl 
  Title Sensory feedback by peripheral nerve stimulation improves task performance in individuals with upper limb loss using a myoelectric prosthesis Type Journal Article
  Year 2016 Publication Journal of Neural Engineering Abbreviated Journal J Neural Eng  
  Volume 13 Issue 1 Pages (down) 016001  
  Keywords Amputation/*rehabilitation; *Artificial Limbs; Electric Stimulation/*instrumentation/methods; Equipment Failure Analysis; *Feedback, Sensory; Hand/innervation/*physiopathology; Hand Strength; Humans; Prosthesis Design; *Task Performance and Analysis; Touch  
  Abstract OBJECTIVE: Tactile feedback is critical to grip and object manipulation. Its absence results in reliance on visual and auditory cues. Our objective was to assess the effect of sensory feedback on task performance in individuals with limb loss. APPROACH: Stimulation of the peripheral nerves using implanted cuff electrodes provided two subjects with sensory feedback with intensity proportional to forces on the thumb, index, and middle fingers of their prosthetic hand during object manipulation. Both subjects perceived the sensation on their phantom hand at locations corresponding to the locations of the forces on the prosthetic hand. A bend sensor measured prosthetic hand span. Hand span modulated the intensity of sensory feedback perceived on the thenar eminence for subject 1 and the middle finger for subject 2. We performed three functional tests with the blindfolded subjects. First, the subject tried to determine whether or not a wooden block had been placed in his prosthetic hand. Second, the subject had to locate and remove magnetic blocks from a metal table. Third, the subject performed the Southampton Hand Assessment Procedure (SHAP). We also measured the subject's sense of embodiment with a survey and his self-confidence. MAIN RESULTS: Blindfolded performance with sensory feedback was similar to sighted performance in the wooden block and magnetic block tasks. Performance on the SHAP, a measure of hand mechanical function and control, was similar with and without sensory feedback. An embodiment survey showed an improved sense of integration of the prosthesis in self body image with sensory feedback. SIGNIFICANCE: Sensory feedback by peripheral nerve stimulation improved object discrimination and manipulation, embodiment, and confidence. With both forms of feedback, the blindfolded subjects tended toward results obtained with visual feedback.  
  Call Number Serial 2022  
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