The Hiv-1 Protein Vpr Targets The Endoribonuclease Dicer For Proteasomal Degradation To Boost Macrophage Infection,
2013
Marquette University
The Hiv-1 Protein Vpr Targets The Endoribonuclease Dicer For Proteasomal Degradation To Boost Macrophage Infection, Laurieann Klockow, Hamayun J. Sharifi, Xiaoyun Wen, Meg Flagg, Andrea K.M. Furuya, Michael Nekorchuk, Carlos M.C. De Noronha
Biomedical Sciences Faculty Research and Publications
The HIV-1 protein Vpr enhances macrophage infection, triggers G2 cell cycle arrest, and targets cells for NK-cell killing. Vpr acts through the CRL4DCAF1 ubiquitin ligase complex to cause G2 arrest and trigger expression of NK ligands. Corresponding ubiquitination targets have not been identified. UNG2 and SMUG1 are the only known substrates for Vpr-directed depletion through CRL4DCAF1. Here we identify the endoribonuclease Dicer as a target of HIV-1 Vpr-directed proteasomal degradation through CRL4DCAF1. We show that HIV-1 Vpr inhibits short hairpin RNA function as expected upon reduction of Dicer levels. Dicer inhibits HIV-1 replication in T …
Osteopontin Expression During The Acute Immune Response Mediates Reactive Synaptogenesis And Adaptive Outcome,
2013
Virginia Commonwealth University
Osteopontin Expression During The Acute Immune Response Mediates Reactive Synaptogenesis And Adaptive Outcome, Julie Chan
Theses and Dissertations
Traumatic brain injury (TBI) is a worldwide epidemic as the number of victims living with the resulting cognitive and physical impairment continues to rise, principally due to limited treatment options which fail to address its multifaceted sequelae. By approaching TBI therapy from a molecular standpoint, we have the opportunity to develop a better understanding of the mechanisms which prevent effective recovery. With this information, we can move toward the identification of novel therapeutic treatments which target specific molecules to improve patient outcome following TBI. Here, we have focused on the therapeutic potential of osteopontin (OPN), an extracellular matrix (ECM) protein …
A Multivariate Method To Determine The Dimensionality Of Neural Representation From Population Activity.,
2013
Institute of Cognitive Neuroscience, University College London, UK
A Multivariate Method To Determine The Dimensionality Of Neural Representation From Population Activity., Jörn Diedrichsen, Tobias Wiestler, Naveed Ejaz
Brain and Mind Institute Researchers' Publications
How do populations of neurons represent a variable of interest? The notion of feature spaces is a useful concept to approach this question: According to this model, the activation patterns across a neuronal population are composed of different pattern components. The strength of each of these components varies with one latent feature, which together are the dimensions along which the population represents the variable. Here we propose a new method to determine the number of feature dimensions that best describes the activation patterns. The method is based on Gaussian linear classifiers that use only the first d most important pattern …
Anticuerpos Contra El Virus De La Parainfluenza 3 En Cerdos De Crianza Tecnificada Y De Traspatio Beneficiados En Mataderos De Lima,
2013
National University of San Marcos
Anticuerpos Contra El Virus De La Parainfluenza 3 En Cerdos De Crianza Tecnificada Y De Traspatio Beneficiados En Mataderos De Lima, Milagros P. Montesinos, Hermelinda G. Rivera, Mariluz Araínga
Journal Articles: Pharmacology & Experimental Neuroscience
Parainfluenza 3 antibodies against (PI3) virus in pigs were determined from commercial (n = 192) and backyard farms (n = 192). Blood samples were collected at the slaughter house from pigs of 2 to 6 months of age of any sex for detecting antibodies against the PI3 virus by viral neutralization test. The 5.5 ± 2.3% (21/384) of the pigs had antibodies against PI3 virus, where 5.2 ± 1.1% (10/192) and 5.7 ± 1.2% (11/192) were from commercial and backyard farms respectively. The antibody titres ranged from 4 to 64 and were detected in pigs older than 3 months of …
Expression Of C-Fos In Hilar Mossy Cells Of The Dentate Gyrus In Vivo.,
2013
The Nathan Kline Institute for Psychiatric Research
Expression Of C-Fos In Hilar Mossy Cells Of The Dentate Gyrus In Vivo., Aine M Duffy, Michael J Schaner, Jeannie Chin, Helen E Scharfman
Department of Neuroscience Faculty Papers
Granule cells (GCs) of the dentate gyrus (DG) are considered to be quiescent--they rarely fire action potentials. In contrast, the other glutamatergic cell type in the DG, hilar mossy cells (MCs) often have a high level of spontaneous activity based on recordings in hippocampal slices. MCs project to GCs, so activity in MCs could play an important role in activating GCs. Therefore, we investigated whether MCs were active under basal conditions in vivo, using the immediate early gene c-fos as a tool. We hypothesized that MCs would exhibit c-fos expression even if rats were examined randomly, under normal housing conditions. …
Alternations Of Nmda And Gabab Receptor Function In Development: A Potential Animal Model Of Schizophrenia,
2013
University of Nevada, Las Vegas
Alternations Of Nmda And Gabab Receptor Function In Development: A Potential Animal Model Of Schizophrenia, Monica Bolton
UNLV Theses, Dissertations, Professional Papers, and Capstones
Schizophrenia is a debilitating mental disorder that affects up to 3% of the world population. The behavioral symptoms are categorized into positive and negative symptoms, which appear during late adolescence/early adulthood. Unfortunately, the underlying cellular and molecular mechanisms of the disease are poorly understood. Several hypotheses exist to explain mechanisms contributing to these behavioral alterations. One model proposes that a reduced function of the NMDA glutamate receptor on specific GABAergic interneurons may be responsible for deficits in schizophrenia. Post-mortem investigations provide evidence of reductions in both glutamate and GABA-related proteins in patients with schizophrenia. Further, GABAergic interneurons that are activated …
Network Dynamics Of Visual Naming,
2013
The University of Texas Graduate School of Biomedcial Sciences at Houston
Network Dynamics Of Visual Naming, Christopher R. Conner
Dissertations and Theses (Open Access)
Recognition and naming of objects and actions are fundamental components of language. They involve several different systems working in coordination to accomplish a complex behavior. During visual naming, sensory and semantic processing are carried out by dedicated cortical substrates in the temporal and occipital lobes, while response selection and articulatory planning are handled by prefrontal cortex. Despite decades of research using lesion analysis, functional MRI and electro-encephalography, the precise dynamics involved remain unknown due to the inadequate spatio-temporal resolution of these methodologies. Of particular interest is the organization of semantic knowledge and the degree of serial and parallel organization of …
Environmental Circadian Disruption Elevates The Il-6 Response To Lipopolysaccharide In Blood,
2013
Morehouse School of Medicine
Environmental Circadian Disruption Elevates The Il-6 Response To Lipopolysaccharide In Blood, Kandis L. Adams, Oscar Castanon-Cervantes, Jennifer A. Evans, Alec J. Davidson
Biomedical Sciences Faculty Research and Publications
The immune system is regulated by circadian clocks within the brain and immune cells. Environmental circadian disruption (ECD), consisting of a 6-h phase advance of the light:dark cycle once a week for 4 weeks, elevates the inflammatory response to lipopolysaccharide (LPS) both in vivo and in vitro. This indicates that circadian disruption adversely affects immune function; however, it remains unclear how the circadian system regulates this response under ECD conditions. Here, we develop an assay using ex vivo whole-blood LPS challenge to investigate the circadian regulation of immune responses in mice and to determine the effects of ECD on these …
Single-Trial Decoding Of Auditory Novelty Responses Facilitates The Detection Of Residual Consciousness,
2013
Institut National de la Santé et de la Recherche Médicale
Single-Trial Decoding Of Auditory Novelty Responses Facilitates The Detection Of Residual Consciousness, J. R. King, F. Faugeras, A. Gramfort, Aaron Schurger, I. El Karoui, J. D. Sitt, B. Rohaut, C. Wacongne, E. Labyt, T. Bekinschtein, L. Cohen, L. Naccache, S. Dehaene
Psychology Faculty Articles and Research
Detecting residual consciousness in unresponsive patients is a major clinical concern and a challenge for theoretical neuroscience. To tackle this issue, we recently designed a paradigm that dissociates two electro-encephalographic (EEG) responses to auditory novelty. Whereas a local change in pitch automatically elicits a mismatch negativity (MMN), a change in global sound sequence leads to a late P300b response. The latter component is thought to be present only when subjects consciously perceive the global novelty. Unfortunately, it can be difficult to detect because individual variability is high, especially in clinical recordings. Here, we show that multivariate pattern classifiers can extract …
Skill Learning Strengthens Cortical Representations Of Motor Sequences.,
2013
Institute of Cognitive Neuroscience, University College London, London, United Kingdom
Skill Learning Strengthens Cortical Representations Of Motor Sequences., Tobias Wiestler, Jörn Diedrichsen
Brain and Mind Institute Researchers' Publications
Motor-skill learning can be accompanied by both increases and decreases in brain activity. Increases may indicate neural recruitment, while decreases may imply that a region became unimportant or developed a more efficient representation of the skill. These overlapping mechanisms make interpreting learning-related changes of spatially averaged activity difficult. Here we show that motor-skill acquisition is associated with the emergence of highly distinguishable activity patterns for trained movement sequences, in the absence of average activity increases. During functional magnetic resonance imaging, participants produced either four trained or four untrained finger sequences. Using multivariate pattern analysis, both untrained and trained sequences could …
Erps Reveal The Temporal Dynamics Of Auditory Word Recognition In Specific Language Impairment.,
2013
The University of Western Ontario, Department of Psychology and Program in Neuroscience, 1151 Richmond Street, London, Ontario, Canada N6A 5B7
Erps Reveal The Temporal Dynamics Of Auditory Word Recognition In Specific Language Impairment., Jeffrey G Malins, Amy S Desroches, Erin K Robertson, Randy Lynn Newman, Lisa M D Archibald, Marc F Joanisse
Brain and Mind Institute Researchers' Publications
We used event-related potentials (ERPs) to compare auditory word recognition in children with specific language impairment (SLI group; N=14) to a group of typically developing children (TD group; N=14). Subjects were presented with pictures of items and heard auditory words that either matched or mismatched the pictures. Mismatches overlapped expected words in word-onset (cohort mismatches; see: DOLL, hear: dog), rhyme (CONE -bone), or were unrelated (SHELL -mug). In match trials, the SLI group showed a different pattern of N100 responses to auditory stimuli compared to the TD group, indicative of early auditory processing differences in SLI. However, the phonological mapping …
Prefrontal Activity Links Nonoverlapping Events In Memory,
2013
Marquette University
Prefrontal Activity Links Nonoverlapping Events In Memory, Marieke R. Gilmartin, Hiroyuki Miyawaki, Fred J. Helmstetter, Kamran Diba
Biomedical Sciences Faculty Research and Publications
The medial prefrontal cortex (mPFC) plays an important role in memory. By maintaining a working memory buffer, neurons in prelimbic (PL) mPFC may selectively contribute to learning associations between stimuli that are separated in time, as in trace fear conditioning (TFC). Until now, evidence for this bridging role was largely descriptive. Here we used optogenetics to silence neurons in the PL mPFC of rats during learning in TFC. Memory formation was prevented when mPFC was silenced specifically during the interval separating the cue and shock. Our results provide support for a working memory function for these cells and indicate that …
Dynamic And Opposing Adjustment Of Movement Cancellation And Generation In An Oculomotor Countermanding Task.,
2013
Department of Physiology and Pharmacology Western University & Department of Psychology Western University & The Brain and Mind Institute Robarts Research Institute
Dynamic And Opposing Adjustment Of Movement Cancellation And Generation In An Oculomotor Countermanding Task., Brian D Corneil, Joshua C Cheng, Samanthi C Goonetilleke
Brain and Mind Institute Researchers' Publications
Adaptive adjustments of strategies help optimize behavior in a dynamic and uncertain world. Previous studies in the countermanding (or stop-signal) paradigm have detailed how reaction times (RTs) change with trial sequence, demonstrating adaptive control of movement generation. Comparatively little is known about the adaptive control of movement cancellation in the countermanding task, mainly because movement cancellation implies the absence of an outcome and estimates of movement cancellation require hundreds of trials. Here, we exploit a within-trial proxy of movement cancellation based on recordings of neck muscle activity while human subjects attempted to cancel large eye-head gaze shifts. On a subset …
Restricted Likelihood Ratio Tests For Functional Effects In The Functional Linear Model,
2013
Johns Hopkins School of Public Health
Restricted Likelihood Ratio Tests For Functional Effects In The Functional Linear Model, Bruce J. Swihart, Jeff Goldsmith, Ciprian M. Crainiceanu
Johns Hopkins University, Dept. of Biostatistics Working Papers
The goal of our article is to provide a transparent, robust, and computationally feasible statistical approach for testing in the context of scalar-on-function linear regression models. In particular, we are interested in testing for the necessity of functional effects against standard linear models. Our methods are motivated by and applied to a large longitudinal study involving diffusion tensor imaging of intracranial white matter tracts in a susceptible cohort. In the context of this study, we conduct hypothesis tests that are motivated by anatomical knowledge and which support recent findings regarding the relationship between cognitive impairment and white matter demyelination. R-code …
Intracranial Injection Of Gammagard, A Human Ivig, Modulates The Inflammatory Response Of The Brain And Lowers AΒ In App/Ps1 Mice Along A Different Time Course Than Anti-AΒ Antibodies,
2013
University of Kentucky
Intracranial Injection Of Gammagard, A Human Ivig, Modulates The Inflammatory Response Of The Brain And Lowers AΒ In App/Ps1 Mice Along A Different Time Course Than Anti-AΒ Antibodies, Tiffany L. Sudduth, Abigail Greenstein, Donna M. Wilcock
Sanders-Brown Center on Aging Faculty Publications
Gammagard IVIg is a therapeutic approach to treat Alzheimer's disease currently in phase 3 clinical trials. Despite the reported efficacy of the approach the mechanism of action is poorly understood. We have previously shown that intracranial injection of anti-Aβ antibodies into the frontal cortex and hippocampus reveals important information regarding the time course of events once the agent is in the brain. In the current study we compared IVIg, mouse-pooled IgG, and the anti-Aβ antibody 6E10 injected intracranially into the frontal cortex and hippocampus of 7-month-old APP/PS1 mice. We established a time course of events ranging from 1 …
Two Distinct Ipsilateral Cortical Representations For Individuated Finger Movements.,
2013
Institute of Cognitive Neuroscience, University College London, London, UK
Two Distinct Ipsilateral Cortical Representations For Individuated Finger Movements., Jörn Diedrichsen, Tobias Wiestler, John W Krakauer
Brain and Mind Institute Researchers' Publications
Movements of the upper limb are controlled mostly through the contralateral hemisphere. Although overall activity changes in the ipsilateral motor cortex have been reported, their functional significance remains unclear. Using human functional imaging, we analyzed neural finger representations by studying differences in fine-grained activation patterns for single isometric finger presses. We demonstrate that cortical motor areas encode ipsilateral movements in 2 fundamentally different ways. During unimanual ipsilateral finger presses, primary sensory and motor cortices show, underneath global suppression, finger-specific activity patterns that are nearly identical to those elicited by contralateral mirror-symmetric action. This component vanishes when both motor cortices are …
Nr2a- And Nr2b-Containing Nmda Receptors In The Prelimbic Medial Prefrontal Cortex Differentially Mediate Trace, Delay, And Contextual Fear Conditioning,
2013
Marquette University
Nr2a- And Nr2b-Containing Nmda Receptors In The Prelimbic Medial Prefrontal Cortex Differentially Mediate Trace, Delay, And Contextual Fear Conditioning, Marieke R. Gilmartin, Janine L. Kwapis, Fred J. Helmstetter
Biomedical Sciences Faculty Research and Publications
Activation of N-methyl-D-aspartate receptors (NMDAR) in the prelimbic medial prefrontal cortex (PL mPFC) is necessary for the acquisition of both trace and contextual fear memories, but it is not known how specific NR2 subunits support each association. The NR2B subunit confers unique properties to the NMDAR and may differentially regulate these two fear memories. Here we show that NR2A-containing NMDARs mediate trace, delay, and contextual fear memories, but NR2B-containing NMDARs are required only for trace conditioning, consistent with a role for PL mPFC in working memory.
Prefrontal Neurons Of Opposite Spatial Preference Display Distinct Target Selection Dynamics.,
2013
Department of Neurology and Neurosurgery, Montreal Neurological Institute, Montreal, Quebec, H3A 2B4, Canada
Prefrontal Neurons Of Opposite Spatial Preference Display Distinct Target Selection Dynamics., Therese Lennert, Julio C Martinez-Trujillo
Brain and Mind Institute Researchers' Publications
Neurons in the primate dorsolateral prefrontal cortex (dlPFC) of one hemisphere are selective for the location of attended targets in both visual hemifields. Whether dlPFC neurons with selectivity for opposite hemifields directly compete with each other for target selection or instead play distinct roles during the allocation of attention remains unclear. We explored this issue by recording neuronal responses in the right dlPFC of two macaques while they allocated attention to a target in one hemifield and ignored a distracter on the opposite side. Forty-nine percent of the recorded neurons were target location selective. Neurons selective for contralateral targets (58%) …
Decoding The Neural Mechanisms Of Human Tool Use.,
2013
Department of Psychology, Queen’s University, Kingston, Canada & Centre for Neuroscience Studies, Queen’s University, Kingston, Canada
Decoding The Neural Mechanisms Of Human Tool Use., Jason P Gallivan, D Adam Mclean, Kenneth F Valyear, Jody C Culham
Brain and Mind Institute Researchers' Publications
Sophisticated tool use is a defining characteristic of the primate species but how is it supported by the brain, particularly the human brain? Here we show, using functional MRI and pattern classification methods, that tool use is subserved by multiple distributed action-centred neural representations that are both shared with and distinct from those of the hand. In areas of frontoparietal cortex we found a common representation for planned hand- and tool-related actions. In contrast, in parietal and occipitotemporal regions implicated in hand actions and body perception we found that coding remained selectively linked to upcoming actions of the hand whereas …
Cannabis And Psychosis: Transition To Psychosis,
2013
University of Western Ontario
Cannabis And Psychosis: Transition To Psychosis, Amresh Srivastava, Kristen , Terpstra, Yves Bureau
Data and Test Instruments
Cannabis has been implicated as a risk factor for the development of schizophrenia, however, but the pathway of cannabis causing psychosis is not well understood. It appears that cannabis does not cause any structural changes per say but deficits in areas of the brain responsible for memory and emotion do show some changes. Recent studies suggest that cannabinoids such as CB1 have a pharmacological profile similar to that of atypical antipsychotic drugs. This mechanisms may involve dopamine, GABA, and glutamate neurotransmission; It is still not known if these changes are transitory or permanent, and whether or not they contribute to …
