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[PMID]: 27160038
[Au] Autor:Parmar R; Patel H; Yadav N; Patidar M; Tyagi RK; Dalai SK
[Ad] Address:Institute of Science, Nirma University, Ahmedabad, Gujarat, India....
[Ti] Title:Route of administration of attenuated sporozoites is instrumental in rendering immunity against Plasmodia infection.
[So] Source:Vaccine;34(28):3229-34, 2016 Jun 14.
[Is] ISSN:1873-2518
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Whole sporozoite vaccine (WSV) approach has been shown to induce efficient CD8(+) T cell response, critical for developing of long-lasting sterile protection against Plasmodium. Although WSV was initiated over four decades ago, we still do not fully understand about the absolute requirements for the generation of liver-stage specific CD8(+) T memory cells. For more than a decade intravenous (IV) route of immunization has been shown to be protective in pre-clinical studies. However, the intradermal (ID) route is preferred over IV route by many researchers as it is perceived to mimic the natural route of parasite delivery through mosquito bite. Various clinical studies have shown that ID route provokes poor protective responses compared to those seen with IV route of administration. The present study highlights the importance of circumsporozoite (CS) protein in preventing sporozoite entry to the hepatocytes, which however, it is not necessarily sufficient to ensure sterile protection. Instead, this article favors the idea that liver-stage development is a prime requirement for generation of antigen specific CD8(+) T cells and suggests the conditions favored by IV inoculation of sporozoite.
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Em] Entry month:1606
[Js] Journal subset:IM
[St] Status:In-Data-Review

  2 / 282631 MEDLINE  
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[PMID]: 26844377
[Au] Autor:Weng JH; Chung BC
[Ad] Address:Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan; Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
[Ti] Title:Nongenomic actions of neurosteroid pregnenolone and its metabolites.
[So] Source:Steroids;111:54-9, 2016 Jul.
[Is] ISSN:1878-5867
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Steroids have been widely used in the clinical setting. They bind and activate nuclear receptors to regulate gene expression. In addition to activating genomic transcription, steroids also exert nongenomic actions. The current article focuses on the nongenomic actions of neurosteroids, including pregnenolone (P5), 7α-hydroxypregnenolone, pregnenolone sulfate and allopregnanolone. Pregnenolone and its derivatives promote neuronal activity by enhancing learning and memory, relieving depression, enhancing locomotor activity, and promoting neuronal cell survival. They exert these effects by activating various target proteins located in the cytoplasm or cell membrane. Pregnenolone and its metabolites bind to receptors such as microtubule-associated proteins and neurotransmitter receptors to elicit a series of reactions including stabilization of microtubules, increase of ion flux into cells, and dopamine release. The wide actions of neurosteroids indicate that pregnenolone derivatives have great potential in future treatment of neurological diseases.
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Em] Entry month:1606
[Js] Journal subset:IM
[St] Status:In-Data-Review

  3 / 282631 MEDLINE  
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[PMID]: 26980143
[Au] Autor:Georgiev D; Yoshihara T; Kawabata R; Matsubara T; Tsubomoto M; Minabe Y; Lewis DA; Hashimoto T
[Ad] Address:Department of Psychiatry and Neurobiology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan;...
[Ti] Title:Cortical Gene Expression After a Conditional Knockout of 67 kDa Glutamic Acid Decarboxylase in Parvalbumin Neurons.
[So] Source:Schizophr Bull;42(4):992-1002, 2016 Jul.
[Is] ISSN:1745-1701
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:In the cortex of subjects with schizophrenia, expression of glutamic acid decarboxylase 67 (GAD67), the enzyme primarily responsible for cortical GABA synthesis, is reduced in the subset of GABA neurons that express parvalbumin (PV). This GAD67 deficit is accompanied by lower cortical levels of other GABA-associated transcripts, including GABA transporter-1, PV, brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B, somatostatin, GABAA receptor α1 subunit, and KCNS3 potassium channel subunit mRNAs. In contrast, messenger RNA (mRNA) levels for glutamic acid decarboxylase 65 (GAD65), another enzyme for GABA synthesis, are not altered. We tested the hypothesis that this pattern of GABA-associated transcript levels is secondary to the GAD67 deficit in PV neurons by analyzing cortical levels of these GABA-associated mRNAs in mice with a PV neuron-specific GAD67 knockout. Using in situ hybridization, we found that none of the examined GABA-associated transcripts had lower cortical expression in the knockout mice. In contrast, PV, BDNF, KCNS3, and GAD65 mRNA levels were higher in the homozygous mice. In addition, our behavioral test battery failed to detect a change in sensorimotor gating or working memory, although the homozygous mice exhibited increased spontaneous activities. These findings suggest that reduced GAD67 expression in PV neurons is not an upstream cause of the lower levels of GABA-associated transcripts, or of the characteristic behaviors, in schizophrenia. In PV neuron-specific GAD67 knockout mice, increased levels of PV, BDNF, and KCNS3 mRNAs might be the consequence of increased neuronal activity secondary to lower GABA synthesis, whereas increased GAD65 mRNA might represent a compensatory response to increase GABA synthesis.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1606
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1093/schbul/sbw022

  4 / 282631 MEDLINE  
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[PMID]: 26873889
[Au] Autor:Liebers DT; Pirooznia M; Seiffudin F; Musliner KL; Zandi PP; Goes FS
[Ad] Address:Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD;...
[Ti] Title:Polygenic Risk of Schizophrenia and Cognition in a Population-Based Survey of Older Adults.
[So] Source:Schizophr Bull;42(4):984-91, 2016 Jul.
[Is] ISSN:1745-1701
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Cognitive impairment is a common feature of the major psychotic disorders, with deficits often present in at risk individuals and unaffected first-degree relatives. Previous studies have suggested that polygenic risk scores (PRS) for schizophrenia (SCZ) are associated with cognitive deficits, but there has been little examination of this association in longitudinal datasets, or comparison with other disorders. We used mixed models to study the association between PRS for 4 adult onset psychiatric disorders with cross-sectional cognitive performance and longitudinal cognitive decline in 8616 older adults from the Health and Retirement Study (HRS), followed for an average of 10 years. PRS were computed for SCZ, bipolar disorder (BD), Major Depressive Disorder (MDD), and Alzheimer's disease (ALZ). SCZ PRS associated with decreased cognitive function (z = -3.00, P = .001, ΔR (2) = 0.04%), which was largely driven by an association with impaired attention and orientation (z = -3.33, P = 4.3×10(-4), ΔR (2) = 0.08%). We found no effect of BD or MDD PRS on cognition, in contrast to a robust effect of the APOE4/TOMM40 locus (z = -5.05, P = 2.2×10(-7), ΔR (2) = 0.36%), which was primarily associated with impaired verbal memory (z = -5.15, P = 1.3×10(-7), ΔR (2) = 0.21%). APOE4/TOMM40 locus and the ALZ PRS, but not the PRS for SCZ, were associated with greater cognitive decline. In summary, using a large, representative sample of older adults, we found evidence for different degrees of association between polygenic risk for SCZ and genetic risk factors for ALZ on cognitive function and decline, highlighting potential differences in the pathophysiology of cognitive deficits seen in SCZ and ALZ.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1606
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1093/schbul/sbw001

  5 / 282631 MEDLINE  
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[PMID]: 26738528
[Au] Autor:Zhang R; Picchioni M; Allen P; Toulopoulou T
[Ad] Address:Department of Psychology, The University of Hong Kong, Hong Kong, China;...
[Ti] Title:Working Memory in Unaffected Relatives of Patients With Schizophrenia: A Meta-Analysis of Functional Magnetic Resonance Imaging Studies.
[So] Source:Schizophr Bull;42(4):1068-77, 2016 Jul.
[Is] ISSN:1745-1701
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Working memory deficits, a core cognitive feature of schizophrenia may arise from dysfunction in the frontal and parietal cortices. Numerous studies have also found abnormal neural activation during working memory tasks in patients' unaffected relatives. The aim of this study was to systematically identify and anatomically localize the evidence for those activation differences across all eligible studies. Fifteen functional magnetic resonance imaging (fMRI) manuscripts, containing 16 samples of 289 unaffected relatives of patients with schizophrenia, and 358 healthy controls were identified that met our inclusion criteria: (1) used a working memory task; and (2) reported standard space coordinates. Activation likelihood estimation (ALE) identified convergence across studies. Compared to healthy controls, patients' unaffected relatives showed decreases in neural activation in the right middle frontal gyrus (BA9), as well as right inferior frontal gyrus (BA44). Increased activation was seen in relatives in the right frontopolar (BA10), left inferior parietal lobe (BA40), and thalamus bilaterally. These results suggest that the familial risk of schizophrenia is expressed in changes in neural activation in the unaffected relatives in the cortical-subcortical working memory network that includes, but is not restricted to the middle prefrontal cortex.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1606
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1093/schbul/sbv221

  6 / 282631 MEDLINE  
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[PMID]: 26675294
[Au] Autor:Thomas N; Rossell SL; Waters F
[Ad] Address:School of Health Sciences, Swinburne University of Technology, Melbourne, Australia; Monash Alfred Psychiatry Research Centre, The Alfred, Melbourne, Australia;
[Ti] Title:The Changing Face of Hallucination Research: The International Consortium on Hallucination Research (ICHR) 2015 Meeting Report.
[So] Source:Schizophr Bull;42(4):891-5, 2016 Jul.
[Is] ISSN:1745-1701
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:This article reports on the Third Biennial Meeting of the International Consortium on Hallucinations Research, held in Melbourne, Australia, in October 2015. Following a public conference in which research findings were considered in relation to subjective experience and practice, 9 multidisciplinary working groups examined key current issues in progressing the conceptualization and research of hallucinations. Work group topics included: multicenter validation of the transdiagnostic and multimodal Questionnaire for Psychotic Experiences; development of an improved outcome measure for psychological therapies; the relationship between inhibition and hallucinations across multiple levels of explanation; hallucinations in relation to sleep phenomena; emotion and hallucinations; multiple interactions between the experience of self and hallucinations; interactions between language, auditory and memory networks; resting state networks including the default mode; and analyses arising from functional magnetic resonance imaging (fMRI) data-sharing. Major themes in hallucinations research identified during the meeting included (1) progression beyond the auditory verbal modality in schizophrenia to consider hallucinations across modalities and different populations; (2) development of new measures; (3) the central role of multisite collaboration through shared data collection and data pooling; (4) study of time-based and interactive models of hallucination; and (5) the need to increase the accessibility and availability of "real-life" interventions for people with persisting and distressing hallucinations.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1606
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1093/schbul/sbv183

  7 / 282631 MEDLINE  
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[PMID]: 27155457
[Au] Autor:Wong VS; Langley B
[Ad] Address:Burke Medical Research Institute, 785 Mamaroneck Avenue, White Plains, NY 10605, United States.
[Ti] Title:Epigenetic changes following traumatic brain injury and their implications for outcome, recovery and therapy.
[So] Source:Neurosci Lett;625:26-33, 2016 Jun 20.
[Is] ISSN:1872-7972
[Cp] Country of publication:Ireland
[La] Language:eng
[Ab] Abstract:Traumatic brain injury (TBI) contributes to nearly a third of all injury-related deaths in the United States. For survivors of TBI, depending on severity, patients can be left with devastating neurological disabilities that include impaired cognition or memory, movement, sensation, or emotional function. Despite the efforts to identify novel therapeutics, the only strategy to combat TBI is risk reduction (helmets, seatbelts, removal of fall hazards, etc.). Enormous heterogeneity exists within TBI, and it depends on the severity, the location, and whether the injury was focal or diffuse. Evidence from recent studies support the involvement of epigenetic mechanisms such as DNA methylation, chromatin post-translational modification, and miRNA regulation of gene expression in the post-injured brain. In this review, we discuss studies that have assessed epigenetic changes and mechanisms following TBI, how epigenetic changes might not only be limited to the nucleus but also impact the mitochondria, and the implications of these changes with regard to TBI recovery.
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Em] Entry month:1606
[Js] Journal subset:IM
[St] Status:In-Data-Review

  8 / 282631 MEDLINE  
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[PMID]: 26806038
[Au] Autor:Alaghband Y; Bredy TW; Wood MA
[Ad] Address:Department of Neurobiology & Behavior, UC Irvine, USA; Center for the Neurobiology of Learning and Memory, UC Irvine, USA; UC Irvine Center for Addiction Neuroscience, UC Irvine, USA.
[Ti] Title:The role of active DNA demethylation and Tet enzyme function in memory formation and cocaine action.
[So] Source:Neurosci Lett;625:40-6, 2016 Jun 20.
[Is] ISSN:1872-7972
[Cp] Country of publication:Ireland
[La] Language:eng
[Ab] Abstract:Active DNA modification is a major epigenetic mechanism that regulates gene expression in an experience-dependent manner, which is thought to establish stable changes in neuronal function and behavior. Recent discoveries regarding the Ten eleven translocation (Tet1-3) family of DNA hydroxylases have provided a new avenue for the study of active DNA demethylation, and may thus help to advance our understanding of how dynamic DNA modifications lead to long-lasting changes in brain regions underlying learning and memory, as well as drug-seeking and propensity for relapse following abstinence. Drug addiction is a complex, relapsing disorder in which compulsive drug-seeking behavior can persist despite aversive consequences. Therefore, understanding the molecular mechanisms that underlie the onset and persistence of drug addiction, as well as the pronounced propensity for relapse observed in addicts, is necessary for the development of selective treatments and therapies. In this mini-review, we provide an overview of the involvement of active DNA demethylation with an emphasis on the Tet family of enzymes and 5-hydroxymethylcytosine (5-hmC) in learning and memory, as well as in drug-seeking behavior. Memory and addiction share overlapping molecular, cellular, and circuit functions allowing research in one area to inform the other. Current discrepancies and directions for future studies focusing on the dynamic interplay between DNA methylation and demethylation, and how they orchestrate gene expression required for neuronal plasticity underlying memory formation, are discussed.
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Em] Entry month:1606
[Js] Journal subset:IM
[St] Status:In-Data-Review

  9 / 282631 MEDLINE  
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[PMID]: 27078863
[Au] Autor:Zhang Q; Bhalerao A; Dickenson E; Hutchinson C
[Ad] Address:Department of Computer Science, University of Warwick, Coventry, CV4 7AL, UK. Electronic address: qiang@dcs.warwick.ac.uk....
[Ti] Title:Active appearance pyramids for object parametrisation and fitting.
[So] Source:Med Image Anal;32:101-14, 2016 Aug.
[Is] ISSN:1361-8423
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Object class representation is one of the key problems in various medical image analysis tasks. We propose a part-based parametric appearance model we refer to as an Active Appearance Pyramid (AAP). The parts are delineated by multi-scale Local Feature Pyramids (LFPs) for superior spatial specificity and distinctiveness. An AAP models the variability within a population with local translations of multi-scale parts and linear appearance variations of the assembly of the parts. It can fit and represent new instances by adjusting the shape and appearance parameters. The fitting process uses a two-step iterative strategy: local landmark searching followed by shape regularisation. We present a simultaneous local feature searching and appearance fitting algorithm based on the weighted Lucas and Kanade method. A shape regulariser is derived to calculate the maximum likelihood shape with respect to the prior and multiple landmark candidates from multi-scale LFPs, with a compact closed-form solution. We apply the 2D AAP on the modelling of variability in patients with lumbar spinal stenosis (LSS) and validate its performance on 200 studies consisting of routine axial and sagittal MRI scans. Intervertebral sagittal and parasagittal cross-sections are typically used for the diagnosis of LSS, we therefore build three AAPs on L3/4, L4/5 and L5/S1 axial cross-sections and three on parasagittal slices. Experiments show significant improvement in convergence range, robustness to local minima and segmentation precision compared with Constrained Local Models (CLMs), Active Shape Models (ASMs) and Active Appearance Models (AAMs), as well as superior performance in appearance reconstruction compared with AAMs. We also validate the performance on 3D CT volumes of hip joints from 38 studies. Compared to AAMs, AAPs achieve a higher segmentation and reconstruction precision. Moreover, AAPs have a significant improvement in efficiency, consuming about half the memory and less than 10% of the training time and 15% of the testing time.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1606
[Js] Journal subset:IM
[St] Status:In-Data-Review

  10 / 282631 MEDLINE  
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[PMID]: 27015792
[Au] Autor:Ryali S; Chen T; Supekar K; Tu T; Kochalka J; Cai W; Menon V
[Ad] Address:Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, United States. Electronic address: sryali@stanford.edu....
[Ti] Title:Multivariate dynamical systems-based estimation of causal brain interactions in fMRI: Group-level validation using benchmark data, neurophysiological models and human connectome project data.
[So] Source:J Neurosci Methods;268:142-53, 2016 Aug 1.
[Is] ISSN:1872-678X
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:BACKGROUND: Causal estimation methods are increasingly being used to investigate functional brain networks in fMRI, but there are continuing concerns about the validity of these methods. NEW METHOD: Multivariate dynamical systems (MDS) is a state-space method for estimating dynamic causal interactions in fMRI data. Here we validate MDS using benchmark simulations as well as simulations from a more realistic stochastic neurophysiological model. Finally, we applied MDS to investigate dynamic casual interactions in a fronto-cingulate-parietal control network using human connectome project (HCP) data acquired during performance of a working memory task. Crucially, since the ground truth in experimental data is unknown, we conducted novel stability analysis to determine robust causal interactions within this network. RESULTS: MDS accurately recovered dynamic causal interactions with an area under receiver operating characteristic (AUC) above 0.7 for benchmark datasets and AUC above 0.9 for datasets generated using the neurophysiological model. In experimental fMRI data, bootstrap procedures revealed a stable pattern of causal influences from the anterior insula to other nodes of the fronto-cingulate-parietal network. COMPARISON WITH EXISTING METHODS: MDS is effective in estimating dynamic causal interactions in both the benchmark and neurophysiological model based datasets in terms of AUC, sensitivity and false positive rates. CONCLUSIONS: Our findings demonstrate that MDS can accurately estimate causal interactions in fMRI data. Neurophysiological models and stability analysis provide a general framework for validating computational methods designed to estimate causal interactions in fMRI. The right anterior insula functions as a causal hub during working memory.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1606
[Js] Journal subset:IM
[St] Status:In-Data-Review


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