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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Jie Xian Dong; Yongam Lee; Michael Kirmiz; Stephanie Palacio; +8 Authors

    Nanobodies (nAbs) are small, minimal antibodies that have distinct attributes that make them uniquely suited for certain biomedical research, diagnostic and therapeutic applications. Prominent uses include as intracellular antibodies or intrabodies to bind and deliver cargo to specific proteins and/or subcellular sites within cells, and as nanoscale immunolabels for enhanced tissue penetration and improved spatial imaging resolution. Here, we report the generation and validation of nAbs against a set of proteins prominently expressed at specific subcellular sites in mammalian brain neurons. We describe a novel hierarchical validation pipeline to systematically evaluate nAbs isolated by phage display for effective and specific use as intrabodies and immunolabels in mammalian cells including brain neurons. These nAbs form part of a robust toolbox for targeting proteins with distinct and highly spatially-restricted subcellular localization in mammalian brain neurons, allowing for visualization and/or modulation of structure and function at those sites.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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    Europe PubMed Central
    Article . 2019
    Data sources: PubMed Central
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
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    Article . 2019
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    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    eLife
    Article . 2019 . Peer-reviewed
    License: CC BY
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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      Europe PubMed Central
      Article . 2019
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      DOAJ-Articles
      Article . 2019
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      eLife
      Article . 2019 . Peer-reviewed
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Pan, Xinlei; Qian, Tianyi; Fernandez-Seara, Maria A; Smith, Robert X; +4 Authors

    ORIGINAL RESEARCH Quantification of Liver Perfusion Using Multidelay Pseudocontinuous Arterial Spin Labeling Xinlei Pan, BS, 1 Tianyi Qian, PhD, 2 Maria A. Fernandez-Seara, PhD, 3 Robert X. Smith, PhD, 4 Kuncheng Li, MD, PhD, 5 Kui Ying, PhD, 6 Kyunghyun Sung, PhD, 7 and Danny J.J. Wang, PhD, MSCE 4,7 * Purpose: To develop a free-breathing multidelay pseudocontinuous arterial spin labeling (pCASL) technique for quanti- tative measurement of liver perfusion of the hepatic artery and portal vein, respectively. Materials and Methods: A navigator-gated pCASL sequence with balanced steady-state free precession (bSSFP) read- out was developed and applied on five healthy young volunteers at 3T. Two labeling schemes were performed with the labeling plane applied on the descending aorta above the liver, and perpendicular to the portal vein before its entry to liver to label the hepatic artery and portal vein, respectively. For each labeling scheme, pCASL scans were performed at five or six postlabeling delays between 200 and 2000 msec or 2500 msec with an interval of 400 or 500 msec. Multide- lay pCASL images were processed offline with nonrigid motion correction, outlier removal, and fitted for estimation of liver perfusion and transit time. Results: Estimated liver perfusion of the hepatic artery and hepatic portal vein were 21.8 6 1.9 and 95.1 6 8.9 mL/100g/ min, with the corresponding transit time of 1227.3 6 355.5 and 667.2 6 85.0 msec, respectively. The estimated liver per- fusion and transit time without motion correction were less reliable with greater residual variance compared to those processed with motion correction (P < 0.05). Conclusion: The liver perfusion measurement using multidelay pCASL showed good correspondence with values noted in the literature. The capability to noninvasively and selectively label the hepatic artery and portal vein is a unique strength of pCASL as compared to other liver perfusion imaging techniques, such as computed tomography perfusion and dynamic contrast-enhanced MRI. J. MAGN. RESON. IMAGING 2015;00:000–000. L iver diseases afflict more than 30 million people in the US, or 1 in 10 Americans. 1 The number of people diag- nosed with liver diseases such as hepatitis C, nonalcoholic fatty liver disease, and liver cancer are on the rise both in the US and worldwide. 2 Liver ultrasonography and magnetic res- onance imaging (MRI) are the two main imaging modalities for detecting, characterizing, and monitoring treatment responses of focal and diffuse liver diseases. 3–5 Ultrasonogra- phy remains the first-line imaging modality for examining liver morphology and blood flow; these are accentuated through the recent development of elastography. MRI offers multiparametric examinations of the morphology, perfusion, and diffusion of the liver. Dynamic contrast-enhanced (DCE) MRI and MR elastography (MRE) are two emerging tech- nologies capable of quantitative assessments of liver perfu- sion/permeability and viscoelasticity, respectively. Liver perfusion imaging is useful in detecting regional and global alterations in liver blood flow caused by a range View this article online at wileyonlinelibrary.com. DOI: 10.1002/jmri.25070 Received Jul 4, 2015, Accepted for publication Sep 24, 2015. *Address reprint requests to: D.J.J.W., Laboratory of Functional MRI Technology (LOFT), Department of Neurology, UCLA, 660 Charles E Young Dr. South, Los Angeles, CA 90095. E-mail: jwang71@gmail.com From the 1 Department of Biomedical Engineering, Tsinghua University, Beijing, China; 2 Siemens Healthcare, MR Collaboration NE Asia, Beijing, China; Neuroimaging Laboratory, Division of Neuroscience, Center for Applied Medical Research, University of Navarra, Spain; 4 Laboratory of Functional MRI Technology (LOFT), Department of Neurology, University of California Los Angeles, Los Angeles, California, USA; 5 Department of Radiology, Xuanwu Hospital of Capital Medical University, Beijing, China; 6 Department of Engineering Physics, Tsinghua University, Beijing, China; and 7 Department of Radiology, University of California Los Angeles, Los Angeles, California, USA. Additional Supporting Information may be found in the online version of this article. C 2015 Wiley Periodicals, Inc. V

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ eScholarship - Unive...arrow_drop_down
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    Journal of Magnetic Resonance Imaging
    Article . 2015 . Peer-reviewed
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ eScholarship - Unive...arrow_drop_down
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
      Journal of Magnetic Resonance Imaging
      Article . 2015 . Peer-reviewed
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Joshua D. Crapser; Miguel A. Arreola; Kate I. Tsourmas; Kim N. Green;

    AbstractMicroglia shape the synaptic environment in health and disease, but synapses do not exist in a vacuum. Instead, pre- and postsynaptic terminals are surrounded by extracellular matrix (ECM), which together with glia comprise the four elements of the contemporary tetrapartite synapse model. While research in this area is still just beginning, accumulating evidence points toward a novel role for microglia in regulating the ECM during normal brain homeostasis, and such processes may, in turn, become dysfunctional in disease. As it relates to synapses, microglia are reported to modify the perisynaptic matrix, which is the diffuse matrix that surrounds dendritic and axonal terminals, as well as perineuronal nets (PNNs), specialized reticular formations of compact ECM that enwrap neuronal subsets and stabilize proximal synapses. The interconnected relationship between synapses and the ECM in which they are embedded suggests that alterations in one structure necessarily affect the dynamics of the other, and microglia may need to sculpt the matrix to modify the synapses within. Here, we provide an overview of the microglial regulation of synapses, perisynaptic matrix, and PNNs, propose candidate mechanisms by which these structures may be modified, and present the implications of such modifications in normal brain homeostasis and in disease.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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    Europe PubMed Central
    Article . 2021
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    Cellular and Molecular Immunology
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    Cellular and Molecular Immunology
    Article . 2021 . Peer-reviewed
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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      Europe PubMed Central
      Article . 2021
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      Cellular and Molecular Immunology
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      Cellular and Molecular Immunology
      Article . 2021 . Peer-reviewed
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Buijsen, Ronald; Sellier, C; Severijnen, Lies-anne; Oulad-Abdelghani, M; +5 Authors

    Fragile X-associated Tremor/Ataxia syndrome (FXTAS), a late-onset monogenetic neurodegenerative disorder, is caused by a CGG-repeat expansion (55-200) in the 5′ UTR of the fragile-X mental retardation 1 gene (FMR1) on the X-chromosome [1]. The prevalence of the FMR1 premutation (PM) is about 1:855 in males and 1:291 in females [2]. Approximately 45.5% of male and 16.5% of female PM carriers older than 50 years will develop signs of FXTAS [3]. In addition to the core features of tremor and gait ataxia, unexplained medical co-morbidities have been reported, including thyroid disease, cardiac arrhythmias, hypertension, migraine, impotence, and neuropathy [4]. PM carriers have increased levels of FMR1 mRNA (2 to 8 fold in leucocytes) and normal to slightly reduced FMR1 protein (FMRP) levels [5]. The current hypothesis is that FXTAS is caused by an RNA gain-of-function mechanism. Ubiquitin-positive intranuclear inclusions, are found in both brain and non-central nervous system (CNS) organs of patients with FXTAS [6,7]. So far, it is not clear whether these inclusions are protective or toxic. Recently, it has been hypothesized that repeat-associated non-AUG (RAN) translation plays a role in disease process and inclusion formation. Todd et al. [8] demonstrated that through initiation at a near-ATG codon located in the 5′UTR of the FMR1 gene a polyGlycine-containing protein, FMRpolyG, is expressed. This protein accumulates in ubiquitin-positive inclusions in Drosophila, cell culture, mouse disease models and brain from FXTAS patients. To investigate the link between FMRpolyG expression and the co-morbid medical problems associated with the PM we have developed two novel mouse monoclonal antibodies against polyGlycine; 8FM and 9FM (for epitopes and specificity see Additional file 1: Figure S1), and performed immunostaining in CNS as well as in non-CNS organs of FXTAS patient J.L. (case 6 in [7]; other cases not available). To establish antibody specificity, we performed immunostaining with both antibodies on brain sections from FXTAS patient J.L., healthy non-demented controls (n = 3) and a patient with Parkinson disease, Alzheimer disease, or C9FTD. In hippocampus and cerebellum from FXTAS patient J.L. we identified FMRpolyG-positive inclusions with both 8FM (1:10) and 9FM (1:10) antibody (Figure 1a-b, Additional file 2: Figure S2a-b), as was described previously [8]. None of the controls showed FMRpolyG-positive inclusions (data not shown). Next, we studied the immunolocalization of FMRpolyG protein in heart, kidney, adrenal gland and thyroid in patient J.L. with 8FM (1:10) and 9FM (1:10), compared to post mortem non-CNS somatic organ tissues from 3 healthy controls. We also examined tissues for FMRP (mouse T1A; 1:200) expression and ubiquitin-positive inclusions (DAKO, ZO458; 1:200). Consistent with our previous report [7], ubiquitin-positive intranuclear inclusions were identified along with a normal distribution of FMRP (data not shown). Intranuclear FMRpolyG-positive inclusions could be detected in all organs examined (Figure 1c-h, Additional file 2: Figure S2c-h). No control tissues showed any FMRpolyG-positive inclusions (data not shown). Colocalization of ubiquitin- and FMRpolyG-positive inclusions was visualized and quantified by immunofluorescent double staining using antibodies against ubiquitin and FMRpolyG (8FM) (Figure 2a-f). For hippocampus, cerebellum and the non-CNS organs most inclusions are positive for both FMRpolyG and ubiquitin, although some rare inclusions positive for only one of the proteins could also be detected (Figure 2g, n = 100 inclusions). In conclusion, using two novel antibodies the present report not only confirms the existence of FMRpolyG-positive aggregates in CNS tissue from a FXTAS individual but also demonstrates for the first time the presence of FMRpolyG-positive intranuclear inclusions in post mortem non-CNS material of a PM carrier with FXTAS. Furthermore, colocalization of FMRpolyG and ubiquitin is found in the vast majority of inclusions. The presence of FMRpolyG-positive intranuclear inclusions in heart, kidney, adrenal gland and thyroid is consistent with the unexplained medical co-morbidities reported in some patients with FXTAS, including thyroid disease, cardiac arrhythmias, hypertension, migraine, impotence, and neuropathy. We hypothesize that the underlying pathological mechanisms of the medical co-morbidities in systemic tissues share common features (protein toxic gain-of-function) with CNS pathology of patients with FXTAS. Our report suggests that in addition to elevated levels of FMR1 mRNA containing an expanded CGG repeat, and ubiquitin-positive inclusions, FMRpolyG expression might also play a role in a toxic gain-of-function mechanism in medical co-morbidities in FXTAS (RNA versus FMRpolyG toxic gain-of-function). Interestingly, a very recent report suggests that RAN translation products in C9FTD/ALS, toxic dipeptide repeat proteins (poly-(glycine-arginine) and poly-(proline-arginine)), are toxic in Drosophila [9]. Further research is needed to understand how FMRpolyG may elicit toxicity in both CNS and non-CNS organs and its precise role in co-morbidities in PM carriers. Importantly, if FMRpolyG production is important for cellular toxicity this will open new avenues for therapeutic intervention studies for FXTAS by developing drugs that block this aberrant translation. Figure 1 9FM FMRpolyG-positive intranuclear inclusions in hippocampus, cerebellum and non-CNS tissues of a FXTAS patient. FMRpolyG-positive (9FM) intranuclear inclusions in a hippocampus, b cerebellum, c glomeruli and d distal tubule of the kidney, e zona glomerulosa ... Figure 2 Colocalization of FMRpolyG (8FM) and ubiquitin in intranuclear inclusions in hippocampus, cerebellum and of non-CNS tissues of a FXTAS patient. Staining for ubiquitin (green), FMRpolyG (8FM; red) and DAPI (blue). Colocalization of ubiquitin and FMRpolyG ...

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    Europe PubMed Central
    Article . 2014
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    Acta Neuropathologica Communications
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    Article . 2014
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      Europe PubMed Central
      Article . 2014
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      Acta Neuropathologica Communications
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    Authors: Mchughen, S.; Rodriguez, P.; Kleim, J.; Kleim, E.; +3 Authors

    International audience; Brain-derived neurotrophic factor (BDNF) is important to brain functions such as plasticity and repair. A single nucleotide polymorphism for this growth factor, val(66)met, is common and associated with decreased activity-dependent BDNF release. The current study evaluated the effects of this polymorphism in relation to human brain motor system function, short-term plasticity, and learning. Functional magnetic resonance imaging (fMRI) scanning during right index finger movement (n = 24) identified activation in a broad sensorimotor network. However, subjects with the polymorphism showed smaller activation volume within several brain regions as compared with subjects without the polymorphism. Repeat fMRI after 25 min of right index finger training found that the 2 genotype groups modulated brain activation differently. In several brain regions, subjects with the polymorphism showed greater activation volume reduction, whereas subjects without the polymorphism showed greater activation volume expansion. On a driving-based motor learning task (independent cohort, n = 29), subjects with the polymorphism showed greater error during short-term learning and poorer retention over 4 days, relative to subjects without the polymorphism. The presence of this BDNF polymorphism is associated with differences in brain motor system function, altered short-term plasticity, and greater error in short-term motor learning. The broader implications of these findings are considered.

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    Europe PubMed Central
    Other literature type . 2009
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    Cerebral Cortex
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    https://doi.org/10.7892/boris....
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    Article . 2010
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    Cerebral Cortex
    Article . 2009 . Peer-reviewed
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      Europe PubMed Central
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      Cerebral Cortex
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      https://doi.org/10.7892/boris....
      Other literature type . 2010
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      Cerebral Cortex
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    Authors: Gruber, Matthias J.; Gelman, Bernard D.; Ranganath, Charan;

    SummaryPeople find it easier to learn about topics that interest them, but little is known about the mechanisms by which intrinsic motivational states affect learning. We used functional magnetic resonance imaging to investigate how curiosity (intrinsic motivation to learn) influences memory. In both immediate and one-day-delayed memory tests, participants showed improved memory for information that they were curious about and for incidental material learned during states of high curiosity. Functional magnetic resonance imaging results revealed that activity in the midbrain and the nucleus accumbens was enhanced during states of high curiosity. Importantly, individual variability in curiosity-driven memory benefits for incidental material was supported by anticipatory activity in the midbrain and hippocampus and by functional connectivity between these regions. These findings suggest a link between the mechanisms supporting extrinsic reward motivation and intrinsic curiosity and highlight the importance of stimulating curiosity to create more effective learning experiences.Video Abstract

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    Neuron
    Article . 2014 . Peer-reviewed
    License: Elsevier Non-Commercial
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    Europe PubMed Central
    Other literature type . 2014
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      Neuron
      Article . 2014 . Peer-reviewed
      License: Elsevier Non-Commercial
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      Europe PubMed Central
      Other literature type . 2014
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    Authors: Julia A Scott; Duygu Tosun; Meredith N Braskie; Pauline Maillard; +4 Authors

    The purpose of this study was to determine whether white matter microstructure measured by diffusion magnetic resonance imaging (dMRI) provides independent information about baseline level or change in executive function (EF) or memory (MEM) in older adults with and without cognitive impairment. Longitudinal data was acquired from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study from phases GO and 2 (2009–2015). ADNI participants included were diagnosed as cognitively normal (n = 46), early mild cognitive impairment (MCI) (n = 48), late MCI (n = 29), and dementia (n = 39) at baseline. We modeled the association between dMRI-based global white matter mean diffusivity (MD) and baseline level and change in EF and MEM composite scores, in models controlling for baseline bilateral hippocampal volume, regional cerebral FDG PET metabolism and global cerebral AV45 PET uptake. EF and MEM composite scores were measured at baseline, 6, 12, 24 and 36 months. In the baseline late MCI and dementia groups, greater global MD was associated with lesser baseline EF, but not EF change nor MEM baseline or change. As expected, lesser hippocampal volume and lesser FDG PET metabolism was associated with greater rates of EF and MEM decline. In ADNI-GO/2 participants, white matter integrity provided independent information about current executive function, but was not sensitive to future cognitive change. Since individuals experiencing executive function declines progress to dementia more rapidly than those with only memory impairment, better biomarkers of future executive function decline are needed. Highlights • In the ADNI cohort, MRI and PET predictors of baseline and change in executive function were tested. • Global mean diffusivity was associated with baseline, but not change in, executive function. • Diffusion MRI provides independent information on current executive function in older adults.

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    Europe PubMed Central
    Article . 2017
    Data sources: PubMed Central
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    NeuroImage: Clinical
    Article . 2017 . Peer-reviewed
    License: CC BY NC ND
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    NeuroImage: Clinical
    Article . 2017
    Data sources: DOAJ-Articles
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      Europe PubMed Central
      Article . 2017
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      NeuroImage: Clinical
      Article . 2017 . Peer-reviewed
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      NeuroImage: Clinical
      Article . 2017
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    Authors: Vincent, Degos; Mervyn, Maze; Susana, Vacas; Jan, Hirsch; +7 Authors

    Abstract Background: Bone fracture increases alarmins and proinflammatory cytokines in the blood, and provokes macrophage infiltration and proinflammatory cytokine expression in the hippocampus. We recently reported that stroke is an independent risk factor after bone surgery for adverse outcome; however, the impact of bone fracture on stroke outcome remains unknown. We tested the hypothesis that bone fracture, shortly after ischemic stroke, enhances stroke-related injuries by augmenting the neuroinflammatory response. Methods: Tibia fracture (bone fracture) was induced in mice one day after permanent occlusion of the distal middle cerebral artery (stroke). High-mobility-group box chromosomal protein-1 (HMGB1) was tested to mimic the bone fracture effects. HMGB1 neutralizing antibody and clodrolip (macrophage depletion) were tested to attenuate the bone fracture effects. Neurobehavioral function (n = 10), infarct volume, neuronal death, and macrophages/microglia infiltration (n = 6–7) were analyzed after 3 days. Results: We found that mice with both stroke and bone fracture had larger infarct volumes (mean percentage of ipsilateral hemisphere ± SD: 30±7% vs.12±3%, n = 6, P &lt; 0.001), more severe neurobehavioral dysfunction, and more macrophages/microglia in the periinfarct region than mice with stroke only. Intraperitoneal injection of HMGB1 mimicked, whereas neutralizing HMGB1 attenuated, the bone fracture effects and the macrophage/microglia infiltration. Depleting macrophages with clodrolip also attenuated the aggravating effects of bone fracture on stroke lesion and behavioral dysfunction. Conclusions: These novel findings suggest that bone fracture shortly after stroke enhances stroke injury via augmented inflammation through HMGB1 and macrophage/microglia infiltration. Interventions to modulate early macrophage/microglia activation could be therapeutic goals to limit the adverse consequences of bone fracture after stroke.

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    Europe PubMed Central
    Other literature type . 2013
    Data sources: PubMed Central
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    Anesthesiology
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    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Anesthesiology
    Article . 2013 . Peer-reviewed
    Data sources: Crossref; NARCIS
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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      Europe PubMed Central
      Other literature type . 2013
      Data sources: PubMed Central
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      Anesthesiology
      Article
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
      Anesthesiology
      Article . 2013 . Peer-reviewed
      Data sources: Crossref; NARCIS
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Sava Sakadžić; Emmanuel Roussakis; Mohammad A. Yaseen; Emiri T. Mandeville; +7 Authors

    The ability to measure oxygen partial pressure (pO2) with high temporal and spatial resolution in three dimensions is crucial for understanding oxygen delivery and consumption in normal and diseased brain. Among existing pO2 measurement methods, phosphorescence quenching is optimally suited for the task. However, previous attempts to couple phosphorescence with two-photon laser scanning microscopy have faced substantial difficulties because of extremely low two-photon absorption cross-sections of conventional phosphorescent probes. Here, we report the first practical in vivo two-photon high-resolution pO2 measurements in small rodents’ cortical microvasculature and tissue, made possible by combining an optimized imaging system with a two-photon-enhanced phosphorescent nanoprobe. The method features a measurement depth of up to 250 µm, sub-second temporal resolution and requires low probe concentration. Most importantly, the properties of the probe allowed for the first direct high-resolution measurement of cortical extravascular (tissue) pO2, opening numerous possibilities for functional metabolic brain studies.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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    Europe PubMed Central
    Article . 2010
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    Nature Methods
    Article
    License: implied-oa
    Data sources: UnpayWall
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Nature Methods
    Article . 2010 . Peer-reviewed
    License: Springer TDM
    Data sources: Crossref
    Nature Methods
    Article . 2009
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      Europe PubMed Central
      Article . 2010
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      Nature Methods
      Article
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
      Nature Methods
      Article . 2010 . Peer-reviewed
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      Article . 2009
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Srivastava, Gyan; Lunnon, Katie; Burgess, Jeremy; Yu, Lei; +27 Authors

    We used a collection of 708 prospectively collected autopsied brains to assess the methylation state of the brain's DNA in relation to Alzheimer's disease (AD). We found that the level of methylation at 71 of the 415,848 interrogated CpGs was significantly associated with the burden of AD pathology, including CpGs in the ABCA7 and BIN1 regions, which harbor known AD susceptibility variants. We validated 11 of the differentially methylated regions in an independent set of 117 subjects. Furthermore, we functionally validated these CpG associations and identified the nearby genes whose RNA expression was altered in AD: ANK1, CDH23, DIP2A, RHBDF2, RPL13, SERPINF1 and SERPINF2. Our analyses suggest that these DNA methylation changes may have a role in the onset of AD given that we observed them in presymptomatic subjects and that six of the validated genes connect to a known AD susceptibility gene network. National Institutes of Health (U.S.) (Grant K25 AG041906-01) National Institutes of Health (U.S.) (Grant KL2 RR024151) National Institutes of Health (U.S.) (Grant U01 ES017155) National Institutes of Health (U.S.) (Grant RC2 AG036547) National Institutes of Health (U.S.) (Grant P50 AG016574) National Institutes of Health (U.S.) (Grant R01 AG032990) National Institutes of Health (U.S.) (Grant R01 AG036042) National Institutes of Health (U.S.) (Grant R01 AG17917) National Institutes of Health (U.S.) (Grant R01 AG18023) National Institutes of Health (U.S.) (Grant R01AG036836) National Institutes of Health (U.S.) (Grant P30 AG10161) National Institutes of Health (U.S.) (Grant R01AG15819)

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Nature Neurosciencearrow_drop_down
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    Nature Neuroscience
    Article . 2014
    Data sources: PubMed Central
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Nature Neuroscience
    Article
    License: implied-oa
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    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    DSpace@MIT
    Article . 2014
    License: CC BY NC SA
    Data sources: DSpace@MIT
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Nature Neuroscience
    Article . 2014 . Peer-reviewed
    License: Springer TDM
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      Nature Neuroscience
      Article . 2014
      Data sources: PubMed Central
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      Nature Neuroscience
      Article
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      DSpace@MIT
      Article . 2014
      License: CC BY NC SA
      Data sources: DSpace@MIT
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
      Nature Neuroscience
      Article . 2014 . Peer-reviewed
      License: Springer TDM
      Data sources: Crossref
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Jie Xian Dong; Yongam Lee; Michael Kirmiz; Stephanie Palacio; +8 Authors

    Nanobodies (nAbs) are small, minimal antibodies that have distinct attributes that make them uniquely suited for certain biomedical research, diagnostic and therapeutic applications. Prominent uses include as intracellular antibodies or intrabodies to bind and deliver cargo to specific proteins and/or subcellular sites within cells, and as nanoscale immunolabels for enhanced tissue penetration and improved spatial imaging resolution. Here, we report the generation and validation of nAbs against a set of proteins prominently expressed at specific subcellular sites in mammalian brain neurons. We describe a novel hierarchical validation pipeline to systematically evaluate nAbs isolated by phage display for effective and specific use as intrabodies and immunolabels in mammalian cells including brain neurons. These nAbs form part of a robust toolbox for targeting proteins with distinct and highly spatially-restricted subcellular localization in mammalian brain neurons, allowing f