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Ryan K C Yuen, Daniele Merico, Hongzhi Cao, Giovanna Pellecchia, Babak Alipanahi, Bhooma Thiruvahindrapuram, Xin Tong, Yuhui Sun, Dandan Cao, Tao Zhang, Xueli Wu, Xin Jin, Ze Zhou, Xiaomin Liu, Thomas Nalpathamkalam, Susan Walker, Jennifer L Howe, Zhuozhi Wang, Jeffrey R MacDonald, Ada Chan, Lia D'Abate, Eric Deneault, Michelle T Siu, Kristiina Tammimies, Mohammed Uddin, Mehdi Zarrei, Mingbang Wang, Yingrui Li, Jun Wang, Jian Wang, Huanming Yang, Matt Bookman, Jonathan Bingham, Samuel S Gross, Dion Loy, Mathew Pletcher, Christian R Marshall, Evdokia Anagnostou, Lonnie Zwaigenbaum, Rosanna Weksberg, Bridget A Fernandez, Wendy Roberts, Peter Szatmari, David Glazer, Brendan J Frey, Robert H Ring, Xun Xu, Stephen W Scherer
De novo mutations (DNMs) are important in Autism Spectrum Disorder (ASD), but so far analyses have mainly been on the ~1.5% of the genome encoding genes. Here, we performed whole genome sequencing (WGS) of 200 ASD parent-child trios and characterized germline and somatic DNMs. We confirmed that the majority of germline DNMs (75.6%) originated from the father, and these increased significantly with paternal age only (p=4.2×10(-10)). However, when clustered DNMs (those within 20kb) were found in ASD, not only did they mostly originate from the mother (p=7...
August 3, 2016: NPJ Genomic Medicine
Isabelle Chang, Marta Parrilla
Homeodomain proteins are encoded by homeobox genes and regulate development and differentiation in many neuronal systems. The mouse vomeronasal organ (VNO) generates in situ mature chemosensory neurons from stem cells. The roles of homeodomain proteins in neuronal differentiation in the VNO are poorly understood. Here we have characterized the expression patterns of 28 homeobox genes in the VNO of C57BL/6 mice at postnatal stages using multicolor fluorescent in situ hybridization. We identified 11 homeobox genes (Dlx3, Dlx4, Emx2, Lhx2, Meis1, Pbx3, Pknox2, Pou6f1, Tshz2, Zhx1, Zhx3) that were expressed exclusively in neurons; 4 homeobox genes (Pax6, Six1, Tgif1, Zfhx3) that were expressed in all non-neuronal cell populations, with Pax6, Six1 and Tgif1 also expressed in some neuronal progenitors and precursors; 12 homeobox genes (Adnp, Cux1, Dlx5, Dlx6, Meis2, Pbx2, Pknox1, Pou2f1, Satb1, Tshz1, Tshz3, Zhx2) with expression in both neuronal and non-neuronal cell populations; and one homeobox gene (Hopx) that was exclusively expressed in the non-sensory epithelium...
July 2016: Gene Expression Patterns: GEP
Lilah M Besser, Michael L Alosco, Liliana Ramirez Gomez, Xiao-Hua Zhou, Ann C McKee, Robert A Stern, John Gunstad, Julie A Schneider, Helena Chui, Walter A Kukull
Vascular risk factors (VRFs) have been associated with clinically diagnosed Alzheimer disease (AD), but few studies have examined the association between VRF and AD neuropathology (ADNP) in cognitively normal individuals. We used longitudinal data from the National Alzheimer's Disease Center's Uniform Data Set and Neuropathology Data Set to examine the association between VRF and ADNP (moderate to frequent neuritic plaques; Braak stage III-VI) in those with normal cognition. Our sample included 53 participants with ADNP and 140 without ADNP...
August 11, 2016: Journal of Neuropathology and Experimental Neurology
Suresh Ambati, Ping Yu, Elizabeth C McKinney, Muthugapatti K Kandasamy, Diane Hartzell, Clifton A Baile, Richard B Meagher
BACKGROUND: Obesity-related comorbidities are thought to result from the reprogramming of the epigenome in numerous tissues and cell types, and in particular, mature adipocytes within visceral and subcutaneous adipose tissue, VAT and SAT. The cell-type specific chromatin remodeling of mature adipocytes within VAT and SAT is poorly understood, in part, because of the difficulties of isolating and manipulating large fragile mature adipocyte cells from adipose tissues. METHODS: We constructed MA-INTACT (Mature Adipocyte-Isolation of Nuclei TAgged in specific Cell Types) mice using the adiponectin (ADIPOQ) promoter (ADNp) to tag the surface of mature adipocyte nuclei with a reporter protein...
2016: BMC Obesity
Yun Sol Jo, Min Sung Kim, Nam Jin Yoo, Sug Hyung Lee, Sang Yong Song
No abstract text is available yet for this article.
October 2016: Scandinavian Journal of Gastroenterology
İbrahim Halil Yelkenli, Emel Ulupinar, Orhan Tansel Korkmaz, Erol Şener, Gökhan Kuş, Zeynep Filiz, Neşe Tunçel
The neurotoxin 6-hydroxydopamine (6-OHDA) is widely used in animal models of Parkinson's disease. In various neurodegenerative diseases, astrocytes play direct, active, and critical roles in mediating neuronal survival and functions. Vasoactive intestinal peptide (VIP) has neurotrophic actions and modulates a number of astrocytic activities. In this study, the effects of VIP on the striatal neurochemistry were investigated in parkinsonian rats. Adult Sprague-Dawley rats were divided into sham-operated, unilaterally 6-OHDA-lesioned, and lesioned + VIP-administered (25 ng/kg i...
June 2016: Journal of Molecular Neuroscience: MN
Małgorzata Krajewska-Walasek, Dorota Jurkiewicz, Dorota Piekutowska-Abramczuk, Marzena Kucharczyk, Krystyna H Chrzanowska, Aleksandra Jezela-Stanek, Elżbieta Ciara
No abstract text is available yet for this article.
June 2016: American Journal of Medical Genetics. Part A
Illana Gozes, Celine Helsmoortel, Geert Vandeweyer, Nathalie Van der Aa, Frank Kooy, Sandra Bedrosian Sermone
No abstract text is available yet for this article.
April 2016: Journal of Molecular Neuroscience: MN
Yaping Chu, Gerardo A Morfini, Jeffrey H Kordower
BACKGROUND: Activity-dependent neuroprotective protein (ADNP) is essential for brain formation and neuronal survival. It is possible that intracellular alpha-synuclein (α-syn) inclusions may be due to, or may cause, down-regulation of ADNP expression. OBJECTIVE: This study were to determine whether ADNP protein levels are altered in nigral dopaminergic neurons, establish whether ADNP alterations are associated with α-syn accumulation, and evaluate potential correlations between levels of ADNP expression and axonal transport motor proteins in sporadic and experimental Parkinson's disease (PD)...
2016: Journal of Parkinson's Disease
Illana Gozes, Shlomo Sragovich, Yulie Schirer, Anat Idan-Feldman
NAPVSIPQ (NAP) and all D-amino acid SALLRSIPA (D-SAL) are neuroprotective peptides derived from activity-dependent neuroprotective protein (ADNP) and activity-dependent neurotrophic factor (ADNF), respectively. Both proteins were shown to protect against cognitive impairment, using different animal models and to increase neuronal survival following exposure to neurotoxins. NAP was extensively tested and found to increase microtubule stability, protect axonal transport, and inhibit apoptosis. Here, we aimed to further evaluate and correlate effects at the behavioral level, in a rat model of diabetes...
June 2016: Journal of Molecular Neuroscience: MN
N Amram, G Hacohen-Kleiman, S Sragovich, A Malishkevich, J Katz, O Touloumi, R Lagoudaki, N C Grigoriadis, E Giladi, A Yeheskel, M Pasmanik-Chor, Y Jouroukhin, I Gozes
Activity-dependent neuroprotective protein (ADNP), essential for brain formation, is a frequent autism spectrum disorder (ASD)-mutated gene. ADNP associates with microtubule end-binding proteins (EBs) through its SxIP motif, to regulate dendritic spine formation and brain plasticity. Here, we reveal SKIP, a novel four-amino-acid peptide representing an EB-binding site, as a replacement therapy in an outbred Adnp-deficient mouse model. We discovered, for the first time, axonal transport deficits in Adnp(+/-) mice (measured by manganese-enhanced magnetic resonance imaging), with significant male-female differences...
October 2016: Molecular Psychiatry
Anna Malishkevich, Gad A Marshall, Aaron P Schultz, Reisa A Sperling, Judith Aharon-Peretz, Illana Gozes
Biomarkers for Alzheimer's disease (AD) are vital for disease detection in the clinical setting. Discovered in our laboratory, activity-dependent neuroprotective protein (ADNP) is essential for brain formation and linked to cognitive functions. Here, we revealed that blood borne expression of ADNP and its paralog ADNP2 is correlated with premorbid intelligence, AD pathology, and clinical stage. Age adjustment showed significant associations between: 1) higher premorbid intelligence and greater serum ADNP, and 2) greater cortical amyloid and lower ADNP and ADNP2 mRNAs...
2015: Journal of Alzheimer's Disease: JAD
Sinaya Vaisburd, Zeev Shemer, Adva Yeheskel, Eliezer Giladi, Illana Gozes
Mutated disrupted in schizophrenia 1 (DISC1), a microtubule regulating protein, leads to schizophrenia and other psychiatric illnesses. It is hypothesized that microtubule stabilization may provide neuroprotection in schizophrenia. The NAP (NAPVSIPQ) sequence of activity-dependent neuroprotective protein (ADNP) contains the SxIP motif, microtubule end binding (EB) protein target, which is critical for microtubule dynamics leading to synaptic plasticity and neuroprotection. Bioinformatics prediction for FDA approved drugs mimicking SxIP-like motif which displace NAP-EB binding identified Risperidone...
2015: Scientific Reports
Anna Malishkevich, Janina Leyk, Olaf Goldbaum, Christiane Richter-Landsberg, Illana Gozes
Oligodendrocytes, the myelin-forming cells of the central nervous system, play important roles in brain development and maintenance. Activity-dependent neuroprotective protein (ADNP), an early marker essential for brain formation, interacts with microtubule end-binding proteins (EB1, EB2, and EB3). EB1 and EB3 are highly expressed in neurons (axons and dendritic spines, respectively) and EB1 enhancement of neurite outgrowth is attenuated by EB2. ADNP/EB presence in oligodendrocytes has not been studied so far...
October 2015: Journal of Molecular Neuroscience: MN
Illana Gozes, Celine Helsmoortel, Geert Vandeweyer, Nathalie Van der Aa, Frank Kooy, Sandra Bedrosian Sermone
No abstract text is available yet for this article.
August 2015: Journal of Molecular Neuroscience: MN
Atanu Biswas, Prashant Kurkute, Suraiya Saleem, Batakrishna Jana, Saswat Mohapatra, Prasenjit Mondal, Anindyasundar Adak, Subhajit Ghosh, Abhijit Saha, Debmalya Bhunia, Subhash Chandra Biswas, Surajit Ghosh
Herein, we report a novel hexapeptide, derived from activity dependent neuroprotective protein (ADNP), that spontaneously self-assembles to form antiparallel β-sheet structure and produces nanovesicles under physiological conditions. This peptide not only strongly binds with β-tubulin in the taxol binding site but also binds with the microtubule lattice in vitro as well as in intracellular microtubule networks. Interestingly, it shows inhibition of amyloid fibril formation upon co-incubation with Aβ peptide following an interesting mechanistic pathway and excellent neuroprotection in PC12 cells treated with anti-nerve growth factor (NGF)...
August 19, 2015: ACS Chemical Neuroscience
Jan Kochanowski, Dorota Uchman, Anna Litwiniuk, Malgorzata Kalisz, Ewa Wolinska-Witort, Lidia Martynska, Boguslawa Baranowska, Wojciech Bik
OBJECTIVE: Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS) characterized by coexisting processes of inflammation, demyelination, axonal neurodegeneration and gliosis. Autoimmune processes play a pivotal role in the disease. The immune system may be modulated by neurotrophins and neurotrophin factors. Aim of the study was to assess plasma levels of brain-derived neurotrophic factor (BDNF), activity-dependent neurotrophin protein (ADNP) and vasoactive intestinal peptide (VIP) in treatment-naïve humans with newly diagnosed multiple sclerosis...
2015: Neuro Endocrinology Letters
Eugênio J P Lages, Fernando O Costa, Sheila C Cortelli, José R Cortelli, Luís O M Cota, Renata Magalhães Cyrino, Elizabeth M B Lages, Gilson C Nobre-Franco, João A R Brito, Ricardo S Gomez
BACKGROUND: There are few studies on periodontal status related to microbiologic and immunologic profiles among individuals not or occasionally using alcohol and those with alcohol dependence. The aim of this study is to determine the effect of alcohol consumption on the levels of subgingival periodontal pathogens and proinflammatory cytokines (interleukin [IL]-1β and tumor necrosis factor [TNF]-α) in the gingival fluid among individuals with and without periodontitis. METHODS: This observational analytic study includes 88 volunteers allocated in four groups (n = 22): individuals with alcohol dependence and periodontitis (ADP), individuals with alcohol dependence and without periodontitis (ADNP), individuals not or occasionally using alcohol with periodontitis (NAP), and individuals not or occasionally using alcohol without periodontitis (NANP)...
September 2015: Journal of Periodontology
Illana Gozes
Fifteen years ago we discovered activity-dependent neuroprotective protein (ADNP), and showed that it is essential for brain formation/function. Our protein interaction studies identified ADNP as a member of the chromatin remodeling complex, SWI/SNF also associated with alternative splicing of tau and prediction of tauopathy. Recently, we have identified cytoplasmic ADNP interactions with the autophagy regulating microtubule-associated protein 1 light chain 3 (LC3) and with microtubule end-binding (EB) proteins...
March 2016: Biological Chemistry
A Malishkevich, N Amram, G Hacohen-Kleiman, I Magen, E Giladi, I Gozes
Activity-dependent neuroprotective protein (ADNP) is a most frequent autism spectrum disorder (ASD)-associated gene and the only protein significantly decreasing in the serum of Alzheimer's disease (AD) patients. Is ADNP associated with ASD being more prevalent in boys and AD more prevalent in women? Our results revealed sex-related learning/memory differences in mice, reflecting hippocampal expression changes in ADNP and ADNP-controlled AD/ASD risk genes. Hippocampal ADNP transcript content was doubled in male vs female mice, with females showing equal expression to ADNP haploinsufficient (ADNP(+/)(-)) males and no significant genotype-associated reduction...
2015: Translational Psychiatry
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