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Starr Dostie, Michel Prévost, Philippe Mochirian, Kashif Tanveer, Nicholas Andrella, Ariana Rostami, Guillaume Tambutet, Yvan Guindon
Nucleoside analogues bearing a fluorine in the C2'-position have been synthesized by SN2-like cyclizations of acyclic thioaminal precursors. This strategy provides access to two scaffolds, D-1',2'-cis thiofuranosides and D-1',2'-trans furanosides, that are difficult to generate using the standard approach for nucleoside synthesis. The addition of silylated nucleobases onto model C2-fluorinated dithioacetal substrates resulted in 1,2-syn diastereoselectivity which is consistent with the C2-F and S-alkyl moiety being in close proximity...
October 13, 2016: Journal of Organic Chemistry
Seyed Mahdi Mohammadi, Zeinab Shirvani Farsani, Rozita Dosti, Mohammad Ali Sahraian, Mehrdad Behmanesh
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by brain inflammation, demyelination and axonal loss. Neuropeptide Y (NPY) has a critical role in the maintenance of homeostasis in the immune system and coping of stress condition. In the current study we analyzed 188 patients suffering from MS and 204 unrelated healthy controls for two functional single nucleotide polymorphisms (SNPs), NPY 20T>C (rs16139) and NPY -485T>C (rs16147) using PCR-RFLP and Mismatch PCR-RFLP methods...
August 8, 2016: Neuropeptides
Jonathan Christopher Dubé, Xue Qing David Wang, Josée Dostie
The role of genome architecture in transcription regulation has become the focus of an increasing number of studies over the past decade. Chromatin organization can have a significant impact on gene expression by promoting or restricting the physical proximity between regulatory DNA elements. Given that any change in chromatin state has the potential to alter DNA folding and the proximity between control elements, the spatial organization of chromatin is inherently linked to its molecular composition. In this review, we explore how modulators of chromatin state and organization might keep gene expression in check...
March 2016: Current Molecular Biology Reports
Roxane Langlois, Sven Joubert, Sophie Benoit, Valérie Dostie, Isabelle Rouleau
Ribot's law refers to the better preservation of remote memories compared with recent ones that presumably characterizes retrograde amnesia. Even if Ribot-type temporal gradient has been extensively studied in retrograde amnesia, particularly in Alzheimer's disease (AD), this pattern has not been consistently found. One explanation for these results may be that rehearsal frequency rather than remoteness accounts for the better preservation of these memories. Thus, the aim of present study was to address this question by studying retrograde semantic memory in subjects with amnestic mild cognitive impairment (aMCI) (n = 20), mild AD (n = 20) and in healthy older controls (HC; n = 19)...
2016: Journal of Alzheimer's Disease: JAD
James Fraser, Carmelo Ferrai, Andrea M Chiariello, Markus Schueler, Tiago Rito, Giovanni Laudanno, Mariano Barbieri, Benjamin L Moore, Dorothee C A Kraemer, Stuart Aitken, Sheila Q Xie, Kelly J Morris, Masayoshi Itoh, Hideya Kawaji, Ines Jaeger, Yoshihide Hayashizaki, Piero Carninci, Alistair R R Forrest, Colin A Semple, Josée Dostie, Ana Pombo, Mario Nicodemi
Mammalian chromosomes fold into arrays of megabase-sized topologically associating domains (TADs), which are arranged into compartments spanning multiple megabases of genomic DNA. TADs have internal substructures that are often cell type specific, but their higher-order organization remains elusive. Here, we investigate TAD higher-order interactions with Hi-C through neuronal differentiation and show that they form a hierarchy of domains-within-domains (metaTADs) extending across genomic scales up to the range of entire chromosomes...
December 2015: Molecular Systems Biology
Abba Malina, Christopher J F Cameron, Francis Robert, Mathieu Blanchette, Josée Dostie, Jerry Pelletier
In CRISPR-Cas9 genome editing, the underlying principles for selecting guide RNA (gRNA) sequences that would ensure for efficient target site modification remain poorly understood. Here we show that target sites harbouring multiple protospacer adjacent motifs (PAMs) are refractory to Cas9-mediated repair in situ. Thus we refine which substrates should be avoided in gRNA design, implicating PAM density as a novel sequence-specific feature that inhibits in vivo Cas9-driven DNA modification.
December 8, 2015: Nature Communications
Stéphanie Moisan, Soizik Berlivet, Chandran Ka, Gérald Le Gac, Josée Dostie, Claude Férec
A mechanism by which control DNA elements regulate transcription over large linear genomic distances is by achieving close physical proximity with genes, and looping of the intervening chromatin paths. Alterations of such regulatory 'chromatin looping' systems are likely to play a critical role in human genetic disease at large. Here, we studied the spatial organization of a ≈790 kb locus encompassing the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Dysregulation of CFTR is responsible for cystic fibrosis, which is the most common lethal genetic disorder in Caucasian populations...
April 7, 2016: Nucleic Acids Research
Hou-Feng Zheng, Vincenzo Forgetta, Yi-Hsiang Hsu, Karol Estrada, Alberto Rosello-Diez, Paul J Leo, Chitra L Dahia, Kyung Hyun Park-Min, Jonathan H Tobias, Charles Kooperberg, Aaron Kleinman, Unnur Styrkarsdottir, Ching-Ti Liu, Charlotta Uggla, Daniel S Evans, Carrie M Nielson, Klaudia Walter, Ulrika Pettersson-Kymmer, Shane McCarthy, Joel Eriksson, Tony Kwan, Mila Jhamai, Katerina Trajanoska, Yasin Memari, Josine Min, Jie Huang, Petr Danecek, Beth Wilmot, Rui Li, Wen-Chi Chou, Lauren E Mokry, Alireza Moayyeri, Melina Claussnitzer, Chia-Ho Cheng, Warren Cheung, Carolina Medina-Gómez, Bing Ge, Shu-Huang Chen, Kwangbom Choi, Ling Oei, James Fraser, Robert Kraaij, Matthew A Hibbs, Celia L Gregson, Denis Paquette, Albert Hofman, Carl Wibom, Gregory J Tranah, Mhairi Marshall, Brooke B Gardiner, Katie Cremin, Paul Auer, Li Hsu, Sue Ring, Joyce Y Tung, Gudmar Thorleifsson, Anke W Enneman, Natasja M van Schoor, Lisette C P G M de Groot, Nathalie van der Velde, Beatrice Melin, John P Kemp, Claus Christiansen, Adrian Sayers, Yanhua Zhou, Sophie Calderari, Jeroen van Rooij, Chris Carlson, Ulrike Peters, Soizik Berlivet, Josée Dostie, Andre G Uitterlinden, Stephen R Williams, Charles Farber, Daniel Grinberg, Andrea Z LaCroix, Jeff Haessler, Daniel I Chasman, Franco Giulianini, Lynda M Rose, Paul M Ridker, John A Eisman, Tuan V Nguyen, Jacqueline R Center, Xavier Nogues, Natalia Garcia-Giralt, Lenore L Launer, Vilmunder Gudnason, Dan Mellström, Liesbeth Vandenput, Najaf Amin, Cornelia M van Duijn, Magnus K Karlsson, Östen Ljunggren, Olle Svensson, Göran Hallmans, François Rousseau, Sylvie Giroux, Johanne Bussière, Pascal P Arp, Fjorda Koromani, Richard L Prince, Joshua R Lewis, Bente L Langdahl, A Pernille Hermann, Jens-Erik B Jensen, Stephen Kaptoge, Kay-Tee Khaw, Jonathan Reeve, Melissa M Formosa, Angela Xuereb-Anastasi, Kristina Åkesson, Fiona E McGuigan, Gaurav Garg, Jose M Olmos, Maria T Zarrabeitia, Jose A Riancho, Stuart H Ralston, Nerea Alonso, Xi Jiang, David Goltzman, Tomi Pastinen, Elin Grundberg, Dominique Gauguier, Eric S Orwoll, David Karasik, George Davey-Smith, Albert V Smith, Kristin Siggeirsdottir, Tamara B Harris, M Carola Zillikens, Joyce B J van Meurs, Unnur Thorsteinsdottir, Matthew T Maurano, Nicholas J Timpson, Nicole Soranzo, Richard Durbin, Scott G Wilson, Evangelia E Ntzani, Matthew A Brown, Kari Stefansson, David A Hinds, Tim Spector, L Adrienne Cupples, Claes Ohlsson, Celia M T Greenwood, Rebecca D Jackson, David W Rowe, Cynthia A Loomis, David M Evans, Cheryl L Ackert-Bicknell, Alexandra L Joyner, Emma L Duncan, Douglas P Kiel, Fernando Rivadeneira, J Brent Richards
The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF ≤ 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants, as well as rare, population-specific, coding variants. Here we identify novel non-coding genetic variants with large effects on BMD (ntotal = 53,236) and fracture (ntotal = 508,253) in individuals of European ancestry from the general population...
October 1, 2015: Nature
Francis Robert, Mathilde Barbeau, Sylvain Éthier, Josée Dostie, Jerry Pelletier
BACKGROUND: The ability to modify the genome of any cell at a precise location has drastically improved with the recent discovery and implementation of CRISPR/Cas9 editing technology. However, the capacity to introduce specific directed changes at given loci is hampered by the fact that the major cellular repair pathway that occurs following Cas9-mediated DNA cleavage is the erroneous non-homologous end joining (NHEJ) pathway. Homology-directed recombination (HDR) is far less efficient than NHEJ and makes screening of clones containing directed changes time-consuming and labor-intensive...
2015: Genome Medicine
James Fraser, Iain Williamson, Wendy A Bickmore, Josée Dostie
In humans, nearly two meters of genomic material must be folded to fit inside each micrometer-scale cell nucleus while remaining accessible for gene transcription, DNA replication, and DNA repair. This fact highlights the need for mechanisms governing genome organization during any activity and to maintain the physical organization of chromosomes at all times. Insight into the functions and three-dimensional structures of genomes comes mostly from the application of visual techniques such as fluorescence in situ hybridization (FISH) and molecular approaches including chromosome conformation capture (3C) technologies...
September 2015: Microbiology and Molecular Biology Reviews: MMBR
Roxane Langlois, Sven Joubert, Sophie Benoit, Valérie Dostie, Isabelle Rouleau
Memory assessment represents an important part of the clinical neuropsychologist's duties in a geriatric context. In fact, in Canada, about one-third of seniors report memory complaints, with different causes. Based on the underlying etiology, different components of memory may be affected in older adults. Nonautobiographical retrograde memory (public or semantic) is an important aspect of memory to assess; nevertheless, there is currently no reliable and standardized clinical tool to evaluate this aspect of memory in the elderly Quebecer population...
September 2015: Canadian Journal on Aging, la Revue Canadienne du Vieillissement
Reza Kazemi Oskuee, Fatemeh Dosti, Leila Gholami, Bizhan Malaekeh-Nikouei
Nowadays gene delivery is a topic in many research studies. Non-viral vectors have many advantages over viral vectors in terms of safety, immunogenicity and gene carrying capacity but they suffer from low transfection efficiency and high toxicity. In this study, polyallylamine (PAA), the cationic polymer, has been modified with hydrophobic branches to increase the transfection efficiency of the polymer. Polyallylamine with molecular weights of 15 and 65kDa was selected and grafted with butyl, hexyl and decyl acrylate at percentages of 10, 30 and 50...
April 2015: Materials Science & Engineering. C, Materials for Biological Applications
Emmanuelle Dionne-Dostie, Natacha Paquette, Maryse Lassonde, Anne Gallagher
A considerable number of cognitive processes depend on the integration of multisensory information. The brain integrates this information, providing a complete representation of our surrounding world and giving us the ability to react optimally to the environment. Infancy is a period of great changes in brain structure and function that are reflected by the increase of processing capacities of the developing child. However, it is unclear if the optimal use of multisensory information is present early in childhood or develops only later, with experience...
2015: Brain Sciences
Iain Williamson, Soizik Berlivet, Ragnhild Eskeland, Shelagh Boyle, Robert S Illingworth, Denis Paquette, Josée Dostie, Wendy A Bickmore
Although important for gene regulation, most studies of genome organization use either fluorescence in situ hybridization (FISH) or chromosome conformation capture (3C) methods. FISH directly visualizes the spatial relationship of sequences but is usually applied to a few loci at a time. The frequency at which sequences are ligated together by formaldehyde cross-linking can be measured genome-wide by 3C methods, with higher frequencies thought to reflect shorter distances. FISH and 3C should therefore give the same views of genome organization, but this has not been tested extensively...
December 15, 2014: Genes & Development
Michel Prévost, Starr Dostie, Marie-Ève Waltz, Yvan Guindon
Reported herein is an experimental and theoretical study that elucidates why silylated nucleobase additions to acyclic α-alkoxythiacarbenium intermediates proceed with high 1,2-syn stereocontrol (anti-Felkin-Anh), which is opposite to what would be expected with corresponding activated aldehydes. The acyclic thioaminals formed undergo intramolecular cyclizations to provide nucleoside analogues with anticancer and antiviral properties. The factors influencing the selectivity of the substitution reaction have been examined thoroughly...
November 7, 2014: Journal of Organic Chemistry
Regina Cencic, Hisashi Miura, Abba Malina, Francis Robert, Sylvain Ethier, T Martin Schmeing, Josée Dostie, Jerry Pelletier
The clustered regularly interspaced short palindromic repeat (CRISPR)-associated enzyme Cas9 is an RNA-guided nuclease that has been widely adapted for genome editing in eukaryotic cells. However, the in vivo target specificity of Cas9 is poorly understood and most studies rely on in silico predictions to define the potential off-target editing spectrum. Using chromatin immunoprecipitation followed by sequencing (ChIP-seq), we delineate the genome-wide binding panorama of catalytically inactive Cas9 directed by two different single guide (sg) RNAs targeting the Trp53 locus...
2014: PloS One
Fabienne Cléard, François Karch, Robert K Maeda
How transcription is controlled by distally located cis-regulatory elements is an active area of research in biology. As such, there have been many techniques developed to probe these long-distance chromatin interactions. Here, we focus on one such method, called DamID (van Steensel and Henikoff, Nat Biotechnol 18(4):424-428, 2000). While other methods like 3C (Dekker et al., Science 295(5558):1306-1311, 2002), 4C (Simonis et al., Nat Genet 38(11):1348-1354, 2006; Zhao et al., Nat Genet 38(11):1341-1347, 2006), and 5C (Dostie et al...
2014: Methods in Molecular Biology
Mathieu Rousseau, Maria A Ferraiuolo, Jennifer L Crutchley, Xue Qing Wang, Hisashi Miura, Mathieu Blanchette, Josée Dostie
BACKGROUND: Although genetic or epigenetic alterations have been shown to affect the three-dimensional organization of genomes, the utility of chromatin conformation in the classification of human disease has never been addressed. RESULTS: Here, we explore whether chromatin conformation can be used to classify human leukemia. We map the conformation of the HOXA gene cluster in a panel of cell lines with 5C chromosome conformation capture technology, and use the data to train and test a support vector machine classifier named 3D-SP...
2014: Genome Biology
Ali Reza Mohammadi Arya, Mahmoud Shirazi, Abbas Ali Hossien Khanzadeh, Fatemeh Lachinnani, Fahimeh Yoosefi Joubari, Zohreh Halajian, Salar Dosti Sarabi, Matloob Ahmed Khan
BACKGROUND: The existing studies have indicated that persons with positive attitude and believe to narcotics have more addiction than those with negative or natural attitudes. The aim of the present study was to specify the effectiveness of cognitive-behavioral training on increasing of self-concept's measure, and the attitude style toward narcotic drugs in addicted prisoners of Tonekabon. OBJECTIVES: The objective of this study was to assess the effects of cognitive-behavioral training on increasing self-concept and the attitude style toward narcotic drugs...
June 2013: International Journal of High Risk Behaviors & Addiction
Soizik Berlivet, Denis Paquette, Annie Dumouchel, David Langlais, Josée Dostie, Marie Kmita
HoxA genes exhibit central roles during development and causal mutations have been found in several human syndromes including limb malformation. Despite their importance, information on how these genes are regulated is lacking. Here, we report on the first identification of bona fide transcriptional enhancers controlling HoxA genes in developing limbs and show that these enhancers are grouped into distinct topological domains at the sub-megabase scale (sub-TADs). We provide evidence that target genes and regulatory elements physically interact with each other through contacts between sub-TADs rather than by the formation of discreet "DNA loops"...
2013: PLoS Genetics
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