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Search Results: 1 - 10 of 461846 matches for " A. Guertin "
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Anxiolytics may promote locomotor function recovery in spinal cord injury patients
Pierre A Guertin
Neuropsychiatric Disease and Treatment , 2008,
Abstract: Pierre A GuertinNeuroscience Unit, Laval University Medical Center (CHUL), Quebec City, CanadaAbstract: Recent findings in animal models of paraplegia suggest that specific nonbenzodiazepine anxiolytics may temporarily restore locomotor functions after spinal cord injury (SCI). Experiments using in vitro models have revealed, indeed, that selective serotonin receptor (5-HTR) ligands such as 5-HTR1A agonists, known as relatively safe anxiolytics, can acutely elicit episodes of rhythmic neuronal activity refered to as fictive locomotion in isolated spinal cord preparations. Along the same line, in vivo studies have recently shown that this subclass of anxiolytics can induce, shortly after systemic administration (eg, orally or subcutaneously), some locomotor-like hindlimb movements during 45–60 minutes in completely spinal cord-transected (Tx) rodents. Using ‘knock-out’ mice (eg, 5-HTR7-/-) and selective antagonists, it has been clearly established that both 5-HTR1A and 5-HTR7 were critically involved in mediating the pro-locomotor effects induced by 8-OH-DPAT (typically referred to as a 5-HTR1A agonist) in Tx animals. Taken together, these in vitro and in vivo data strongly support the idea that 5-HTR1A agonists may eventually become constitutive elements of a novel first-in-class combinatorial treatment aimed at periodically inducing short episodes of treadmill stepping in SCI patients.Keywords: 5-HT agonists, anxiolytics, locomotion, SCI
Can the Spinal Cord Learn and Remember?
Pierre A. Guertin
The Scientific World Journal , 2008, DOI: 10.1100/tsw.2008.106
Preclinical evidence supporting the clinical development of central pattern generator-modulating therapies for chronic spinal cord-injured patients
Pierre A. Guertin
Frontiers in Human Neuroscience , 2014, DOI: 10.3389/fnhum.2014.00272
Abstract: Ambulation or walking is one of the main gaits of locomotion. In terrestrial animals, it may be defined as a series of rhythmic and bilaterally coordinated movement of the limbs which creates a forward movement of the body. This applies regardless of the number of limbs—from arthropods with six or more limbs to bipedal primates. These fundamental similarities among species may explain why comparable neural systems and cellular properties have been found, thus far, to control in similar ways locomotor rhythm generation in most animal models. The aim of this article is to provide a comprehensive review of the known structural and functional features associated with central nervous system (CNS) networks that are involved in the control of ambulation and other stereotyped motor patterns—specifically Central Pattern Generators (CPGs) that produce basic rhythmic patterned outputs for locomotion, micturition, ejaculation, and defecation. Although there is compelling evidence of their existence in humans, CPGs have been most studied in reduced models including in vitro isolated preparations, genetically-engineered mice and spinal cord-transected animals. Compared with other structures of the CNS, the spinal cord is generally considered as being well-preserved phylogenetically. As such, most animal models of spinal cord-injured (SCI) should be considered as valuable tools for the development of novel pharmacological strategies aimed at modulating spinal activity and restoring corresponding functions in chronic SCI patients.
Central Pattern Generator for Locomotion: Anatomical, Physiological, and Pathophysiological Considerations
Pierre A. Guertin
Frontiers in Neurology , 2013, DOI: 10.3389/fneur.2012.00183
Abstract: This article provides a perspective on major innovations over the past century in research on the spinal cord and, specifically, on specialized spinal circuits involved in the control of rhythmic locomotor pattern generation and modulation. Pioneers such as Charles Sherrington and Thomas Graham Brown have conducted experiments in the early twentieth century that changed our views of the neural control of locomotion. Their seminal work supported subsequently by several decades of evidence has led to the conclusion that walking, flying, and swimming are largely controlled by a network of spinal neurons generally referred to as the central pattern generator (CPG) for locomotion. It has been subsequently demonstrated across all vertebrate species examined, from lampreys to humans, that this CPG is capable, under some conditions, to self-produce, even in absence of descending or peripheral inputs, basic rhythmic, and coordinated locomotor movements. Recent evidence suggests, in turn, that plasticity changes of some CPG elements may contribute to the development of specific pathophysiological conditions associated with impaired locomotion or spontaneous locomotor-like movements. This article constitutes a comprehensive review summarizing key findings on the CPG as well as on its potential role in Restless Leg Syndrome, Periodic Leg Movement, and Alternating Leg Muscle Activation. Special attention will be paid to the role of the CPG in a recently identified, and uniquely different neurological disorder, called the Uner Tan Syndrome.
Spinal Cord Injury Research in Mice: 2008 Review
Inge Steuer,Pierre A. Guertin
The Scientific World Journal , 2009, DOI: 10.1100/tsw.2009.63
HPV Prevalence and Prognostic Value in a Prospective Cohort of 255 Patients with Locally Advanced HNSCC: A Single-Centre Experience
E. Thibaudeau,B. Fortin,F. Coutlée,P. Nguyen-Tan,X. Weng,M.-L. Audet,O. Abboud,L. Guertin,A. Christopoulos,J. Tabet,D. Soulières
International Journal of Otolaryngology , 2013, DOI: 10.1155/2013/437815
Abstract: Background. HPV is a positive prognostic factor in HNSCC. We studied the prevalence and prognostic impact of HPV on survival parameters and treatment toxicity in patients with locally advanced HNSCC treated with concomitant chemoradiation therapy. Methods. Data on efficacy and toxicity were available for 560 patients. HPV was detected by PCR. Analysis was performed using Kaplan-Meier survival curves, Fisher’s test for categorical data, and log-rank statistics for failure times. Results. Median follow-up was 4.7 years. DNA extraction was successful in 255 cases. HPV prevalence was 68.6%, and 53.3% for HPV 16. For HPV+ and HPV?, median LRC was 8.9 and 2.2 years ( ), median DFS was 8.9 and 2.1 years ( ), and median OS was 8.9 and 3.1 years ( ). Survival was different based on HPV genotype, stage, treatment period, and chemotherapy regimen. COX adjusted analysis for T, N, age, and treatment remained significant ( ). Conclusions. Oropharyngeal cancer is increasingly linked to HPV. This study confirms that HPV status is associated with improved prognosis among H&N cancer patients receiving CRT and should be a stratification factor for clinical trials including H&N cases. Toxicity of CRT is not modified for the HPV population. 1. Introduction Tobacco and alcohol consumption has long been known as the major risk factor for HNSCC. However, HPV has recently been recognised to play a role in the pathogenesis of a subset of clinically and molecularly distinct HNSCC, most often located in the oropharynx and associated with wild-type p53 and downregulation of cyclin D and retinoblastoma protein pRb [1–5], and in which viral oncoproteins E6 and E7 play a crucial part [6]. HPV prevalence in HNSCC has been increasing significantly in the past few decades [5, 7]; it is estimated at 25% in HNSCC [8], but reaches up to 70% or more in tonsillar SCCs [9–11]. Unlike the HPV-negative oropharyngeal cancers, the HPV-positive subset is not associated with tobacco or alcohol use, but with certain types of sexual behaviours [12, 13]. The HPV 16 subtype is present in up to 90% of HPV-related oropharyngeal cancers, while HPVs 18, 31, and 33 have been identified in the remainder [14, 15]. HPV has recently been recognised as a good prognostic factor in head and neck (H&N) cancer [5, 16–26], which has been attributed to several mechanisms, including absence of field cancerisation and increased sensitivity to chemoradiation therapy [5, 16, 20, 22–24, 26]. Most of the available data is derived from small randomised trials with different treatment options or small heterogeneous cohorts;
Targeted H3R26 Deimination Specifically Facilitates Estrogen Receptor Binding by Modifying Nucleosome Structure
Michael J. Guertin equal contributor,Xuesen Zhang equal contributor ,Lynne Anguish,Sohyoung Kim,Lyuba Varticovski,John T. Lis,Gordon L. Hager,Scott A. Coonrod
PLOS Genetics , 2014, DOI: doi/10.1371/journal.pgen.1004613
Abstract: Transcription factor binding to DNA in vivo causes the recruitment of chromatin modifiers that can cause changes in chromatin structure, including the modification of histone tails. We previously showed that estrogen receptor (ER) target gene activation is facilitated by peptidylarginine deiminase 2 (PAD2)-catalyzed histone H3R26 deimination (H3R26Cit). Here we report that the genomic distributions of ER and H3R26Cit in breast cancer cells are strikingly coincident, linearly correlated, and observed as early as 2 minutes following estradiol treatment. The H3R26Cit profile is unlike that of previously described histone modifications and is characterized by sharp, narrow peaks. Paired-end MNase ChIP-seq indicates that the charge-neutral H3R26Cit modification facilitates ER binding to DNA by altering the fine structure of the nucleosome. Clinically, we find that PAD2 and H3R26Cit levels correlate with ER expression in breast tumors and that high PAD2 expression is associated with increased survival in ER+ breast cancer patients. These findings provide insight into how transcription factors gain access to nucleosomal DNA and implicate PAD2 as a novel therapeutic target for ER+ breast cancer.
Itinerant Ferromagnetism and Metamagnetism in Cr Doped Perovskite Ruthenates
V. Durairaj,E. Elhami,S. Chikara,X. N. Lin,A. Douglass,G. Cao P. Schlottmann,E. S. Choi,R. P. Guertin
Physics , 2005,
Abstract: We report results of structural, magnetic and transport properties of single crystal CaRu1-xCrxO3 (0≤x≤0.36) and SrRu1-xCrxO3 (0≤x≤0.30). Cr substitution as low as x=0.08 drives CaRu1-xCrxO3 from the paramagnetic state to an itinerant ferromagnetic state with field-driven first-order metamagnetic transitions leading to a sizeable saturation moment (~0.4?B/f.u.within the ab plane). The ferromagnetism occurs abruptly and reaches as high as TC=123 K for x=0.22. The Cr-driven ferromagnetism is highly anisotropic, suggesting an important role for spin-orbit coupling. Lattice constant and magnetic measurements strongly support the valence of the Cr as tetravalent (Cr4+, 3d2 configuration). Cr substitution for Ru in SrRuO3 (TC=165 K) enhances the itinerant ferromagnetism, with TC reaching 290 K for x=0.30, consistent with Cr-induced ferromagnetism in paramagnetic CaRuO3. Preliminary pressure-dependent magnetization of CaRu0.85Cr0.15O3 shows strong enhancement of the saturation magnetization (25% for P~0.7 GPa). All results indicate a coupling of Ru 4d and Cr 3d electrons that is unexpectedly favorable for itinerant ferromagnetism which often exists delicately in the ruthenates.
Chromatin Landscape Dictates HSF Binding to Target DNA Elements
Michael J. Guertin,John T. Lis
PLOS Genetics , 2010, DOI: 10.1371/journal.pgen.1001114
Abstract: Sequence-specific transcription factors (TFs) are critical for specifying patterns and levels of gene expression, but target DNA elements are not sufficient to specify TF binding in vivo. In eukaryotes, the binding of a TF is in competition with a constellation of other proteins, including histones, which package DNA into nucleosomes. We used the ChIP-seq assay to examine the genome-wide distribution of Drosophila Heat Shock Factor (HSF), a TF whose binding activity is mediated by heat shock-induced trimerization. HSF binds to 464 sites after heat shock, the vast majority of which contain HSF Sequence-binding Elements (HSEs). HSF-bound sequence motifs represent only a small fraction of the total HSEs present in the genome. ModENCODE ChIP-chip datasets, generated during non-heat shock conditions, were used to show that inducibly bound HSE motifs are associated with histone acetylation, H3K4 trimethylation, RNA Polymerase II, and coactivators, compared to HSE motifs that remain HSF-free. Furthermore, directly changing the chromatin landscape, from an inactive to an active state, permits inducible HSF binding. There is a strong correlation of bound HSEs to active chromatin marks present prior to induced HSF binding, indicating that an HSE's residence in “active” chromatin is a primary determinant of whether HSF can bind following heat shock.
CellProfiler: image analysis software for identifying and quantifying cell phenotypes
Anne E Carpenter, Thouis R Jones, Michael R Lamprecht, Colin Clarke, In Kang, Ola Friman, David A Guertin, Joo Chang, Robert A Lindquist, Jason Moffat, Polina Golland, David M Sabatini
Genome Biology , 2006, DOI: 10.1186/gb-2006-7-10-r100
Abstract: Examining cells by microscopy has long been a primary method for studying cellular function. When cells are stained appropriately, visual analysis can reveal biological mechanisms. Advanced microscopes can now, in a single day, easily collect thousands of high resolution images of cells from time-lapse experiments and from large-scale screens using chemical compounds, RNA interference (RNAi) reagents, or expression plasmids [1-5]. However, a bottleneck exists at the image analysis stage. Several pioneering large screens have been scored through visual inspection by expert biologists [6,7], whose interpretive ability will not soon be replicated by a computer. Still, for most applications, image cytometry (automated cell image analysis) is strongly preferable to analysis by eye. In fact, in some cases image cytometry is absolutely required to extract the full spectrum of information present in biological images, for reasons we discuss here.First, while human observers typically score one or at most a few cellular features, image cytometry simultaneously yields many informative measures of cells, including the intensity and localization of each fluorescently labeled cellular component (for example, DNA or protein) within each subcellular compartment, as well as the number, size, and shape of those subcellular compartments. Image-based analysis is thus versatile, inherently multiplexed, and high in information content. Like flow cytometry, image cytometry measures the per-cell amount of protein and DNA, but can more conveniently handle hundreds of thousands of distinct samples and is also compatible with adherent cell types, time-lapse samples, and intact tissues. In addition, image cytometry can accurately measure protein texture and localization as well as cell shape and size.Second, human-scored image analysis is qualitative, usually categorizing samples as 'hits' (where normal physiology is grossly disturbed) or 'non-hits'. By contrast, automated analysis rapidly pr
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