Latest advances in intervertebral disc development and progenitor cells

This paper is a concise review aiming to assemble the most relevant topics presented by the authors at ORS-Philadelphia Spine Research Society Fourth International Spine Research Symposium. It centers on the latest advances in disc development, its main structural entities, and the populating cells, with emphasis on the advances in pivotal molecular pathways responsible for forming the intervertebral discs (IVD). The objective of finding and emphasizing pathways and mechanisms that function to control tissue formation is to identify and to explore modifications occurring during normal aging, disease, and tissue repair. Thus, to comprehend that the cellular and molecular basis of tissue degeneration are crucial in the study of the dynamic interplay that includes cell-cell communication, gene regulation, and growth factors required to form a healthy and functional tissue during normal development

Proteomic signature of the murine intervertebral disc

© 2015 McCann et al. Low back pain is the most common musculoskeletal problem and the single most common cause of disability, often attributed to degeneration of the intervertebral disc. Lack of effective treatment is directly related to our limited understanding of the pathways responsible for maintaining disc health. While transcriptional analysis has permitted initial insights into the biology of the intervertebral disc, complete proteomic characterization is required. We therefore employed liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) protein/peptide separation and mass spectrometric analyses to characterize the protein content of intervertebral discs from skeletally mature wild-type mice. A total of 1360 proteins were identified and categorized using PANTHER. Identified proteins were primarily intracellular/plasma membrane (35%), organelle (30%), macromolecular complex (10%), extracellular region (9%). Molecular function categorization resulted in three distinct categories: catalytic activity (33%), binding (molecule interactions) (29%), and structural activity (13%). To validate our list, we confirmed the presence of 14 of 20 previously identified IVD-associated markers, including matrix proteins, transcriptional regulators, and secreted proteins. Immunohistochemical analysis confirmed distinct localization patterns of select protein with the intervertebral disc. Characterization of the protein composition of healthy intervertebral disc tissue is an important first step in identifying cellular processes and pathways disrupted during aging or disease progression

A lower bound for the two-variable Artin conjecture and prime divisors of recurrence sequences

The final publication is available at Elsevier via https://dx.doi.org/10.1016/j.jnt.2018.06.017 © 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/In 1927, Artin conjectured that any integer other than −1 or a perfect square generates the multiplicative group (Z/pZ)× for infinitely many p. In 2000, Moree and Stevenhagen considered a two-variable version of this problem, and proved a positive density result conditionally to the generalized Riemann Hypothesis by adapting a proof by Hooley for the original conjecture. In this article, we prove an unconditional lower bound for this two-variable problem. In particular, we prove an estimate for the number of distinct primes which divide one of the first N terms of a non-degenerate binary recurrence sequence. We also prove a weaker version of the same theorem, and give three proofs that we consider to be of independent interest. The first proof uses a transcendence result of Stewart, the second uses a theorem of Bombieri and Schmidt on Thue equations and the third uses Mumford's gap principle for counting points on curves by their height. We finally prove a disjunction theorem, where we consider the set of primes satisfying either our two-variable condition or the original condition of Artin's conjecture. We give an unconditional lower bound for the number of such primes.Natural Sciences and Engineering Research Council of CanadaFonds de Recherche du Québec - Nature et TechnologiesCanada Research Chair

Protocol for parallel proteomic and metabolomic analysis of mouse intervertebral disc tissues

The comprehensiveness of data collected by “omics” modalities has demonstrated the ability to drastically transform our understanding of the molecular mechanisms of chronic, complex diseases such as musculoskeletal pathologies, how biomarkers are identified, and how therapeutic targets are developed. Standardization of protocols will enable comparisons between findings reported by multiple research groups and move the application of these technologies forward. Herein, we describe a protocol for parallel proteomic and metabolomic analysis of mouse intervertebral disc (IVD) tissues, building from the combined expertise of our collaborative team. This protocol covers dissection of murine IVD tissues, sample isolation, and data analysis for both proteomics and metabolomics applications. The protocol presented below was optimized to maximize the utility of a mouse model for “omics” applications, accounting for the challenges associated with the small starting quantity of sample due to small tissue size as well as the extracellular matrix-rich nature of the tissue

Differences and similarities in instant countertransference towards patients with suicidal ideation and personality disorders.

Previous findings showed that suicidal patients elicit mostly negative countertransference such as distress, hopelessness, feelings of inadequacy, and apprehension, and that a concurrent personality disorder is associated with more feelings of entrapment and mistreatment, among other adverse reactions. No studies were however conducted on instant countertransference (iCT), i.e., after a single encounter, for example in an emergency setting. We aimed to evaluate the impact of suicidal ideations, self-harm and presence of personality disorders on instant Countertransference (iCT). Caregivers rated their iCT with two validated and standardized questionnaires after a first emergency or outpatient consultation. Suicidal ideation, self-harm and personality disorders were tested as predictors for iCT in a multivariate and multilevel analysis. Thirty caregivers rated their iCT towards 321 patients. Personality disorders and suicidal ideation, but neither recent nor past history of self-harm, predicted iCT. Common iCT included tension, lack of self-confidence and feeling of being tied. iCT specifically associated with suicidal ideation included distress, lack of hope, confusion, and sense that the patient's life had little worth. In contrast, iCT towards patients with personality disorders suggested tension in the therapeutic relationship (low affiliation with patient, anger, disappointment, devaluation). Caregiver's characteristics were not considered in the analysis. Furthermore, while countertransference also includes unconscious phenomena, only conscious iCT was assessed. Patients with suicidal ideation and personality disorders elicit common but also specific negative iCT. Mental health institutions need to devote specific resources (such as clinical supervision and training) to help caregivers manage their iCT

Gene family structure, expression and functional analysis of HD-Zip III genes in angiosperm and gymnosperm forest trees

BACKGROUND: Class III Homeodomain Leucine Zipper (HD-Zip III) proteins have been implicated in the regulation of cambium identity, as well as primary and secondary vascular differentiation and patterning in herbaceous plants. They have been proposed to regulate wood formation but relatively little evidence is available to validate such a role. We characterised and compared HD-Zip III gene family in an angiosperm tree, Populus spp. (poplar), and the gymnosperm Picea glauca (white spruce), representing two highly evolutionarily divergent groups. RESULTS: Full-length cDNA sequences were isolated from poplar and white spruce. Phylogenetic reconstruction indicated that some of the gymnosperm sequences were derived from lineages that diverged earlier than angiosperm sequences, and seem to have been lost in angiosperm lineages. Transcript accumulation profiles were assessed by RT-qPCR on tissue panels from both species and in poplar trees in response to an inhibitor of polar auxin transport. The overall transcript profiles HD-Zip III complexes in white spruce and poplar exhibited substantial differences, reflecting their evolutionary history. Furthermore, two poplar sequences homologous to HD-Zip III genes involved in xylem development in Arabidopsis and Zinnia were over-expressed in poplar plants. PtaHB1 over-expression produced noticeable effects on petiole and primary shoot fibre development, suggesting that PtaHB1 is involved in primary xylem development. We also obtained evidence indicating that expression of PtaHB1 affected the transcriptome by altering the accumulation of 48 distinct transcripts, many of which are predicted to be involved in growth and cell wall synthesis. Most of them were down-regulated, as was the case for several of the poplar HD-Zip III sequences. No visible physiological effect of over-expression was observed on PtaHB7 transgenic trees, suggesting that PtaHB1 and PtaHB7 likely have distinct roles in tree development, which is in agreement with the functions that have been assigned to close homologs in herbaceous plants. CONCLUSIONS: This study provides an overview of HD-zip III genes related to woody plant development and identifies sequences putatively involved in secondary vascular growth in angiosperms and in gymnosperms. These gene sequences are candidate regulators of wood formation and could be a source of molecular markers for tree breeding related to wood properties