NCube/papyrus huggingface dataset:
Elucidating the crosstalk between condensin subunits and its relevance in chromosome condensation

DNA undergoes a series of complex structural transformations during cell division, resulting in its compaction into intact mitotic chromosomes called chromosome condensation. The pentameric condensin complex has been strongly implicated as a major effector of this phenomenon. It is a multi-subunit protein complex with two catalytic “Structural maintenance of chromosome” [SMC] subunits and three regulatory subunits, highly conserved from yeast to humans. The condensin complex in Saccharomyces cerevisiae is made up of two SMC subunits [Smc2 and Smc4] and three regulatory non-SMC proteins [Brn1, Ycs4, Ycg1]. Despite its importance, the mechanism of action of condensin remains largely unknown.  Hence, the objective of this research is to understand the mechanism of action of condensin and how it is affected by interaction between its regulatory and non-regulatory sub-units. This thesis identifies four distinct cell cycle dependent morphologies of the rDNA locus. The transformation of the rDNA phenotype from G1 to mitosis is condensin dependent. In order to determine the role of the interaction between the catalytic and regulatory subunits of condensin in the regulation of the condensin complex, we have identified six positive residues on the C-terminus of Brn1 which affect complex formation, condensation activity and interaction with tubulin, suggesting that these residues have a role in condensin regulation. Together, our results suggest a model for condensin regulation by interaction between condensin subunits.

Keyphrases: Chromosome Condensation, Cell Cycle, Condensin Complex, Regulation of Condensin, rDNA, BRN1, SMC4
Asymmetric cell division intersects with cell geometry : a method to extrapolate and quantify geometrical parameters of sensory organ precursors

Asymmetric cell division (ACD) consists in a cellular division during which specific cell fate determinants are distributed preferentially in one daughter cell, which then differentiate from its sibling. Hence, ACD is important to generate cell diversity and is used to regulate stem cells homeostasis. For proper asymmetric distribution of cell fate determinants, the positioning of the mitotic spindle has to be tightly controlled. Frequently, this induces a cell size asymmetry, since the spindle is then not centered during mitosis, leading to an asymmetric positioning of the cleavage furrow.   Although small small GTPases have been shown to act directly on the spindle, the exact mechanism controlling spindle positioning during ACD is not understood. Recent studies suggest that an independent, yet uncharacterized pathway is involved in spindle positioning, which is likely to involve an asymmetric regulation of the actin cytoskeleton. Indeed, actin enables spindle anchoring to the cortex. Hence we hypothesize that asymmetric actin contractions during cytokinesis might displace the mitotic spindle and the cleavage furrow, leading to cell size asymmetry. Interestingly, from our preliminary results we observed that cortical blebbing, which is a read-out of cortical tension/contraction, preferentially occurs on the anterior side of the dividing sensory organ precursor (SOP) cells at telophase.  Our preliminary data support the idea that Rho small GTPases might be implicated in regulation of the mitotic spindle hence controlling asymmetric cell division of SOP cells. The experimental settings developed for this thesis, for studying regulation of the mitotic spindle orientation and positioning will serve as proof of concept of how geneticist and biochemist experts could design ways to control such process by different means in cancerous cells.  The preliminary results from this project open novel insights on how the Rho small GTPases might be implicated in controlling asymmetric cell division hence their dynamics in vivo of such process during SOP development. Furthermore, the assays and the theoretical model developed in this study can be used as background that could serve to design improved quantitative experimental methods for cell biology synchronizing sub-networks of ACD mechanism.

Keyphrases: Sensory organ precursors (SOP), Mitotic spindle mechanism, cell fate determinants, Cortical blebbing
Identification de nouvelles cibles transcriptionnelles d’ETV6, un facteur de transcription fréquemment altéré dans la leucémie aiguë lymphoblastique

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Many chromosomal rearrangements have been identified in leukemia, including the translocation t(12;21), which is observed in approximately 25% of children diagnosed with pre-B ALL. This translocation results in the expression of the ETV6-AML1 chimera. However, the fusion protein ETV6-AML1 is not sufficient to initiate leukemia by itself, suggesting that additional mutations are required to promote oncogenic transformation. Accordingly, the expression of the non-rearranged ETV6 allele is lost in 75% of the t(12;21) cases. This deletion leads to the complete inactivation of ETV6 transcription factor and the abolition of its biological function. Because ETV6 seems to be a tumor suppressor, we believe that its inactivation could promote the development of leukemia through the deregulation of its downstream target genes. This project aimed to identify new transcriptional targets of ETV6, in order to elucidate its role in leukemogenesis. A RNA-Seq experiment has led to the identification of more than 200 genes whose expression is correlated with ETV6 mRNA levels in CD34 + hematopoietic stem cells. Among these, several genes are involved in immune and inflammatory responses, cell migration, ion homeostasis and intracellular signaling. We also implemented a chromatin immunoprecipitation approach to identify the binding sites of ETV6. This approach confirmed an interaction between ETV6 and SLCO2B1 gene, whose expression is also co-regulated with ETV6. This study suggests that ETV6 may contribute to leukemogenesis by deregulating the expression levels of several oncogenes.

Keyphrases: RNA-Seq, ChIP-Seq, pediatric cancer, acute lymphoblastic leukemia, ETV6 transcription factor, transcriptional regulation
Overexpression of catalase prevents gentamicin – induced apoptosis of renal proximal tubular cells in transgenic mice

Background: Nephrotoxicity is a major complication of gentamicin, which is widely used in the treatment of severe gram-negative infections. Gentamicin promotes tubular apoptosis, but the mechanisms by which this occurs are incompletely understood. In the present study, we investigated whether the underlying mechanism(s) of gentamycin-induced renal proximal tubular (RPT) apoptosis is mediated, at least in part, via reactive oxygen species (ROS) generation in mice. Methods: Adult (age 18-19 weeks) male non-Tg mice and transgenic (Tg) mice specifically overexpressing catalase (Cat) in their renal proximal tubular cells (RPTCs) were administered i.p. with gentamicin (20mg/kg/days) for five days consecutively and then euthanized at two different time point. Kidneys were processed for morphological analysis, apoptosis study (TUNEL assay), presence of increased ROS generation, immunostaining for Bax, Bmf and Casp12 proteins and Casp12 activity. We also examined the effect of gentamicin on apoptosis in immortalized rat RPTCs in vitro. Results: In vivo, gentamicin induced significant tubular apoptosis, ROS generation, increased expression of Bax and Bmf proteins and Casp12 activity in non-Tg mice. Most of these changes were normalized in Cat-Tg mice..In vitro, gentamicin induced apoptosis of iRPTCs while co-treatment with Cat increased cells viability and reduced apoptosis of the cells. Conclusions: These data demonstrate that gentamicin-induced RPTC apoptosis is mediated, at least in part, via ROS generation.   Keywords: gentamicin,  nephrotoxicity,  apoptos,  ROS,  catalase

Keyphrases: Gentamicin, Nephrotoxicity, Apoptos, Catalase, ROS
L’altération des interactions neurone-glie à la jonction neuromusculaire de souris âgées

Aging comes with an alteration and organism functions including cognitive and motor functions. Major weakening of the neuromuscular system occurs which includes muscle weight loss, difficulties in initiating voluntary movement and reduced muscle strength. The possible role of the alteration of the neuromuscular junction has been examined but always only considering the pre- and postsynaptic elements. However, perisynaptic Schwann cells (PSCs), glial cells at the neuromuscular junction (NMJ), play fundamental roles in the regulation of the synaptic efficacy of the NMJ as well as in its maintenance and stability. Hence, we analysed NMJ properties and their glial cells in aging. This study shows that PSCs function at the old NMJ are dysregulated. Indeed, PSCs ability to detect synaptic transmission, determined using imaging of intracellular Ca2+, was maintained in PSCs at NMJs from old mice, but the contribution of the muscarinic component was greatly reduced. On the other hand, our results using synaptic recordings are showing that a number of synaptic plasticity events known to be regulated by PSCs are reduced at NMJs of old mice. Finally, morphological NMJ reorganisation and sprouting of PSCs were also observed. These data suggest that PSC properties are consistent with the repair of the NMJ that may also result in their reduced ability in regulating synaptic efficacy.

Keyphrases: Synapse tripartite, Aging, Neuromuscular junction, Glia, Perisynaptic Schwann cells, Synaptic plasticity, Muscarinic receptors
Studies on lipid production of microalgae under mixotrophic growth, utilizing glycerol as a carbon source, combined with nitrogen starvation

Rampant increases in oil prices and detrimental effects of fossil fuels on the environment have been the main impetus for the development of environmentally friendly and sustainable energy sources. Amongst the many possibilities, microalgae have been proposed as a new alternative energy source to fossil fuels, as their growth is both sustainable and ecologically safe. By definition, microalgae are unicellular photosynthetic microorganisms containing chlorophyll a. These organisms are capable of producing large quantities of oils, surpassing that of traditional oil-seed crops, which can be transformed, through chemical processes, into biofuels such as biodiesel or bio-gasoline. Thus, recent research has gone into discovering high lipid producing algal strains, optimising growth media for increased lipid production and developing metabolic engineering to make microalgae a source of biofuel that is competitive to more traditional sources of biofuel and even to fossil fuel.  In this context, the research reported here focused on using a mixotrophic growth mode as a way to increase lipid production for certain strains of microalgae. In addition, nitrogen starvation combined with mixotrophy was studied to analyse its effects on lipid production. Mixotrophy is the parallel usage of two trophic modes, in our case photoautotrophy and heterotrophy. Consequently, 12 algal strains were screened for mixotrophic growth, using glycerol as a carbon source. Glycerol is a waste product of the current biodiesel industry; it is a cheap and abundant carbon source present in many metabolic pathways. From this initial screening, several strains were chosen for subsequent experiments involving nitrogen starvation. Nitrogen starvation has been shown to induce lipid accumulation. The results obtained show that a mixotrophic growth mode, using glycerol as a carbon source, enhances lipid production for certain strains. Moreover, lipid enhancement was shown for nitrogen starvation combined with mixotrophic growth mode. This was dependant on time spent under nitrogen starvation and on initial concentrations of the nitrogen source.

Keyphrases: Biodiesel, Glycerol, Microalgae, Mixotrophy, Nitrogen Starvation
Centor : concept d’interface de spatialisation sonore additive

This research takes a critical look at current sound spatialisation interfaces and places spatial music composition, traditionally studied in music research, at the forefront of a research in design. This thesis presents a research approach focused on understanding the spatial composition process and mental models of electroacoustic music composers in order to build a design brief for a new sound spatialisation software tool : Centor. This research combines the study of interface and interaction design with music theory in order to generate an innovative sound spatialisation method that is meaningful from both an interaction design and musical standpoint. We present the research and development process of additive spatialisation: a pattern based method that integrates aspects of spectromorphology, developed by Denis Smalley. The proposed spatilisation tool for in studio work is meant to complement current digital audio workstations and to offer new opportunities for spatial sound exploration in electroacoustic music. This work is a contribution to the field of new musical interface design, specifically for spatialisation but also, more broadly, suggests a design process that could be used for the creation of new digital tools for artistic expression.

Keyphrases: Interaction musicale, Spatialisation, Interface musicale, IHM, Music interaction, Spatialization, Interface for musical expression
Selective inhibition of inducible nitric oxide synthase prevents lipid peroxidation in cartilage from patients with osteoarthritis

INTRODUCTION: Emerging evidence indicates that nitric oxide (NO), which is increased in osteoarthritic (OA) cartilage, plays a role in 4-hydroxynonenal (HNE) generation through peroxynitrite formation. HNE is considered as the most reactive product of lipid peroxidation (LPO). We have previously reported that HNE levels in synovial fluids are more elevated in knees of OA patients compared to healthy individuals. We also demonstrated that HNE induces a panoply of inflammatory and catabolic mediators known for their implication in OA cartilage degradation. The aim of the present study was to investigate the ability of inducible NO synthase (iNOS) inhibitor, L-NIL (L-N6-(L-Iminoethyl)Lysine), to prevent HNE generation through NO inhibition in human OA chondrocytes.   METHOD: Cells and cartilage explants were treated with or without either an NO generator (SIN or interleukin 1beta (IL-1β)) or HNE in absence or presence of L-NIL. Protein expression of both iNOS and free-radical-generating NOX subunit p47 (phox) were investigated by western blot. iNOS mRNA detection was measured by real-time RT-PCR. HNE production was analysed by ELISA, Western blot and immunohistochemistry. S-nitrosylated proteins were evaluated by Western Blot. Prostaglandin E2 (PGE2) and metalloproteinase 13 (MMP-13) levels as well as glutathione S-transferase (GST) activity were each assessed with commercial kits. NO release was determined using improved Griess method. Reactive oxygen species (ROS) generation was revealed using fluorescent microscopy with the use of commercial kits.   RESULTS: L-NIL prevented IL-1β-induced NO release, iNOS expression at protein and mRNA levels, S-nitrosylated proteins and HNE in a dose dependent manner after 24h of incubation. Interestingly, we revealed that L-NIL abolished IL-1β-induced NOX component p47phox as well as ROS release. The HNE-induced PGE2 release and both cyclooxygenase-2 (COX-2) and MMP-13 expression were significantly reduced by L-NIL addition. Furthermore, L-NIL blocked the IL-1β induced inactivation of GST, an HNE-metabolizing enzyme. Also, L-NIL prevented HNE induced cell death at cytotoxic levels.   CONCLUSION: Altogether, our findings support a beneficial effect of L-NIL in OA by preventing LPO process in NO-dependent and/or independent mechanisms.

Keyphrases: Osteoarthritis, Chondrocyte, Lipid peroxydation, Nitric Oxide, L-N6-(L-Iminoethyl)Lysine, Inducible Nitric Oxide Synthase, Oxydative Stress, Reactive Oxygen Species, Cartilage, Chondrocytes, 4-Hydroxynonénal, L-N6-(L-Iminoethyl)Lysine
Effet de la galanine sur le système nerveux cardiaque intrinsèque.‎

Cholinergic and adrenergic efferent neurons of the intrinsic cardiac nervous system ‎‎(ICNS) regulate cardiac chronotropic function. Galanin, a peptide present and released in ‎cardiac nerve endings, is able to reduce the acetylcholine release. Our aim was to investigate ‎the proposition that galanin can act as an inhibitory neuromodulatory peptide in the rat ICNS. ‎Atria and associated ICNS tissues were isolated from Sprague-Dawley rats and superfused in ‎vitro. Beat to beat atrial rate measurements were derived from an atrial bipolar recording. ‎Nicotine bolus infusion (bath concentrations of 20-250 µM) induced biphasic responses ‎consisting of an early negative followed by a positive chronotropic response. During galanin ‎superfusion (170 nM), positive chronotropic responses to nicotine were reduced in 12/14 ‎preparations (control: 21.35±17.4 to galanin: 5.46±8.0 bpm, n=14, p=0.02) whereas the ‎negative chronotropic responses were reduced in 8/14 preparations and displayed an overall ‎tendency towards reduction (control: -16.09±14.7, galanin: -12.53±13.2 bpm). It is concluded ‎that galanin may act as an inhibitory neuromodulatory peptide in the rat ICNS, preferentially ‎modifying nicotinic stimulation of adrenergic neurons.‎

Keyphrases: Nicotine, Intrinsic cardiac nervous system, Nicotine, Galanin, Heart rate, Isolated rat atria
Réduction d'expansion volumique au cours de la gestation : conséquence sur la circulation utéro-placentaire

Pregnancy is characterized by an increase of circulating maternal volume and blood flow to respond to the growing needs of the fetus. By decreasing maternal volume expansion, we have developed a model of intrauterine growth restriction (IUGR) in pregnant rat in which there is a reduction in the diameter of the uterine arteries and decreased response to angiotensin II. We hypothesize that, there is a dysfunction of endothelial dependant relaxation mechanisms in response to vasoactive agents in radial uterine arteries from IUGR rats compared to those from normal pregnant rats. Our aim was to characterize the influence of the endothelium on the regulation of uterine radial artery reactivity in a model of decreased uteroplacental perfusion. Concentration-response curves to vasoactive agents (Phenylephrin (Pe), Carbachol (Cbc) et Sodium Nitroprusside (SNP)) were done on radial uterine vessels in pressurized flow chamber in presence of inhibitors of endothelium dependant relaxation pathways (nitric oxide (NO), prostacyclin (PGI2) and endothelium dependant hypolarizing factors (EDHF)). Firstly we demonstrated that the radial uterine arteries of IUGR rats had a smaller diameter compared to control ones. We also demonstrated a greater use of NO in relaxation response to Cbc in IUGR rats. Finally, the inhibition of EDHF by addition of KCl to other inhibitors (L-NAME and Ibuprofen (Ibu)) almost completely blocked the relaxation in both groups.  In conclusion, our results demonstrate that there is significant involvement of EDHF in endothelium-dependent dilation in the radial uterine arteries in both groups. Moreover, in our model of IUGR, characterized by a reduction in maternal circulating volume, the NO pathway is activated, probably to compensate for the uterine arteries diameter reduction and decreased uterine perfusion.

Keyphrases: EDHF, NO, Vascular reactivity, IUGR
Longitudinal assessment of neural activity in Parkinson’s disease with mild cognitive impairment using task based fMRI

PD was traditionally thought of as purely a movement disorder, now it is considered a multisystem disorder, with multiple non-motor aspects including damages to the cognitive circuits. Mild cognitive impairment (MCI) in PD has been linked with structural gray matter, white matter as well as functional brain changes. Specifically, significantly reduced activity was observed in the ‘cognitive’ corticostriatal loop in patients with PD-MCI vs. PD non-MCI using fMRI. Little is known regarding the course of these functional patterns over time. In this study we present longitudinal follow up of 24 non-demented PD who underwent neuropsychological investigation and were separated in two groups - with and without MCI (MCI n=11, Non-MCI n=13) according to the MDS level 2 recommendation for diagnosis of PD-MCI. Afterwards, each participant underwent an fMRI investigation by performing the Wisconsin Card Sorting Task over two sessions, 19 months apart. Our longitudinal results show that during planning set-shift period of the task, PD Non-MCI patients were engaging the normal cortical resources but they also activated more cortical areas at time 2 that are related to decision-making such as the medial prefrontal cortex (PFC), parietal lobe and the superior PFC, whilst the patients with MCI failed to engage these areas at both time points. The striatum was not engaged for both groups at time 2 and for MCI group at time 1. Furthermore, medial temporal lobe structures (MTLS) were under-recruited overtime for both the MCI and Non-MCI PD patients, and were positively correlated with MoCA scores over time. Parietal cortex, anterior PFC, superior PFC, and posterior putamen were negatively correlated with MoCA scores. These results reveal functional alteration along the basal ganglial-thalamo-cortical axis in early PD, as well as different cortical involvement levels along the course cognitive impairment. This discrepancy in cortical resources recruitment over time might reflect deficient circuitry distinct to cognitive impairment in Parkinson’s disease.

Keyphrases: Parkinson’s disease, fMRI, WCST, mild cognitive impairment