Collision induced spatial organization of microtubules

The dynamic behavior of microtubules in solution can be strongly modified by interactions with walls or other structures. We examine here a microtubule growth model where the increase in size of the plus-end is perturbed by collisions with other microtubules. We show that such a simple mechanism of constrained growth can induce ordered structures and patterns from an initially isotropic and homogeneous suspension. First, microtubules self-organize locally in randomly oriented domains that grow and compete with each other. By imposing even a weak orientation bias, external forces like gravity or cellular boundaries may bias the domain distribution eventually leading to a macroscopic sample orientation.Comment: Submitted to Biophysical Journa

Photo-crosslinkable recombinant collagen mimics for tissue engineering applications

Gelatin is frequently used in various biomedical applications. However, gelatin is generally extracted from an animal source, which can result in issues with reproducibility as well as pathogen transmittance. Therefore, we have investigated the potential of a recombinant peptide based on collagen I (RCPhC1) for tissue engineering applications and more specifically for adipose tissue regeneration. In the current paper, RCPhC1 was functionalized with photo-crosslinkable methacrylamide moieties to enable subsequent UV-induced crosslinking in the presence of a photo-initiator. The resulting biomaterial (RCPhC1-MA) was characterized by evaluating the crosslinking behaviour, the mechanical properties, the gel fraction, the swelling properties and the biocompatibility. The obtained results were compared with the data obtained for methacrylamide-modified gelatin (Gel-MA). The results indicated that the properties of RCPhC1-MA networks are comparable to those of animal-derived Gel-MA. RCPhC1-MA is thus an attractive synthetic alternative for animal-derived Gel-MA and is envisioned to be applicable for a wide range of tissue engineering purposes

High-resolution 3D bioprinting of photo-cross-linkable recombinant collagen to serve tissue engineering applications

Various biopolymers, including gelatin, have already been applied to serve a plethora of tissue engineering purposes. However, substantial concerns have arisen related to the safety and the reproducibility of these materials due to their animal origin and the risk associated with pathogen transmission as well as batch-to-batch variations. Therefore, researchers have been focusing their attention toward recombinant materials that can be produced in a laboratory with full reproducibility and can be designed according to specific needs (e.g., by introducing additional RGD sequences). In the present study, a recombinant protein based on collagen type I (RCPhC1) was functionalized with photo-cross-linkable methacrylamide (RCPhC1-MA), norbornene (RCPhC1-NB), or thiol (RCPhC1-SH) functionalities to enable high-resolution 3D printing via two-photon polymerization (2PP). The results indicated a clear difference in 2PP processing capabilities between the chain-growth-polymerized RCPhC1-MA and the step-growth-polymerized RCPhC1-NB/SH. More specifically, reduced swelling-related deformations resulting in a superior CAD-CAM mimicry were obtained for the RCPhC1-NB/SH hydrogels. In addition, RCPhC1-NB/SH allowed the processing of the material in the presence of adipose tissue-derived stem cells that survived the encapsulation process and also were able to proliferate when embedded in the printed structures. As a consequence, it is the first time that successful HD bioprinting with cell encapsulation is reported for recombinant hydrogel bioinks. Therefore, these results can be a stepping stone toward various tissue engineering applications

Investigating species composition in the Early Aurignacian of le Piage (France) through collagen fingerprinting (ZooMS) of screen-recovered small bone fragments

In the field of paleoproteomics, ZooMS (Zooarcheology by Mass Spectrometry) has been developed to identify morphologically non-diagnostic animal remains to taxon, offering insights into human subsistence practices. Here, we report new ZooMS analyses of 1,050 Early Aurignacian (ca. 37,000–34,000 cal BP) bone fragments from the site of Le Piage (Lot, France). The studied sample is heavily fragmented and was retrieved through water sieving. In our analysis, we compare the taxonomic identifications of bone remains using traditional morphological attributes with remains identified using ZooMS and discuss the implications of the taxonomic patterns that we uncovered. Our results indicate that, despite small effect sizes, the faunal spectrum identified through ZooMS differs from that obtained through morphological analyses. While reindeer remains the dominant species, bovids and other cervids are more abundantly represented in the ZooMS fraction. Two rare taxa, a hare (Lepus sp.) and a previously unidentified carnivore (Pantherinae/Hyaenidae/Mustelidae), were also identified using ZooMS. In addition, we note an increase of Bos/Bison remains in the sample of spongy fragments that is possibly explained by the use of grease-rich bones and bone portions as fuel. Our work adds new data on patterns of reindeer dominance during the Early Aurignacian and illustrates how ZooMS identifications of screen-recovered fragments can enhance our understanding of Paleolithic subsistence strategies and patterns of site occupation

Ribosomal RNA 2′O-methylation as a novel layer of inter-tumour heterogeneity in breast cancer

International audienceRecent epitranscriptomics studies unravelled that ribosomal RNA (rRNA) 2′O-methylation is an additional layer of gene expression regulation highlighting the ribosome as a novel actor of translation control. However, this major finding lies on evidences coming mainly, if not exclusively, from cellular models. Using the innovative next-generation RiboMeth-seq technology, we established the first rRNA 2′O-methylation landscape in 195 primary human breast tumours. We uncovered the existence of compulsory/stable sites, which show limited inter-patient variability in their 2′O-methylation level, which map on functionally important sites of the human ribosome structure and which are surrounded by variable sites found from the second nucleotide layers. Our data demonstrate that some positions within the rRNA molecules can tolerate absence of 2′O-methylation in tumoral and healthy tissues. We also reveal that rRNA 2′O-methylation exhibits intra- and inter-patient variability in breast tumours. Its level is indeed differentially associated with breast cancer subtype and tumour grade. Altogether, our rRNA 2′O-methylation profiling of a large-scale human sample collection provides the first compelling evidence that ribosome variability occurs in humans and suggests that rRNA 2′O-methylation might represent a relevant element of tumour biology useful in clinic. This novel variability at molecular level offers an additional layer to capture the cancer heterogeneity and associates with specific features of tumour biology thus offering a novel targetable molecular signature in cancer

Low level of Fibrillarin, a ribosome biogenesis factor, is a new independent marker of poor outcome in breast cancer

International audienceBackground: A current critical need remains in the identification of prognostic and predictive markers in early breast cancer. It appears that a distinctive trait of cancer cells is their addiction to hyperactivation of ribosome biogenesis. Thus, ribosome biogenesis might be an innovative source of biomarkers that remains to be evaluated. Methods: Here, fibrillarin (FBL) was used as a surrogate marker of ribosome biogenesis due to its essential role in the early steps of ribosome biogenesis and its association with poor prognosis in breast cancer when overexpressed. Using 3,275 non-metastatic primary breast tumors, we analysed FBL mRNA expression levels and protein nucleolar organisation. Usage of TCGA dataset allowed transcriptomic comparison between the different FBL expression levelsrelated breast tumours. Results: We unexpectedly discovered that in addition to breast tumours expressing high level of FBL, about 10% of the breast tumors express low level of FBL. A correlation between low FBL mRNA level and lack of FBL detection at protein level using immunohistochemistry was observed. Interestingly, multivariate analyses revealed that these low FBL tumors displayed poor outcome compared to current clinical gold standards. Transcriptomic data revealed that FBL expression is proportionally associated with distinct amount of ribosomes, low FBL level being associated with low amount of ribosomes. Moreover, the molecular programs supported by low and high FBL expressing tumors were distinct. Conclusion: Altogether, we identified FBL as a powerful ribosome biogenesis-related independent marker of breast cancer outcome. Surprisingly we unveil a dual association of the ribosome biogenesis FBL factor with prognosis. These data suggest that hyper-but also hypo-activation of ribosome biogenesis are molecular traits of distinct tumors

Geomagnetic origin of the radio emission from cosmic ray induced air showers observed by CODALEMA

The new setup of the CODALEMA experiment installed at the Radio Observatory in Nancay, France, is described. It includes broadband active dipole antennas and an extended and upgraded particle detector array. The latter gives access to the air shower energy, allowing us to compute the efficiency of the radio array as a function of energy. We also observe a large asymmetry in counting rates between showers coming from the North and the South in spite of the symmetry of the detector. The observed asymmetry can be interpreted as a signature of the geomagnetic origin of the air shower radio emission. A simple linear dependence of the electric field with respect to vxB is used which reproduces the angular dependencies of the number of radio events and their electric polarity.Comment: 9 pages, 15 figures, 1 tabl

Long-term effects of evolocumab in participants with HIV and dyslipidemia: results from the open-label extension period

Objectives: People with HIV (PWH) are at an increased risk of atherosclerotic cardiovascular disease. Suboptimal responses to statin therapy in PWH may result from antiretroviral therapies (ARTs). This open-label extension study aimed to evaluate the long-term safety and efficacy of evolocumab up to 52\u200aweeks in PWH. Design: This final analysis of a multinational, placebo-controlled, double-blind, randomized phase 3 trial evaluated the effect of monthly subcutaneous evolocumab 420\u200amg on low-density lipoprotein cholesterol (LDL-C) during the open-label period (OLP) following 24\u200aweeks of double-blind period in PWH with hypercholesterolemia/mixed dyslipidemia. All participants enrolled had elevated LDL-C or nonhigh-density lipoprotein cholesterol (non-HDL-C) and were on stable maximally tolerated statin and stable ART. Methods: Efficacy was assessed by percentage change from baseline in LDL-C, triglycerides, and atherogenic lipoproteins. Treatment-emergent adverse events (TEAEs) were examined. Results: Of the 467 participants randomized in the double-blind period, 451 (96.6%) received at least one dose of evolocumab during the OLP (mean age of 56.4\u200ayears, 82.5% male, mean duration with HIV of 17.4\u200ayears). By the end of the 52-week OLP, the overall mean (SD) percentage change in LDL-C from baseline was -57.8% (22.8%). Evolocumab also reduced triglycerides, atherogenic lipid parameters (non-HDL-C, apolipoprotein B, total cholesterol, very-low-density lipoprotein cholesterol, and lipoprotein[a]), and increased HDL-C. TEAEs were similar between placebo and evolocumab during the OLP. Conclusion: Long-term administration of evolocumab lowered LDL-C and non-HDL-C, allowing more PWH to achieve recommended lipid goals with no serious adverse events. Trail registration: NCT02833844. Video abstract: http://links.lww.com/QAD/C441

High Resolution Mass Spectrometry : Application to Two-Dimensional FT-ICR and Proteomics in the Fields of Archeology and Paleontology

La spectrométrie de masse est une méthode d’analyse qui permet de travailler sur une large gamme d’échantillons. Elle est utilisée dans de nombreux domaines de recherche comme la chimie analytique, la protéomique, la lipidomique et la métabolomique…Dans un premier temps, mon travail s’est focalisé sur le développement d’une méthode indépendante d’analyse de données par spectrométrie de masse à transformée de Fourier bidimensionnelle. Pour augmenter la résolution en première dimension, une analyse FT-ICR 2D avec un échantillonnage non uniforme (NUS) a été développée. L’augmentation de la résolution dans la première dimension a permis l’obtention d’une haute résolution pour les ions précurseurs. La FT-ICR 2D a été utilisée avec succès pour l’analyse de triacylglycérols contenus dans du plasma mais aussi pour l’analyse d’échantillons archéologiques.Dans un second temps, une stratégie protéomique conjointe bottom-up et top-down a été appliquée à l’analyse d’échantillons archéologiques et paléontologiques à partir d’ossements ou de céramiques. Le développement d’une méthodologie bottom-up, a permis à partir d’ossements archéologiques d’espèces inconnues l’identification des protéines et leurs modifications chimiques. Cet ossement a pu être attribué comme appartenant à l’espèce Homo sapiens. Une analyse top-down a été utilisée pour l’analyse d’échantillons archéologiques. Pour la première fois, une protéine (la caséine de lait) a été identifiée dans un échantillon archéologique d’amphore de l’époque de l’empereur Claude (1er siècle de notre ère) grâce la détection de grands fragments de caséine.Mass spectrometry is a method of analysis which works on a wide range of sample types. It is used in many research fields such as analytical chemistry, proteomics, lipidomics and metabolomics...Firstly, my work was dedicated to the development of an independent data analysis methodology based on two-dimensional Fourier transform mass spectrometry. For increasing the resolution on the first dimension a 2D FT-ICR analysis with non-uniform sampling was developed. The resolution increase in the first dimension leading to high resolution for the precursor ions. The 2D FT-ICR has been successfully applied for the analysis of triacylglycerol contained on plasma and also for archaeological samples. This methodology led to 2D maps allowing a rapid classification of plants or animals samples.Secondly, a joint bottom-up and top-down proteomics strategy was applied for the analysis of archaeological and paleontological samples from bones or ceramics. The development of a bottom-up methodology, allowed the identification of proteins and their chemical modifications from archeological bones. These bones have been attributed to Homo sapiens. The development of a top-down methodology was applied to the analysis of archaeological ceramic. For the first time, a protein (milk casein) was identified in an archaeological sample of an amphora from Claudius emperor era (1st century A.D) via the detection of large fragments of casein. This first application of the top down proteomics showed that new information can be provided such as the in situ molecular degradation

Jeux de données issus des recherches sur le gisement de Waziers le Bas-Terroir (opérations 2013-2015) en lien avec les articles des volumes 33-4 (2022) et 34-1 (2023) de la revue Quaternaire.

International audienceThe present dataset comes from rechearch led on the Waziers le Bas-Terroir site since 2013 (Hérisson et al., 2022, for detailsabout the research and fieldwork). The present data paper aims to share with the scientific community the raw or supplementary datato those presented in the papers of the volume 1 and 2 dedicated to Waziers le Bas-Terroir eemian site, corresponding to volumes33-4 (2022) et 34-1 (2023) of Quaternaire. Data (except for data set #5) is stored in the Research Data Warehouse for Human andSocial Sciences called Nakala. Nakala data is stored on servers managed by Huma-Num, at the IN2P3 data centre in France. Alldata in this data paper are grouped in a collection entitled « Waziers le Bas-Terroir tome 1 & 2 Data paper revue Quaternaire » andaccessible through the DOI 10.34847/nkl.de671e05 or through the DOI indicated for each file in the data paper. Data set #5 has beendeposited on the PRIDE platform PRIDE (PRoteomics IDEntifications Database). The files are provided under a licence CreativeCommons Attribution Non Commercial No Derivates 4.0 International (CC-BY-NC-ND-4.0).Les jeux de données présentés ci-après sont issus des recherches menées sur le gisement de Waziers le Bas-Terroir depuis 2013 (Hérisson et al., 2022, pour les détails des recherches et opérations de terrain). Le présent data paper vise donc à mettre à disposition de la communauté scientifique des données brutes ou complémentaires à celles présentées au sein des articles des tomes 1 et 2 consacrés au gisement eemien de Waziers le Bas-Terroir, à savoir les numéros 33-4 (2022) et 34-1 (2023) de la revue Quaternaire. Les données (hormis le set de données n°5) sont stockées au sein de l'entrepôt de données de recherche pour les Sciences Humaines et Sociales Nakala. Les données de Nakala sont stockées sur des serveurs gérés par Huma-Num, au centre de calcul de l'IN2P3 en France. Toutes les données du présent data paper sont regroupées au sein d'une collection intitulée « Waziers le Bas-Terroir tome 1 & 2 Data paper revue Quaternaire » et accessible via le DOI 10.34847/nkl.de671e05 ou via le DOI indiqué pour chaque fichier dans le data paper. Le set de données n°5 a été déposé sur la plateforme PRIDE (PRoteomics IDEntifications Database). Les fichiers sont mis à disposition sous une licence Creative Commons Attribution Non Commercial No Derivates 4.0 International (CC-BY-NC-ND-4.0)