Aillaud C.,Institut Universitaire de France |
Aillaud C.,French Institute of Health and Medical Research |
Bosc C.,Institut Universitaire de France |
Bosc C.,French Institute of Health and Medical Research |
And 27 more authors.
Molecular Biology of the Cell | Year: 2016
Cellular α-tubulin can bear various carboxy-terminal sequences: full-length tubulin arising from gene neosynthesis is tyrosinated, and two truncated variants, corresponding to detyrosinated and δ2 α.-tubulin, result from the sequential cleavage of one or two C-terminal residues, respectively. Here, by using a novel antibody named 3EG that is highly specific to the IEEEG C-terminal sequence, we demonstrate the occurrence in neuronal tissues of a new αδ3.-tubulin variant corresponding to α1A/B.-tubulin deleted of its last three residues (EEY). αδ3.-tubulin has a specific distribution pattern: its quantity in the brain is similar to that of αδ2-tubulin around birth but is much lower in adult tissue. This truncated α1A/B-tubulin variant can be generated from αδ2-tubulin by the deglutamylases CCP1, CCP4, CCP5, and CCP6 but not by CCP2 and CCP3. Moreover, using 3EG antibody, we identify a C.-terminally truncated β-tubulin form with the same IEEEG C-terminal sequence. Using mass spectrometry, we demonstrate that β2A/B-tubulin is modified by truncation of the four C-terminal residues (EDEA). We show that this newly identified βδ4-tubulin is ubiquitously present in cells and tissues and that its level is constant throughout the cell cycle. These new C-terminally truncated α-and β-tubulin variants, both ending with IEEEG sequence, are expected to regulate microtubule physiology. Of interest, the αδ3-tubulin seems to be related to dynamic microtubules, resembling tyrosinated-tubulin rather than the other truncated variants, and may have critical function(s) in neuronal development. © 2016 Zhou et al.
Gkatzis K.,Leiden University |
Thalgott J.,The Interdisciplinary Center |
Thalgott J.,Paris science et Lettres Research University |
Dos-Santos-Luis D.,The Interdisciplinary Center |
And 17 more authors.
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2016
Objective - To determine the role of Gja5 that encodes for the gap junction protein connexin40 in the generation of arteriovenous malformations in the hereditary hemorrhagic telangiectasia type 2 (HHT2) mouse model. Approach and Results - We identified GJA5 as a target gene of the bone morphogenetic protein-9/activin receptor-like kinase 1 signaling pathway in human aortic endothelial cells and importantly found that connexin40 levels were particularly low in a small group of patients with HHT2. We next took advantage of the Acvrl1+/- mutant mice that develop lesions similar to those in patients with HHT2 and generated Acvrl1+/-; Gja5EGFP/+ mice. Gja5 haploinsufficiency led to vasodilation of the arteries and rarefaction of the capillary bed in Acvrl1+/- mice. At the molecular level, we found that reduced Gja5 in Acvrl1+/- mice stimulated the production of reactive oxygen species, an important mediator of vessel remodeling. To normalize the altered hemodynamic forces in Acvrl1+/-; Gja5EGFP/+ mice, capillaries formed transient arteriovenous shunts that could develop into large malformations when exposed to environmental insults. Conclusions - We identified GJA5 as a potential modifier gene for HHT2. Our findings demonstrate that Acvrl1 haploinsufficiency combined with the effects of modifier genes that regulate vessel caliber is responsible for the heterogeneity and severity of the disease. The mouse models of HHT have led to the proposal that 3 events - heterozygosity, loss of heterozygosity, and angiogenic stimulation - are necessary for arteriovenous malformation formation. Here, we present a novel 3-step model in which pathological vessel caliber and consequent altered blood flow are necessary events for arteriovenous malformation development. © 2016 American Heart Association, Inc.
Rajaei B.,Laue Langevin Institute |
Rajaei B.,Sadjad University of Technology |
Rajaei B.,Paris science et Lettres Research University |
Gigan S.,Paris science et Lettres Research University |
And 6 more authors.
IEEE Signal Processing Letters | Year: 2016
This paper addresses fundamental scaling issues that hinder phase retrieval (PR) in high dimensions. We show that, if the measurement matrix can be put into a generalized block-diagonal form, a large PR problem can be solved on separate blocks, at the cost of a few extra global measurements to merge the partial results. We illustrate this principle using two distinct PR methods, and discuss different design trade-offs. Experimental results indicate that this block-based PR framework can reduce computational cost and memory requirements by several orders of magnitude. © 1994-2012 IEEE.
Janke C.,Institute Curie |
Janke C.,French National Center for Scientific Research |
Janke C.,French Institute of Health and Medical Research |
Janke C.,Paris science et Lettres Research University
Journal of Cell Biology | Year: 2014
Microtubules are cytoskeletal filaments that are dynamically assembled from α/β-tubulin heterodimers. The primary sequence and structure of the tubulin proteins and, consequently, the properties and architecture of microtubules are highly conserved in eukaryotes. Despite this conservation, tubulin is subject to heterogeneity that is generated in two ways: by the expression of different tubulin isotypes and by posttranslational modifications (PTMs). Identifying the mechanisms that generate and control tubulin heterogeneity and how this heterogeneity affects microtubule function are long-standing goals in the field. Recent work on tubulin PTMs has shed light on how these modifications could contribute to a "tubulin code" that coordinates the complex functions of microtubules in cells. © 2014 Janke.
Colombi A.,Joseph Fourier University |
Colombi A.,Imperial College London |
Roux P.,Joseph Fourier University |
Guenneau S.,Aix - Marseille University |
And 2 more authors.
Journal of the Acoustical Society of America | Year: 2015
This paper deals with the numerical design of a directional invisibility cloak for backward scattered elastic waves propagating in a thin plate (A0 Lamb waves). The directional cloak is based on a set of resonating beams that are attached perpendicular to the plate and are arranged at a sub-wavelength scale in ten concentric rings. The exotic effective properties of this locally resonant metamaterial ensure coexistence of bandgaps and directional cloaking for certain beam configurations over a large frequency band. The best directional cloaking was obtained when the resonators' length decreases from the central to the outermost ring. In this case, flexural waves experience a vanishing index of refraction when they cross the outer layers, leading to a frequency bandgap that protects the central part of the cloak. Numerical simulation shows that there is no back-scattering in these configurations. These results might have applications in the design of seismic-wave protection devices. © 2015 Acoustical Society of America.
Hirsch M.-R.,French Institute of Health and Medical Research |
Hirsch M.-R.,Paris Science et Lettres Research University |
d'Autreaux F.,French Institute of Health and Medical Research |
d'Autreaux F.,Paris Science et Lettres Research University |
And 5 more authors.
Genesis | Year: 2013
Phox2b is a transcription factor expressed in the central and peripheral neurons that control cardiovascular, respiratory, and digestive functions and essential for their development. Several populations known or suspected to regulate visceral functions express Phox2b in the developing hindbrain. Extensive cell migration and lack of suitable markers have greatly hampered studying their development. Reasoning that intersectional fate mapping may help to overcome these impediments, we have generated a BAC transgenic mouse line, P2b::FLPo, which expresses codon-optimized FLP recombinase in Phox2b expressing cells. By partnering the P2b::FLPo with the FLP-responsive RC::Fela allele, we show that FLP recombination switches on lineage tracers in the cells that express or have expressed Phox2b, permanently marking them for study across development. Taking advantage of the dual-recombinase feature of RC::Fela, we further show that the P2b::FLPo transgene can be partnered with Lbx1Cre as Cre driver to generate triple transgenics in which neurons having a history of both Phox2b and Lbx1 expression are specifically labeled. Hence, the P2b::FLPo line when partnered with a suitable Cre driver provides a tool for tracking and accessing genetically subsets of Phox2b-expressing neuronal populations, which has not been possible by Cre-mediated recombination alone. genesis 51:506-514. © 2013 Wiley Periodicals, Inc.