HAL Portal ESPCI (Ecole Supérieure de Physique et de Chimie Industrielles)
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Thyroidectomy without radioiodine in patients with low-risk thyroid cancer: 5 years of follow-up of the prospective randomised ESTIMABL2 trial
No full textInternational audienceBackground ESTIMABL2, a multicentre randomised phase 3 trial in patients with low-risk differentiated thyroid cancer (ie, pT1am or pT1b, N0 [no evidence of regional nodal involvement] or Nx [involvement of regional lymph nodes that cannot be assessed in the absence of neck dissection]), showed the non-inferiority of a follow-up strategy without radioactive iodine (¹³¹I) administration compared with a postoperative ¹³¹I administration at 3 years post-randomisation. Here, we report a pre-specified analysis after 5 years of follow-up.Methods Patients treated with total thyroidectomy with or without prophylactic neck lymph node dissection, without postoperative suspicious findings on neck ultrasonography, were randomly assigned to the no-radioiodine group or to the radioiodine group (1•1 GBq-30 mCi after recombinant human thyrotropin-stimulating hormone). Follow-up consisted of annual thyroglobulin and thyroglobulin antibody determinations during levothyroxine treatment and neck ultrasonography in odd-numbered years. An event was defined as abnormal foci of ¹³¹I uptake on the post-treatment whole-body-scan requiring subsequent treatment, abnormal neck ultrasonography, elevated thyroglobulin levels, increasing titres or appearance of thyroglobulin antibody (using the same laboratory assay), or a combination of these definitions. Non-inferiority of the proportion of patients without an event in one group compared with the other at 5 years after randomisation was shown if this proportion and its CI did not differ by more than -5%. This study was registered on ClinicalTrials.gov (NCT01837745) and is completed. FindingsOf the 776 patients (n=642 [82•7%] female and n=134 [17•3%] male, median age 52•9 years [IQR 42•6-63•1]) enrolled, 698 were evaluable at 5 years. The proportions of patients without events were 93•2% in the no-radioiodine group and 94•8% in the radioiodine group, for a difference of -1•6% (90% CI -4•5 to 1•4). Events consisted of structural or functional abnormalities (n=11) and biological abnormalities (n=31).Interpretation The non-inferiority of a follow-up strategy compared with postoperative ¹³¹I administration in low risk differentiated thyroid cancer was confirmed at 5 years. There is no loss of opportunity in following these patients without postoperative ablation.Funding Programme de Recherche Hospitalier Clinique.</div
Differentiation of Tumor vs. Peritumoral Cortex in Gliomas by Intraoperative Electrocorticography
No full textInternational audienceBackground: Brain diffuse gliomas are highly epileptic and infiltrative tumors. Glioma surgery consists in the resection of the tumor core and the maximum of the peritumoral zone, infiltrated by tumor cells, guided by the intraoperative assessment of brain functionality and connectivity. However, its electrophysiological characteristics are poorly characterized.Methods: We studied the characteristics of Electrocorticographic (ECoG) signals, in the context of glioma surgery in awake condition on 29 patients, using EEG activity sampled on the tumor itself versus on its borders and in healthy areas. We assessed the features of frequency bands and aperiodic components (offset and slope) of ECoG power spectra during awake glioma surgery, according to cortical tumoral vs peritumoral and healthy status.Results: We found that tumor contacts present a decrease in activity for all the frequency bands except for delta activity, which was increased. Second, the peritumoral cortex was characterized by an increase in relative beta activity and slopes between 20-40 Hz. Low cortical tumor cell infiltration was directly correlated with a reduction in the production of physiological brain rhythms. Finally, an automatic classifier based on neural networks allowed the classification of the electrodes based on their power spectrum characteristics.Conclusions: This intraoperative study shows that ECoG during glioma surgery in awake condition may characterize the peritumoral cortices, key for pathophysiology and therapy, and deepens our knowledge of the effects of tumor cells infiltration on nervous tissue activity. Its assessment during the surgical procedure should better delineation of the cortical areas to be removed
Encoding and Expressing the Handedness of a Möbius π System in a Totemic Architecture
No full textInternational audienceThe efficient control of the chirality of Möbius π systems remains a challenging task that hinders the development of such molecules into information processing systems. Achieving such control through a redox process would thus open new opportunities. In this context, redox behaviors of Ni(II) and Pd(II) complexes of a Möbius aromatic [28]hexaphyrin doubly linked to an α-cyclodextrin have been investigated. This totemic architecture embedding three types of chirality elements generates two pseudoenantiomers after coordination with either metal. These isomeric pairs possess marked and opposite chiroptical signatures resulting from the P and M configurations of the Möbius π systems. Chemical oxidation to 26-π systems led to behaviors reminiscent to The Oak and the Reeds fable, due to a N3C coordination sphere of Ni(II) being more robust than that of Pd(II). Oxidized Ni(II) complexes (the Oak) maintain a Möbius-type conformation at the expense of the π-systems, which undergo an interruption due to inevitable water insertion. In contrast, oxidation of Pd(II) complexes (the Reeds) converts the Möbius aromatic systems into Hückel (rectangular) aromatic ones that are maintained in the chiral environment provided by the linking pattern with the cyclodextrin. This constitutes an effective chiral instructing site, as reduction back to their original Möbius configuration occurs with high stereoselectivity. Such a reversible shape-shifting process corresponds to a chiral memory phenomenon where the handedness of a cyclic π system is encoded in a scaffold and expressed upon changing an electronic state. For both metals, spectroelectrochemical studies ultimately revealed robust ON-OFF chiroptical switches, which is unprecedented with Möbius π-systems
Synthetic chaperone based on Hsp90-Tau interaction inhibits pathological Tau aggregation and rescues physiological Tau-Microtubule interaction
No full textInternational audienceThe accumulation of intracellular aggregates of Tau protein is one main hallmark of Alzheimer’s disease (AD) and is the consequence of Tau conformational changes, increased phosphorylation, and self-association to form fibrillar aggregates. This pathological process prevents the physiological interaction of Tau with microtubules to the detriment of the structural integrity of neurons. In healthy cells, aberrant protein misfolding and aggregation are counteracted by chaperone proteins whose protective capacity decreases with age. The role of the chaperone Hsp90 and the mechanism by which it can prevent Tau aggregation toxicity are controversial. The innovative strategy of mimicking Hsp90 through the design of the β-hairpin like peptidomimetic β-Hsp90 , inspired by two Hsp90/Tau interaction sequences, is presented here. β-Hsp90 inhibits Tau aggregation both in vitro and in cells , restoring Tau’s physiological interaction with microtubules. β-Hsp90 , which interacts with the P1 region of Tau, is more effective than individual peptide sequences from the chaperone HSP90 and another β-hairpin mimic based on Tau sequences. Moreover, β-Hsp90 dramatically reduces AD-associated Aβ 1-42 aggregation, offering the development of a dual inhibitor. This work paves the way for the design of new drugs targeting devastating untreated amyloid diseases, by mimicking physiological chaperones with small synthetic peptide drugs
Pyridylidene transition metal complexes – An underexplored class of organometallic carbenes
No full textInternational audiencePyridylidene compounds, carbene isomers of related pyridines, remain a fascinating class of intermediates in organic synthesis. Although of high interest as ligands in organometallic and coordination chemistry, this aspect is by far underexplored because of obvious lack of general and efficient synthetic methodologies. This review summarizes the relatively few reported examples of organometallic compounds with pyridylidene ligands. Several important reported examples recently open the way to a promising development of this class of carbenes in organometallic catalysis, biology or materials sciences
Transverse vortices induced by modulated granular shear flows of elongated particles
No full textInternational audienceWe perform discrete element method (DEM) simulations of elongated grains in a shear cell for various particle aspect ratios and contact frictions, with an additional heterogeneous force perturbation in the flow direction. For a perturbation in the form of a single Fourier mode, we show that the response of the system consists of transverse secondary flows that average onto a pattern of four vortices. We also theoretically studied this phenomenon by generalizing the granular rheology µ(I) to the case of elongated grains and computing the linear response to such a perturbation. Even if the agreement between theory and simulations remains qualitative only, we can reproduce and understand the inversion of the vortex pattern when the cell aspect ratio is increased from a vertically to a horizontally elongated cell shape, emphasizing the key role of the second normal stress difference as well as the cell geometry
Single-cell Epigenomic Profiling with High-throughput Droplet scChIP-seq
No full textInternational audienceOur high-throughput scChIP-seq approach combines droplet microfluidics with single-cell DNA barcoding to study the heterogeneity of epigenomes (H3K27me3, H3K4me3, H3K27Ac, H3K4me1) in a cellular population of several thousand cells with a coverage of up to 10,000 unique loci per cell
Emergent scales and spatial correlations at the yielding transition of glassy materials
No full textInternational audienceGlassy materials yield under large external mechanical solicitations. Under oscillatory shear, yielding shows a well-known rheological fingerprint, common to samples with widely different microstructures. At the microscale, this corresponds to a transition between slow, solid-like dynamics and faster liquid-like dynamics, which can coexist at yielding in a finite range of strain amplitudes. Here, we capture this phenomenology in a lattice model with two main parameters: glassiness and disorder, describing the average coupling between adjacent lattice sites, and their variance, respectively. In absence of disorder, our model yields a law of correspondent states equivalent to trajectories on a cusp catastrophe manifold, a well-known class of problems including equilibrium liquid-vapour phase transitions. Introducing a finite disorder in our model entails a qualitative change, to a continuous and rounded transition, whose extent is controlled by the magnitude of the disorder. We show that a spatial correlation length ξ emerges spontaneously from the coupling between disorder and bifurcating dynamics. With vanishing disorder, ξ diverges and yielding becomes discontinuous, suggesting that the abruptness of yielding can be rationalized in terms of a lengthscale of dynamic heterogeneitie
Les astrocytes au cœur du sommeil : des gènes à la dynamique des réseaux
No full textInternational audienceAstrocytes have transcended their role from mere structural scaffolds to pivotal regulators of neural circuitry and sleep–wake dynamics. The strategic proximity of their fine processes to blood vessels and synapses positions them as key players in neurobiology, contributing to the tripartite synapse concept. Gap-junction proteins also enable astrocytes to form an extensive network interacting with neuronal assemblies to influence sleep physiology. Recent advances in genetic engineering, neuroimaging and molecular biology have deepened our understanding of astrocytic functions. This review highlights the different mechanisms by which astrocytes regulate sleep, notably through transcriptomic and morphological changes, as well as gliotransmission, whereby intracellular calcium (Ca 2+ ) dynamics plays a significant role in modulating the sleep–wake cycle. In vivo optogenetic stimulation of astrocytes indeed induces ATP release, which is subsequently degraded into adenosine, modulating neuronal excitability in sleep–wake regulatory brain regions. Astrocytes also participate in synaptic plasticity, potentially modulating sleep-associated downscaling, a process essential for memory consolidation and preventing synaptic saturation. Although astrocytic involvement in synaptic maintenance is well supported, the precise molecular mechanisms linking these processes to sleep regulation remain to be elucidated. By highlighting astrocytes' multiple roles in sleep physiology, these insights deepen our understanding of sleep mechanisms and pave the way for improving sleep quality.Traditionnellement considérés comme de simples éléments de soutien du système nerveux central, les astrocytes sont désormais reconnus comme des régulateurs clés des circuits neuronaux et de la dynamique veille–sommeil. Leur proximité stratégique avec les vaisseaux sanguins et les synapses, via leurs prolongements fins, en fait des acteurs majeurs de la neurobiologie, contribuant pleinement au concept de synapse tripartite. Grâce aux protéines des jonctions communicantes, les astrocytes forment un vaste réseau interagissant avec les ensembles neuronaux pour moduler la physiologie du sommeil. Les avancées récentes en génétique, neuroimagerie et biologie moléculaire ont considérablement approfondi notre compréhension de leurs fonctions.Cette revue explore les mécanismes par lesquels les astrocytes influencent le sommeil, notamment par des modifications transcriptomiques et morphologiques, ainsi que par la gliotransmission. Dans ce cadre, la dynamique du calcium intracellulaire (Ca²⁺) joue un rôle central dans la modulation du cycle veille–sommeil. En effet, la stimulation optogénétique des astrocytes in vivo induit la libération d’ATP, rapidement dégradé en adénosine, ce qui module l’excitabilité neuronale dans les régions cérébrales impliquées dans la régulation du sommeil.Les astrocytes participent également à la plasticité synaptique, notamment à travers la modulation du processus de réduction synaptique associé au sommeil, essentiel à la consolidation de la mémoire et à la prévention de la saturation synaptique. Bien que leur rôle dans le maintien synaptique soit bien établi, les mécanismes moléculaires précis liant ces fonctions à la régulation du sommeil demeurent à élucider. En soulignant les multiples rôles des astrocytes dans la physiologie du sommeil, ces travaux approfondissent notre compréhension des mécanismes du sommeil et ouvrent de nouvelles perspectives pour en améliorer la qualité
