Past volcanic activity predisposes an endemic threatened seabird to negative anthropogenic impacts.

Humans are regularly cited as the main driver of current biodiversity extinction, but the impact of historic volcanic activity is often overlooked. Pre-human evidence of wildlife abundance and diversity are essential for disentangling anthropogenic impacts from natural events. Réunion Island, with its intense and well-documented volcanic activity, endemic biodiversity, long history of isolation and recent human colonization, provides an opportunity to disentangle these processes.

Uncovering immune checkpoint heterogeneity in oral squamous cell carcinoma using single cell RNA-sequencing data highlights three subgroups of patients with distinct immune phenotypes.

Objectives: In head and neck squamous cell carcinoma (HNSCC), PD-1/PD-L1 inhibitors remain inefficient in most patients, which points to the need for better characterization of immune checkpoint (ICP) molecule expression.

Material And Methods: We evaluated the expression of 22 ICP ligands (ICPL) in 2,176 malignant cells from 10 patients in a public single-cell RNA-sequencing dataset and in two cohorts of HNSCC patients for which gene expression data are available.

Results: Based on ICPL expression, malignant cells formed three distinct clusters characterized either by a strong expression of ICPL together with an immune phenotype linked to IFN-γ response (cluster 1) or by a weak ICPL expression and little response to IFN-γ (clusters 2 and 3).

Evaluation of Asphalt Aging Using Multivariate Analysis Applied to Saturates, Aromatics, Resins, and Asphaltene Determinator Data.

Asphalt is subjected to aging, leading to physical and chemical modifications reducing its performance. Recently, the Western Research Institute developed the SAR-AD method that allowed the separation of asphalt into eight fractions (saturates, aromatics 1, aromatics 2, aromatics 3, resins, asphaltenes 1, asphaltene 2, and asphaltenes 3). In this work, this analytical method was used to study asphalt aging processes in greater detail.

Investigation of Oxidation Homogeneity in Asphalt Puck after Simulation of Long-Term Aging (Pressure Aging Vessel).

For decades, it has been known that the creation of oxygenated functional groups, especially carbonyl and sulfoxide, is among the main causes of chemical aging and degradation of asphalt. However, is the oxidation of a bitumen homogeneous? The focus of this paper was to follow the oxidation phenomena through an asphalt puck during a pressure aging vessel (PAV) test. According to the literature, the asphalt oxidation process that leads to the creation of oxygenated functions can be divided into the following successive main steps: the absorption of oxygen in asphalt at the air/asphalt interface, diffusion into the matrix, and reaction with asphalt molecules.

Condensation of the fusion focus by the intrinsically disordered region of the formin Fus1 is essential for cell-cell fusion.

Secretory vesicle clusters transported on actin filaments by myosin V motors for local secretion underlie various cellular processes, such as neurotransmitter release at neuronal synapses, hyphal steering in filamentous fungi, and local cell wall digestion preceding the fusion of yeast gametes. During fission yeast Schizosaccharomyces pombe gamete fusion, the actin fusion focus assembled by the formin Fus1 concentrates secretory vesicles carrying cell wall digestive enzymes. The position and coalescence of the vesicle focus are controlled by local signaling and actin-binding proteins to prevent inappropriate cell wall digestion that would cause lysis, but the mechanisms of focusing have been elusive.

Immunologically active phenotype by gene expression profiling is associated with clinical benefit from PD-1/PD-L1 inhibitors in real-world head and neck and lung cancer patients.

Introduction: Identification of tumours harbouring an overall active immune phenotype may help for selecting patients with advanced head and neck squamous cell carcinomas (HNSCC) and non-small cell lung cancer (NSCLC) who may benefit from immunotherapies. Our objective was to develop a reliable and stable scoring system to identify those immunologically active tumours.

Methods: Using gene expression profiles of 421 HNSCC, we developed a score to identify immunologically active tumours.

Actin assembly requirements of the formin Fus1 to build the fusion focus.

In formin-family proteins, actin filament nucleation and elongation activities reside in the formin homology 1 (FH1) and FH2 domains, with reaction rates that vary by at least 20-fold between formins. Each cell expresses distinct formins that assemble one or several actin structures, raising the question of what confers each formin its specificity. Here, using the formin Fus1 in Schizosaccharomyces pombe, we systematically probed the importance of formin nucleation and elongation rates in vivo.

Epithelial-to-mesenchymal transition promotes immune escape by inducing CD70 in non-small cell lung cancer.

Introduction: Epithelial-to-mesenchymal transition (EMT) is associated with tumor aggressiveness, drug resistance, and poor survival in non-small cell lung cancer (NSCLC) and other cancers. The identification of immune-checkpoint ligands (ICPLs) associated with NSCLCs that display a mesenchymal phenotype (mNSCLC) could help to define subgroups of patients who may benefit from treatment strategies using immunotherapy.

Methods: We evaluated ICPL expression in silico in 130 NSCLC cell lines.

Teaching how to break bad news in Oncology: In-class vs. virtual peer role-plays.

Background: We report two different peer role-play training courses for breaking bad news (BBN) in Oncology, the classic "in-class" model and the "virtual" peer role-play (VPRP) model developed during the SARS-CoV-2 pandemic.

Methods: Each session included 20-25 4th year medical students supervised by two practitioners experienced in oncology. After an ice breaking activity to exchange with students on means to promote hope to patients when BBN, peer role-plays started.

PD-1 Blockade in Solid Tumors with Defects in Polymerase Epsilon.

Unlabelled: Missense mutations in the polymerase epsilon (POLE) gene have been reported to generate proofreading defects resulting in an ultramutated genome and to sensitize tumors to checkpoint blockade immunotherapy. However, many POLE-mutated tumors do not respond to such treatment. To better understand the link between POLE mutation variants and response to immunotherapy, we prospectively assessed the efficacy of nivolumab in a multicenter clinical trial in patients bearing advanced mismatch repair-proficient POLE-mutated solid tumors.

MEK1/2 inhibition transiently alters the tumor immune microenvironment to enhance immunotherapy efficacy against head and neck cancer.

Background: Although the mitogen-activated protein kinases (MAPK) pathway is hyperactive in head and neck cancer (HNC), inhibition of MEK1/2 in HNC patients has not shown clinically meaningful activity. Therefore, we aimed to characterize the effect of MEK1/2 inhibition on the tumor microenvironment (TME) of MAPK-driven HNC, elucidate tumor-host interaction mechanisms facilitating immune escape on treatment, and apply rationale-based therapy combination immunotherapy and MEK1/2 inhibitor to induce tumor clearance.

Methods: Mouse syngeneic tumors and xenografts experiments were used to analyze tumor growth in vivo.

Ultrastructural plasma membrane asymmetries in tension and curvature promote yeast cell fusion.

Cell-cell fusion is central for sexual reproduction, and generally involves gametes of different shapes and sizes. In walled fission yeast Schizosaccharomyces pombe, the fusion of h+ and h- isogametes requires the fusion focus, an actin structure that concentrates glucanase-containing vesicles for cell wall digestion. Here, we present a quantitative correlative light and electron microscopy (CLEM) tomographic dataset of the fusion site, which reveals the fusion focus ultrastructure.

Early changes in the immune microenvironment of oral potentially malignant disorders reveal an unexpected association of M2 macrophages with oral cancer free survival.

Understanding the dynamics of the immune microenvironment is critical to the development of immuno-based strategies for the prevention of oral potentially malignant disorders transformation to oral squamous cell carcinoma (OSCC). We used laser capture microdissection and RNA-sequencing to profile the expression of 13 matched pairs of epithelial stromal compartments from normal mucosa, hyperplasia, dysplasia, and invasive tumors in the 4-nitroquinolein (4-NQO) murine model of oral carcinogenesis. Genes differentially expressed at each step of transformation were defined.

Longitudinal assessment of PD-L1 expression and gene expression profiles in patients with head and neck cancer reveals temporal heterogeneity.

Background: Programmed death-ligand 1 (PD-L1) is the most validated predictive biomarker used for the treatment of head and neck squamous cell carcinoma (HNSCC) with immune checkpoint inhibitors (ICI). Several gene expression-based signatures surrogate of the activation of IFN-gamma pathway and of the presence of tertiary lymphoid structures (TLS) have also been proposed as potential biomarkers. While they may have a potential therapeutic implication, the longitudinal changes of either PD-L1 or gene expression profiles between the initial and recurrent HNSCC lesions is unknown.

Evidence for a cluster of rare birth defects in the Ain department (France).

Background: REMERA (REgistre des Malformations En Rhône-Alpes) is a registry of congenital malformations that covers 58,000 births annually in Central-East France. In 2010, the registry raised an alarm to the health authorities (Santé publique France, SpF) about three cases of a unilateral isolated transverse upper limb reduction defect (UITULRD) in a small subarea; the general prevalence of this defect is one case in 10,000 births. In the following years, more infants were born with the same malformation in the same territory of the Ain department.

Patient and Partner Perspectives on Health-Related Quality of Life in Adrenocortical Carcinoma.

Little is known about the impact of adrenocortical carcinoma (ACC) on health-related quality of life (HRQoL), and no disease-specific questionnaire exists. This qualitative study aimed to identify relevant domains of HRQoL for patients with ACC. In 2 focus group interviews, we discussed concerns regarding living with ACC and its treatments.

Health-Related Quality of Life in Adrenocortical Carcinoma.

Insight into the health-related quality of life (HRQoL) impact of adrenocortical carcinoma (ACC) is important. The disease and its treatment options potentially have an impact on HRQoL. For patients with limited survival, HRQoL research is of utmost importance.

Very- and ultra-long-period seismic signals prior to and during caldera formation on La Réunion Island.

Early detection of the onset of a caldera collapse can provide crucial information to understand their formation and thus to minimize risks for the nearby population and visitors. Here, we analyse the 2007 caldera collapse of Piton de la Fournaise on La Réunion Island recorded by a broadband seismic station. We show that this instrument recorded ultra-long period (ULP) signals with frequencies in the range (0.

Multi-phosphorylation reaction and clustering tune Pom1 gradient mid-cell levels according to cell size.

Protein concentration gradients pattern developing organisms and single cells. In rod-shaped cells, Pom1 kinase forms gradients with maxima at cell poles. Pom1 controls the timing of mitotic entry by inhibiting Cdr2, which forms stable membrane-associated nodes at mid-cell.

Placental Pathology in Beckwith-Wiedemann Syndrome According to Genotype/Epigenotype Subgroups.

Objectives: To evaluate the frequency of placental pathological lesions in Beckwith-Wiedemann syndrome (BWS), an overgrowth disorder that exhibits etiologic molecular heterogeneity and variable phenotypic expression.

Materials And Methods: The study included 60 BWS patients with a proven molecular diagnosis and a placental pathological examination. Placentomegaly, placental mesenchymal dysplasia (PMD), chorangioma/chorangiomatosis, and extravillous trophoblastic (EVT) cytomegaly were evaluated and their frequencies in the different molecular subgroups were compared.

Assisted Reproductive Technologies and imprinting disorders: Results of a study from a French congenital malformations registry.

Introduction: Assisted Reproductive Technologies (ART) is increasingly used to help infertile couples to have children around the world. A number of studies have been published reporting an increased risk of major malformations in children born following ART, especially an increased incidence of epigenetic diseases (ED). This study aimed to assess the incidence of epigenetic diseases with affected imprinting genes in infants or children from pregnancies obtained through IVF/ICSI compared to infants or children from pregnancies obtained spontaneously.

Inhibition of Ras activity coordinates cell fusion with cell-cell contact during yeast mating.

In the fission yeast , pheromone signaling engages a signaling pathway composed of a G protein-coupled receptor, Ras, and a mitogen-activated protein kinase (MAPK) cascade that triggers sexual differentiation and gamete fusion. Cell-cell fusion requires local cell wall digestion, which relies on an initially dynamic actin fusion focus that becomes stabilized upon local enrichment of the signaling cascade on the structure. We constructed a live-reporter of active Ras1 (Ras1-guanosine triphosphate [GTP]) that shows Ras activity at polarity sites peaking on the fusion structure before fusion.

Apical sorting of lysoGPI-anchored proteins occurs independent of association with detergent-resistant membranes but dependent on their N-glycosylation.

Most glycosylphosphatidylinositol-anchored proteins (GPI-APs) are located at the apical surface of epithelial cells. The apical delivery of GPI-APs is believed to result from their association with lipid rafts. We find that overexpression of C-terminally tagged PGAP3 caused predominant production of lysoGPI-APs, an intermediate precursor in the GPI lipid remodeling process in Madin-Darby canine kidney cells.