Exploration naturaliste sous-marine des petits fonds rocheux du Cap Santa Clara au Cap Esterias, Province de l’Estuaire, Gabon: les poissons marins

Bien que située à moins de vingt kilomètres du centre de la capitale Libreville, la zone marine comprise entre le Cap Santa Clara et le Cap Esterias n’avait fait l’objet que de travaux scientifiques limités, essentiellement orientés vers les tortues marines, emblématiques des efforts de conservation du milieu marin au Gabon. Aucun véritable inventaire de la faune spécifique aux estrans et aux petits fonds rocheux n’avait été entrepris, et l’évidence d’une mission d’exploration s’imposait, renforcée par la probabilité de découvrir de nouvelles espèces, pour le Gabon, voire peut-être même pour la Science.info:eu-repo/semantics/publishedVersio

Multicenter performance evaluation of a second generation cortisol assay

Background: Untreated disorders of the adrenocortical system, such as Cushing's or Addison's disease, can be fatal, and accurate quantification of a patient's cortisol levels is vital for diagnosis. The objective of this study was to assess the analytical performance of a new fully-automated Elecsys (R) Cortisol II assay (second generation) to measure cortisol levels in serum and saliva. Methods: Four European investigational sites assessed the intermediate precision and reproducibility of the Cortisol II assay (Roche Diagnostics) under routine conditions. Method comparisons of the Cortisol II assay vs. liquid chromatography-tandem mass spectrometry (LC-MS/MS), the gold standard for cortisol measurement, were performed. Cortisol reference ranges from three US sites were determined using samples from self-reported healthy individuals. Results: The coefficients of variation (CVs) for repeatability, intermediate precision, and reproducibility for serum samples were <= 2.6%, <= 5.8%, and <= 9.5%, respectively, and for saliva were <= 4.4% and <= 10.9%, and <= 11.4%, respectively. Agreement between the Cortisol II assay and LC-MS/MS in serum samples was close, with a slope of 1.02 and an intercept of 4.473 nmol/L. Reference range samples were collected from healthy individuals (n = 300) and serum morning cortisol concentrations (5-95th percentile) were 166.1-507 nmol/L and afternoon concentrations were 73.8-291 nmol/L. Morning, afternoon, and midnight saliva concentrations (95th percentile) were 20.3, 6.94, and 7.56 nmol/L, respectively. Conclusions: The Cortisol II assay had good precision over the entire measuring range and had excellent agreement with LC-MS/MS. This test was found suitable for routine diagnostic application and will be valuable for the diagnosis of adrenocortical diseases

ERBB2mRNA expression and response to Ado-Trastuzumab Emtansine (T-DM1) in HER2-positive breast cancer

Trastuzumab emtansine (T-DM1) is approved for the treatment of human epidermal growth factor receptor 2 (HER2)-positive (HER2+) metastatic breast cancer (BC) and for residual disease after neoadjuvant therapy; however, not all patients benefit. Here, we hypothesized that the heterogeneity in the response seen in patients is partly explained by the levels of human epidermal growth factor receptor 2 gene (ERBB2) mRNA.We analyzed ERBB2 expression using a clinically applicable assay in formalin-fixed para n-embedded (FFPE) tumors (primary or metastatic) from a retrospective series of 77 patients with advanced HER2+ BC treated with T-DM1. The association of ERBB2 levels and response was further validated in 161 baseline tumors from the West German Study (WGS) Group ADAPT phase II trial exploring neoadjuvant T-DM1 and 9 in vitro BC cell lines. Finally

Tight Junction Proteins and Signaling Pathways in Cancer and Inflammation: A Functional Crosstalk.

The ability of epithelial cells to organize through cell-cell adhesion into a functioning epithelium serves the purpose of a tight epithelial protective barrier. Contacts between adjacent cells are made up of tight junctions (TJ), adherens junctions (AJ), and desmosomes with unique cellular functions and a complex molecular composition. These proteins mediate firm mechanical stability, serves as a gatekeeper for the paracellular pathway, and helps in preserving tissue homeostasis. TJ proteins are involved in maintaining cell polarity, in establishing organ-specific apical domains and also in recruiting signaling proteins involved in the regulation of various important cellular functions including proliferation, differentiation, and migration. As a vital component of the epithelial barrier, TJs are under a constant threat from proinflammatory mediators, pathogenic viruses and bacteria, aiding inflammation and the development of disease. Inflammatory bowel disease (IBD) patients reveal loss of TJ barrier function, increased levels of proinflammatory cytokines, and immune dysregulation; yet, the relationship between these events is partly understood. Although TJ barrier defects are inadequate to cause experimental IBD, mucosal immune activation is changed in response to augmented epithelial permeability. Thus, the current studies suggest that altered barrier function may predispose or increase disease progression and therapies targeted to specifically restore the barrier function may provide a substitute or supplement to immunologic-based therapies. This review provides a brief introduction about the TJs, AJs, structure and function of TJ proteins. The link between TJ proteins and key signaling pathways in cell proliferation, transformation, and metastasis is discussed thoroughly. We also discuss the compromised intestinal TJ integrity under inflammatory conditions, and the signaling mechanisms involved that bridge inflammation and cancer

Les poissons cryptobenthiques de la baie d’Agay (Var): Découverte de deux gobies, espèces nouvelles pour la France

International audienceCryptobenthic fishes are bottom dwelling species that are easily overlooked because of their small size, their colouring similar to the surrounding, or because they live hidden. These species are also often difficult to identify. For these reasons, the diversity of cryptobenthic fishes is one of the least known of the marine world. This Notebook presents the observations of cryptobenthic fishes made in the Bay of Agay, in the French Mediterranean, by a group of naturalist divers, in particular during two missions targeting these species in 2021. Notably, we describe the first records for France of two species of gobies (Buenia massutii and Speleogobius llorisi), the first mention of Gobius gasteveni and the second of Lebetus guilleti for the French Mediterranean. These missions demonstrate that the marine cryptobenthic ichthyofauna of our territory is still understudied, including in the coastal zone accessible to recreational diving.Les poissons cryptobentiques regroupent les espèces de fond qui passent facilement inaperçues à cause de leur petite taille, de leurs couleurs proches de celles de l’environnement, ou parce qu’elles vivent cachées. Ces espèces sont aussi souvent difficiles à identifier. Pour ces raisons, la diversité des poissons cryptobentiques est l’une des plus méconnues du monde marin. Ce cahier présente les observations de poissons cryptobenthiques effectuées dans la baie d’Agay, en Méditerranée française, par un groupe de plongeurs naturalistes, en particulier lors de deux missions, menées en 2021. Nous y décrivons notamment les premières observations en France des deux espèces de gobies (Buenia massutii et Speleogobius llorisi), la première mention de Gobius gasteveni et la seconde de Lebetus guilleti pour Méditerranée française. Ces missions démontrent que l’ichtyofaune marine cryptobenthique de notre territoire demeure sous-étudiée y compris dans la zone littorale accessible à la plongée loisir

Potential selection of genetically balanced spermatozoa based on the hypo-osmotic swelling test in chromosomal rearrangement carriers

International audienceChromosomal translocations and other balanced rearrangements, although usually associated with a normal phenotype, can lead to the transmission of an abnormal unbalanced genome to the offspring. Balanced and unbalanced spermatozoa, being indistinguishable, cannot be selected or deselected for prior to IVF and pre-implantation genetic diagnosis. Spermatozoa from 16 chromosomal rearrangement carriers were studied. After incubation in a hypo-osmotic solution (hypo-osmotic swelling test, or HOST), spermatozoa were fixed on microscope slides. The chromosomally balanced or unbalanced status corresponding to each observed class of flagellar conformation was evaluated through fluorescent in-situ hybridization (FISH). We show here a specific type of spermatozoa, with a distinct flagellar conformation that was associated with a balanced genetic content. HOST is a simple, low-cost and time-honoured procedure initially developed to distinguish immotile viable from non-viable spermatozoa. We demonstrate that it can also be used to identify genetically balanced spermatozoa in chromosomal rearrangement carriers, with a 96% decrease in the proportion of unbalanced spermatozoa after selection. This may potentially improve reproductive prognosis in affected couples if used prior to pre-implantation genetic diagnosis (PGD), and clinical utility and efficacy should be evaluated in further studies

Efficacy of deescalated chemotherapy according to PAM50 subtypes, immune and proliferation genes in triple-negative early breast cancer: Primary translational analysis of the WSG-ADAPT-TN trial

In the neoadjuvant WSG-ADAPT-TN trial, 12-week nab-paclitaxel + carboplatin (nab-pac/carbo) was highly effective and superior to nab-paclitaxel + gemcitabine (nab-pac/gem) in triple-negative breast cancer regarding pathological complete response (pCR). Predictive markers for deescalated taxane/carbo use in TNBC need to be identified. Patients received 4 x nab-pac 125 mg/m(2) (plus carbo AUC2 or gem 1,000 mg/m(2) d1,8 q21). Expression of 119 genes and PAM50 scores by nCounter were available in 306/336 pretherapeutic samples. Interim survival analysis was planned after 36 months median follow-up. Basal-like (83.3%) compared to other subtypes was positively associated with pCR (38% vs. 20%, p = 0.015), as was lower HER2 score (p < 0.001). Proliferation biomarkers were positively associated with pCR, that is, PAM50 proliferation, ROR scores (all p < 0.004), higher Ki-67 (IHC; p < 0.001). For nab-pac/carbo, expression of immunological (CD8, PD1 and PFDL1) genes and proliferation markers (proliferation and ROR scores, MKI67, CDC20, NUF2, KIF2C, CENPF, EMP3 and TYMS) were positively associated with pCR (p < 0.05 for all). For nab-pac/gem, angiogenesis genes were negatively associated with pCR (ANGPTL4: p = 0.05; FGFR4: p = 0.02; VEGFA: p = 0.03). pCR after 12 weeks was strongly associated with favorable outcome (3y event-free survival: 92% vs. 71%, p < 0.001). In early TNBC, basal-like subtype, higher Ki-67 (IHC) and lower HER2 score were, associated with chemosensitivity. Chemoresistance pathways differed between the two taxane based combinations. Combination of proliferation/immune markers and PAM50 subtype could allow patient selection for further deescalated chemotherapy and/or immune treatment approaches

Gut-licensed IFNγ+ NK cells drive LAMP1+TRAIL+ anti-inflammatory astrocytes

Astrocytes are glial cells that are abundant in the central nervous system (CNS) and that have important homeostatic and disease-promoting functions1. However, little is known about the homeostatic anti-inflammatory activities of astrocytes and their regulation. Here, using high-throughput flow cytometry screening, single-cell RNA sequencing and CRISPR–Cas9-based cell-specific in vivo genetic perturbations in mice, we identify a subset of astrocytes that expresses the lysosomal protein LAMP12 and the death receptor ligand TRAIL3. LAMP1+TRAIL+ astrocytes limit inflammation in the CNS by inducing T cell apoptosis through TRAIL–DR5 signalling. In homeostatic conditions, the expression of TRAIL in astrocytes is driven by interferon-γ (IFNγ) produced by meningeal natural killer (NK) cells, in which IFNγ expression is modulated by the gut microbiome. TRAIL expression in astrocytes is repressed by molecules produced by T cells and microglia in the context of inflammation. Altogether, we show that LAMP1+TRAIL+ astrocytes limit CNS inflammation by inducing T cell apoptosis, and that this astrocyte subset is maintained by meningeal IFNγ+ NK cells that are licensed by the microbiome.Fil: Sanmarco, Liliana Maria. Harvard Medical School; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Wheeler, Michael A.. Harvard Medical School; Estados UnidosFil: Gutiérrez Vázquez, Cristina. Harvard Medical School; Estados UnidosFil: Polonio Manganeli, Carolina. Harvard Medical School; Estados UnidosFil: Linnerbauer, Mathias. Harvard Medical School; Estados UnidosFil: Pinho Ribeiro, Felipe A.. Harvard Medical School; Estados UnidosFil: Li, Zhaorong. Harvard Medical School; Estados UnidosFil: Giovannoni, Federico. Harvard Medical School; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Batterman, Katelyn V.. University Of Boston. School Of Medicine.; Estados UnidosFil: Scalisi, Giulia. Harvard Medical School; Estados UnidosFil: Zandee, Stephanie E. J.. University of Montreal; CanadáFil: Heck, Evelyn Sabrina. Harvard Medical School; Estados Unidos. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Alsuwailm, Moneera. Harvard Medical School; Estados UnidosFil: Rosene, Douglas L.. University Of Boston. School Of Medicine.; Estados UnidosFil: Becher, Burkhard. Universitat Zurich; SuizaFil: Chiu, Isaac M.. Harvard Medical School; Estados UnidosFil: Prat, Alexandre. University of Montreal; CanadáFil: Quintana, Francisco Javier. Harvard Medical School; Estados Unido