Fine-Needle Aspirates v2.0 — The Molecular Era

Tissue biopsies are required for diagnosis, prognosis, and to measure individual drug response markers for patient management. For pancreatic adenocarcinoma, surgically harvested tissues are often used to collect data and perform genomic analysis to identify driver oncogenes and specific mutations, or to quantify a handpick of (micro)RNAs and proteins biomarkers. However, such strategy raises many concerns not only because 80% of patients diagnosed with pancreatic adenocarcinoma are not eligible for surgery, meaning that biopsies are not collected, but also because repeated core biopsies are related to higher risk of morbidity, are expensive and logistics can be limiting. Alternative sample collection methods include fine-needle aspirates (FNA) collected under endoscopic ultrasound (EUS). In this chapter, we will describe how EUS-FNA material can be a wealthy source of biomarkers for pancreatic cancer patient management. In greater details, we will review how DNA, micro(RNA), or protein analysis can help stratify pancreatic adenocarcinoma patients, from single events analysis, to cutting-edge, high-throughput studies

Fate of metals in coastal sediments of a Mediterranean flood-dominated system: An approach based on total and labile fractions

The dynamics of sediment-bound metals (Cs, Cu, Ni, Pb, Ti and Zn) were studied off the Têt River (western Gulf of Lion), a typical Mediterranean coastal river punctuated by short and violent flash-floods. Spatial and temporal sampling strategies were combined to elucidate the fate of these elements in response to both the riverine sediment input and the offshore transport of these sediments through hydrodynamics. Our results show the temporal entrapment of riverborne particles and associated metals, consecutively to a major flood event, in the nearshore sedimentary unit called prodelta. Here, deposition and resuspension mechanisms define a sedimentological cycle that could be followed completely in this study. In terms of speciation between reactive (labile) and residual fractions along the fluvio-deltaic continuum, our results show that Cu, Pb and Zn are the most labile (potentially mobile) metals in the river, in accordance with their contributions from anthropogenic sources. But in the marine surficial sediments, two main behaviours can be discriminated when compared to the riverine suspended particulate matter. While Pb and Zn depict rather a constant labile fraction, Cu is characterized by decreasing levels (up to 50% difference). In terms of environmental impact, these contrasting trends have direct repercussions for the contaminant dispersal in the coastal area. Whereas Pb and Zn conserve their enhanced levels because of their stronger affinity with fine sediments, Cu is marked by the entire loss of its anthropogenic component that is progressively transferred to the dissolved phase, likely mediated by organic ligands. We ascribe these behaviours to different post-depositional partition mechanisms with respect to oxidation of the particulate organic phase at the bottom sediment/water interface. Also, analysis of one sediment core from the prodelta indicates that these early diagenetic processes govern the chemical forms of land-derived contaminants sequestrated in the nearshore sedimentary archives

Sources and sinks of sediment-bound contaminants in the Gulf of Lions (NW Mediterranean Sea): A multi-tracer approach

Surficial sediments collected in 2002 throughout the Gulf of Lions continental shelf (NW Mediterranean) were analysed for trace metals (Cd, Co, Cr, Cs, Cu, Ni, Pb, Sr, Zn and Zr), major elements (Al, Ca, Fe, P and Ti) and the sewage marker coprostanol. In addition, particle size distribution, organic carbon (OC) and carbonates were also determined. Results showed that the metal contamination (Cd, P, Cu, Pb and Zn) is mainly introduced by the local rivers and accumulates—via a regulation by OC and silt fraction (2–63 mm)—in the direct vicinity of the mouths, in high shear stress environments. Here also the signal of sewage contamination is the best preserved, especially off the eastern point sources where local sedimentation rates save the faecal marker from biodegradation processes. It is demonstrated that the shallow prodeltas are the first repository areas for land-derived particles, exposing local ecosystems to both inorganic and organic contaminations. When going seaward, however, sediment dilution, particle sorting and biodegradation processes make that most riverborne contaminants rapidly reach natural levels. Only some metals (i.e. Pb and Zn)—closely associated with the clay fraction—still depict anthropogenic enrichment, which seems to be inherited from man-made aerosols

Le domaine royal : entre territoires et réseaux

RésuméMarie-Pierre Buscail, Le domaine royal : entre territoires et réseauxLe domaine royal est un objet emblématique de l’histoire médiévale française. C’est dans une perspective spatiale que nous le réexaminons ici. Sont d’abord envisagés les possibles effets déformants du contexte dans lequel cet objet est apparu à la fin du xixe siècle. Puis est proposée une analyse archéogéographique d’un document exceptionnel : la prisée de 1332 en Gâtinais. La notion de saisine simultanée et multiple est essentielle pour comprendre la nature des liens sociaux et fonciers entre le roi et les autres acteurs. Le domaine royal peut ainsi être entendu comme un espace social complexe qui, au xive siècle, est en cours de transformation via un processus de centralisation s’effectuant à des degrés divers et à différentes échelles. L’hypothèse que nous avançons ici est que les domaines royaux s’organisent tels des réseaux de réseaux socio-fonciers entremêlés. Plusieurs logiques sont à l’œuvre, qui témoignent de stratégies d’équilibre de la part du pouvoir royal, de l’émergence de têtes de réseaux et de pôles de la fiscalité.AbstractMarie-Pierre Buscail, The royal domain: between territories and networksThe royal domain (or crown estate) is a major feature of French medieval history. The purpose of this study is to re-examine the royal domain from a spatial perspective. The paper begins by examining the potentially distorting effects of the context in which the object emerged in the late 19th century, before focusing on an archeogeographical analysis of an exceptional document: the 1332 prisée (or land evaluation) in Gâtinais. The notion of multiple and simultaneous seisin is essential for understanding the nature of the social and land relationships between the King and others in society. The royal domain can thus be viewed as a complex social space that changed radically in the 14th century as a result of centralization (a process that occurred at different levels and to varying degrees). This paper posits that crown lands were organized as networks of interconnected social-land networks. Several logics are at work in this process, illustrating the balancing act of the monarchy and the emergence of network leaders and local taxation authorities

Tracing tetraether lipids from source to sink in the Rhône River system (NW Mediterranean)

In this study, we investigated soils and river suspended particulate matter (SPM) collected in the Rhône and its tributary basins as well as marine surface sediments taken in the Rhône prodelta (Gulf of Lions, NW Mediterranean). Thereby, we traced the signal of branched glycerol dialkyl glycerol tetraethers (brGDGTs) from the source to sink via the Rhône River and its tributaries and identified sources of brGDGTs in rivers and marine sediments. Soil pH rather than the mean annual air temperature (MAAT) explains most of the observed variances of the brGDGT distribution in our soil dataset. The observed changes in the distribution of brGDGTs in the river SPM indicate that brGDGTs brought by the river to the sea are primarily derived from the lower Rhône and its tributary soils, even though in situ production in the river itself cannot be excluded. In marine surface sediments, it appears that the input of riverine brGDGTs is the primary source of brGDGTs in the Rhône prodelta, although the brGDGT composition may be further modified by the in situ production in the marine environment. More work is required to assess fully whether brGDGTs can be used to reconstruct the terrestrial paleoenvironmental changes using marine sediment cores taken in the Rhône prodelta close to the river mouth

Expression and Function of Kruppel Like-Factors (KLF) in Carcinogenesis

Krüppel-like factor (KLF) family members share a three C2H2 zinc finger DNA binding domain, and are involved in cell proliferation and differentiation control in normal as in pathological situations. Studies over the past several years support a significant role for this family of transcription factors in carcinogenesis. KLFs can both activate and repress genes that participate in cell-cycle regulation. Among them, many up-regulated genes are inhibitors of proliferation, whereas genes that promote cell proliferation are repressed. However, several studies do present KLFs as positive regulator of cell proliferation. KLFs can be deregulated in multiple cancers either by loss of heterozygosity (LOH), somatic mutation or transcriptional silencing by promoter hypermethylation. Accordingly, KLF expression was shown to mediate growth inhibition when ectopically expressed in multiple cancer-derived cell lines through the inhibition of a number of key oncogenic signaling pathways, and to revert the tumorogenic phenotype in vivo. Taken together, these observations suggest that KLFs act as tumor suppressor. However, in some occasion, KLFs could act as tumor promoters, depending on “cellular context”. Thus, this review will discuss the roles and the functions of KLF family members in carcinogenesis, with a special focus on cancers from epithelial origin

The activation of neuronal NO synthase is mediated by Gâ protein βγ subunit and the tyrosine phosphatase SHPâ 2

In CHO cells we had found that CCK positively regulated cell proliferation via the activation of a soluble guanylate cyclase. Here we demonstrate that CCK stimulated a nitric oxide synthase (NOS) activity. The production of NO was involved in the proliferative response elicited by CCK regarding the inhibitory effect of NOS inhibitors Lâ NAME and αâ guanidinoglutaric acid. We identified the NOS activated by the peptide as the neuronal isoform: the expression of the C415A neuronal NOS mutant inhibited both CCKâ induced stimulation of NOS activity and cell proliferation. These two effects were also inhibited after expression of the C459S tyrosine phosphatase SHPâ 2 mutant and the βARKl (495â 689) sequestrant peptide, indicating the requirement of activated SHPâ 2 and Gâ βγ subunit. Kinetic analysis (Western blot after coimmunoprecipitation and specific SHPâ 2 activity) revealed that in response to CCKâ treatment, SHPâ 2 associated to Gâ β1 subunit, became activated, and then dephosphorylated the neuronal NOS through a direct association. These data demonstrate that the neuronal NOS is implicated in proliferative effect evoked by CCK. A novel growth signaling pathway is described, involving the activation of neuronal NOS by dephosphorylation of tyrosyl residues.â Cordelier, P., Estève, J.â P., Rivard, N., Marletta, M., Vaysse, N., Susini, C., Buscail, L. The activation of neuronal no synthase is mediated by Gâ protein βγ subunit and the tyrosine phosphatase SHPâ 2. FASEB J. 13, 2037â 2050 (1999)Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154447/1/fsb2fasebj13142037.pd

Genetic and Epigenetic Alterations in Pancreatic Carcinogenesis

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers worldwide. Despite significant progresses in the last decades, the origin of this cancer remains unclear and no efficient therapy exists. PDAC does not arise de novo: three remarkable different types of pancreatic lesions can evolve towards pancreatic cancer. These precursor lesions include: Pancreatic intraepithelial neoplasia (PanIN) that are microscopic lesions of the pancreas, Intraductal Papillary Mucinous Neoplasms (IPMN) and Mucinous Cystic Neoplasms (MCN) that are both macroscopic lesions. However, the cellular origin of these lesions is still a matter of debate

Temporal variability of live (stained) benthic foraminiferal faunas in a river-dominated shelf – Faunal response to rapid changes of the river influence (Rhône prodelta, NW Mediterranean)

In the context of the French research project CHACCRA (Climate and Human-induced Alterations in Carbon Cycling at the River-seA connection), living (rose Bengal-stained) benthic foraminifera were investigated at two stations (24 and 67 m depth) in the Rhône prodelta (NW Mediterranean, Gulf of Lions). The aim of this study was to precise the response of benthic foraminiferal faunas to temporal changes of the Rhône River inputs (e.g. organic and terrigeneous material). Each site was sampled in April 2007, September 2007, May 2008 and December 2008, permitting to observe foraminiferal faunas of the 63–150 and >150 μm size fractions under a wide range of environmental conditions. Obvious variations in foraminiferal faunal composition were observed during the four investigated periods at the shallowest Station A located in the close vicinity of the Rhône River mouth. After major Rhône River flood events, different colonisation stages were observed with foraminiferal faunas responding with an opportunistic strategy few days to weeks after the creation of a peculiar sedimentary environment (<i>Leptohalysis scottii</i>, May 2008) or high organic matter supplies (<i>Ammonia tepida</i>, December 2008). Under more stable conditions, relatively diverse and equilibrated faunas grew in the sediments. Species benefited from noticeable input of riverine phytodetritus to the sediment during spring bloom conditions (April 2007; e.g. <i>Bolivina dilatata</i>, <i>Nonionella stella</i>, <i>Stainforthia fusiformis</i>), or high amounts of still bio-available organic matter under more oligotrophic conditions (September 2007; e.g. <i>Ammonia tepida</i>, <i>Psammosphaera fusca</i>). The reduced influence of the Rhône River input at the farther Station N led to less contrasted environmental conditions during the four sampling periods, and so to less obvious variations in foraminiferal faunal composition. During reduced riverine influence (i.e. low Rhône discharge), species able to feed on fresh phytodetritus (e.g. <i>Clavulina cylindrica</i>, <i>Hopkinsina atlantica</i>, <i>Nonionella iridea</i> and <i>Nonionella turgida</i>) benefited from eutrophic conditions of the spring bloom (April 2007, May 2008). Conversely, the occurrence of <i>Nouria polymorphinoides</i> under oligotrophic conditions (September 2007, December 2008) was indicative of a benthic environment potentially disturbed by bottom currents. This study put into evidence the extremely rapid response of benthic foraminiferal faunas to strong variations in environmental conditions mostly induced by the Rhône dynamics