Timing of organogenesis support basal position of turtles in the amniote tree of life

Background: The phylogenetic position of turtles is the most disputed aspect in the reconstruction of the land vertebrate tree of life. This controversy has arisen after many different kinds and revisions of investigations of molecular and morphological data. Three main hypotheses of living sister-groups of turtles have resulted from them: all reptiles, crocodiles + birds or squamates + tuatara. Although embryology has played a major role in morphological studies of vertebrate phylogeny, data on developmental timing have never been examined to explore and test the alternative phylogenetic hypotheses. We conducted a comprehensive study of published and new embryological data comprising 15 turtle and eight tetrapod species belonging to other taxa, integrating for the first time data on the side-necked turtle clade. Results: The timing of events in organogenesis of diverse character complexes in all body regions is not uniform across amniotes and can be analysed using a parsimony-based method. Changes in the relative timing of particular events diagnose many clades of amniotes and include a phylogenetic signal. A basal position of turtles to the living saurian clades is clearly supported by timing of organogenesis data. Conclusion: The clear signal of a basal position of turtles provided by heterochronic data implies significant convergence in either molecular, adult morphological or developmental timing characters, as only one of the alternative solutions to the phylogenetic conundrum can be right. The development of a standard reference series of embryological events in amniotes as presented here should enable future improvements and expansion of sampling and thus the examination of other hypotheses about phylogeny and patterns of the evolution of land vertebrate development

Les Amphibiens branchiosauridés du Permien inférieur de Buxières-les-Mines, bassin de Bourbon l’Archambault (Allier, France) et sa signification biostratigraphique

Les Branchiosauridés sont rares dans la faune lacustre du Permien inférieur de Buxières-les-Mines, bassin de Bourbon l’Archambault (Massif central, Allier, France). Tous les spécimens connus appartiennent à Melanerpeton gracile qui est caractéristique de la zone à Melanerpeton gracile-Discosauriscus pulcherrimus issue de l’échelle biostratigraphique basée sur les amphibiens aquatiques du Carbonifère supérieur et du Permien inférieur. Cette espèce de branchiosauridés permet l’attribution d’un âge assélien (juste au dessus de “l’Autunien inférieur”/Rotliegend) pour la série des schistes bitumineux de Buxières-les-Mines appartenant à l’assise de Buxières du bassin de Bourbon l’Archambault (Allier, France)

Conchostracans in continental deposits of the Zechstein-Buntsandstein transition in central Germany: Taxonomy and biostratigraphic implications for the position of the Permian-Triassic boundary within the Zechstein Group

© 2016 Elsevier B.V.The end-Permian mass extinction marks the largest biotic crisis in the geologic record. The stratigraphic position of this boundary in continental deposits is still under discussion. In the present study, conchostracans from the Zechstein-Buntsandstein (Late Permian to Early Triassic) transition in central Germany have been taxonomically reinvestigated in order to better understand their utility for fine-scale biostratigraphy in continental Permian-Triassic boundary sections. The studied material was obtained from both collections and recent sampling activities in classical key sections and new outcrops of the Zechstein and Buntsandstein Groups. The sedimentary environments of the conchostracan occurrences are interpreted as lacustrine to fluvial facies depending on the paleogeographic position within the basin of the respective sections. The conchostracan fauna in the Zechstein-Buntsandstein transition consists of Euestheria gutta, Palaeolimnadiopsis vilujensis, Cornia germari, Estheriella marginostriata, Estheriella costata, Estheriella nodosocostata, Magniestheria mangaliensis, and Euestheria nordvikensis. Based on comparison with the Early Triassic conchostracan record in the Moscow syncline, the Palaeolimnadiopsis vilujensis-Euestheria gutta association in the upper part of the Fulda Formation indicates both its Early Triassic age and a position of the continental Permian-Triassic boundary within the Zechstein Group

miR-25 targets TNF-related apoptosis inducing ligand (TRAIL) death receptor-4 and promotes apoptosis resistance in cholangiocarcinoma.

It has been established that microRNA expression and function contribute to phenotypic features of malignant cells, including resistance to apoptosis. Although targets and functional roles for a number of microRNAs have been described in cholangiocarcinoma, many additional microRNAs dysregulated in this tumor have not been assigned functional roles. In this study, we identify elevated miR-25 expression in malignant cholangiocarcinoma cell lines as well as patient samples. In cultured cells, treatment with the Smoothened inhibitor, cyclopamine, reduced miR-25 expression, suggesting Hedgehog signaling stimulates miR-25 production. Functionally, miR-25 was shown to protect cells against TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. Correspondingly, antagonism of miR-25 in culture sensitized cells to apoptotic death. Computational analysis identified the TRAIL Death Receptor-4 (DR4) as a potential novel miR-25 target, and this prediction was confirmed by immunoblot, cell staining, and reporter assays. CONCLUSION: These data implicate elevated miR-25 levels in the control of tumor cell apoptosis in cholangiocarcinoma. The identification of the novel miR-25 target DR4 provides a mechanism by which miR-25 contributes to evasion of TRAIL-induced cholangiocarcinoma apoptosis

JNK1-dependent PUMA expression contributes to hepatocyte lipoapoptosis.

Free fatty acids (FFA) induce hepatocyte lipoapoptosis by a c-Jun N-terminal kinase (JNK)-dependent mechanism. However, the cellular processes by which JNK engages the core apoptotic machinery during lipotoxicity, especially activation of BH3-only proteins, remain incompletely understood. Thus, our aim was to determine whether JNK mediates induction of BH3-only proteins during hepatocyte lipoapoptosis. The saturated FFA palmitate, but not the monounsaturated FFA oleate, induces an increase in PUMA mRNA and protein levels. Palmitate induction of PUMA was JNK1-dependent in primary murine hepatocytes. Palmitate-mediated PUMA expression was inhibited by a dominant negative c-Jun, and direct binding of a phosphorylated c-Jun containing the activator protein 1 complex to the PUMA promoter was identified by electrophoretic mobility shift assay and a chromatin immunoprecipitation assay. Short hairpin RNA-targeted knockdown of PUMA attenuated Bax activation, caspase 3/7 activity, and cell death. Similarly, the genetic deficiency of Puma rendered murine hepatocytes resistant to lipoapoptosis. PUMA expression was also increased in liver biopsy specimens from patients with non-alcoholic steatohepatitis as compared with patients with simple steatosis or controls. Collectively, the data implicate JNK1-dependent PUMA expression as a mechanism contributing to hepatocyte lipoapoptosis

Neuronal vulnerability and multilineage diversity in multiple sclerosis.

Multiple sclerosis (MS) is a neuroinflammatory disease with a relapsing-remitting disease course at early stages, distinct lesion characteristics in cortical grey versus subcortical white matter and neurodegeneration at chronic stages. Here we used single-nucleus RNA sequencing to assess changes in expression in multiple cell lineages in MS lesions and validated the results using multiplex in situ hybridization. We found selective vulnerability and loss of excitatory CUX2-expressing projection neurons in upper-cortical layers underlying meningeal inflammation; such MS neuron populations exhibited upregulation of stress pathway genes and long non-coding RNAs. Signatures of stressed oligodendrocytes, reactive astrocytes and activated microglia mapped most strongly to the rim of MS plaques. Notably, single-nucleus RNA sequencing identified phagocytosing microglia and/or macrophages by their ingestion and perinuclear import of myelin transcripts, confirmed by functional mouse and human culture assays. Our findings indicate lineage- and region-specific transcriptomic changes associated with selective cortical neuron damage and glial activation contributing to progression of MS lesions.Includes NIHR, ERC and Wellcome Trust

Agonistic Interventions into Public Commemorative Art:An Innovative Form of Counter-memorial Practice?

In light of recent controversies around the removal or modification of public commemorative art, such as memorials and monuments, this paper interrogates the value of competing approaches to counter-memorial practice using the framework of agonistic memory. It argues that much counter-memorial practice today, as it relates to historical memory, is dominated by a “cosmopolitan” mode that fails to offer a convincing response to the rise of right-wing populism and its instrumentalization of conflicts over public commemorative art. The article investigates two case studies of counter-memorial interventions that focus on the memory of fascism in Europe today and seeks to identify and assess emergent agonistic practices