Trocar Site Recurrence after Laparoscopic Cholecystectomy for Unsuspected Isolated Gallbladder Metastasis of Melanoma: A Case Report and Review of the Literature

Cutaneous melanoma can metastasize to almost any organ, including in-transit metastases, lymph nodes, liver, lungs, brain, and bones. Spread to the gastrointestinal tract is less common and generally concerns the small bowel, colon, and stomach. Gallbladder involvement is rarer, and only few cases describe it as the sole site of metastasis upon diagnosis. Melanoma metastases to the gallbladder are usually detected on staging or surveillance imaging, as patients usually show few or no symptoms. In resectable stage IV melanoma patients, complete surgical resection appears to improve the prognosis. However, due to the rarity of isolated gallbladder metastasis of melanoma, there are no guidelines regarding the optimal surgical approach (endoscopic or open cholecystectomy). Here, we report the case of isolated gallbladder melanoma metastasis found after laparoscopic cholecystectomy performed in a 46-year-old female patient with no known history of cancer presenting with acute cholecystitis symptoms. Six weeks after surgery, the patient developed trocar site recurrence. This case highlights the importance of a planned and open surgery for resectable melanoma metastases rather than a laparoscopic approach

Optimization of iTRAQ labelling coupled to OFFGEL fractionation as a proteomic workflow to the analysis of microsomal proteins of <it>Medicago truncatula</it> roots

Abstract Background Shotgun proteomics represents an attractive technical framework for the study of membrane proteins that are generally difficult to resolve using two-dimensional gel electrophoresis. The use of iTRAQ, a set of amine-specific isobaric tags, is currently the labelling method of choice allowing multiplexing of up to eight samples and the relative quantification of multiple peptides for each protein. Recently the hyphenation of different separation techniques with mass spectrometry was used in the analysis of iTRAQ labelled samples. OFFGEL electrophoresis has proved its effectiveness in isoelectric point-based peptide and protein separation in solution. Here we describe the first application of iTRAQ-OFFGEL-LC-MS/MS on microsomal proteins from plant material. The investigation of the iTRAQ labelling effect on peptide electrofocusing in OFFGEL fractionator was carried out on Medicago truncatula membrane protein digests. Results In-filter protein digestion, with easy recovery of a peptide fraction compatible with iTRAQ labelling, was successfully used in this study. The focusing quality in OFFGEL electrophoresis was maintained for iTRAQ labelled peptides with a higher than expected number of identified peptides in basic OFFGEL-fractions. We furthermore observed, by comparing the isoelectric point (pI) fractionation of unlabelled versus labelled samples, a non-negligible pI shifts mainly to higher values. Conclusions The present work describes a feasible and novel protocol for in-solution protein digestion in which the filter unit permits protein retention and buffer removal. The data demonstrates an impact of iTRAQ labelling on peptide electrofocusing behaviour in OFFGEL fractionation compared to their native counterpart by the induction of a substantial, generally basic pI shift. Explanations for the occasionally observed acidic shifts are likewise presented.</p

The Cell Wall Proteome of Craterostigma plantagineum Cell Cultures Habituated to Dichlobenil and Isoxaben.

peer reviewedThe remarkable desiccation tolerance of the vegetative tissues in the resurrection species Craterostigma plantagineum (Hochst.) is favored by its unique cell wall folding mechanism that allows the ordered and reversible shrinking of the cells without damaging neither the cell wall nor the underlying plasma membrane. The ability to withstand extreme drought is also maintained in abscisic acid pre-treated calli, which can be cultured both on solid and in liquid culture media. Cell wall research has greatly advanced, thanks to the use of inhibitors affecting the biosynthesis of e.g., cellulose, since they allowed the identification of the compensatory mechanisms underlying habituation. Considering the innate cell wall plasticity of C. plantagineum, the goal of this investigation was to understand whether habituation to the cellulose biosynthesis inhibitors dichlobenil and isoxaben entailed or not identical mechanisms as known for non-resurrection species and to decipher the cell wall proteome of habituated cells. The results showed that exposure of C. plantagineum calli/cells triggered abnormal phenotypes, as reported in non-resurrection species. Additionally, the data demonstrated that it was possible to habituate Craterostigma cells to dichlobenil and isoxaben and that gene expression and protein abundance did not follow the same trend. Shotgun and gel-based proteomics revealed a common set of proteins induced upon habituation, but also identified candidates solely induced by habituation to one of the two inhibitors. Finally, it is hypothesized that alterations in auxin levels are responsible for the increased abundance of cell wall-related proteins upon habituation

Études d'après nature. 1948 : [photographie] / J. V. de Villeneuve

Background: Lignin and lignans are both derived from the monolignol pathway. Despite the similarity of their building blocks, they fulfil different functions in planta. Lignin strengthens the tissues of the plant, while lignans are involved in plant defence and growth regulation. Their biosyntheses are tuned both spatially and temporally to suit the development of the plant (water conduction, reaction to stresses). We propose to study the general molecular events related to monolignol-derived product biosynthesis, especially lignin. It was previously shown that the growing hemp hypocotyl (between 6 and 20 days after sowing) is a valid system to study secondary growth and the molecular events accompanying lignification. The present work confirms the validity of this system, by using it to study the regulation of lignin and lignan biosynthesis. Microscopic observations, lignin analysis, proteomics, together with in situ laccase and peroxidase activity assays were carried out to understand the dynamics of lignin synthesis during the development of the hemp hypocotyl. Results: Based on phylogenetic analysis and targeted gene expression, we suggest a role for the hemp dirigent and dirigent-like proteins in lignan biosynthesis. The transdisciplinary approach adopted resulted in the gene- and protein-level quantification of the main enzymes involved in the biosynthesis of monolignols and their oxidative coupling (laccases and class III peroxidases), in lignin deposition (dirigent-like proteins) and in the determination of the stereoconformation of lignans (dirigent proteins). Conclusions: Our work sheds light on how, in the growing hemp hypocotyl, the provision of the precursors needed to synthesize the aromatic biomolecules lignin and lignans is regulated at the transcriptional and proteomic level

Additional file 2: of Insights into the molecular regulation of monolignol-derived product biosynthesis in the growing hemp hypocotyl

provides the CNRQ from the RT-qPCR experiment used for the Fig. 4. (XLS 13 kb

Myotonic dystrophy CTG expansion affects synaptic vesicle proteins, neurotransmission and mouse behaviour.: Synaptic dysfunction in myotonic dystrophy

International audienceMyotonic dystrophy type 1 is a complex multisystemic inherited disorder, which displays multiple debilitating neurological manifestations. Despite recent progress in the understanding of the molecular pathogenesis of myotonic dystrophy type 1 in skeletal muscle and heart, the pathways affected in the central nervous system are largely unknown. To address this question, we studied the only transgenic mouse line expressing CTG trinucleotide repeats in the central nervous system. These mice recreate molecular features of RNA toxicity, such as RNA foci accumulation and missplicing. They exhibit relevant behavioural and cognitive phenotypes, deficits in short-term synaptic plasticity, as well as changes in neurochemical levels. In the search for disease intermediates affected by disease mutation, a global proteomics approach revealed RAB3A upregulation and synapsin I hyperphosphorylation in the central nervous system of transgenic mice, transfected cells and post-mortem brains of patients with myotonic dystrophy type 1. These protein defects were associated with electrophysiological and behavioural deficits in mice and altered spontaneous neurosecretion in cell culture. Taking advantage of a relevant transgenic mouse of a complex human disease, we found a novel connection between physiological phenotypes and synaptic protein dysregulation, indicative of synaptic dysfunction in myotonic dystrophy type 1 brain pathology

IMPACT OF RADIOACTIVITY ON MICROORGANISMS LIVING IN MINERAL SPRINGS

International audienceAlthough many studies have explored the responses of living organisms or ecosystems exposed to radioelements from human activities, very few studies have focused on the characterization of microbial biodiversity and the adaptations developed in environments characterized by natural, chronic and old radioactivity. Radioactive mineral springs are insulated ecosystems that have barely evolved in the last centuries. They therefore offer exceptional windows on the history of life on earth. Within the framework of the TIRAMISU project (biodiversiTy In RAdioactive MIneral Springs of the aUvergne region), biologists, ecologists, geologists, physicists, radiochemists and sociologists explore if and how natural ionizing radiation can be an "abiotic driver" impacting the diversity and structuring of microbial communities in food webs exposed to this radiation for long periods

Increased misfolding and truncation of tau in APP/PS1/tau transgenic mice compared to mutant tau mice.

Neurofibrillary degeneration in transgenic models of tauopathies has been observed to be enhanced when these models are crossed with transgenic models developing an Aβ pathology. The mechanisms leading to this enhanced tau pathology are not well understood. We have performed a detailed analysis of tau misprocessing in a new transgenic mouse model combining APP, PS1 and tau mutations (5xFAD×Tg30 mice) by comparison with littermates expressing only a FTD mutant tau (Tg30 mice). These 5xFAD×Tg30 mice showed a more severe deficient motor phenotype than Tg30 mice and developed with age a dramatically accelerated NFT load in the brain compared to Tg30 mice. Insoluble tau in 5xFAD×Tg30 mice compared to insoluble tau in Tg30 mice showed increased phosphorylation, enhanced misfolding and truncation changes mimicking more closely the post-translational changes characteristic of PHF-tau in Alzheimer's disease. Endogenous wild-type mouse tau was recruited at much higher levels in insoluble tau in 5xFAD×Tg30 than in Tg30 mice. Extracellular amyloid load, Aβ40 and Aβ42, β-CTFs and β-CTF phosphorylation levels were lower in 5xFAD×Tg30 mice than in 5xFAD mice. Despite this reduction of Aβ, a significant hippocampal neuronal loss was observed in 5xFAD×Tg30 but not in 5xFAD mice indicating its closer association with increased tau pathology. This 5xFAD×Tg30 model thus mimics more faithfully tau pathology and neuronal loss observed in AD and suggests that additional post-translational changes in tau and self-recruitment of endogenous tau drive the enhanced tau pathology developing in the presence of Aβ pathology.JOURNAL ARTICLESCOPUS: ar.jinfo:eu-repo/semantics/publishe

Caffeine intake exerts dual genome-wide effects on hippocampal metabolism and learning-dependent transcription

Caffeine is the most consumed psychoactive substance worldwide. Strikingly, molecular pathways engaged by its regular consumption remain unclear. We herein addressed the mechanisms associated with habitual (chronic) caffeine consumption in the mouse hippocampus using untargeted orthogonal-omics techniques. Our results revealed that chronic caffeine exerts concerted pleiotropic effects in the hippocampus, at the epigenomic, proteomic and metabolomic levels. Caffeine lowers metabolic-related processes in the bulk tissue, while it induces neuronal-specific epigenetic changes at synaptic transmission/plasticity-related genes and increased experience-driven transcriptional activity. Altogether, these findings suggest that regular caffeine intake improves the signal-to-noise ratio during information encoding, in part through a fine-tuning of metabolic genes while boosting the salience of information processing during learning in neuronal circuits.This work was supported by grants from Hauts-de-France (PARTEN-AIRR, COGNADORA; START-AIRR, INS-SPECT) and Programs d’Investissements d’Avenir LabEx (excellence laboratory) DISTALZ (Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer’s disease) and EGID (European Genomic Institute for Diabetes ANR-10LABX-46). Our laboratories are also supported by ANR (GRAND to LB, ADORATAU, ADORASTrAU, METABOTAU to DB and BETAPLASTICITY to JSA), COEN (5008), Fondation pour la Recherche Médicale, France Alzheimer/Fondation de France, FHU VasCog research network (Lille, France), Fondation Vaincre Alzheimer (ADOMEMOTAU), European Foundation for the Study of Diabetes (EFSD to JSA), Fondation Plan Alzheimer as well as Inserm, CNRS, Université Lille, Lille Métropole Communauté Urbaine, DN2M. KC hold a doctoral grant from Lille University. VG-M was supported by Fondation pour la Recherche Médicale (SPF20160936000). CM was supported by Région Hauts753 30 754 de-France. ALB is supported by CNRS, Unistra (Strasbourg, France), ANR-16-CE92-0031 755 756 757 758 759 760 761 762 (EPIFUS), ANR-18-CE16-0008-02 (ADORASTrAU), Alsace Alzheimer 67, France Alzheimer (AAP SM 2017 #1664). IP is supported by Fondation pour la Recherche Médicale (SPF201909009162). CEM is grateful for the support by the Alzheimer Forschung Initiative e.V. (AFI, Düsseldorf, Germany). LC was funded by SIF Italian Society of Pharmacology. RAC was supported by LaCaixa Foundation (LCF/PR/HP17/52190001) and FCT (POCI-01-0145-FEDER-03127). Santa Casa da Misericórdia (MB-7-2018) and CEECIND/01497/2017 to LVL