L’évolution fatale d’une thrombose de la veine porte

La thrombose du système portal est rare et ses étiologies sont multiples. Nous rapportons le cas d’un jeune patient de 26 ans, sans antécédents pathologiques particuliers admis pour douleurs abdominales diffuses d’installation brutale. Le diagnostic de la thrombose porte a été établi par le scanner abdominal sans mise en évidence d’un foyer infectieux intra-abdominal. Le bilan biologique a mis en évidence une hyperleucocytose mais la procalcitonine était négative. Le traitement anticoagulant a été démarré le jour de l’admission et le patient est décédé le jour même.  

Emotional ratings and skin conductance response to visual, auditory and haptic stimuli

The human emotional reactions to stimuli delivered by different sensory modalities is a topic of interest for many disciplines, from Human-Computer-Interaction to cognitive sciences. Different databases of stimuli eliciting emotional reaction are available, tested on a high number of participants. Interestingly, stimuli within one database are always of the same type. In other words, to date, no data was obtained and compared from distinct types of emotion-eliciting stimuli from the same participant. This makes it difficult to use different databases within the same experiment, limiting the complexity of experiments investigating emotional reactions. Moreover, whereas the stimuli and the participants’ rating to the stimuli are available, physiological reactions of participants to the emotional stimuli are often recorded but not shared. Here, we test stimuli delivered either through a visual, auditory, or haptic modality in a within participant experimental design. We provide the results of our study in the form of a MATLAB structure including basic demographics on the participants, the participant’s self-assessment of his/her emotional state, and his/her physiological reactions (i.e., skin conductance)

Role of Palladin Phosphorylation by Extracellular Signal-Regulated Kinase in Cell Migration

Phosphorylation of actin-binding proteins plays a pivotal role in the remodeling of the actin cytoskeleton to regulate cell migration. Palladin is an actin-binding protein that is phosphorylated by growth factor stimulation; however, the identity of the involved protein kinases remains elusive. In this study, we report that palladin is a novel substrate of extracellular signal-regulated kinase (ERK). Suppression of ERK activation by a chemical inhibitor reduced palladin phosphorylation, and expression of active MEK alone was sufficient for phosphorylation. In addition, an in vitro kinase assay demonstrated direct palladin phosphorylation by ERK. We found that Ser77 and Ser197 are essential residues for phosphorylation. Although the phosphorylation of these residues was not required for actin cytoskeletal organization, we found that expression of non-phosphorylated palladin enhanced cell migration. Finally, we show that phosphorylation inhibits the palladin association with Abl tyrosine kinase. Taken together, our results indicate that palladin phosphorylation by ERK has an anti-migratory function, possibly by modulating interactions with molecules that regulate cell migration

Resistance to chemotherapy: new treatments and novel insights into an old problem

Resistance to cancer chemotherapeutic treatment is a common phenomenon, especially in progressive disease. The generation of cellular models of drug resistance has been pivotal in unravelling the main effectors of resistance to traditional chemotherapy at the molecular level (i.e. intracellular drug inactivation, detoxifying systems, defects in DNA repair, apoptosis evasion, membrane transporters and cell adhesion). The development of targeted therapies has also been followed by resistance, reminiscent of an evolutionary arms race, as exemplified by imatinib and other BCR-ABL inhibitors for the treatment of chronic myelogenous leukaemia. Although traditionally associated with the last stages of the disease, recent findings with minimally transformed pretumorigenic primary human cells indicate that the ability to generate drug resistance arises early during the tumorigenic process, before the full transformation. Novel technologies, such as genome profiling, have in certain cases predicted the outcome of chemotherapy and undoubtedly have tremendous potential for the future. In addition, the novel cancer stem cell paradigm raises the prospect of cell-targeted therapies instead of treatment directed against the whole tumour

Heterologous Amyloid Seeding: Revisiting the Role of Acetylcholinesterase in Alzheimer's Disease

Neurodegenerative diseases associated with abnormal protein folding and ordered aggregation require an initial trigger which may be infectious, inherited, post-inflammatory or idiopathic. Proteolytic cleavage to generate vulnerable precursors, such as amyloid-β peptide (Aβ) production via β and γ secretases in Alzheimer's Disease (AD), is one such trigger, but the proteolytic removal of these fragments is also aetiologically important. The levels of Aβ in the central nervous system are regulated by several catabolic proteases, including insulysin (IDE) and neprilysin (NEP). The known association of human acetylcholinesterase (hAChE) with pathological aggregates in AD together with its ability to increase Aβ fibrilization prompted us to search for proteolytic triggers that could enhance this process. The hAChE C-terminal domain (T40, AChE575-614) is an exposed amphiphilic α-helix involved in enzyme oligomerisation, but it also contains a conformational switch region (CSR) with high propensity for conversion to non-native (hidden) β-strand, a property associated with amyloidogenicity. A synthetic peptide (AChE586-599) encompassing the CSR region shares homology with Aβ and forms β-sheet amyloid fibrils. We investigated the influence of IDE and NEP proteolysis on the formation and degradation of relevant hAChE β-sheet species. By combining reverse-phase HPLC and mass spectrometry, we established that the enzyme digestion profiles on T40 versus AChE586-599, or versus Aβ, differed. Moreover, IDE digestion of T40 triggered the conformational switch from α- to β-structures, resulting in surfactant CSR species that self-assembled into amyloid fibril precursors (oligomers). Crucially, these CSR species significantly increased Aβ fibril formation both by seeding the energetically unfavorable formation of amyloid nuclei and by enhancing the rate of amyloid elongation. Hence, these results may offer an explanation for observations that implicate hAChE in the extent of Aβ deposition in the brain. Furthermore, this process of heterologous amyloid seeding by a proteolytic fragment from another protein may represent a previously underestimated pathological trigger, implying that the abundance of the major amyloidogenic species (Aβ in AD, for example) may not be the only important factor in neurodegeneration

Using C. elegans to decipher the cellular and molecular mechanisms underlying neurodevelopmental disorders

Prova tipográfica (uncorrected proof)Neurodevelopmental disorders such as epilepsy, intellectual disability (ID), and autism spectrum disorders (ASDs) occur in over 2 % of the population, as the result of genetic mutations, environmental factors, or combination of both. In the last years, use of large-scale genomic techniques allowed important advances in the identification of genes/loci associated with these disorders. Nevertheless, following association of novel genes with a given disease, interpretation of findings is often difficult due to lack of information on gene function and effect of a given mutation in the corresponding protein. This brings the need to validate genetic associations from a functional perspective in model systems in a relatively fast but effective manner. In this context, the small nematode, Caenorhabditis elegans, presents a good compromise between the simplicity of cell models and the complexity of rodent nervous systems. In this article, we review the features that make C. elegans a good model for the study of neurodevelopmental diseases. We discuss its nervous system architecture and function as well as the molecular basis of behaviors that seem important in the context of different neurodevelopmental disorders. We review methodologies used to assess memory, learning, and social behavior as well as susceptibility to seizures in this organism. We will also discuss technological progresses applied in C. elegans neurobiology research, such as use of microfluidics and optogenetic tools. Finally, we will present some interesting examples of the functional analysis of genes associated with human neurodevelopmental disorders and how we can move from genes to therapies using this simple model organism.The authors would like to acknowledge Fundação para a Ciência e Tecnologia (FCT) (PTDC/SAU-GMG/112577/2009). AJR and CB are recipients of FCT fellowships: SFRH/BPD/33611/2009 and SFRH/BPD/74452/2010, respectively

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

There is no such thing as ‘undisturbed’ soil and sediment sampling: sampler-induced deformation of salt marsh sediments revealed by 3D X-ray computed tomography

Purpose: Within most environmental contexts, the collection of 'undisturbed' samples is widely relied-upon in studies of soil and sediment properties and structure. However, the impact of sampler-induced disturbance is rarely acknowledged, despite the potential significance of modification to sediment structure for the robustness of data interpretation. In this study, 3D-computed X-ray microtomography (μCT) is used to evaluate and compare the disturbance imparted by four commonly-used sediment sampling methods within a coastal salt-marsh. Materials and methods: Paired sediment core samples from a restored salt-marsh at Orplands Farm, Essex, UK were collected using four common sampling methods (push, cut, hammer and gouge methods). Sampling using two different area-ratio cores resulted in a total of 16 cores that were scanned using 3D X-Ray computed tomography, to identify and evaluate sediment structural properties of samples that can be attributed to sampling method. Results and discussion: 3D qualitative analysis identifies a suite of sampling-disturbance structures including gross-scale changes to sediment integrity and substantial modification of pore-space, structure and distribution, independent of sediment strength and stiffness. Quantitative assessment of changes to pore-space and sediment density arising from the four sampling methods offer a means of direct comparison between the impact of depth-sampling methods. Considerable disturbance to samples result from use of push, hammer and auguring samplers, whilst least disturbance is found in samples recovered by cutting and advanced trimming approaches. Conclusions: It is evident that with the small-bore tubes and samplers commonly used in environmental studies, all techniques result in disturbance to sediment structure to a far greater extent than previously reported, revealed by μCT. This work identifies and evaluates for the first time the full nature, extent and significance of internal sediment disturbance arising from common sampling methods