Effect of alpha tocopherol acetate in Walker 256/B cells-induced oxidative damage in a rat model of breast cancer skeletal metastases

The pathophysiological changes and the oxidative–antioxidative status were evaluated in the bone microenvironment of rat inoculated with Walker 256/B mammary gland carcinoma cells, and used α-tocopherol acetate (ATA) as a countermeasure.Walker 256/B cells were injected into the right femora of aged male rats. Animals were randomized into three groups: 12 rats were injected with saline (control group); 14 rats were injected with Walker 256/B cells (5 × 104) in the medullar cavity (W256 group); 14 rats were inoculated with Walker 256/B cells and treated with ATA (45 mg/kg BW) (W256 + ATA group). After 20 days, rats were euthanized and the femurs were radiographed. Micro architectural parameters were measured by microcomputed tomography and histology. Serum, bone and bone marrow were evaluated for oxidative damage. In parallel, cell cultures were done in the presence of ATA and ROS were measured by fluorescence; apoptotic cells were determined in parallel. W256 groups had osteolytic damages with marked resorption of cortical and trabecular bone. W256 + ATA animals presented marked osteosclerotic areas associated with tumor necrosis areas inside the bone cavity. Levels of lipid peroxidation and protein oxidation were found to increase in W256 rats; a significant reduction in SOD and GSH-p activities was also observed. W256 + ATA group had significantly reduced oxidative damage, but not reversed back to the control levels. The present study shows that Walker 256/B cells induce skeletal metastases associated with oxidative damage in the bone microenvironment. ATA reduced the oxidative stress damage, enhanced osteosclerosis and tumor cell apoptosis both in vitro and in vivo

Optical Detection of Ultrasound by Two-Wave Mixing in Photorefractive Semiconductor Crystals Under Applied Field

The optical detection of transient surface motion has many practical applications which include, in particular, the vibration monitoring of engineering structures (aircraft, power plants,...) and the detection of ultrasound produced by piezoelectric transducer or by pulse laser excitation. This last application where ultrasound is generated and detected by lasers, presents many advantages over conventional piezoelectric based methods. First, laser-ultrasonics is a remote sensing technique. Consequently it can be used, for example, for inspecting hot materials and products moving on a production line. Second, surfaces of complex shapes can also very easily be probed. For many applications, these advantages compensate the usually lower sensitivity of the laser-based technique compared to piezoelectric transduction

A robust SNP barcode for typing Mycobacterium tuberculosis complex strains

Strain-specific genomic diversity in the Mycobacterium tuberculosis complex (MTBC) is an important factor in pathogenesis that may affect virulence, transmissibility, host response and emergence of drug resistance. Several systems have been proposed to classify MTBC strains into distinct lineages and families. Here, we investigate single-nucleotide polymorphisms (SNPs) as robust (stable) markers of genetic variation for phylogenetic analysis. We identify ~92k SNP across a global collection of 1,601 genomes. The SNP-based phylogeny is consistent with the gold-standard regions of difference (RD) classification system. Of the ~7k strain-specific SNPs identified, 62 markers are proposed to discriminate known circulating strains. This SNP-based barcode is the first to cover all main lineages, and classifies a greater number of sublineages than current alternatives. It may be used to classify clinical isolates to evaluate tools to control the disease, including therapeutics and vaccines whose effectiveness may vary by strain type

La maladie de von-hippel lindau dans une famille togolaise

La maladie de Von Hippel Lindau(VHL) est une affection héréditaire autosomique dominante dont l’expression phénotypique est variable et multiviscérale. Le diagnostic nécessite des arguments cliniques et un plateau technique de pointe. nous rapportons les résultats d’une enquête au sein d’une famille togolaise à partir de deux observations cliniques. Ces observations mettent en exergue les difficultés de la pratique médicale en Afrique subsaharienne liées à un plateau technique inexistant

Sensor Data Visualisation: A Composition-Based Approach to Support Domain Variability

International audienceIn the context of the Internet of Things, sensors are surrounding our environment. These small pieces of electronics are inserted in everyday life's elements (e.g., cars, doors, radiators, smartphones) and continuously collect information about their environment. One of the biggest challenges is to support the development of accurate monitoring dashboard to visualise such data. The one-size-fits-all paradigm does not apply in this context, as user's roles are variable and impact the way data should be visualised: a building manager does not need to work on the same data as classical users. This paper presents an approach based on model composition techniques to support the development of such monitoring dashboards, taking into account the domain variability. This variability is supported at both implementation and modelling levels. The results are validated on a case study named SmartCampus, involving sensors deployed in a real academic campus

Enhanced insulin sensitivity associated with provision of mono and polyunsaturated fatty acids in skeletal muscle cells involves counter modulation of PP2A

International audienceAims/Hypothesis: Reduced skeletal muscle insulin sensitivity is a feature associated with sustained exposure to excess saturated fatty acids (SFA), whereas mono and polyunsaturated fatty acids (MUFA and PUFA) not only improve insulin sensitivity but blunt SFA-induced insulin resistance. The mechanisms by which MUFAs and PUFAs institute these favourable changes remain unclear, but may involve stimulating insulin signalling by counter-modulation/repression of protein phosphatase 2A (PP2A). This study investigated the effects of oleic acid (OA; a MUFA), linoleic acid (LOA; a PUFA) and palmitate (PA; a SFA) in cultured myotubes and determined whether changes in insulin signalling can be attributed to PP2A regulation. Principal Findings: We treated cultured skeletal myotubes with unsaturated and saturated fatty acids and evaluated insulin signalling, phosphorylation and methylation status of the catalytic subunit of PP2A. Unlike PA, sustained incubation of rat or human myotubes with OA or LOA significantly enhanced Akt-and ERK1/2-directed insulin signalling. This was not due to heightened upstream IRS1 or PI3K signalling nor to changes in expression of proteins involved in proximal insulin signalling, but was associated with reduced dephosphorylation/inactivation of Akt and ERK1/2. Consistent with this, PA reduced PP2Ac demethylation and tyrosine 307 phosphorylation-events associated with PP2A activation. In contrast, OA and LOA strongly opposed these PA-induced changes in PP2Ac thus exerting a repressive effect on PP2A.Conclusions/Interpretation: Beneficial gains in insulin sensitivity and the ability of unsaturated fatty acids to oppose palmitate-induced insulin resistance in muscle cells may partly be accounted for by counter-modulation of PP2A

Vestibular signal processing in a subject with somatosensory deafferentation: The case of sitting posture

<p>Abstract</p> <p>Background</p> <p>The vestibular system of the inner ear provides information about head translation/rotation in space and about the orientation of the head with respect to the gravitoinertial vector. It also largely contributes to the control of posture through vestibulospinal pathways. Testing an individual severely deprived of somatosensory information below the nose, we investigated if equilibrium can be maintained while seated on the sole basis of this information.</p> <p>Results</p> <p>Although she was unstable, the deafferented subject (DS) was able to remain seated with the eyes closed in the absence of feet, arm and back supports. However, with the head unconsciously rotated towards the left or right shoulder, the DS's instability markedly increased. Small electrical stimulations of the vestibular apparatus produced large body tilts in the DS contrary to control subjects who did not show clear postural responses to the stimulations.</p> <p>Conclusion</p> <p>The results of the present experiment show that in the lack of vision and somatosensory information, vestibular signal processing allows the maintenance of an active sitting posture (i.e. without back or side rests). When head orientation changes with respect to the trunk, in the absence of vision, the lack of cervical information prevents the transformation of the head-centered vestibular information into a trunk-centered frame of reference of body motion. For the normal subjects, this latter frame of reference enables proper postural adjustments through vestibular signal processing, irrespectively of the orientation of the head with respect to the trunk.</p

Self-recognition in corals facilitates deep-sea habitat engineering

The ability of coral reefs to engineer complex three-dimensional habitats is central to their success and the rich biodiversity they support. In tropical reefs, encrusting coralline algae bind together substrates and dead coral framework to make continuous reef structures, but beyond the photic zone, the cold-water coral Lophelia pertusa also forms large biogenic reefs, facilitated by skeletal fusion. Skeletal fusion in tropical corals can occur in closely related or juvenile individuals as a result of non-aggressive skeletal overgrowth or allogeneic tissue fusion, but contact reactions in many species result in mortality if there is no ‘self-recognition’ on a broad species level. This study reveals areas of ‘flawless’ skeletal fusion in Lophelia pertusa, potentially facilitated by allogeneic tissue fusion, are identified as having small aragonitic crystals or low levels of crystal organisation, and strong molecular bonding. Regardless of the mechanism, the recognition of ‘self’ between adjacent L. pertusa colonies leads to no observable mortality, facilitates ecosystem engineering and reduces aggression-related energetic expenditure in an environment where energy conservation is crucial. The potential for self-recognition at a species level, and subsequent skeletal fusion in framework-forming cold-water corals is an important first step in understanding their significance as ecological engineers in deep-seas worldwide

Insertions and the emergence of novel protein structure: a structure-based phylogenetic study of insertions

<p>Abstract</p> <p>Background</p> <p>In protein evolution, the mechanism of the emergence of novel protein domain is still an open question. The incremental growth of protein variable regions, which was produced by stochastic insertions, has the potential to generate large and complex sub-structures. In this study, a deterministic methodology is proposed to reconstruct phylogenies from protein structures, and to infer insertion events in protein evolution. The analysis was performed on a broad range of SCOP domain families.</p> <p>Results</p> <p>Phylogenies were reconstructed from protein 3D structural data. The phylogenetic trees were used to infer ancestral structures with a consensus method. From these ancestral reconstructions, 42.7% of the observed insertions are nested insertions, which locate in previous insert regions. The average size of inserts tends to increase with the insert rank or total number of insertions in the variable regions. We found that the structures of some nested inserts show complex or even domain-like fold patterns with helices, strands and loops. Furthermore, a basal level of structural innovation was found in inserts which displayed a significant structural similarity exclusively to themselves. The β-Lactamase/D-ala carboxypeptidase domain family is provided as an example to illustrate the inference of insertion events, and how the incremental growth of a variable region is capable to generate novel structural patterns.</p> <p>Conclusion</p> <p>Using 3D data, we proposed a method to reconstruct phylogenies. We applied the method to reconstruct the sequences of insertion events leading to the emergence of potentially novel structural elements within existing protein domains. The results suggest that structural innovation is possible via the stochastic process of insertions and rapid evolution within variable regions where inserts tend to be nested. We also demonstrate that the structure-based phylogeny enables the study of new questions relating to the evolution of protein domain and biological function.</p

Interactions between microenvironment and cancer cells in two animal models of bone metastasis

The preferential proliferation of cancer cells in the bone microenvironment is poorly characterised. Expression pattern of bone marrow and other organ microenvironment in contact with osteolytic (Walker W256) and osteoblastic (MatLyLu MLL) metastases were investigated. Fisher and Copenhagen rats received, respectively, W256 and MLL cells injection. Bone and soft tissues were analysed by immunochemistry for DKK1, cathepsin K, RANKL, MCSF or IL6 expression. Tartrate-resistant acid phosphatase (TRAcP)-positive cells were detected by a histoenzymatic technique. In bone, expressions of MCSF and DKK1 were shown in stromal cells of the bone marrow, in contact with metastatic foci of both tumours. Many stromal cells were found RANKL positive in the vicinity of the tumours. Cells expressing cathepsin K and multinucleated TRAcP+ cells were found in direct contact with trabeculae but also in bone marrow spaces near metastatic cells. In extraosseous tumours, cells in contact with malignant cells did not expressed DKK1, MCSF, cathepsin K and IL6. Some RANKL+ cells were found in the periphery of subcutaneous tumours but may represent Langerhans cells. Abnormal presence of TRAcP+ cells was never observed in the vicinity of malignant cells. Interaction between stromal and cancer cells induces the expression on the formers of characteristics leading to osteoclastogenesis only in the bone microenvironment