919 research outputs found

    Fluid-Assisted Strain Localization in Quartz at the Brittle/Ductile Transition

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    A mylonitic quartzite with conjugate and synthetic shear bands was investigated by Electron Backscatter Diffraction and optical microscopy to obtain insights on recrystallization mechanisms and strain localization in quartz at plastic to semibrittle conditions close to the brittle-ductile transition. The mylonitic quartzite deformed during late Miocene thrusting coeval with contact metamorphism in the high-strain domains of the Calamita Schists (Elba Island, Italy). Mylonitic deformation occurred from amphibolite to lower greenschist facies conditions during cooling of the aureole. Dynamic recrystallization, dominated by the activity of dislocation creep by prism slip, produced recrystallized quartz layers mantling relic large quartz porphyroclasts. Under decreasing temperature and fluid-rich conditions, quartz porphyroclasts acted as relatively rigid bodies and fractured along synthetic and conjugate C′ shear bands. Shear bands developed along kinematically favored orientations, just locally assisted by weak crystallographic planes in quartz. Fracturing along shear bands was assisted by cataclasis and fluid infiltration enhancing fracture propagation and healing by recrystallization and authigenesis of new quartz and phyllosilicate grains. The process enhanced the propagation of and strain localization in shear bands, with the development of bands of weak phyllosilicates. Furthermore, we observed the development of a c axis preferred orientation (CPO) related to dissolution and precipitation of new grains with their c axis oriented parallel to shear bands. This study highlights the importance of the interplay between brittle and crystal-plastic processes and fluid ingress in the semibrittle regime to understand deformation partitioning and strain localization

    Analysis of conglutin seed storage proteins across lupin species using transcriptomic, protein and comparative genomic approaches

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    Background - The major proteins in lupin seeds are conglutins that have primary roles in supplying carbon, sulphur and nitrogen and energy for the germinating seedling. They fall into four families; α, β, γ and δ. Interest in these conglutins is growing as family members have been shown to have beneficial nutritional and pharmaceutical properties. Results - An in-depth transcriptome and draft genome from the narrow-leafed lupin (NLL; Lupinus angustifolius) variety, Tanjil, were examined and 16 conglutin genes were identified. Using RNAseq data sets, the structure and expression of these 16 conglutin genes were analysed across eight lupin varieties from five lupin species. Phylogenic analysis suggest that the α and γ conglutins diverged prior to lupin speciation while β and δ members diverged both prior and after speciation. A comparison of the expression of the 16 conglutin genes was performed, and in general the conglutin genes showed similar levels of RNA expression among varieties within species, but quite distinct expression patterns between lupin species. Antibodies were generated against the specific conglutin families and immunoblot analyses were used to compare the levels of conglutin proteins in various tissues and during different stages of seed development in NLL, Tanjil, confirming the expression in the seed. This analysis showed that the conglutins were expressed highly at the mature seed stage, in all lupin species, and a range of polypeptide sizes were observed for each conglutin family. Conclusions - This study has provided substantial information on the complexity of the four conglutin families in a range of lupin species in terms of their gene structure, phylogenetic relationships as well as their relative RNA and protein abundance during seed development. The results demonstrate that the majority of the heterogeneity of conglutin polypeptides is likely to arise from post-translational modification from a limited number of precursor polypeptides rather than a large number of different genes. Overall, the results demonstrate a high degree of plasticity for conglutin expression during seed development in different lupin species

    po 268 the interaction of herg1 potassium channels with integrin receptors perturbs the force transduction machinery in pancreatic cancer

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    Introduction Ion channels regulate cell proliferation, differentiation, and migration through cell-cell and cell–extracellular matrix interactions mediated by integrins. K + flux through the human ether-a-gogo–related gene 1 (hERG1) channel shapes action potential firing in excitable cells, e.g. cardiomyocytes. Its abundance is often aberrantly high in human tumours, including the pancreatic ductal adenocarcinoma (PDAC). We recently demonstrated that the direct interaction of β1 integrins with hERG1 channels in cancer cells stimulated distinct signalling pathways that depended on the conformational state of hERG1 and affected different aspects of tumour progression. 1 We hypothesised that hERG1 channels compromise the PDAC mechano-reciprocity, the ability to dynamically respond to externally applied forces by exerting forces, which enhances invasion and compromises treatment. Material and methods Using elastic micropillar arrays of varying stiffness, 2 we quantified the β1-integrin mediated forces exerted by PANC-1 cells. Micropillars coating with collagen and/or fibronectin derived peptides allowed us to direct cell surface receptor binding specificity (i.e. α 2 β 1 and α 5 β 1 integrins). Results and discussions Independently of the substrate coating, PANC-1 cells exerted higher forces as a function of substrate stiffness, as already demonstrated for other cell types. Remarkably, the disruption of the β1/hERG1 interaction through E4031 inhibition of hERG1 channels resulted in a significant increase in the detected cellular forces. Our results suggest that in addition to alter distinct signalling pathways 1 the direct interaction of β1 integrins and hERG1 channels perturbs the force transduction machinery. Conclusion These findings encouraged us to develop bispecific antibodies (scDb, single-chain diabody) binding to the β1/hERG1 complex that are now being validated in PDAC cell lines. In particular, we have developed a bispecific antibody (scDb-β1/hERG1), 3 which is composed by the variable domains (VH and VL chains) of monoclonal antibodies binding two different antigens, hERG1 and β1 integrin. References Becchetti, et al. Science Signaling2017;10, eaaf3236. van Hoorn, et al. Nano Lett2014;14:4257. A. Arcangeli, C. Duranti, S. Crescioli, L. Carraresi. Patent Ref: 102017000083637 (University of Florence)

    Sildenafil Reduces Expression and Release of IL-6 and IL-8 Induced by Reactive Oxygen Species in Systemic Sclerosis Fibroblasts

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    Oxidative stress linked to vascular damage plays an important role in the pathogenesis of systemic sclerosis (SSc). Indeed, vascular damage at nailfold capillaroscopy in patients with Raynaud’s Phenomenon (RP) is a major risk factor for the development of SSc together with the presence of specific autoantiobodies. Here, we investigated the effects of the phosphodiesterase type 5 inhibitor (PDE5i) sildenafil, currently used in the management of RP, in modulating the proinflammatory response of dermal fibroblasts to oxidative stress in vitro. Human fibroblasts isolated from SSc patients and healthy controls were exposed to exogenous reactive oxygen species (ROS) (100 µM H2O2), in the presence or absence of sildenafil (1 µM). Treatment with sildenafil significantly reduced dermal fibroblast gene expression and cellular release of IL-6, known to play a central role in the pathogenesis of tissue damage in SSc and IL-8, directly induced by ROS. This reduction was associated with suppression of STAT3-, ERK-, NF-κB-, and PKB/AKT-dependent pathways. Our findings support the notion that the employment of PDE5i in the management of RP may be explored for its efficacy in modulating the oxidative stress-induced proinflammatory activation of dermal fibroblasts in vivo and may ultimately aid in the prevention of tissue damage caused by SSc

    Penetrating particle ANalyzer (PAN)

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    PAN is a scientific instrument suitable for deep space and interplanetary missions. It can precisely measure and monitor the flux, composition, and direction of highly penetrating particles (>> \sim100 MeV/nucleon) in deep space, over at least one full solar cycle (~11 years). The science program of PAN is multi- and cross-disciplinary, covering cosmic ray physics, solar physics, space weather and space travel. PAN will fill an observation gap of galactic cosmic rays in the GeV region, and provide precise information of the spectrum, composition and emission time of energetic particle originated from the Sun. The precise measurement and monitoring of the energetic particles is also a unique contribution to space weather studies. PAN will map the flux and composition of penetrating particles, which cannot be shielded effectively, precisely and continuously, providing valuable input for the assessment of the related health risk, and for the development of an adequate mitigation strategy. PAN has the potential to become a standard on-board instrument for deep space human travel. PAN is based on the proven detection principle of a magnetic spectrometer, but with novel layout and detection concept. It will adopt advanced particle detection technologies and industrial processes optimized for deep space application. The device will require limited mass (~20 kg) and power (~20 W) budget. Dipole magnet sectors built from high field permanent magnet Halbach arrays, instrumented in a modular fashion with high resolution silicon strip detectors, allow to reach an energy resolution better than 10\% for nuclei from H to Fe at 1 GeV/n

    Deciphering the Bifidobacterial Populations within the Canine and Feline Gut Microbiota

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    During the course of evolution, dogs and cats have been subjected to extensive domestication, becoming the principal companion animals for humans. For this reason, their health care, including their intestinal microbiota, is considered of considerable importance. However, the canine and feline gut microbiota still represent a largely unexplored research area. In the present work, we profiled the microbiota of 23 feline fecal samples by 16S rRNA gene and bifidobacterial internally transcribed spacer (ITS) approaches and compared this information with previously reported data from 138 canine fecal samples. The obtained data allowed the reconstruction of the core gut microbiota of the above-mentioned samples coupled with their classification into distinct community state types at both genus and species levels, identifying Bacteroides, Fusobacterium, and Prevotella 9 as the main bacterial components of the canine and feline gut microbiota. At the species level, the intestinal bifidobacterial gut communities of dogs and cats differed in terms of both species number and composition, as emphasized by a covariance analysis. Together, our findings show that the intestinal populations of cats and dogs are similar in terms of genus-level taxonomical composition, while at the bifidobacterial species level, clear differences were observed, indicative of host-specific colonization behavior by particular bifidobacterial taxa.IMPORTANCE Currently, domesticated dogs and cats are the most cherished companion animals for humans, and concerns about their health and well-being are therefore important. In this context, the gut microbiota plays a crucial role in maintaining and promoting host health. However, despite the social relevance of domesticated dogs and cats, their intestinal microbial communities are still far from being completely understood. In this study, the taxonomical composition of canine and feline gut microbiota was explored at genus and bifidobacterial species levels, allowing classification of these microbial populations into distinct gut community state types at either of the two investigated taxonomic levels. Furthermore, the reconstruction of core gut microbiota coupled with covariance network analysis based on bifidobacterial internally transcribed spacer (ITS) profiling revealed differences in the bifidobacterial compositions of canine and feline gut microbiota, suggesting that particular bifidobacterial species have developed a selective ability to colonize a specific host

    The infant gut microbiome as a microbial organ influencing host well-being

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    Initial establishment of the human gut microbiota is generally believed to occur immediately following birth, involving key gut commensals such as bifidobacteria that are acquired from the mother. The subsequent development of this early gut microbiota is driven and modulated by specific dietary compounds present in human milk that support selective colonization. This represents a very intriguing example of host-microbe co-evolution, where both partners are believed to benefit. In recent years, various publications have focused on dissecting microbial infant gut communities and their interaction with their human host, being a determining factor in host physiology and metabolic activities. Such studies have highlighted a reduction of microbial diversity and/or an aberrant microbiota composition, sometimes referred to as dysbiosis, which may manifest itself during the early stage of life, i.e., in infants, or later stages of life. There are growing experimental data that may explain how the early human gut microbiota affects risk factors related to adult health conditions. This concept has fueled the development of various nutritional strategies, many of which are based on probiotics and/or prebiotics, to shape the infant microbiota. In this review, we will present the current state of the art regarding the infant gut microbiota and the role of key commensal microorganisms like bifidobacteria in the establishment of the first microbial communities in the human gut

    Comparative 1D- and 2D-electrophoretic protein profiles of ancestral and modern buckwheat seeds grown in the italian alpine region

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    Buckwheat is an old crop whose seeds are under-utilized. The protein composition of these seeds, however, makes them suitable as much needed ingredients for the production of gluten-free products. Several buckwheat species and local cultivars are known worldwide. In this work, 1D and 2D electrophoresis were used to characterize and compare the seed protein profiles of two buckwheat species (Fagopyrum esculentum and Fagopyrum tataricum). The two analyzed cultivars of F. esculentum represent authentic landraces of an Italian Alpine valley, named Valtellina. The protein profiles of F. tataricum and the two F. esculentum cultivars did not show major differences. However, narrow but significant differences were present between these two landraces, allowing their discrimination at protein level. This work represents a molecular-based approach to the designation of origin and authenticity of local buckwheat varieties and their tracing in flours for human food

    Estrogen-receptor-positive breast cancer in postmenopausal women: The role of body composition and physical exercise

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    Breast cancer (BC) is the most commonly diagnosed cancer among women worldwide and the most common cause of cancer-related death. To date, it is still a challenge to estimate the magnitude of the clinical impact of physical activity (PA) on those parameters producing significative changes in future BC risk and disease progression. However, studies conducted in recent years highlight the role of PA not only as a protective factor for the development of ER+ breast cancer but, more generally, as a useful tool in the management of BC treatment as an adjuvant to traditional therapies. In this review, we focused our attention on data obtained from human studies analyzing, at each level of disease prevention (i.e., primary, secondary, tertiary and quaternary), the positive impact of PA/exercise in ER+ BC, a subtype representing approximately 70% of all BC diagnoses. Moreover, given the importance of estrogen receptors and body composition (i.e., adipose tissue) in this subtype of BC, an overview of their role will also be made throughout this review
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