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991.
Della Santina L Piano I Cangiano L Caputo A Ludwig A Cervetto L Gargini C 《PloS one》2012,7(1):e29812
This study investigates the role of two different HCN channel isoforms in the light response of the outer retina. Taking advantage of HCN-deficient mice models and of in vitro (patch-clamp) and in vivo (ERG) recordings of retinal activity we show that HCN1 and HCN2 channels are expressed at distinct retinal sites and serve different functions. Specifically, HCN1 operate mainly at the level of the photoreceptor inner segment from where, together with other voltage sensitive channels, they control the time course of the response to bright light. Conversely, HCN2 channels are mainly expressed on the dendrites of bipolar cells and affect the response to dim lights. Single cell recordings in HCN1−/− mice or during a pharmacological blockade of Ih show that, contrary to previous reports, Ikx alone is able to generate the fast initial transient in the rod bright flash response. Here we demonstrate that the relative contribution of Ih and Ikx to the rods'' temporal tuning depends on the membrane potential. This is the first instance in which the light response of normal and HCN1- or HCN2-deficient mice is analyzed in single cells in retinal slice preparations and in integrated full field ERG responses from intact animals. This comparison reveals a high degree of correlation between single cell current clamp data and ERG measurements. A novel picture emerges showing that the temporal profile of the visual response to dim and bright luminance changes is separately determined by the coordinated gating of distinct voltage dependent conductances in photoreceptors and bipolar cells. 相似文献
992.
Ilaria Bonaduce Leslie Carlyle Maria Perla Colombini Celia Duce Carlo Ferrari Erika Ribechini Paola Selleri Maria Rosaria Tiné 《PloS one》2012,7(11)
This paper presents an analytical investigation of paint reconstructions prepared with linseed oil that have undergone typical 19th century treatments in preparation for painting. The oil was mechanically extracted from the same seed lot, which was then processed by various methods: water washing, heat treatments, and the addition of driers, with and without heat. A modern process lead white (Dutch source, Schoonhoven) and a commercially available vine black were used as pigments. The reconstructions were prepared in 1999, and naturally aged from then onwards. We compared thermogravimetric analysis (TG), which yields macromolecular information, with gas chromatography-mass spectrometry (GC-MS) and direct exposure mass spectrometry (DEMS), which both provide molecular information. The study enabled us to quantitatively demonstrate, for the first time, that the parameters used to identify drying oils are deeply influenced by the history of the paint. In particular, here we show that the ratio between the relative amounts of palmitic and stearic acid (P/S), which is used as an index for differentiating between drying oils, is extremely dependent on the pigments present and the age of the paint. Moreover the study revealed that neither the P/S parameter nor the ratios between the relative amounts of the various dicarboxylic acids (azelaic over suberic and azelaic over sebacic) can be used to trace the sorts of pre-treatment undergone by the oil investigated in this study. The final results represent an important milestone for the scientific community working in the field, highlighting that further research is still necessary to solve the identification of drying oils in works of art. 相似文献
993.
994.
Neyraud V Aushev VN Hatzoglou A Meunier B Cascone I Camonis J 《The Journal of biological chemistry》2012,287(35):29397-29405
Ras GTPases signal by orchestrating a balance among several effector pathways, of which those driven by the GTPases RalA and RalB are essential to Ras oncogenic functions. RalA and RalB share the same effectors but support different aspects of oncogenesis. One example is the importance of active RalA in anchorage-independent growth and membrane raft trafficking. This study has shown a new post-translational modification of Ral GTPases: nondegradative ubiquitination. RalA (but not RalB) ubiquitination increases in anchorage-independent conditions in a caveolin-dependent manner and when lipid rafts are endocytosed. Forcing RalA mono-ubiquitination (by expressing a protein fusion consisting of ubiquitin fused N-terminally to RalA) leads to RalA enrichment at the plasma membrane and increases raft exposure. This study suggests the existence of an ubiquitination/de-ubiquitination cycle superimposed on the GDP/GTP cycle of RalA, involved in the regulation of RalA activity as well as in membrane raft trafficking. 相似文献
995.
996.
Berlanda Scorza F Colucci AM Maggiore L Sanzone S Rossi O Ferlenghi I Pesce I Caboni M Norais N Di Cioccio V Saul A Gerke C 《PloS one》2012,7(6):e35616
Gram-negative bacteria naturally shed particles that consist of outer membrane lipids, outer membrane proteins, and soluble periplasmic components. These particles have been proposed for use as vaccines but the yield has been problematic. We developed a high yielding production process of genetically derived outer membrane particles from the human pathogen Shigella sonnei. Yields of approximately 100 milligrams of membrane-associated proteins per liter of fermentation were obtained from cultures of S. sonnei ΔtolR ΔgalU at optical densities of 30-45 in a 5 L fermenter. Proteomic analysis of the purified particles showed the preparation to primarily contain predicted outer membrane and periplasmic proteins. These were highly immunogenic in mice. The production of these outer membrane particles from high density cultivation of bacteria supports the feasibility of scaling up this approach as an affordable manufacturing process. Furthermore, we demonstrate the feasibility of using this process with other genetic manipulations e.g. abolition of O antigen synthesis and modification of the lipopolysaccharide structure in order to modify the immunogenicity or reactogenicity of the particles. This work provides the basis for a large scale manufacturing process of Generalized Modules of Membrane Antigens (GMMA) for production of vaccines from gram-negative bacteria. 相似文献
997.
Loro G Drago I Pozzan T Schiavo FL Zottini M Costa A 《The Plant journal : for cell and molecular biology》2012,69(1):1-13
The existence of a transport protein that imports cytosolic NAD(+) into peroxisomes has been controversially discussed for decades. Nevertheless, the biosynthesis of NAD(+) in the cytosol necessitates the import of NAD(+) into peroxisomes for numerous reduction/oxidation (redox) reactions. However, a gene encoding such a transport system has not yet been identified in any eukaryotic organism. Here, we describe the peroxisomal NAD(+) carrier in Arabidopsis. Our candidate gene At2g39970 encodes for a member of the mitochondrial carrier family. We confirmed its peroxisomal localization using fluorescence microscopy. For a long time At2g39970 was assumed to represent the peroxisomal ATP transporter. In this study, we could show that the recombinant protein mediated the transport of NAD(+) . Hence, At2g39970 was named PXN for peroxisomal NAD(+) carrier. The loss of PXN in Arabidopsis causes defects in NAD(+) -dependent β-oxidation during seedling establishment. The breakdown of fatty acid released from storage oil was delayed, which led to the retention of oil bodies in pxn mutant seedlings. Based on our results, we propose that PXN delivers NAD(+) for optimal fatty acid degradation during storage oil mobilization. 相似文献
998.
Melissa J. Collins Ilaria Napoli Sara Ribeiro Sinead Roberts Alison C. Lloyd 《Current biology : CB》2012,22(19):1765-1773
Highlights? Oncogenic Ras drives weak growth through the PI3K canonical growth pathway ? A novel E2F-independent role for the Rb family in cell biogenesis ? Ras and loss of Rb synergize to give robust and sustained cell growth ? PI3K pathway is crucial for sustained growth, acting to maintain nutrient uptake 相似文献
999.
A central role for the ERK-signaling pathway in controlling Schwann cell plasticity and peripheral nerve regeneration in vivo 总被引:1,自引:0,他引:1
Napoli I Noon LA Ribeiro S Kerai AP Parrinello S Rosenberg LH Collins MJ Harrisingh MC White IJ Woodhoo A Lloyd AC 《Neuron》2012,73(4):729-742
Following damage to peripheral nerves, a remarkable process of clearance and regeneration takes place. Axons downstream of the injury degenerate, while the nerve is remodeled to direct axonal regrowth. Schwann cells are important for this regenerative process. "Sensing" damaged axons, they dedifferentiate to a progenitor-like state, in which they aid nerve regeneration. Here, we demonstrate that activation of an inducible Raf-kinase transgene in myelinated Schwann cells is sufficient to control this plasticity by inducing severe demyelination in the absence of axonal damage, with the period of demyelination/ataxia determined by the duration of Raf activation. Remarkably, activation of Raf-kinase also induces much of the inflammatory response important for nerve repair, including breakdown of the blood-nerve barrier and the influx of inflammatory cells. This reversible in vivo model identifies a central role for ERK signaling in Schwann cells in orchestrating nerve repair and is a powerful system for studying peripheral neuropathies and cancer. 相似文献
1000.
Morphology and ultrastructure of the skin of Lissotriton italicus (previously named Triturus italicus) have been described in different phases of its biological cycle: larval stage, metamorphic stage and adult stage with emphasis on modifications occurring between aquatic and terrestrial adults. In the present study, light microscopy and both scanning and transmission electron microscopy were employed to analyze the histological and cytological remodelling that occurs in the skin of L. italicus during metamorphosis. The ultrastructure of the larval epidermis is arranged into three principal layers comprising an external layer of pavement cells, a basal layer and 1-3 intermediate layers consisting of Leydig cells along with accessory cells and mitochondria-rich cells. By the onset of metamorphosis, morphological changes of the skin include stratification and flattening of epidermal layers and disappearance of typical larval cells. In both aquatic and terrestrial adult phases the thin, cornified epidermis shows the same general arrangement as found in other vertebrates with an external stratum corneum and a variable number of intermediate cell layers. During the terrestrial adult phase, the skin is characterized by the presence of numerous tubercles; moreover, the lower epithelium is thicker than in the aquatic phase. Ultrastructural analysis revealed no substantial differences in the cellular composition of the skin between aquatic and terrestrial phases. 相似文献