Brain State Dependence of Hippocampal Subthreshold Activity in Awake Mice

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Hypolipoproteinemia and hyperinflammatory cytokines in serum of severe and moderate traumatic brain injury (TBI) patients

Traumatic brain injury (TBI) acts as an inducer of the inflammatory reaction expressed by the release of pro-inflammatory cytokines (interleukin-1beta [IL-1beta], interleukin-6 [IL-6] and interleukin-8 [IL-8]), and causes metabolic alterations in the early, post-traumatic state, either in the brain or/and the systemic circulation. The metabolic changes involve carbohydrates, proteins and lipids. We focused on the serum lipid profile, the impact of trauma on lipoproteins, and their subsequent effects, on inflammation. We investigated the role of cytokines and serum lipids, in patient outcome, reviewing 30-day mortality and the Glasgow Coma Scale (GCS). A total of 75 patients with severe or moderate TBI (GCS 相似文献   

Proferrorosamines and phytopathogenicity in Erwinia spp.

Proferrorosamine A (pFR A) of the plant pathogenic bacterium Erwinia rhapontici was shown to inhibit growth of wheat and cress seedlings at the 10 ppm level. When the seeds were continuously exposed to 100 ppm pFR A, the germination of cress and wheat seeds was inhibited up to 90% and 80%, respectively. The inhibition could be reversed through addition of equimolar amounts of ferrous iron, which indicates that the strong iron chelating capability of pFR A is responsible for the observed effect. The Fe(II) in the corresponding iron complex, ferrorosamine A, was found to be remarkably resistant towards oxidation by hydrogen peroxide and therefore redox-cycling in the Haber-Weiss cycle. It is thus conceivable that pFR A may also attenuate the generation of reactive hydroxyl radicals during the resistant and wound reaction. The apparent correlation between proferrorosamine production and virulence in erwiniae was further corroborated through the analysis of Erwinia persicinus, a newly described species. Using electrospray ionization mass spectrometry, E. persicinus was shown to produce pFR A and pFR B, and preliminary evidence for the phytopathogenicity of E. persicinus was found in cress. Inhibition of wheat seedlings by E. persicinus could not be demonstrated, but this may be due to technical difficulties or different host specificities. Taken together, our results indicate that the phytopathogenicity of E. rhapontici and E. persicinus may, as least in part, be due to the release of proferrorosamines.     

Tripolin A,a Novel Small-Molecule Inhibitor of Aurora A Kinase,Reveals New Regulation of HURP's Distribution on Microtubules

Mitotic regulators exhibiting gain of function in tumor cells are considered useful cancer therapeutic targets for the development of small-molecule inhibitors. The human Aurora kinases are a family of such targets. In this study, from a panel of 105 potential small-molecule inhibitors, two compounds Tripolin A and Tripolin B, inhibited Aurora A kinase activity in vitro. In human cells however, only Tripolin A acted as an Aurora A inhibitor. We combined in vitro, in vivo single cell and in silico studies to demonstrate the biological action of Tripolin A, a non-ATP competitive inhibitor. Tripolin A reduced the localization of pAurora A on spindle microtubules (MTs), affected centrosome integrity, spindle formation and length, as well as MT dynamics in interphase, consistent with Aurora A inhibition by RNAi or other specific inhibitors, such as MLN8054 or MLN8237. Interestingly, Tripolin A affected the gradient distribution towards the chromosomes, but not the MT binding of HURP (Hepatoma Up-Regulated Protein), a MT-associated protein (MAP) and substrate of the Aurora A kinase. Therefore Tripolin A reveals a new way of regulating mitotic MT stabilizers through Aurora A phosphorylation. Tripolin A is predicted to bind Aurora A similarly but not identical to MLN8054, therefore it could be used to dissect pathways orchestrated by Aurora kinases as well as a scaffold for further inhibitor development.     

Differences in life‐cycle stage components between native and introduced ranges of five woody Fabaceae species

Understanding differences in the components of life‐cycle stages of species between their native and introduced ranges can provide insights into the process of species transitioning from introduction to naturalization and invasion. We examined reproductive variables of the germination (seed predation, seed viability, time to germination), seed output (crown projection, seed production, seed weight) and dispersal (seed weight, dispersal investment) stages of five woody Fabaceae species, comparing native and introduced ranges. We predicted that each species would differ in reproductive variables of at least one life‐cycle stage between their native and introduced ranges, thus allowing us to determine the life‐cycle stage most associated with invasion success in the introduced range. Acacia melanoxylon and Paraserianthes lophantha had reduced seed predation in their introduced ranges while P. lophantha also had higher seed viability indicating that the germination life‐cycle stage is most strongly associated with their invasion success in the introduced range. Only Acacia longifolia varied between ranges for the seed output stage due to larger plant size, greater seed production and smaller seed size in its introduced range. Similar to A. longifolia, Acacia cyclops had smaller seed size in its introduced range but did not have any other variable differences between ranges suggesting that the dispersal stage is best associated with its invasion success in the introduced range. Surprisingly, Acacia saligna was the only species without a clear life‐cycle stage difference between ranges despite it being one of the more invasive acacia species in Australia. Although we found clear differences in reproductive variables associated with life‐cycle stages between native and introduced ranges of these five species, these differences were largely species‐specific. This suggests that a species invasion strategy into a novel environment is complex and varies among species depending on the environmental context, phenotypic plasticity and genotypic variation in particular traits.     

Apoptosis and autophagy function cooperatively for the efficacious execution of programmed nurse cell death during Drosophila virilis oogenesis

Programmed cell death consists of two major types, apoptotic and autophagic, both of which are mainly defined by morphological criteria. Our findings indicate that both types of programmed cell death occur in the ovarian nurse cells during middle- and late-oogenesis of Drosophila virilis. During mid-oogenesis, the spontaneously degenerated egg chambers exhibit typical characteristics of apoptotic cell death. Their nurse cells contain condensed chromatin and fragmented DNA, whereas active caspase assays and immunostaining procedures demonstrate the presence of highly activated caspases. Distinct features of autophagic cell death are also observed during D. virilis mid-oogenesis, as shown by monodansylcadaverine staining and ultrastructural examination performed by transmission electron microscopy. Additionally, atretic egg chambers exhibit an accumulation of lysosomal proteases. At the late stages of D. virilis oogenesis, apoptosis and autophagy coexist, manifesting cell death features that are similar to the ones described above, being also escorted by the involvement of an altered cytochrome c conformational display. We propose that apoptosis and autophagy operate synergistically during D. virilis oogenesis for a more efficient elimination of the degenerated nurse cells.     

Serine 34 Phosphorylation of Rho Guanine Dissociation Inhibitor (RhoGDI��) Links Signaling from Conventional Protein Kinase C to RhoGTPase in Cell Adhesion

Conventional protein kinase C (PKC) isoforms are essential serine/threonine kinases regulating many signaling networks. At cell adhesion sites, PKCα can impact the actin cytoskeleton through its influence on RhoGTPases, but the intermediate steps are not well known. One important regulator of RhoGTPase function is the multifunctional guanine nucleotide dissociation inhibitor RhoGDIα that sequesters several related RhoGTPases in an inactive form, but it may also target them through interactions with actin-associated proteins. Here, it is demonstrated that conventional PKC phosphorylates RhoGDIα on serine 34, resulting in a specific decrease in affinity for RhoA but not Rac1 or Cdc42. The mechanism of RhoGDIα phosphorylation is distinct, requiring the kinase and phosphatidylinositol 4,5-bisphosphate, consistent with recent evidence that the inositide can activate, localize, and orient PKCα in membranes. Phosphospecific antibodies reveal endogenous phosphorylation in several cell types that is sensitive to adhesion events triggered, for example, by hepatocyte growth factor. Phosphorylation is also sensitive to PKC inhibition. Together with fluorescence resonance energy transfer microscopy sensing GTP-RhoA levels, the data reveal a common pathway in cell adhesion linking two essential mediators, conventional PKC and RhoA.