Prions are infectious proteins that possess multiple self-propagating structures. The information for strains and structural specific barriers appears to be contained exclusively in the folding of the pathological isoform, PrPSc. Many recent studies determined that de novo prion strains could be generated in vitro from the structural conversion of recombinant (rec) prion protein (PrP) into amyloidal structures. Our aim was to elucidate the conformational diversity of pathological recPrP amyloids and their biological activities, as well as to gain novel insights in characterizing molecular events involved in mammalian prion conversion and propagation. To this end we generated infectious materials that possess different conformational structures. Our methodology for the prion conversion of recPrP required only purified rec full-length mouse (Mo) PrP and common chemicals. Neither infected brain extracts nor amplified PrPSc were used. Following two different in vitro protocols recMoPrP converted to amyloid fibrils without any seeding factor. Mouse hypothalamic GT1 and neuroblastoma N2a cell lines were infected with these amyloid preparations as fast screening methodology to characterize the infectious materials. Remarkably, a large number of amyloid preparations were able to induce the conformational change of endogenous PrPC to harbor several distinctive proteinase-resistant PrP forms. One such preparation was characterized in vivo habouring a synthetic prion with novel strain specified neuropathological and biochemical properties. 相似文献
The cryptic diversity in the polychaete Syllis gracilis Grube, 1840, in the Mediterranean Sea was examined with an integrative morpho-molecular approach. Individuals of S. gracilis were collected at eleven Mediterranean localities to provide an insight into the role of brackish environments in inducing cryptic speciation. The examination of morphological features combined with a molecular genetic analysis based on a partial sequence of the 16S rRNA gene highlighted discrepancies between morphological and molecular diversity. Morphological data allowed to identify a morphotype with short appendages occurring in coralline algae communities and another one with long appendages observed in brackish-water environments and Sabellaria reefs. Multivariate analyses showed that sampling localities were the greatest source of morphological divergence, suggesting that phenotypic plasticity may play a role in local adaptations of S. gracilis populations. Molecular data showed the occurrence of four divergent lineages not corresponding to morphological clusters. Different species delimitation tests gave conflicting results, retrieving, however, at least four separated entities. Some lineages occurred in sympatry and were equally distributed in marine and brackish-water environments, excluding a biogeographic or ecological explanation of the observed pattern and suggesting instead ancient separation between lineages and secondary contact. The co-occurrence of different lineages hindered the identification of the lineage corresponding to S. gracilis sensu stricto. The discrepancy between morphological and molecular diversity suggests that different environmental and biogeographic features may interact in a complex and unpredictable way in shaping diversity patterns. An integrative approach is needed to provide a satisfactory insight on evolutionary processes in marine invertebrates. 相似文献
The conservation actions towards artworks holding a common patrimony for the community are of primary importance, but also those related to their "container" as museums, libraries or archives are to consider. Fungal spores and bacteria carried by air flows to the artwork surface can colonize it causing biodeterioration through physical and/or chemical alterations of the materials with the irreversible loss of their value. The quality control of the indoor air surrounding the historic building is essential, as well as for the protection and conservation of the artwork, also for the protection of the health of operators and visitors. The aim of this study was to monitor airborne fungal particles, through volumetric spore traps, for improving the knowledge about the conservation and protection of artworks in the museum environment analysing the principal relationships between indoor environmental conditions and potentially biodeteriogen fungal spore growth. The evidence of no significant relationships between spore concentrations and environmental conditions recorded inside the different expositive rooms testified the regular and correct maintenance of the air conditioning system inside the considered building (National Gallery of Umbria, central Italy). Moreover, in a specific museum room a significant spore concentration decreasing trend was recorded mainly due to a structural modification in the same building.
Photoperiod‐dependent flowering in rice is regulated by HEADING DATE 1 (Hd1), which acts as both an activator and repressor of flowering in a daylength‐dependent manner. To investigate the use of microProteins as a tool to modify rice sensitivity to the photoperiod, we designed a synthetic Hd1 microProtein (Hd1miP) capable of interacting with Hd1 protein, and overexpressed it in rice. Transgenic OX‐Hd1miP plants flowered significantly earlier than wild type plants when grown in non‐inductive long day conditions. Our results show the potential of microProteins to serve as powerful tools for modulating crop traits and unraveling protein function. 相似文献
A novel class of timolol derivatives with nitric oxide (NO)-donating moieties achieved chemical stability yet under physiologically relevant conditions released timolol and NO. Hindered esters A were designed and synthesized, whose ‘triggered’ release relied on enzymatic hydrolysis of the nitrate ester in A to B, that in turn cyclized to liberate timolol. 相似文献
A COST Action is a consortium of -mainly- European scientists (but open to international cooperation) working on a common research area, with the same subject; COST provides funding to the Actions for networking and dissemination activities, thus the participating scientists must have secured research funding from other national or European sources. COST funding is in the scale of approximately 100 kEuros per year and in this vein, it is often criticized both in that it does not fund research and the core science and in that its funding is ‘limited’. However, COST with its instruments is an integral pillar of the European Research Area, and it is through its mission that a variety of aspects of the research environment, fundamental to the success of the research, are catered for; these include scientific networking, collaboration/exchange/training and dissemination activities. Through fast procedures, proposals are evaluated and approved for funding in less than one year from submission date and Actions become operational immediately, managed on flexible management. In this way, COST contributes to reducing the fragmentation in European research investments, while opening the European Research Area to cooperation worldwide. COST Actions have an excellent record of building the critical mass for follow up activities in the EU FP or other similarly competitive programmes. 相似文献
Hypoxia occurs in physiological and pathological conditions. T cells experience hypoxia in pathological and physiological conditions as well as in lymphoid organs. Indeed, hypoxia-inducible factor 1α (HIF-1α) affects T cell survival and functions. Rai, an Shc family protein member, exerts pro-survival effects in hypoxic neuroblastoma cells. Since Rai is also expressed in T cells, we here investigated its role in hypoxic T cells. In this work, hypoxia differently affected cell survival, proapoptotic, and metabolic programs in T cells, depending upon Rai expression. By using Jurkat cells stably expressing Rai and splenocytes from Rai−/−mice, we demonstrated that Rai promotes T cell survival and affects cell metabolism under hypoxia. Upon exposure to hypoxia, Jurkat T cells expressing Rai show (a) higher HIF-1α protein levels; (b) a decreased cell death and increased Akt/extracellular-signal-regulated kinase phosphorylation; (c) a decreased expression of proapoptotic markers, including caspase activities and poly(ADP-ribose) polymerase cleavage; (d) an increased glucose and lactate metabolism; (e) an increased activation of nuclear factor-kB pathway. The opposite effects were observed in hypoxic splenocytes from Rai−/−mice. Thus, Rai plays an important role in hypoxic signaling and may be relevant in the protection of T cells against hypoxia. 相似文献