The “River Disease” (RD), a disorder impacting honeybee colonies located close to waterways with abundant riparian vegetation (including Sebastiania schottiana, Euphorbiaceae), kills newly hatched larvae. Forager bees from RD-affected colonies collect honeydew excretions from Epormenis cestri (Hemiptera: Flatidae), a planthopper feeding on trees of S. schottiana. First-instar honeybee larvae fed with this honeydew died. Thus, we postulated that the nectars of RD-affected colonies had a natural toxin coming from either E. cestri or S. schottiana. An untargeted metabolomics characterization of fresh nectars extracts from colonies with and without RD allowed to pinpoint xanthoxylin as one of the chemicals present in higher amounts in nectar from RD-affected colonies than in nectars from healthy colonies. Besides, xanthoxylin was also found in the aerial parts of S. schottiana and the honeydew excreted by E. cestri feeding on this tree. A larva feeding assay where xanthoxylin-enriched diets were offered to 1st instar larvae showed that larvae died in the same proportion as larvae did when offered enriched diets with nectars from RD-colonies. These findings demonstrate that a xenobiotic can mimic the RD syndrome in honeybee larvae and provide evidence of an interspecific flow of xanthoxylin among three trophic levels. Further, our results give information that can be considered when implementing measures to control this honeybee disease.
We recently reported that in vivo phosphorylation of urokinase-type plasminogen activator on Ser138/303 prevents its catalytic-independent ability to promote myelomonocytic cell adherence and motility. We now show that Ca2+ activated, phospholipid-dependent protein kinase C from rat brain phosphorylates in vitro a peptide corresponding to prourokinase residues 133-143 (DGKKPSSPPEE) and the full-length molecule on Ser138/139. The in vivo involvement of the protein kinase C isoenzyme family is supported by the finding that inhibition of kinase C activity prevents prourokinase phosphorylation on Ser138/303 in A431 human carcinoma cells. Conversely, a short treatment of A431 cells with phorbol myristate acetate increases the extent of phosphorylated prourokinase and, concomitantly, affects its function; under these conditions, the capability of prourokinase to up-regulate U937 monocyte-like cell adherence is severely impaired, although receptor binding is unaltered. By the aid of a "phosphorylation-like" variant (Ser138 to Glu) we show that modification of Ser138 is sufficient to confer to prourokinase the antagonistic properties observed following in vivo stimulation of protein kinase C activity. These observations provide the first evidence that protein kinase C directs the formation of a receptor competitive antagonist by regulating the in vivo phosphorylation state of prourokinase. 相似文献
Economic globalization, together with heightened market competition and increasingly short product life cycles are motivating
companies to use advanced manufacturing technologies. Use of high speed machining is increasingly widespread; however, as
the technology is relatively new, it lacks a deep-rooted knowledge base which would facilitate implementation. One of the
most frequent problems facing companies wishing to adopt this technology is selecting the most appropriate machine tool for
the product in question and own enterprise characteristics. This paper presents a decision support system for high speed milling
machine tool selection based on machine characteristics and performance tests. Profile machining tests are designed and conducted
in participating machining centers. The decision support system is based on product dimension accuracy, process parameters
such as feed rate and interpolation scheme used by CNC and machine characteristics such as machine accuracy and cost. Experimental
data for process error and cycle operation time are obtained from profile machining tests with different geometrical feature
zones that are often used in manufacturing of discrete parts or die/moulds. All those input parameters have direct impact
on productivity and manufacturing cost. Artificial neural network models are utilized for decision support system with reasonable
prediction capability. 相似文献
Experimental batches of linear rubber-like polyurethanes characterized by the presence of chemically different hard segments are studied and their thermal and dynamic-mechanical properties are related to the differences in chemical compositions. Interesting correlations are found between the development of crystallinity in such elastomeric poly(urethaneurea)s and the aromatic or alicyclic nature of the diisocyanate. Moreover, for a fixed ratio between hard and soft segments, and for a given composition of the soft segment, the results seem to indicate a better degree of phase separation in cycloaliphatic-based hard segment poly(urethaneurea)s than in aromatic-based hard segment poly(urethaneurea)s. 相似文献
Muscle invasive bladder cancer (MIBC) is a widespread malignancy with a worse prognosis often related to a late diagnosis. For early-stage MIBC pts, a multidisciplinary approach is mandatory to evaluate the timing of neoadjuvant chemotherapy (NAC) and surgery. The current standard therapy is platinum-based NAC (MVAC-methotrexate, vinblastine, doxorubicin, and cisplatin or Platinum–Gemcitabine regimens) followed by radical cystectomy (RC) with lymphadenectomy. However, preliminary data from Vesper trial highlighted that dose-dense NAC MVAC is endowed with a good pathological response but shows low tolerability. In the last few years, translational-based research approaches have identified several candidate biomarkers of NAC esponsiveness, such as ERCC2, ERBB2, or DNA damage response (DDR) gene alterations. Moreover, the recent consensus MIBC molecular classification identified six molecular subtypes, characterized by different sensitivity to chemo- or targeted or immunotherapy, that could open a novel procedure for patient selection and also for neoadjuvant therapies. The Italian PURE-01 phase II Trial extended data on efficacy and resistance to Immune Checkpoint Inhibitors (ICIs) in this setting. In this review, we summarize the most relevant literature data supporting NAC use in MIBC, focusing on novel therapeutic strategies such as immunotherapy, considering the better patient stratification and selection emerging from novel molecular classification. 相似文献
We studied the influence of initial pH on hydrogen (H2) production using permeate from scotta (a partially deproteinized cheese whey from ricotta production) as substrate (51 g L?1 lactose). Dark fermentation was carried out at 35 °C in laboratory batch reactors, in an unbuffered system. Hydrogen production and metabolite (volatile fatty acids, ethanol, and lactic acid) evolution during a 96-h period were monitored in reactors with initial pH varying in the range 4–10. In all reactors, H2 production started only when pH fell below 6. However, it was much higher (+31%) in the reactors with initial alkaline pH. We conclude that H2 production occurs only at acidic pH values, but initial alkaline pH values increase the overall H2 production in dark fermentation of lactose-rich substrates. 相似文献
This study addresses for the first time the influence of initial pH on the evolution of microbial consortia in dark fermentation of scotta permeate, using a high-throughput sequencing approach. Three fermentation phases could be detected: 1) a lag phase with no substantial differences in microbial composition at different initial pH values; 2) an exponential H2 production phase, accompanied by a general increase of Clostridium genus components and higher incidence of Trichococcus genus at neutral and alkaline pH; 3) a final stationary phase, characterized by a general increase of Bifidobacterium and Lactobacillus genera in all reactors. The initial pH value influenced the relative abundance of Trichococcus at 16–48 h of incubation. The metabolic activity of this genus increased the amount of metabolic precursors of H2 so that, when pH lowered to 5.4, clostridia in the reactors with initial alkaline pH become more active H2-producers than those in the others. 相似文献
Owing to their ability to efficiently deliver biological cargo and sense the intracellular milieu, vertical arrays of high aspect ratio nanostructures, known as nanoneedles, are being developed as minimally invasive tools for cell manipulation. However, little is known of the mechanisms of cargo transfer across the cell membrane‐nanoneedle interface. In particular, the contributions of membrane piercing, modulation of membrane permeability and endocytosis to cargo transfer remain largely unexplored. Here, combining state‐of‐the‐art electron and scanning ion conductance microscopy with molecular biology techniques, it is shown that porous silicon nanoneedle arrays concurrently stimulate independent endocytic pathways which contribute to enhanced biomolecule delivery into human mesenchymal stem cells. Electron microscopy of the cell membrane at nanoneedle sites shows an intact lipid bilayer, accompanied by an accumulation of clathrin‐coated pits and caveolae. Nanoneedles enhance the internalization of biomolecular markers of endocytosis, highlighting the concurrent activation of caveolae‐ and clathrin‐mediated endocytosis, alongside macropinocytosis. These events contribute to the nanoneedle‐mediated delivery (nanoinjection) of nucleic acids into human stem cells, which distribute across the cytosol and the endolysosomal system. This data extends the understanding of how nanoneedles modulate biological processes to mediate interaction with the intracellular space, providing indications for the rational design of improved cell‐manipulation technologies. 相似文献