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1.
Connecdenn 1/2 are DENN (differentially expressed in normal and neoplastic cells) domain-bearing proteins that function as GEFs (guanine nucleotide exchange factors) for the small GTPase Rab35. Disruption of connecdenn/Rab35 function leads to defects in the recycling of multiple cargo proteins from endosomes with altered cell function, yet the regulation of connecdenn GEF activity is unexplored. We now demonstrate that connecdenn 1/2 are autoinhibited such that the purified, full-length proteins have significantly less Rab35 binding and GEF activity than the isolated DENN domain. Both proteins are phosphorylated with prominent phosphorylation sites between residues 500 and 600 of connecdenn 1. A large scale proteomics screen revealed that connecdenn 1 is phosphorylated at residues Ser-536 and Ser-538 in an Akt-dependent manner in response to insulin stimulation of adipocytes. Interestingly, we find that an Akt inhibitor reduces connecdenn 1 interaction with Rab35 after insulin treatment of adipocytes. Remarkably, a peptide flanking Ser-536/Ser-538 binds the DENN domain of connecdenn 1, whereas a phosphomimetic peptide does not. Moreover, connecdenn 1 interacts with 14-3-3 proteins, and this interaction is also disrupted by Akt inhibition and by mutation of Ser-536/Ser-538. We propose that Akt phosphorylation of connecdenn 1 downstream of insulin activation regulates connecdenn 1 function through an intramolecular interaction.  相似文献   
2.
Axonal regeneration after injury to the CNS is hampered by myelin‐derived inhibitors, such as Nogo‐A. Natural products, such as green tea, which are neuroprotective and safe for long‐term therapy, would complement ongoing various pharmacological approaches. In this study, using nerve growth factor‐differentiated neuronal‐like Neuroscreen‐1 cells, we show that extremely low concentrations of unfractionated green tea polyphenol mixture (GTPP) and its active ingredient, epigallocatechin‐3‐gallate (EGCG), prevent both the neurite outgrowth‐inhibiting activity and growth cone‐collapsing activity of Nogo‐66 (C‐terminal domain of Nogo‐A). Furthermore, a synergistic interaction was observed among GTPP constituents. This preventive effect was dependent on 67‐kDa laminin receptor (67LR) to which EGCG binds with high affinity. The antioxidants N‐acetylcysteine and cell‐permeable catalase abolished this preventive effect of GTPP and EGCG, suggesting the involvement of sublethal levels of H2O2 in this process. Accordingly, exogenous sublethal concentrations of H2O2, added as a bolus dose (5 μM) or more effectively through a steady‐state generation (1–2 μM), mimicked GTPP in counteracting the action of Nogo‐66. Exogenous H2O2 mediated this action by bypassing the requirement of 67LR. Taken together, these results show for the first time that GTPP and EGCG, acting through 67LR and elevating intracellular sublethal levels of H2O2, inhibit the antineuritogenic action of Nogo‐A.

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There is a diverse range of microbiological challenges facing the food, healthcare and clinical sectors. The increasing and pervasive resistance to broad‐spectrum antibiotics and health‐related concerns with many biocidal agents drives research for novel and complementary antimicrobial approaches. Biofilms display increased mechanical and antimicrobial stability and are the subject of extensive research. Cold plasmas (CP) have rapidly evolved as a technology for microbial decontamination, wound healing and cancer treatment, owing to the chemical and bio‐active radicals generated known collectively as reactive oxygen and nitrogen species. This review outlines the basics of CP technology and discusses the interactions with a range of microbiological targets. Advances in mechanistic insights are presented and applications to food and clinical issues are discussed. The possibility of tailoring CP to control specific microbiological challenges is apparent. This review focuses on microbiological issues in relation to food‐ and healthcare‐associated human infections, the role of CP in their elimination and the current status of plasma mechanisms of action.  相似文献   
5.
Ethanol fermentation from Jerusalem artichoke tubers was performed at elevated temperatures by the consolidated bioprocessing strategy using Saccharomyces cerevisiae MK01 expressing inulinase through cell surface display. No significant difference was observed in yeast growth when temperature was controlled at 38 and 40 °C, respectively, but inulinase activity with yeast cells was substantially enhanced at 40 °C. As a result, enzymatic hydrolysis of inulin was facilitated and ethanol production was improved with 89.3 g/L ethanol produced within 72 h from 198.2 g/L total inulin sugars consumed. Similar results were also observed in ethanol production from Jerusalem artichoke tubers with 85.2 g/L ethanol produced within 72 h from 185.7 g/L total sugars consumed. On the other hand, capital investment on cooling facilities and energy consumption for running the facilities would be saved, since regular cooling water instead of chill water could be used to cool down the fermentation system.  相似文献   
6.
Dissecting the genetic basis for the traits of northern-style Chinese steamed bread (NCSB) is of great significance for wheat quality breeding. Quantitative trait loci (QTLs) for the processing quality of NCSB were studied using a recombinant inbred line (RIL) consisting of 173 lines derived from a “Shannong01–35 × Gaocheng9411” cross. Twenty-four putative additive QTLs were detected on chromosomes 1A, 1B, 1D, 3A, 3B, 4A, 4B, 5B, 6B, and 7B. Of these QTLs, QTex1A.1-27, QHei5B.5-488, and QGum4B.4-17 had the highest contribution and accounted for 9.33, 10.9, and 12.0% of the phenotypic variations, respectively. Several co-located QTLs with additive effects were detected on chromosomes 1A, 1D, 4B, and 5B. Two clusters (RFL_CONTIG2160_524-WSNP_CAP12_C2438_1180601 and EX_C101685_705-RAC875_C27536_611) for height, total score, and texture and for chewiness, gumminess, and hardness were detected on chromosomes 1A and 4B, respectively. Two QTLs for chewiness and hardness (QCh1D-4, QHa1D-4) with additive effects were detected; these alleles could be good targets for improving the processing quality of steamed bread from common wheat (Triticum aestivum L.). In addition, QTLs for wheat flour quality and the associated correlations with NCSB were simultaneously analyzed. Negative correlations were detected between chewiness and the wet/dry gluten content (WGC/DGC) or protein content. Two QTLs (QCh4B.4-17 and QPr4B.4-17) and three QTLs (QCh4B.4-13, QWG4B.4-13, and QDG4B.4-13) clustered in the same chromosomal region. The detected QTL clusters should be further investigated during wheat breeding and could be used by breeders to improve wheat quality and especially the processing quality of NCSB.  相似文献   
7.
Podosphaera leucotricha is the causal agent of powdery mildew (PM) in apple. To reduce the amount of fungicides required to control this pathogen, the development of resistant apple cultivars should become a priority. Resistance to PM was achieved in various crops by knocking out specific members of the MLO gene family that are responsible for PM susceptibility (S-genes). In apple, the knockdown of MdMLO19 resulted in PM resistance. However, since gene silencing technologies such as RNAi are perceived unfavorably in Europe, a different approach that exploits this type of resistance is needed. This work evaluates the presence of non-functional naturally occurring alleles of MdMLO19 in apple germplasm. The screening of the re-sequencing data of 63 apple individuals led to the identification of 627 single nucleotide polymorphisms (SNPs) in five MLO genes (MdMLO5, MdMLO7, MdMLO11, MdMLO18, and MdMLO19), 127 of which were located in exons. The T-1201 insertion of a single nucleotide in MdMLO19 caused the formation of an early stop codon, resulting in a truncated protein lacking 185 amino acids, including the calmodulin-binding domain. The presence of the insertion was evaluated in 115 individuals. It was heterozygous in 64 and homozygous in 25. Twelve of the 25 individuals carrying the insertion in homozygosity were susceptible to PM. After barley, pea, cucumber, and tomato, apple would be the fifth species for which a natural non-functional mlo allele has been found.  相似文献   
8.
Crop improvement is a long-term, expensive institutional endeavor. Genomic selection (GS), which uses single nucleotide polymorphism (SNP) information to estimate genomic breeding values, has proven efficient to increasing genetic gain by accelerating the breeding process in animal breeding programs. As for crop improvement, with few exceptions, GS applicability remains in the evaluation of algorithm performance. In this study, we examined factors related to GS applicability in line development stage for grain yield using a hard red winter wheat (Triticum aestivum L.) doubled-haploid population. The performance of GS was evaluated in two consecutive years to predict grain yield. In general, the semi-parametric reproducing kernel Hilbert space prediction algorithm outperformed parametric genomic best linear unbiased prediction. For both parametric and semi-parametric algorithms, an upward bias in predictability was apparent in within-year cross-validation, suggesting the prerequisite of cross-year validation for a more reliable prediction. Adjusting the training population’s phenotype for genotype by environment effect had a positive impact on GS model’s predictive ability. Possibly due to marker redundancy, a selected subset of SNPs at an absolute pairwise correlation coefficient threshold value of 0.4 produced comparable results and reduced the computational burden of considering the full SNP set. Finally, in the context of an ongoing breeding and selection effort, the present study has provided a measure of confidence based on the deviation of line selection from GS results, supporting the implementation of GS in wheat variety development.  相似文献   
9.
Electrophysiological effects produced by selective activation of M3 cholinoreceptors were studied in isolated left atrium preparations from rat using the standard sharp glass microelectrode technique. The stimulation of M3 receptors was obtained by application of muscarinic agonist pilocarpine (10?5 M) in the presence of selective M2 antagonist methoctramine (10?7 M). Stimulation of M3 receptors induced marked reduction of action potential duration by 14.4 ± 2.4% and 16.1 ± 2.5% of control duration measured at 50 and 90% of repolarization, respectively. This effect was completely abolished by selective M3 blocker 4-DAMP (10?8 M). In isolated myocytes obtained from the rat left atrium, similar pharmacological stimulation of M3 receptors led to suppression of peak L-type calcium current by 13.9 ± 2.6% of control amplitude (measured at +10 mV), but failed to affect K+ currents I to, I Kur, and I Kir. In the absence of M2 blocker methoctramine, pilocarpine (10?5 M) produced stronger attenuation of I CaL and induced an increase in I Kir. This additive inward rectifier current could be abolished by highly selective blocker of Kir3.1/3.4 channels tertiapin-Q (10?6 M) and therefore was identified as I KACh. Thus, in the rat atrial myocardium activation of M3 receptors leads to shortening of action potentials via suppression of I CaL, but does not enhance the major potassium currents involved in repolarization. Joint stimulation of M2 and M3 receptors produces stronger action potential shortening due to M2-mediated activation of I KACh.  相似文献   
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