The SH2/SH3 Adaptor Protein Dock Interacts with the Ste20-like Kinase Misshapen in Controlling Growth Cone Motility

AbstractRecent studies suggest that the SH2/SH3 adaptor Dock/Nck transduces tyrosine phosphorylation signals to the actin cytoskeleton in regulating growth cone motility. The signaling cascade linking the action of Dock/Nck to the reorganization of cytoskeleton is poorly understood. We now demonstrate that Dock interacts with the Ste20-like kinase Misshapen (Msn) in the Drosophila photoreceptor (R cell) growth cones. Loss of msn causes a failure of growth cones to stop at the target, a phenotype similar to loss of dock, whereas overexpression of msn induces pretarget growth cone termination. Physical and genetic interactions between Msn and Dock indicate a role for Msn in the Dock signaling pathway. We propose that Msn functions as a key controller of growth cone cytoskeleton in response to Dock-mediated signals

Nitrogen transport and assimilation in tea plant (Camellia sinensis): a review

Nitrogen is one of the most important nutrients for tea plants, as it contributes significantly to tea yield and serves as the component of amino acids, which in turn affects the quality of tea produced. To achieve higher yields, excessive amounts of N fertilizers mainly in the form of urea have been applied in tea plantations where N fertilizer is prone to convert to nitrate and be lost by leaching in the acid soils. This usually results in elevated costs and environmental pollution. A comprehensive understanding of N metabolism in tea plants and the underlying mechanisms is necessary to identify the key regulators, characterize the functional phenotypes, and finally improve nitrogen use efficiency (NUE). Tea plants absorb and utilize ammonium as the preferred N source, thus a large amount of nitrate remains activated in soils. The improvement of nitrate utilization by tea plants is going to be an alternative aspect for NUE with great potentiality. In the process of N assimilation, nitrate is reduced to ammonium and subsequently derived to the GS-GOGAT pathway, involving the participation of nitrate reductase (NR), nitrite reductase (NiR), glutamine synthetase (GS), glutamate synthase (GOGAT), and glutamate dehydrogenase (GDH). Additionally, theanine, a unique amino acid responsible for umami taste, is biosynthesized by the catalysis of theanine synthetase (TS). In this review, we summarize what is known about the regulation and functioning of the enzymes and transporters implicated in N acquisition and metabolism in tea plants and the current methods for assessing NUE in this species. The challenges and prospects to expand our knowledge on N metabolism and related molecular mechanisms in tea plants which could be a model for woody perennial plant used for vegetative harvest are also discussed to provide the theoretical basis for future research to assess NUE traits more precisely among the vast germplasm resources, thus achieving NUE improvement

Semi-Supervised Active Learning for Sound Classification in Hybrid Learning Environments

Coping with scarcity of labeled data is a common problem in sound classification tasks. Approaches for classifying sounds are commonly based on supervised learning algorithms, which require labeled data which is often scarce and leads to models that do not generalize well. In this paper, we make an efficient combination of confidence-based Active Learning and Self-Training with the aim of minimizing the need for human annotation for sound classification model training. The proposed method pre-processes the instances that are ready for labeling by calculating their classifier confidence scores, and then delivers the candidates with lower scores to human annotators, and those with high scores are automatically labeled by the machine. We demonstrate the feasibility and efficacy of this method in two practical scenarios: pool-based and stream-based processing. Extensive experimental results indicate that our approach requires significantly less labeled instances to reach the same performance in both scenarios compared to Passive Learning, Active Learning and Self-Training. A reduction of 52.2% in human labeled instances is achieved in both of the pool-based and stream-based scenarios on a sound classification task considering 16,930 sound instances

HSP60, a protein downregulated by IGFBP7 in colorectal carcinoma

<p>Abstract</p> <p>Background</p> <p>In our previous study, it was well defined that <it>IGFBP7 </it>was an important tumor suppressor gene in colorectal cancer (CRC). We aimed to uncover the downstream molecules responsible for <it>IGFBP7</it>'s behaviour in this study.</p> <p>Methods</p> <p>Differentially expressed protein profiles between PcDNA3.1(<it>IGFBP7</it>)-transfected RKO cells and the empty vector transfected controls were generated by two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS) identification. The selected differentially expressed protein induced by IGFBP7 was confirmed by western blot and ELISA. The biological behaviour of the protein was explored by cell growth assay and colony formation assay.</p> <p>Results</p> <p>Six unique proteins were found differentially expressed in PcDNA3.1(<it>IGFBP7</it>)-transfected RKO cells, including albumin (ALB), 60 kDa heat shock protein(HSP60), Actin cytoplasmic 1 or 2, pyruvate kinase muscle 2(PKM2), beta subunit of phenylalanyl-tRNA synthetase(FARSB) and hypothetical protein. The downregulation of HSP60 by IGFBP7 was confirmed by western blot and ELISA. Recombinant human HSP60 protein could increase the proliferation rate and the colony formation ability of PcDNA3.1(<it>IGFBP7</it>)-RKO cells.</p> <p>Conclusion</p> <p>HSP60 was an important downstream molecule of IGFBP7. The downregulation of HSP60 induced by IGFBP7 may be, at least in part, responsible for IGFBP7's tumor suppressive biological behaviour in CRC.</p

Polyelectrolyte interlayers with a broad processing window for high efficiency inverted organic solar cells towards mass production

Neutral polyelectrolyte interfacial layers in organic solar cells are well-known for their ability to tailor the work function of electrodes, improve charge carrier extraction and maximize open circuit voltage. However, they also suffer from low charge carrier conductivity, and therefore the interlayer must be kept thin, which in turn requires very precise deposition. This prerequisite significantly reduces the robustness of the fabrication process and makes such structures difficult to up-scale for roll-to-roll mass production. Herein, we find that by washing the polyelectrolyte layer with N,N-dimethylformamide (DMF) after deposition, solar cell efficiency jumps to near optimum levels, no matter what the original thickness of the polyelectrolyte layer. Subsequent characterization of the DMF-washed ZnO/PEI interlayer reveals a changed surface structure, passivated surface trap states, and thus improved transport properties and lower recombination losses. We demonstrate the general applicability of the method to other state-of-the-art material systems, namely P3HT:ICBA, PTB7:PC71BM and PTB7-Th:PC71BM. We find that the more efficient the material system, the larger the improvement in efficiency after DMF washing. Thus, this method represents a general way to relax the fabrication criteria for high efficiency organic solar cells. We anticipate that this method could be of use in other classes of devices such as OTFTs and OLEDs

IGFBP-rP1, a potential molecule associated with colon cancer differentiation

<p>Abstract</p> <p>Background</p> <p>In our previous studies, we have demonstrated that insulin-like growth factor binding protein-related protein1 (IGFBP-rP1) played its potential tumor suppressor role in colon cancer cells through apoptosis and senescence induction. In this study, we will further uncover the role of IGFBP-rP1 in colon cancer differentiation and a possible mechanism by revealing responsible genes.</p> <p>Results</p> <p>In normal colon epithelium, immunohistochemistry staining detected a gradient IGFBP-rP1 expression along the axis of the crypt. IGFBP-rP1 strongly expressed in the differentiated cells at the surface of the colon epithelium, while weakly expressed at the crypt base. In colon cancer tissues, the expression of IGFBP-rP1 correlated positively with the differentiation status. IGFBP-rP1 strongly expressed in low grade colorectal carcinoma and weakly expressed in high grade colorectal carcinoma. In vitro, transfection of PcDNA3.1(IGFBP-rP1) into RKO, SW620 and CW2 cells induced a more pronounced anterior-posterior polarity morphology, accompanied by upregulation with alkaline phosphatase (AKP) activity. Upregulation of carcino-embryonic antigen (CEA) was also observed in SW620 and CW2 transfectants. The addition of IGFBP-rP1 protein into the medium could mimic most but not all effects of IGFBP-rP1 cDNA transfection. Seventy-eight reproducibly differentially expressed genes were detected in PcDNA3.1(IGFBP-rP1)-RKO transfectants, using Affymetrix 133 plus 2.0 expression chip platform. Directed Acyclic Graph (DAG) of the enriched GO categories demonstrated that differential expression of the enzyme regulator activity genes together with cytoskeleton and actin binding genes were significant. IGFBP-rP1 could upreguate Transgelin (TAGLN), downregulate SRY (sex determining region Y)-box 9(campomelic dysplasia, autosomal sex-reversal) (SOX9), insulin receptor substrate 1(IRS1), cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) (CDKN2B), amphiregulin(schwannoma-derived growth factor) (AREG) and immediate early response 5-like(IER5L) in RKO, SW620 and CW2 colon cancer cells, verified by Real time Reverse Transcription Polymerase Chain Reaction (rtRT-PCR). During sodium butyrate-induced Caco2 cell differentiation, IGFBP-rP1 was upregulated and the expression showed significant correlation with the AKP activity. The downregulation of IRS1 and SOX9 were also induced by sodium butyrate.</p> <p>Conclusion</p> <p>IGFBP-rP1 was a potential key molecule associated with colon cancer differentiation. Downregulation of IRS1 and SOX9 may the possible key downstream genes involved in the process.</p

Analysis of the Influence of the Russia-Ukraine Conflict on the Global Energy Development Trend

The conflict between Russia and Ukraine that broke out in February 2022 directly gave birth to the energy crisis in Europe, but its impact is not limited to the European region, but also limited to the short term. It is a major change in the world in a century, and will profoundly and long-term change the global energy system and pattern. The outbreak of the conflict between Russia and Ukraine will reshape the global energy system, energy security will be promoted to an unprecedented order by all countries, accelerating the development of renewable energy is considered as an important measure to strengthen national energy security, and the global energy clean transformation will show a further accelerated development trend. Energy enterprises will face new opportunities and challenges. This paper analyzes the global energy development trend under the conflict between Russia and Ukraine, and puts forward the challenges that energy enterprises may face

Identification of the downstream target of misshapen in regulating photoreceptor growth-cone targeting in Drosophila

Neuronal growth cones guide the growing axons toward their target to establish precise neuronal connections during embryogenesis. The growth cone expresses cell surface receptors for recognizing guidance and targeting signals. It also possesses the intracellular signal transduction machinery to convert the extracellular signals into the reorganization of cytoskeletal structures in controlling growth-cone movement. Previous studies identified the SH2/SH3 adapter protein Dock as a key component of an evolutionarily conserved signaling pathway that transduces signals from cell-surface receptors to the growth-cone cytoskeleton to regulate growth cone motility. My M.Sc. studies (Ruan et al., 1999) demonstrated that the Ste20-like Serine/Threonine kinase Misshapen (Msn) functions downstream of Dock to regulate the proper targeting of a subset of R cell (R1-6) growth cones in the developing Drosophila visual system. To identify downstream targets of Msn, I have undertaken a genetic approach to search for second-site mutations that suppress a growth cone premature termination phenotype induced by Msn overexpression. We found that reducing the dosage of bifocal (bif), a gene encoding a putative cytoskeletal regulator, substantially suppressed the msn overexpression phenotype. Phenotypic analysis of bif mutants demonstrates that like loss of msn, loss of bif also specifically caused a failure of R1-6 growth cones to stop at lamina. Eye-specific expression of bif in bif mutants substantially rescued R1-6 targeting defect, indicating that bif is required in R1-6 growth cones for targeting decisions. Like overexpression of Msn, overexpression of Bif also caused pre-target growth cone termination. Biochemical studies show that Msn associated directly with Bif and phosphorylated Bif in vitro. Expression of Bif in cultured cells dramatically increased F-actin level and induced filopodium formation. Bif-induced cytoskeletal changes could be modulated subs

The SH2/SH3 adaptor protein dock interacts with the Ste20-like kinase misshapen in controlling growth cone motility /

Establishment of precise neuronal connections requires the proper guidance and targeting of growing axons during embryogenesis. The growth cone, a sensori motor structure at the leading edge of the axon, expresses cell surface receptors for recognizing guidance and targeting signals. It also possesses the intracellular signal transduction machinery to convert the extracellular signals into the reorganization of cytoskeletal structures in inducing directed movement (guidance) or the cessation of movement (targeting). Accumulated evidence points to the importance of protein tyrosine phosphorylation in growth cone signaling. The signaling cascade linking tyrosine phosphorylation into the changes in growth cone motility, however, remains largely undefined. Previous studies suggest that the Dock/Nck adapter protein play a role in transducing tyrosine phosphorylation signals to the actin-based cytoskeleton to regulate growth cone motility. To gain insight into the Dock signaling pathway, we have sought to identify the downstream effector of Dock in photoreceptor (R-cell) growth cones in the Drosophila visual system. Our recent results indicate that Misshapen (Msn), a Ste20-like Ser/Thr kinase, functions downstream of Dock to terminate R-cell growth cones in the target region. First, like loss of dock, mutations in msn cause R-cell growth cone targeting defects. Second, Msn is expressed in R-cells and predominantly localized in R-cell growth cones. Third, overexpression of Msn induces the early growth cone termination, a phenotype that is opposite to the msn loss-of-function phenotype. Finally, Msn interacts with Dock physically and genetically. We propose that Dock-linked target-derived signals activate Msn, which in turn modulates cytoskeletal-related proteins within the growth cones in decelerating their motility when the axons reach their targets. To identify genes that genetically interact with Msn, I screened &sim;150 deficiency lines. I identified 29 cytologica