Comparative phosphoproteomic analysis reveals signaling networks regulating monopolar and bipolar cytokinesis.

The successful completion of cytokinesis requires the coordinated activities of diverse cellular components including membranes, cytoskeletal elements and chromosomes that together form partly redundant pathways, depending on the cell type. The biochemical analysis of this process is challenging due to its dynamic and rapid nature. Here, we systematically compared monopolar and bipolar cytokinesis and demonstrated that monopolar cytokinesis is a good surrogate for cytokinesis and it is a well-suited system for global biochemical analysis in mammalian cells. Based on this, we established a phosphoproteomic signature of cytokinesis. More than 10,000 phosphorylation sites were systematically monitored; around 800 of those were up-regulated during cytokinesis. Reconstructing the kinase-substrate interaction network revealed 31 potentially active kinases during cytokinesis. The kinase-substrate network connects proteins between cytoskeleton, membrane and cell cycle machinery. We also found consensus motifs of phosphorylation sites that can serve as biochemical markers specific to cytokinesis. Beyond the kinase-substrate network, our reconstructed signaling network suggests that combination of sumoylation and phosphorylation may regulate monopolar cytokinesis specific signaling pathways. Our analysis provides a systematic approach to the comparison of different cytokinesis types to reveal alternative ways and a global overview, in which conserved genes work together and organize chromatin and cytoplasm during cytokinesis.EMBO (European Molecular Biology Organization) Installation Grant; Young Scientist Award Program BAGEP of the Science Academy (Turkey); TUBITAK-Marie Curie Co-funded Brain Circulation Schem

Methylseleninic acid promotes antitumour effects via nuclear FOXO3a translocation through Akt inhibition

Selenium supplement has been shown in clinical trials to reduce the risk of different cancers including lung carcinoma. Previous studies reported that the antiproliferative and pro-apoptotic activities of methylseleninic acid (MSA) in cancer cells could be mediated by inhibition of the PI3K pathway. A better understanding of the downstream cellular targets of MSA will provide information on its mechanism of action and will help to optimize its use in combination therapies with PI3K inhibitors. For this study, the effects of MSA on viability, cell cycle, metabolism, apoptosis, protein and mRNA expression, and reactive oxygen species production were analysed in A549 cells. FOXO3a subcellular localization was examined in A549 cells and in stably transfected human osteosarcoma U2foxRELOC cells. Our results demonstrate that MSA induces FOXO3a nuclear translocation in A549 cells and in U2OS cells that stably express GFP-FOXO3a. Interestingly, sodium selenite, another selenium compound, did not induce any significant effects on FOXO3a translocation despite inducing apoptosis. Single strand break of DNA, disruption of tumour cell metabolic adaptations, decrease in ROS production, and cell cycle arrest in G1 accompanied by induction of apoptosis are late events occurring after 24h of MSA treatment in A549 cells. Our findings suggest that FOXO3a is a relevant mediator of the antiproliferative effects of MSA. This new evidence on the mechanistic action of MSA can open new avenues in exploiting its antitumour properties and in the optimal design of novel combination therapies. We present MSA as a promising chemotherapeutic agent with synergistic antiproliferative effects with cisplatin. (C) 2015 Elsevier Ltd. All rights reserved.Ministerio de Ciencia e Innovacion, Spain [SAF2011-25726]; Agencia de Gestio d'Ajuts Universitaris i de Recerca (AGAUR)-Generalitat de Catalunya [2014SGR1017]; Ministerio de Economia y Competitividad, Spain [SAF2014-56059-R]; Fundacao para a Ciencia e a Tecnologia (FCT) Research Center [UID/BIM/04773/2013CBMR 1334]; National Institute of Health, USA [1R01CA118434-01A2, 1P01CA163223-01A1]; National Science Foundation, USA [EPS-0447479]; FCT [SFRH/BPD/84634/2012]; prize ICREA Academia for excellence in research; ICREA Foundation-Generalitat de Cataluny

Language development after cochlear implantation: an epigenetic model

Growing evidence supports the notion that dynamic gene expression, subject to epigenetic control, organizes multiple influences to enable a child to learn to listen and to talk. Here, we review neurobiological and genetic influences on spoken language development in the context of results of a longitudinal trial of cochlear implantation of young children with severe to profound sensorineural hearing loss in the Childhood Development after Cochlear Implantation study. We specifically examine the results of cochlear implantation in participants who were congenitally deaf (N = 116). Prior to intervention, these participants were subject to naturally imposed constraints in sensory (acoustic–phonologic) inputs during critical phases of development when spoken language skills are typically achieved rapidly. Their candidacy for a cochlear implant was prompted by delays (n = 20) or an essential absence of spoken language acquisition (n = 96). Observations thus present an opportunity to evaluate the impact of factors that influence the emergence of spoken language, particularly in the context of hearing restoration in sensitive periods for language acquisition. Outcomes demonstrate considerable variation in spoken language learning, although significant advantages exist for the congenitally deaf children implanted prior to 18 months of age. While age at implantation carries high predictive value in forecasting performance on measures of spoken language, several factors show significant association, particularly those related to parent–child interactions. Importantly, the significance of environmental variables in their predictive value for language development varies with age at implantation. These observations are considered in the context of an epigenetic model in which dynamic genomic expression can modulate aspects of auditory learning, offering insights into factors that can influence a child’s acquisition of spoken language after cochlear implantation. Increased understanding of these interactions could lead to targeted interventions that interact with the epigenome to influence language outcomes with intervention, particularly in periods in which development is subject to time-sensitive experience

Spatiotemporal Evolution of Tourism Eco-Efficiency in Major Tourist Cities in China

Tourism development consumes ecological resources to varying extents while bringing economic benefits; tourism eco-efficiency (TEE) assessment has thus become an area of major focus in destination sustainability research. This paper intends to examine the spatiotemporal characteristics and driving factors of eco-efficiency changes in 36 tourist cities on the Chinese mainland from 2010 to 2019, using a super-slacks-based measure (SBM) model, the data envelopment analysis (DEA)–Malmquist index, spatial correlation, and regression analysis. In contrast to the previous work, this work explores TEE among major tourist cities in China by considering the undesirable outputs of carbon emissions and sewage. The results show that (1) the TEE of most cities during the study period was low but increasing; there were significant spatial differences among different cities, and the eco-efficiency of the same city fluctuated over time. (2) The TEE was globally uncorrelated, but low-eco-efficiency areas were adjacent to each other and formed agglomerates, enhancing the negative spillover effect. (3) Despite fluctuations, the Malmquist indices exhibited positive trends, which resulted from the technical progress index rather than the technical efficiency index. (4) Socioeconomic development significantly promoted TEE. This research reveals the evolutionary law of TEE on the urban scale and explores the impact of social and economic development on TEE, which can provide a reference for policymaking and enrich research on destination sustainability

Comparison of some yield and quality criteria in organically and conventionally-grown lettuce

The simplest definition organic farming is a production system, which excludes synthetic inputs and resorts to external inputs only where the system cannot be sustained by internal recycling. Recentstudies comparing conventional and organic farming have shown an increase in organic matter, nutrient content, and microbial biomass in organically managed soils. The present study was undertaken to evaluate how conventional and organic farming systems affected the yield and some quality properties of lettuce by investigating the effects of some natural substances (blood flour, manure, liquid seaweed extract etc.) on yield, quality and nutrient content of organically versusconventionally-grown lettuces. As a conclusion, results of both years showed that the conventional growing had higher yield than organic growing, respectively 20% in total yield and 21% in marketableyield. On the other hand there was no difference in terms of food nutrition value and quality and that is why it is possible to recommend organic lettuce growing as it has much more positive effects onhuman health

Spatiotemporal Evolution of Tourism Eco-Efficiency in Major Tourist Cities in China

Tourism development consumes ecological resources to varying extents while bringing economic benefits; tourism eco-efficiency (TEE) assessment has thus become an area of major focus in destination sustainability research. This paper intends to examine the spatiotemporal characteristics and driving factors of eco-efficiency changes in 36 tourist cities on the Chinese mainland from 2010 to 2019, using a super-slacks-based measure (SBM) model, the data envelopment analysis (DEA)–Malmquist index, spatial correlation, and regression analysis. In contrast to the previous work, this work explores TEE among major tourist cities in China by considering the undesirable outputs of carbon emissions and sewage. The results show that (1) the TEE of most cities during the study period was low but increasing; there were significant spatial differences among different cities, and the eco-efficiency of the same city fluctuated over time. (2) The TEE was globally uncorrelated, but low-eco-efficiency areas were adjacent to each other and formed agglomerates, enhancing the negative spillover effect. (3) Despite fluctuations, the Malmquist indices exhibited positive trends, which resulted from the technical progress index rather than the technical efficiency index. (4) Socioeconomic development significantly promoted TEE. This research reveals the evolutionary law of TEE on the urban scale and explores the impact of social and economic development on TEE, which can provide a reference for policymaking and enrich research on destination sustainability

Influence of Glycyl-L-Glutamic Acid Dipeptide on Calcium Pyrophosphate Dihydrate Crystallization

The increasing prevalence of calcium pyrophosphate dihydrate (CPPD) deposition disease, a form of arthritis with high inflammatory potential, has triggered considerable interest in the search for additives to prevent CPPD crystal formation, particularly in the field of biomineralization. In this context, CPPD crystallization in aqueous solution with and without glycine, glutamic acid, or glycyl-L-glutamic acid as crystal-growth modifier was experimentally investigated. The produced crystals were characterized structurally, morphologically, and in terms of their surface charge. In addition, the thermal degradation profiles of CPPD crystals obtained with and without the modifiers were characterized by TGA-FTIR, and the major volatile product was H2O.Complex Fluid Processin

Development and characterization of <i>in situ </i>gelling system containing atorvastatin-loaded polycaprolactone nanoparticles for periodontal diseases

The periodontal pocket provides a suitable environment for bacterial accumulation and growth which results in ultimately tooth loss. The clinical efficacy of current therapy for periodontal pocket is low because the flushing actions within the mouth causes to rapid clearance of the solution. The antioxidant and anti-inflammatory effects of atorvastatin (ATV) can facilitate healing process of periodontal diseases. The aim of this study was to develop in situ gel formulation containing ATV-loaded polycaprolactone nanoparticles (PCL-NPs). PCL NPs were prepared by nanoprecipitation method. The NPs had spherical shape with a particle size range of 176-329 nm. They showed 59% encapsulation efficiency and prolonged release profile. In order to increase the mucoadhesive properties of the formulation and the residence time of the drug at the site of action, NPs were incorporated to in situ gel to provide a combination therapy. In situ gel formulation was prepared by cold method and characterized in terms of pH, gelation temperature and time, viscosity, syringeability, and rheological behaviours. In vitro release studies revealed that in situ gel formulation remarkably extend the release time of ATV and mathematical release kinetic modelling shows formulations can fit multiple models. The overall findings indicated that the combination therapy strategy of locally administration of in situ gel containing ATV-loaded polycaprolactone nanoparticles to periodontal pockets is a promising and innovative approach

Fully automated isotopic dimethyl labeling and phosphopeptide enrichment using a microfluidic HPLC phosphochip.

Quantitative detection of phosphorylation levels is challenging and requires an expertise in both stable isotope labeling as well as enrichment of phosphorylated peptides. Recently, a microfluidic device incorporating a nanoliter flow rate reversed phase column as well as a titania (TiO(2)) enrichment column was released. This HPLC phosphochip allows excellent recovery and separation of phosphorylated peptides in a robust and reproducible manner with little user intervention. In this work, we have extended the abilities of this chip by defining the conditions required for on-chip stable isotope dimethyl labeling allowing for automated quantitation. The resulting approach will make quantitative phosphoproteomics more accessible

Effects of spent mushroom compost on quality and productivity of cucumber (Cucumis sativus L.) grown in greenhouses

This study was conducted to determine the effects of spent mushroom compost (SMC), which is a waste product of mushroom processing through a year, on greenhouse cucumber growth as an organicmatter source for the soil. The effects of SMC on several yield related characteristics, such as total yield, fruit width, fruit length, total soluble solids, first quality fruit yield in total yield and nutritioncontent of the cucumber fruit were investigated. The effects of SMC on total yield and fruit width obtained during the whole vegetation period were statistically significant. On the other hand, no significant differences were determined among the SMC treatments for the first quality fruit yield, total soluble solids and fruit length. The highest total fruit yield was obtained at 40 ton ha-1 and it was followed by 80 and 20 ton ha-1 SMC applications. The highest values of fruit width and the nitrogen contents in cucumber were found at 80 ton ha-1 SMC application. Based on the present study it was concluded that as an organic material source and amendment of greenhouse soil application of at least 6 months waited SMC was very effective and beneficiary for cucumber growth, productivity and recycling the spent mushroom compost