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How genetic errors in GPCRs affect their function:Possible therapeutic strategies

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Genes & Diseases 2015年第2期2卷 108-132页

作者： Henriette Stoy vsevolod v.gurevich University of Tu¨bingen Tu¨bingen 72074Germany Department of Pharmacology Vanderbilt UniversityNashvilleTN 37232USA

Activating and inactivating mutations in numerous human G protein-coupled receptors(GPCRs)are associated with a wide range of disease *** we use several class A GPCRs with a particularly large set of identified disease-associated mutations,many of which were biochemically characterized,along with known GPCR structures and current models of GPCR activation,to understand the molecular mechanisms yielding pathological *** on this mechanistic understanding we also propose different therapeutic approaches,both conventional,using small molecule ligands,and novel,involving gene therapy.

关键词： Activation Agonist Mutation Gene therapy Genetic disorder GPCR

Contemporary climate infuence on variability patterns of Anadenanthera colubrina ***,a key species in seasonally dry tropical forests

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Journal of Forestry Research 2022年第1期33卷 89-101页

作者： María victoria García María eugenia Barrandeguy Kathleen Prinz Genética de Poblaciones y Cuantitativa-Departamento de Genética-Facultad de Ciencias Exactas Químicas y Naturales-Universidad Nacional deMisionesInstituto de Biología Subtropical(UNaM-CONICET)Nodo PosadasFélix de Azara 15523300 PosadasArgentina Consejo Nacional de Investigaciones Científicas Y Técnicas(CONICET) PosadasMisionesArgentina Institute of Systematic Botany With Herbarium Haussknecht and Botanical Gardens Friedrich-Schiller-University Jena07743 JenaGermany

The distribution of many plant species has been shaped by climate changes,and their current phenotypic and genetic variability refect microclimatically suitable *** study relates contemporary climate to variability patterns of phenotypic traits and molecular markers in the Argentinean distribution of Anadenanthera colubrina ***,as well as to identify the most relevant phenotypic trait or molecular marker associated with those *** from four populations in both biogeographic provinces,Paranaense and Yungas,were *** analyses and multiple linear regressions were carried out to determine relationships among phenotypic traits and nuclear microsatellites,respectively,to climatic variables,and to identify the phenotypic traits as well as nuclear microsatellite loci most sensitive to *** and three clusters of individuals were detected based on genetic and phenotypic data,*** clusters based on genetic data refected the biogeographic origin of *** traits were the most relevant indicators of climatic *** microsatellite locus Ac41.1 appeared to be non-neutral presenting a strong correlation with climate variable temperature *** findings show complex patterns of genetic and phenotypic variability in the Argentinean distribution of *** *** related to the present or contemporary climate,and provides an example for an integrative approach to better understand climate impact on contemporary genetic and phenotypic variability in light of global climate change.

关键词： Contemporary climate Curupay Genetic variability Phenotypic variability Seasonally dry tropical forests

Arrestin-mediated signaling: Is there a controversy?

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World Journal of Biological Chemistry 2018年第3期9卷 25-35页

作者： vsevolod v.gurevich eugenia v.gurevich Department of Pharmacology Vanderbilt University

The activation of the mitogen-activated protein(MAP) kinases extracellular signal-regulated kinase(ERK)1/2 was traditionally used as a readout of signaling of G protein-coupled receptors(GPCRs) via arrestins, as opposed to conventional GPCR signaling via G proteins. Several recent studies using HEK293 cells where all G proteins were genetically ablated or inactivated, or both non-visual arrestins were knocked out, demonstrated that ERK1/2 phosphorylation requires G protein activity, but does not necessarily require the presence of non-visual arrestins. This appears to contradict the prevailing paradigm. Here we discuss these results along with the recent data on gene edited cells and arrestinmediated signaling. We suggest that there is no real controversy. G proteins might be involved in the activation of the upstream-most MAP3Ks, although in vivo most MAP3K activation is independent of heterotrimeric G proteins, being initiated by receptor tyrosine kinases and/or integrins. As far as MAP kinases are concerned, the best-established role of arrestins is scaffolding of the three-tiered cascades(MAP3K-MAP2 K-MAPK). Thus, it seems likely that arrestins, GPCRbound and free, facilitate the propagation of signals in these cascades, whereas signal initiation via MAP3K activation may be independent of arrestins. Different MAP3Ks are activated by various inputs, some of which are mediated by G proteins, particularly in cell culture, where we artificially prevent signaling by receptor tyrosine kinases and integrins, thereby favoring GPCR-induced signaling. Thus, there is no reason to change the paradigm: Arrestins and G proteins play distinct non-overlapping roles in cell signaling.

关键词： G protein-coupled receptors Arrestin G protein Signaling Extracellular signal-regulated kinase 1/2 c-Jun N-terminal kinase 3

The crossroads of receptor-mediated signaling and endocytosis in plants

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Journal of Integrative Plant Biology 2018年第9期60卷 827-840页

作者： Lucas Alves Neubus Claus Daniel v.Savatin eugenia Russinova Department of Plant Biotechnology and Bioinformatics Ghent University9052 GhentBelgium Center for Plant Systems Biology VIB9052 GhentBelgium

Plants deploy numerous plasma membrane receptors to sense and rapidly react to environmental changes. Correct localization and adequate protein levels of the cell-surface receptors are critical for signaling activation and modulation of plant development and defense against pathogens. After ligand binding, receptors are internalized for degradation and signaling attenuation. However, one emerging notion is that the Iigand-induced endocytosis of reCeptor complexes is important for the signal duration, amplitude, and specificity. Recently, mutants of maior endocytosis players, including clathrin and dynamin, have been shown to display defects in activation of a subset of signal transduction pathways, implying that signaling in plants might not be solely restricted to the plasma membrane. Here, we summarize the up-to-date knowledge of receptor complex endocytosis and its effect on the signaling outcome, in the context of plant development and immunity.

关键词： The crossroads of receptor-mediated signaling and endocytosis in plants BRI PM

Characterization of Formacell Lignin Derived from Black Liquor as a Potential Green Additive for Advanced Biocomposites

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Journal of Renewable Materials 2023年第6期11卷 2865-2879页

作者： Sri Hidayati eugenia Fonny Budiyanto Hadi Saputra Sutopo Hadi Apri Heri Iswanto Nissa Nurfajrin Solihat Petar Antov Lee Seng Hua Widya Fatriasari MohdSapuan Salit Agricultural Product Technology Department Faculty of AgricultureThe University of LampungJl.Sumantri Brojonegoro No.1Bandar LampungIndonesia Department of Forest Product Faculty of ForestryUniversitas Sumatera UtaraKampus USU Padang BulanNorth SumatraIndonesia JATI-Sumatran Forestry Analysis Study Center Jl.Tridharma Ujung No.1Kampus USUMedanNorth SumatraIndonesia Research Center for Biomass and Bioproducts National Research and Innovation Agency(BRIN)Jl.Raya BogorCibinongIndonesia Faculty of Forest Industry University of ForestrySofiaBulgaria Department of Wood Industry Faculty of Applied SciencesUniversiti Teknologi MARA(UiTM)Cawangan Pahang Kampus JengkaLintasan SemarakBandar JengkaMalaysia Institute of Tropical Forestry and Forest Products Universiti Putra MalaysiaSelangorMalaysia Research Collaboration Center for Marine Biomaterials Jl.Ir.SukarnoJatinangorSumedangWest JavaIndonesia Advanced Engineering Materials and Composites Research Centre Department of Mechanical and Manufacturing EngineeringUniversiti Putra MalaysiaSelangorMalaysia

Black liquor is obtained as a by-product of the pulping process,which is used to convert biomass into pulp by removing lignin,hemicelluloses and other extractives from wood to free cellulose *** represents a major constituent in black liquor,with quantities varying from 20%to 30%,of which a very low share is used for manufacturing value-added products,while the rest is mainly burned for energy purposes,thus underestimating its great potential as a raw ***,it is essential to establish new isolation and extraction methods to increase lignin valorization in the development of bio-based *** aim of this research work was to determine the effect of KOH or ethanol concentration as an isolation agent on lignin yields and the chemical characteristics of lignin isolated from formacell black liquor of oil palm empty fruit bunch(OPEFB).Isolation of lignin was carried out using KOH with various concentrations ranging from 5%to 15%(w/v).Ethanol was also used to precipitate lignin from black liquor at concentrations varying from 5%to 30%(v/v).The results obtained showed that the addition of KOH solution at 12.5%and 15%concentrations resulted in better lignin yield and chemical properties of lignin,i.e.,pH values of 3.86 and 4.27,lignin yield of 12.78%and 14.95%,methoxyl content of 11.33%and 10.13%,and lignin equivalent weights of 476.25 and 427.03,*** to its phenolic structure and rich functional groups that are favorable for modifications,lignin has the potential to be used as a green additive in the development of advanced biocomposite products in various applications to replace current fossil fuel-based material,ranging from fillers,fire retardants,formaldehyde scavengers,carbon fibers,aerogels,and wood adhesives.

关键词： Formacell black liquor lignin properties KOH ethanol oil palm empty fruit bunch advanced biocomposite

The Cretaceous Turn of Geological Evolution: Key Evidence from East Asia

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Acta Geologica Sinica(English Edition) 2018年第5期92卷 1991-2003页

作者： victor P.NECHAEv DAI Shifeng F.Lin SUTHERLAND Ian T.GRAHAM eugenia v.NECHAEvA Far East Geological Institute Far Eastern Branch Russian Academy of Sciences Engineering School Far Eastern Federal University State Key Laboratory of Coal Resources and Safe Mining China University of Mining and Technology School of Resources and Geosciences China University of Mining and Technology Geoscience Australian Museum PANGEA Research Centre School of Biological Earth and Environmental Sciences University of New South Wales

this work focuses on one of the critical points of Earth＇s history when the Solar System passed through the most distant point of its galactic orbit. During this event, Earth may have suffered from maximum extension, associated with its relative proximity to the Sun at that time, followed by long-term contraction related to its later distancing. This paper is based on generalized data on the Cretaceous evolution of the Earth as a whole and of East Asia in particular. The evidence suggests that major geological processes at this time may be interpreted as transitional changes in the state of Earth. A liquid nature of its core may have reacted to the gravitational and electromagnetic transformations. When the cosmic changes took place at 135-120 Ma, more turbulent flows in the outer core would have favoured the rise of voluminous magmatic plumes and associated fluid flows. These would substantially transform the mantle, crust, hydrosphere, biosphere and atmosphere. In particular, plume-related melting of overlying subducting slabs and lower continental crust could have initiated numerous adakitic melts that formed the East Asian Adakitic Province. These and associated juvenile events produced numerous metallic ore, coal, gas and oil deposits. The Cretaceous is one of the most significant resource-producing periods.

关键词： Cretaceous geological evolution galactic orbit super plume adakitic rocks coal ore and petroleum resources

Notch signaling in female cancers: a multifaceted node to overcome drug resistance

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Cancer Drug Resistance 2021年第4期4卷 805-836页

作者： Maria v.Giuli Angelica Mancusi eugenia Giuliani Isabella Screpanti Saula Checquolo Laboratory of Molecular Pathology Department of Molecular MedicineSapienza UniversityRome 00161Italy Scientific Direction San Gallicano Dermatological Institute IRCCSRome 00144Italy Department of Medico-Surgical Sciences and Biotechnology Sapienza UniversityLatina 04100Italy Center for Life Nano Science@Sapienza Istituto Italiano di TecnologiaRome 00161Italy

Drug resistance is one of the main challenges in cancer therapy,including in the treatment of female-specific malignancies,which account for more than 60%of cancer cases among ***,elucidating the underlying molecular mechanisms is an urgent need in gynecological cancers to foster novel therapeutic ***,Notch signaling,including either receptors or ligands,has emerged as a promising candidate given its multifaceted role in almost all of the hallmarks of *** the connection between Notch pathway and drug resistance in the afore-mentioned tumor contexts,several studies focused on the Notch-dependent regulation of the cancer stem cell(CSC)subpopulation or the induction of the epithelial-to-mesenchymal transition(EMT),both features implicated in either intrinsic or acquired ***,the present review provides an up-to-date overview of the published results on Notch signaling and EMT-or CSC-driven drug ***,other drug resistance-related mechanisms are examined such as the involvement of the Notch pathway in drug efflux and tumor ***,there is a long way to go before every facet will be fully understood;nevertheless,some small pieces are falling neatly into ***,the main aim of this review is to provide strong evidence in support of Notch signaling inhibition as an effective strategy to evade or reverse resistance in female-specific cancers.

关键词： Notch signaling drug resistance female-specific cancers cancer stem cells epithelial-to-mesenchymal transition drug efflux tumor microenvironment

Assessment of Key Players in the Special Rice value Chain in Nueva Ecija, Philippines

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Open Journal of Ecology 2023年第6期13卷 422-433页

作者： Johnah Jefferson S. Mercado Edilyn v. Lansangan eugenia G. Baltazar Armando C. Lagasca Erwin M. valiente University Extension Program Office Central Luzon State University Science City of Mu&#241oz Philippines Department of Agri-Management College of Agriculture Central Luzon State University Science City of Mu&#241oz Philippines

This study traced the special rice value chain, described the various players’ roles, assessed the identified chains’ performance, determined the constraints and opportunities, and identified interventions to improve the special rice value chain in the province. Key informant interviews with government and nongovernment organizations (NGOs) and surveys among different special rice value chain players were done. The special rice industry in Nueva Ecija is relatively limited and consists of aromatic, pigmented, and glutinous rice. The value chain mapping for special rice in Nueva Ecija starts downstream (traders) and moves upstream (input provider). Some of the identified constraints within the market levels of the chain are as follows: Farmers’ limited access to affordable yet quality seeds, the volatility of the price of paddy rice in the market, and the rapid changes in the prices of production inputs, such as seeds, fertilizers, pesticides, and others. Moreover, natural factors like typhoons, floods, droughts, insect pests, and weeds were noted. One major problem identified by the institutional buyers was the limited demand for special rice. To improve competitiveness, the special rice industry should focus on developing and promoting pest-resistant varieties and cost-reducing technologies. Furthermore, promoting special rice among consumers is needed to increase demand and encourage more farmers to engage in special rice production. The government agencies should continue supporting special rice farmers not only in production but also in postharvest and marketing aspects. Provision of seminars, trainings, and machinery related to special rice is recommended. Regression analysis using backward method of analysis was found to be significant in three (3) variables, namely, household size, years in school, and labor.

关键词： Constraints Interventions value-Addition

L-Norvaline, a new therapeutic agent against Alzheimer’s disease

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Neural Regeneration Research 2019年第9期14卷 1562-1572页

作者： Baruh Polis Kolluru D.Srikanth vyacheslav.gurevich Hava Gil-Henn Abraham O.Samson Drug Discovery Laboratory The Azrieli Faculty of MedicineBar-Ilan UniversitySafedIsrael Laboratory of Cell Migration and Invasion The Azrieli Faculty of MedicineBar-Ilan UniversitySafedIsrael Laboratory of Cancer Personalized Medicine and Diagnostic Genomics The Azrieli Faculty of MedicineBar-Ilan UniversitySafedIsrael

Growing evidence highlights the role of arginase activity in the manifestation of Alzheimer’s disease(AD).Upregulation of arginase was shown to contribute to *** of arginase activity appears to be a promising approach for interfering with the pathogenesis of ***,the enzyme represents a novel therapeutic *** this study,we administered an arginase inhibitor,L-norvaline(250 mg/L),for 2.5 months to a triple-transgenic model(3×Tg-AD)harboring PS1M146v,APPSwe,and tauP301L ***,the neuroprotective effects of L-norvaline were evaluated using immunohistochemistry,proteomics,and quantitative polymerase chain reaction ***,we identified the biological pathways activated by the ***,L-norvaline treatment reverses the cognitive decline in AD *** treatment is neuroprotective as indicated by reduced beta-amyloidosis,alleviated microgliosis,and reduced tumor necrosis factor transcription ***,elevated levels of neuroplasticity related postsynaptic density protein 95 were detected in the hippocampi of mice treated with ***,we disclosed several biological pathways,which were involved in cell survival and neuroplasticity and were activated by the *** these modes of action,L-norvaline has the potential to improve the symptoms of AD and even interferes with its *** such,L-norvaline is a promising neuroprotective molecule that might be tailored for the treatment of a range of neurodegenerative *** study was approved by the Bar-Ilan University Animal Care and Use Committee(approval No.82-10-2017)on October 1,2017.

关键词： dementia arginase inhibition arginine urea cycle microgliosis neuroinflammation cytokines tumor necrosis factor mTOR neurodegeneration