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Protein synthesis modulation as a therapeutic approach for amyotrophic lateral sclerosis and frontotemporal dementia

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Neural Regeneration Research 2022年第7期17卷 1423-1430页

作者： Santiago E.Charif M.Florencia Vassallu lara Salvañal Lionel M.Igaz IFIBIO Houssay Grupo de Neurociencia de SistemasFacultad de MedicinaUniversidad de Buenos Aires-CONICETBuenos AiresArgentina

Protein synthesis is essential for cells to perform life metabolic *** alterations of protein content can lead to particular *** have an intrinsic array of mechanisms and pathways that are activated when protein misfolding,accumulation,aggregation or mislocalization *** of them(like the unfolded protein response)represent complex interactions between endoplasmic reticulum sensors and elongation factors that tend to increase expression of chaperone proteins and/or repress translation in order to restore protein homeostasis(also known as proteostasis).This is even more important in neurons,as they are very susceptible to harmful effects associated with protein overload and proteostatic mechanisms are less effective with *** neurodegenerative pathologies such as Alzheimer’s,Parkinson’s,and Huntington’s diseases,amyotrophic lateral sclerosis and frontotemporal dementia exhibit a particular molecular signature of distinct,unbalanced protein *** amyotrophic lateral sclerosis and frontotemporal dementia,the majority of cases present intracellular inclusions of ubiquitinated transactive response DNA-binding protein of 43 kDa(TDP-43).TDP-43 is an RNA binding protein that participates in RNA metabolism,among other *** of TDP-43(*** and mislocalization)can dramatically affect neurons,and this has been linked to disease *** of amyotrophic lateral sclerosis/frontotemporal dementia TDP-43-related mutations in cellular and animal models has been shown to recapitulate key features of the amyotrophic lateral sclerosis/frontotemporal dementia disease *** variants can be causative of degeneration onset and *** neurodegenerative diseases(including amyotrophic lateral sclerosis and frontotemporal dementia)have no cure at the moment;however,modulating translation has recently emerged as an attractive approach that can be performed at several steps(***

关键词： amyotrophic lateral sclerosis frontotemporal dementia neurodegeneration neurodegenerative diseases protein imbalance protein synthesis modulation proteostasis therapeutical compounds transactive response DNA-binding protein of 43 kDa translation unfolded protein response

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Modified Usability Framework for Disaster Apps:A Qualitative Thematic Analysis of User Reviews

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International Journal of Disaster Risk Science 2020年第5期11卷 615-629页

作者： Marion lara Tan Raj Prasanna Kristin Stock Emma EHDoyle Graham Leonard David Johnston Joint Centre for Disaster Research Massey UniversityWellington 6021New Zealand School of Natural and Computational Sciences Massey UniversityAlbany 0632New Zealand GNS Science AvalonLower Hutt 5010New Zealand

The public has access to a range of mobile applications(apps)for ***,there has been limited academic research conducted on disaster apps and how the public perceives their *** study explores end-users'perceptions of the usability of disaster *** proposes a conceptual framework based on insights gathered from thematically analyzing online *** study identifies new usability concerns particular to disaster apps'use:(1)content relevance depends on the app's purpose and the proximate significance of the information to the hazard event's time and location;(2)app dependability affects users'perceptions of usability due to the lifesafety association of disaster apps;(3)users perceive advertisements to contribute to their cognitive load;(4)users expect apps to work efficiently without unnecessary consumption of critical phone resources;(5)appropriate audio interface can improve usability,as sounds can boost an app's alerting aspect;and,finally(6)in-app browsing may potentially enhance users'impression of the structure of a disaster *** a result,this study argues for focussed research and development on public-facing disaster *** research should consider the conceptual framework and concerns presented in this study when building design guidelines and theories for disaster apps.

关键词： Disaster apps End-user perspective Human-computer interaction Usability

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Temporal-spatial segregation among hummingbirds foraging on honeydew in a temperate forest in Mexico

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Current Zoology 2011年第1期57卷 56-62页

作者： Carlos lara Vanessa MARTINEZ-GARCIA Raul ORTIZ-PULIDO Jessica BRAVO-CADENA Salvador LORANCA Alex CORDOBA-AGUILAR Laboratorio de Ecologfa de la Conducta Centro Tlaxcala de Biologfa de la Conducta UAT-UNAM Km 1.5 carretera Tlaxcala- Puebla s/n Colonia Xicohtencatl Apdo. Postal 262 Tlaxcala Tlaxcala 90070 Mexico Laboratorio de Ecologfa de Poblaciones. Centro de Investigaciones Biologicas. Universidad Autonoma del Estado de Hidalgo Mexico Departamento de Quimica y Biologia. Universidad de las Ameficas-Puebla. Cholula Puebla Mexico Departamento de Ecologfa Evolutiva. lnstituto de Ecologfa Universidad Nacional Autonoma de Mexico Distrito Federal Mexico

Spatial and temporal variation in interactions between hummingbirds and plants have often been examined, and hummingbirds and insects are known to indirectly interact in networks of nectar plants. In a highland temperate forest in Hidalgo, Mexico some oak trees were heavily infested by honeydew-producing insects （family Margarodidae, tribe Xylococcini, genus Strigmacoccus） and the honeydew was consumed by hummingbirds. Here using survival analysis we investigate how the honey- dew produced by dense populations of these margarodids is temporally and spatially partitioned by hummingbirds. We also measured the availability and quality of honeydew exudates, and then we recorded the time until a bird visited and used such re- sources. Four hummingbird species consumed this resource （Atthis eloisa, Hylocharis leucotis, Colibri thalassinus and Eugenes fulgens）. Data from 294 hours of observation on seven focal trees suggested temporal and spatial segregation among visiting birds according to body size and territorial behavior during the most honeydew-limited time. Hummingbird species differed in the dally times they foraged, as well as in the location where honeydew-producing insects were visited on the trees. Temporal and spatial segregation among hummingbird species is interpreted as an adaptation to reduce the risk of aggressive encounters. This may facilitate multispecies coexistence and allow these birds to exploit honeydew more effectively

关键词： Honeydew Hummingbirds Mexico Nectarivory Niche partitioning

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Glycosylation of N-hydroxy-pipecolic acid equilibrates between systemic acquired resistance response and plant growth

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Molecular Plant 2021年第3期14卷 440-455页

作者： Jianghua Cai Adam Jozwiak lara Holoidovsky Michael MMeijler Sagit Meir Ilana Rogachev Asaph Aharoni Department of Plant and Environmental Sciences Weizmann Institute of ScienceRehovot 761001Israel Department of Chemistry and the National Institute for Biotechnology in the Negev Ben-Gurion University of the NegevBe’er-Sheva 8410501Israel

N-hydroxy-pipecolic acid(NHP)activates plant systemic acquired resistance(SAR).Enhanced defense responses are typically accompanied by deficiency in plant development and *** of extensive studies on SAR induction,the effects of NHPmetabolismon plant growth remain largely *** this study,we discovered that NHP glycosylation is a critical factor that fine-tunes the tradeoff between SAR defense and plant *** demonstrated that a UDP-glycosyltransferase(UGT76B1)forming NHP glycoside(NHPG)controls the NHP to NHPG ***,the ugt76b1 mutant exhibits enhanced SAR response and an inhibitory effect on plant growth,while UGT76B1 overexpression attenuates SAR response,promotes growth,and delays senescence,indicating that NHP levels are dependent on UGT76B1 function in the course of ***,our results suggested that,upon pathogen attack,UGT76B1-mediated NHP glycosylation forms a‘‘hand brake’’on NHP accumulation by attenuating the positive regulation of NHP biosynthetic pathway genes,highlighting the complexity of SAR-associated *** addition,we showed that UGT76B1-mediated NHP glycosylation in the local site is important for fine-tuning SAR *** results implicate that engineering plant immunity through manipulating the NHP/NHPG ratio is a promising method to balance growth and defense response in crops.

关键词： N-hydroxy-pipecolic acid N-hydroxy-pipecolic acid glycoside UDP-glycosyltransferase glycosylation systemic acquired resistance plant growth

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Embedding MSCs in Si-HPMC hydrogel decreased MSC-directed host immune response and increased the regenerative potential of macrophages

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Regenerative Biomaterials 2022年第1期9卷 490-500页

作者： Christelle Demarquay lara Moussa Gildas Réethorée Fabien Milliat Pierre Weiss Noëlle Mathieu Human Health Department IRSNFrench Institute for Radiological Protection and Nuclear SafetySERAMEDLRMedFontenay-aux-Roses 92262France Facultéde Chirurgie Dentaire Regenerative Medicine and Skeleton(RMeS)LaboratoryUniversite de NantesNantes 44042France

Embedding mesenchymal stromal cells(MSCs)in biomaterial is a subject of increasing interest in the field of Regenerative *** up the clinical use of MSCs is dependent on the use of non-syngeneic models in accordance with Good Manufacturing Practices(GMP)requirements and on *** this end,in this study,we analyzed the in vivo host immune response following local injection of silanized hydroxypropyl methylcellulose(Si-HPMC)-embedded human MSCs in a rat model developing colorectal damage induced by ionizing *** and lymphocytes from mesenteric lymph nodes were harvested in addition to colonic *** set up tests,using flow cytometry and a live imaging system,to highlight the response to specific antibodies and measure the cytotoxicity of lymphocytes against injected *** demonstrated that Si-HPMC protects MSCs from specific antibodies production and from apoptosis by *** also observed that Si-HPMC does not modify innate immune response infiltrate in vivo,and that in vitro co-culture of Si-HPMC-embedded MSCs impacts macrophage inflammatory response depending on the microenvironment but,more importantly,increases the macrophage regenerative response through Wnt-family and VEGF gene *** study furthers our understanding of the mechanisms involved,with a view to improving the therapeutic benefits of biomaterial-assisted cell therapy by modulating the host immune *** decrease in specific immune response against injected MSCs protected by Si-HPMC also opens up new possibilities for allogeneic clinical use.

关键词： Si-HPMC hydrogel mesenchymal stromal cells host immune response regenerative medicine

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An experimental study on the conversion between IFPUG and UCP functional size measurement units

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Journal of Zhejiang University-Science C(Computers and Electronics) 2014年第3期15卷 161-173页

作者： Juan J.CUADRADO-GALLEGO Alain ABRAN Pablo RODRíGUEZ-SORIA Miguel A.lara Ecole de Technologie Supérieure-ETS 1100 Notre-Dame Ouest Computer Science Department University of Alcala

The use of functional size measurement(FSM) methods in software development organizations is growing during the years. Also, object oriented(OO) techniques have become quite a standard to design the software and, in particular, Use Cases is one of the most used techniques to specify functional requirements. Main FSM methods do not include specific rules to measure the software functionality from its Use Cases analysis. To deal with this issue some other methods like Kramer's functional measurement method have been developed. Therefore, one of the main issues for those organizations willing to use OO functional measurement method in order to facilitate the use cases count procedure is how to convert their portfolio functional size from the previously adopted FSM method towards the new method. The objective of this research is to find a statistical relationship for converting the software functional size units measured by the International Function Point Users Group(IFPUG) function point analysis(FPA) method into Kramer-Smith's use cases points(UCP) method and vice versa. Methodologies for a correct data gathering are proposed and results obtained are analyzed to draw the linear and non-linear equations for this correlation. Finally, a conversion factor and corresponding conversion intervals are given to establish the statistical relationship.

关键词： Software engineering Requirements analysis Functional size measurement Use cases analysis Object oriented Function point analysis Use cases points

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Proteomic dynamics revealed sex-biased responses to combined heat-drought stress in Marchantia

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Journal of Integrative Plant Biology 2024年第10期66卷 2226-2241页

作者： Sara Guerrero Víctor Roces lara García-Campa Luis Valledor Mónica Meijón Department of Organisms and Systems BiologyFaculty of Biology/BiotechnologyInstitute of AsturiasUniversity of OviedoOviedoAsturias 33071Spain

Recent studies have documented plant responses to climate change extensively, particularly to single-stress exposures. However, critical factors for stress survival, such as sexual differentiation,are not often considered. The dioicous Marchantia polymorpha stands as an evolutionary milestone,potentially preserving ancestral traits from the early colonizers. In this study, we employed proteomic analyses complemented with physiological monitoring to investigate combined heat and drought responses in Tak-1(male) and Tak-2(female)accessions of this liverwort. Additionally, targeted transcriptomics was conducted using different natural populations from contrasting *** findings revealed sex-biased dynamics among natural accessions, particularly evident under control conditions and during early stress responses. Although Tak-2 exhibited greater diversity than Tak-1 under control conditions, male accession demonstrated distinct and more rapid stress sensing and signaling. These differences in stress response appeared to be strongly related to sex-specific plasticity influenced by geoclimatic origin. Furthermore, we established distinct protein gene ages and genomic distribution trends, underscoring the importance of protein diversification over time. This study provides an evolutionary perspective on sexual divergence and stress emergence employing a systems biology approach, which allowed for the establishment of global and sex-specific interaction networks in the stress response.

关键词： abiotic stress land adaptation liverwort sex-biased response systems biology

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Auranofin and its analogs as prospective agents for the treatment of colorectal cancer

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Cancer Drug Resistance 2022年第1期5卷 1-14页

作者： lara Massai Damiano Cirri Tiziano Marzo Luigi Messori Department of Chemistry University of FlorenceSesto Fiorentino 50019Italy Department of Chemistry and Industrial Chemistry University of PisaPisa 56124Italy Department of Pharmacy University of PisaPisa 56126Italy CISUP-Centre for Instrumentation Sharing(Centro per l’Integrazione della Strumentazione Scientifica) University of PisaPisa 56126Italy University Consortium for Research in the Chemistry of Metal ions in Biological Systems(CIRCMSB) Bari 70126Italy

Today colorectal cancer(CRC)is one of the leading causes of cancer death *** disease is poorly chemo-sensitive toward the existing medical treatments so that new and more effective therapeutic agents are urgently needed and intensely *** drugs,oxaliplatin in particular,were reported to produce some significant benefit in CRC treatment,triggering the general interest of medicinal chemists and oncologists for metal-based compounds as candidate anti-CRC *** this frame,gold compounds and,specifically,the established antiarthritic drug auranofin with its analogs,form a novel group of promising anticancer *** to its innovative mechanism of action and its favorable pharmacological profile,auranofin together with its derivatives are proposed here as novel experimental agents for CRC treatment,capable of overcoming resistance to platinum *** encouraging results in this direction have already been obtained.A few recent studies demonstrate that the action of auranofin may be further potentiated through the preparation of suitable pharmaceutical formulations capable of protecting the gold pharmacophore from unselective reactivity or through the design of highly synergic drug *** perspectives of the research in this field are outlined.

关键词： Auranofin CRC colorectal cancer metallodrugs anticancer agents gold gold-based drugs

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Carbon dioxide fixation into cyclic carbonates at room temperature catalyzed by heteroscorpionate aluminum complexes

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Green Chemical Engineering 2022年第3期3卷 280-287页

作者： Felipe de la Cruz-Martinez Jose A.Castro-Osma Agustin lara-Sanchez Universidad de Castilla-La Mancha Departamento de Quimica InorganicaOrganica y Bioquimica-Centro de Innovacion en Quimica Avanzada(ORFEO-CINQA)Facultad de Ciencias y Tecnologias QuimicasCiudad Real13071Spain Instituto de Investigaciones Quimicas(IIQ) Departamento de Quimica Inorganica and Centro de Innovacion en Quimica Avanzada(ORFEO-CINQA)Consejo Superior de Investigaciones Cientificas(CSIC)and University of SevillaSevilla41092Spain Universidad de Castilla-La Mancha Departamento de Quimica InorganicaOrganica y Bioquimica-Centro de Innovacion en Quimica Avanzada(ORFEO-CINQA)Facultad de FarmaciaAlbacete02071Spain

Novel mono-and bimetallic scorpionate aluminum compounds have been designed and characterized by spec-troscopic *** organometallics complexes,in combination with tetrabutylammonium bromide as cocatalyst,displayed good catalytic activity for the cycloaddition of styrene oxide and CO_(2) under ambient *** the compounds tested,monometallic complex 3 featuring diethylamino groups showed the highest catalytic *** catalytic system catalyzed the formation of cyclic carbonate products from their corresponding epoxides at room temperature and 1 bar of CO_(2) pressure in the absence of a solvent in good yields and excellent selectivities.

关键词： CO_(2) Epoxides Cyclic carbonates Aluminum complexes

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Nitrate regulates rhizobial and mycorrhizal symbiosis in common bean(Phaseolus vulgaris L.)

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Journal of Integrative Plant Biology 2014年第3期56卷 281-298页

作者： Kalpana Nanjareddy Lourdes Blanco Manoj‐Kumar Arthikala Xochitl Alvarado Affantrange Federico Sánchez Miguel lara Genómica Funcional de Eucariotes Centro de Ciencias Genómicas Universidad Nacional Autónoma de México UNAM Apartado Postal 510‐3Cuernavaca Morelos 62271 México Escuela Nacional de Estudios Superiores‐UNAM León Blvd.UNAM 2011 Predio El Saucillo y El PotreroComunidad de los Tepetates León Gto.C.P.37684 Mexico Departamento de Biología Molecular de Plantas Instituto de BiotecnologíaUniversidad Nacional Autónoma de México UNAM Apartado Postal 510‐3 Cuernavaca Morelos 62271 México

Nitrogen-limited conditions are considered to be a prerequisite for legume-rhizobial symbiosis, but the effects of nitrate-rich conditions on symbiotic status remain poorly understood. We addressed this issue by examining rhizobial （Rhizobim tropici） and arbusclar mycorrhizal （Glomus intraradices） symbiosis in Phaseolus vulgaris L. cv. Negro Jamapa under nitrate pre-incubation and continuous nitrate conditions. Our results indicate that nitrate pre-incubation, independent of the concentration, did not affect nodule development. However, the continuous supply of nitrate at high concentrations impaired nodule maturation and nodule numbers. Low nitrate conditions, in addition to positively regulating nodule number, biomass, and nitrogenase activity, also extended the span of nitrogen-fixing activity. By contrast, for arbuscular mycorrhizae, continuous 1o and 50mmol/L nitrate increased the percent root length colonization, concomitantly reduced arbuscule size, and enhanced ammonia transport without affecting phosphate transport. Therefore, in this manuscript, we have proposed the importance of nitrate as a positive regulator in promoting both rhizobial and mycorrhizal symbiosis in the common bean.

关键词： Arbuscule common bean mycorrhiza nitrate nodule Rhizobium

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