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The biosynthetic pathway of the hallucinogen mescaline and its heterologous reconstruction

Molecular Plant 2024年第7期17卷 1129-1150页

作者： paula berman Luis Alejandro de Haro Ana-Rita Cavaco Sayantan Panda Younghui Dong Nikolay Kuzmich Gabriel Lichtenstein Yoav Peleg Hila Harat Adam Jozwiaki Jianghua Cai Uwe Heinig Sagit Meir Ilana Rogachev Asaph Aharoni Department of Plant and Environmental Sciences Weizmann Institute of ScienceRehovot 7610001Israel Life Sciences Core Facilities Weizmann Institute of ScienceRehovot 7610001Israel The Maurice and Vivienne Wohl Institute for Drug Discovery Weizmann Institute of ScienceRehovot 7610001Israel Present address:Department of Cell and Metabolic Biology Leibniz Institute of Plant BiochemistryWeinberg 306120 Halle(Saale)Germany Department of Molecular&Cellular Pharmacology University of Miami Miler School of MedicineMiamiFL 33136USA Department of Botany and Plant Sciences University of California RiversideRiversideCA 92521USA Laboratory of Plant Hormones and Development Regulation of Chongqing School of Life SciencesChongqing UniversityChongqing 401331China

Mescaline,among the earliest identified natural hallucinogens,holds great potential in psychotherapy ***,despite the existence of a postulated biosynthetic pathway for more than half a century,the specific enzymes involved in this process are yet to be *** this study,we investigated the cactus Lophophora williamsii(Peyote),the largest known natural producer of the phenethylamine *** employed a multi-faceted approach,combining de novo whole-genome and transcriptome sequencing with comprehensive chemical profiling,enzymatic assays,molecular modeling,and pathway engineering for pathway *** identified four groups of enzymes responsible for the six catalytic steps in the mescaline biosynthetic pathway,and an N-methyltransferase enzyme that N-methylates all phenethylamine intermediates,likely modulating mescaline levels in ***,we reconstructed the mescaline biosynthetic pathway in both Nicotiana benthamiana plants and yeast cells,providing novel insights into several challenges hindering complete heterologous mescaline *** together,our study opens up avenues for exploration of sustainable production approaches and responsible utilization of mescaline,safeguarding this valuable natural resource for future generations.

关键词： mescaline Lophophora williamsi Peyote biosynthetic pathway de novo genome sequencing mo-lecular modeling

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Antitumoral effects of cannabis in Notch1-mutated T-cell acute lymphoblastic leukemia

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Cancer Communications 2023年第6期43卷 711-715页

作者： Elazar Besser Anat Gelfand Gil Moshe Lewitus Hila Novak-Kotzer Shiri Procaccia paula berman Igal Louria-Hayon Inbar Shreiber-Livne Yishai Ofran David Meiri The Laboratory of Cancer Biology and Cannabinoid Research Faculty of BiologyTechnion-Israel Institute of TechnologyHaifaIsrael Department of Hematology and Bone Marrow Transplantation Rambam Health Care CampusHaifaIsrael

Dear Editor,In T-cell acute lymphoblastic leukemia(T-ALL),an aggressive hematologic cancer with poor clinical outcomes,more than 50%of cases show NOTCH1-driven transformation[1].The NOTCH1 receptor signaling pathway is activated through a series of proteolytic cleavages,ultimately causing the release of the active intracellular domain(NICD),which translocates to the nucleus where it promotes transcription of target genes involved in cell *** importance of NOTCH1 mutations in T-ALL has generated great interest in the development of anti-NOTCH1 targeted therapies.A new and promising emerging field in cancer treatment is medical *** evidence suggests the direct effects of cannabis on tumor progression in cell lines and animal models[2].Cannabis,and its unique secondary metabolites,known as phytocannabinoids,directly affect the propagation of cancer cells by modulating key cellsignaling pathways[3].We have previously demonstrated that different cannabis extracts,each containing a unique composition of metabolites,selectively impaired the survival of cancer cell lines depending on amatch between the chemical composition of the extract and the characteristics of the specific cancer cell line[4].In the present work,we set out to investigate whether cannabis extracts with unique phytocannabinoid profiles can selectively facilitate antitumor effects in T-ALL cells that harbor a Notch1 mutation.

关键词： Notch1 impaired lymphoblastic

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Proximity to corridors benefits bird communities in vegetated interrow vineyards in Mendoza, Argentina

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Avian Research 2024年第2期15卷 147-155页

作者： Andrea paula Goijman Agustín Zarco EEA La Consulta Instituto Nacional de Tecnología Agropecuaria(INTA)San CarlosMendozaArgentina Instituto Argentino de Investigacion en las Zonas Aridas(IADIZA)CONICET 5500MendozaArgentina

Management under ecological schemes and increasing habitat heterogeneity,are essential for enhancing biodiversity in *** provide several contributions to agriculture,for example pest control,recreation and enhancing human mental health,and have intrinsic *** are also ideal model organisms because they are easy to survey,and species respond differently to agricultural land use at different *** borders of crops are key for many species of birds,and distance to the border have been found to be an important factor in vineyard-dominated *** evaluate if there are differences in the bird assemblage,between the interior compared to borders within vineyards,using a hierarchical community occupancy *** hypoth-esized that occupancy of birds is greater in environments with greater heterogeneity,which in this study was considered to be contributed by the proximity to vegetated *** expected that vineyard borders close to corridors will have higher bird occupancy than the center of the *** research was conducted in three vineyards with biodiversity-friendly management practices,in Gualtallary,Mendoza,*** surveys were conducted over three breeding seasons from 2018 to *** and richness of the bird community was more closely associated with the borders adjacent to the corridors than with the interior of the vineyards,as we initially predicted,although the assemblage of birds did not differ *** than 75%of the registered species consume exclusively or partially ***-friendly management and ecological schemes,together with vegetated corridors provide multiple benefits for biodiversity *** ap-proaches not only minimize the use of agrochemicals but also prioritize soil cover with spontaneous vegetation,which supports a diverse community of insectivorous bird species,potentially contributing to pest control.

关键词： Avian Bayesian analysis Field scale agroecosystem Management Multi-species occupancy model Nature’s contributions to people

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Tracking the change in Spanish greenhouse gas emissions through an LMDI decomposition model:A global and sectoral approach

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Journal of Environmental Sciences 2024年第5期139卷 114-122页

作者： paula Fernández González María José Presno Manuel Landajo Department of Applied Economics University of OviedoAuda del Cristos/n 33011 OviedoSpain

The reduction of GHG emissions to reverse the greenhouse effect is one of the main challenges in this *** this paper we pursue two ***,we analyze the evolution of GHG emissions in Spain in 2008–2018,at both the global and sectoral levels,with the variation in emissions decomposed into a set of determining ***,we propose several actions specifically oriented to more tightly controlling the level of *** results showed a remarkable reduction(18.44%)in GHG emissions,mainly due to the intensity effect,but also to the production-per-capita *** detected somewhat different patterns among the various sectors *** the intensity effect was the most influential one in the agricultural,transport,and others sectors,the production-per-capita effect was predominant in the case of *** carbonization effect was revealed as crucial in the commerce *** above findings highlight the importance of the energy efficiency measures taken in recent years in the Spanish economy,also pointing to the need to deepen those strategies and to propose new measures that entail greater efficiency in *** efforts in areas like innovation,R&D,diffusion of more eco-friendly technologies,and a greater use of greener energies all prove to be essential reduction actions to fight the greenhouse effect.

关键词： LMDI Decomposition Spain GHG emissions

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Lax-Oleinik-Type Formulas and Efficient Algorithms for Certain High-Dimensional Optimal Control Problems

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Communications on Applied Mathematics and Computation 2024年第2期6卷 1428-1471页

作者： paula Chen Jerome Darbon Tingwei Meng Division of Applied Mathematics Brown UniversityProvidenceRIUSA Department of Mathematics UCLALos AngelesCAUSA

Two of the main challenges in optimal control are solving problems with state-dependent running costs and developing efficient numerical solvers that are computationally tractable in high *** this paper,we provide analytical solutions to certain optimal control problems whose running cost depends on the state variable and with constraints on the *** also provide Lax-Oleinik-type representation formulas for the corresponding Hamilton-Jacobi partial differential equations with state-dependent ***,we present an efficient,grid-free numerical solver based on our representation formulas,which is shown to scale linearly with the state dimension,and thus,to overcome the curse of *** existing optimization methods and the min-plus technique,we extend our numerical solvers to address more general classes of convex and nonconvex initial *** demonstrate the capabilities of our numerical solvers using implementations on a central processing unit(CPU)and a field-programmable gate array(FPGA).In several cases,our FPGA implementation obtains over a 10 times speedup compared to the CPU,which demonstrates the promising performance boosts FPGAs can *** numerical results show that our solvers have the potential to serve as a building block for solving broader classes of high-dimensional optimal control problems in real-time.

关键词： Optimal control Hamilton-Jacobi partial differential equations Grid-free numerical methods High dimensions Field-programmable gate arrays(FPGAs)

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Pathological and therapeutic effects of extracellular vesicles in neurological and neurodegenerative diseases

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Neural Regeneration Research 2024年第1期19卷 55-61页

作者： paula lzquierdo-Altarejos Victoria Moreno-Manzano Vicente Felipo Laboratory of Neurobiology Centro Investigación Príncipe FelipeValenciaSpain Neuronal and Tissue Regeneration Laboratory Centro Investigación Príncipe FelipeValenciaSpain

Extracellular vesicles are released by all cell types and contain proteins,microRNAs,mRNAs,and other bioactive *** vesicles play an important role in intercellular communication and in the modulation of the immune system and *** cargo of extra cellular vesicles(e.g.,proteins and microRNAs)is altered in pathological *** vesicles contribute to the pathogenesis of many pathologies associated with sustained inflammation and neuroinflammation,including cance r,diabetes,hype rammonemia and hepatic encephalopathy,and other neurological and neurodegenerative *** vesicles may cross the blood-brain barrier and transfer pathological signals from the periphery to the *** contributes to inducing neuroinflammation and cognitive and motor impairment in hyperammonemia and hepatic encephalopathy and in neurodegenerative *** mechanisms involved are beginning to be unde *** example,increased tumor necrosis factor a in extracellular vesicles from plasma of hype rammonemic rats induces neuroinflammation and motor impairment when injected into normal *** the mechanisms by which extracellular vesicles contribute to the pathogenesis of these diseases will help to develop new treatments and diagnostic tools for their easy and early *** contrast,extra cellular vesicles from mesenchymal stem cells have therapeutic utility in many of the above pathologies,by reducing inflammation and neuroinflammation and improving cognitive and motor *** extra cellular vesicles recapitulate the beneficial effects of mesenchymal stem cells and have advantages as therapeutic tools:they are less immunoge nic,may not diffe rentiate to malignant cells,cross the blood-brain barrier,and may reach more easily target *** vesicles from mesenchymal stem cells have beneficial effects in models of ischemic brain injury,Alzheimer's and Parkinson's diseases,hyperammonemia,and

关键词： extracellular vesicles inflammation cognitive function mesenchymal stem cells neurodegenerative diseases neuroinflammation therapy transforming growth factor-β

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The relationship between morphology and flight in Drosophila:a study of two pairs of sibling species from a natural population

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Insect Science 2024年第3期31卷 885-900页

作者： Nicolás Flaibani Victoría Estefania Ortiz Juan JoséFanara Valeria paula Carreira Laboratorio de Evolucion Departamento de EcologiaGenética y Evolucion(DEGE)Facultad de Ciencias Exactas y Naturales(FCEN)Universidad de Buenos Aires(UBA)Instituto de GenéticaEcologia y Evolucion de Buenos Aires(IEGEBA)Consejo Nacional de Investigaciones Cientificasy Tecnicas(CONICET)-UBABuenos AiresArgentina

Insect flight is a complex trait involved in different behaviors,from the search for sexual partners,food,or breeding *** studies have postulated the adaptive advantages of certain morphological traits in relation to increased flight capacity,such as low values of wing loading or high values of wing:thorax ratio and wing-aspect ***,few studies have evaluated the relationship between variables related to flight and morphological traits in *** work aimed to study morphological traits in males and females of two pairs of sibling species:Drosophila buzzati Patterson and Wheeler-Drosophila koeferae Fontdevila and Wasserman,and Drosophila melanogaster Meigen-Drosophila simulans Sturtevant,and to analyze its relationship with *** detected the highest proportion of flight time in *** and *** compared to *** and ***,*** results also revealed sexual dimorphism,with males exhibiting a higher proportion of flight time than ***,we did not find a general pattern to explain the relationship between morphology and the proportion of flight time because associations varied depending upon the analyses(considering all groups together or each sex-species combination separately).Moreover,these associations explained a low percentage of variation,suggesting that other nonmorphological components related to flight,such as physiological variables,should be taken into *** work allowed us to show the variability and complexity of an aspect of flight,suggesting that the adaptive role of the morphological traits studied might have been overestimated.

关键词： morphological traits time in flight wing loading wing:thorax ratio wingaspect ratio wing second moment of area

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Unraveling the gut-brain axis:the impact of steroid hormones and nutrition on Parkinson's disease

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Neural Regeneration Research 2024年第10期19卷 2219-2228页

作者： paula Maria Neufeld Ralf A.Nettersheim Veronika Matschke Matthias Vorgerd Sarah Stahlke Carsten Theiss Department of Cytology Institute of AnatomyMedical FacultyRuhr-University BochumBochumGermany Department of Visceral Surgery University Hospital BergmannsheilRuhr-University BochumBochumGermany Department of Neurology Heimer Institute for Muscle ResearchUniversity Hospital BergmannsheilRuhr-University BochumBochumGermany

This comprehensive review explores the intricate relationship between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the context of the gut-brain *** gut-brain axis plays a pivotal role in neurodegenerative diseases like Parkinson's disease,encompassing diverse components such as the gut microbiota,immune system,metabolism,and neural *** gut microbiome,profoundly influenced by dietary factors,emerges as a key *** during the first 1000 days of life shapes the gut microbiota composition,influencing immune responses and impacting both child development and adult ***-fat,high-sugar diets can disrupt this delicate balance,contributing to inflammation and immune *** nutritional strategies,the Mediterranean diet's anti-inflammatory and antioxidant properties show promise in reducing Parkinson's disease ***-targeted dietary approaches and the ketogenic diet hold the potential in improving brain *** nutrition,emerging research uncovers potential interactions between steroid hormones,nutrition,and Parkinson's ***,with its anti-inflammatory properties and presence in the nervous system,offers a novel option for Parkinson's disease *** ability to enhance neuroprotection within the enteric nervous system presents exciting *** review addresses the hypothesis thatα-synuclein aggregates originate from the gut and may enter the brain via the vagus *** symptoms preceding motor symptoms support this *** gut-brain signaling during gut dysbiosis contributes to inflammation and neurotransmitter imbalances,emphasizing the potential of microbiota-based *** summary,this review uncovers the complex web of interactions between nutrition,the gut microbiome,steroid hormones,and Parkinson's disease within the gut-brain axis *** these connections not only offers novel therapeutic insi

关键词： diet gut-brain axis microbiome neurodegenerative diseases nutrition Parkinson's disease progesterone steroid hormones

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Review of the Cretaceous avian diversity of Antarctica:a changing scenario for the evolution of early Neornithine birds

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Advances in Polar Science 2024年第1期35卷 1-13页

作者： Carolina ACOSTA HOSPITALECHE Facundo IRAZOQUI paula BONA Ariana PAULINA-CARABAJAL División Paleontología de Vertebrados Museo de La PlataFacultad de Ciencias Naturales y MuseoUniversidad Nacional de La PlataPaseo del Bosque s/nLa Plata B1900FWAArgentina Consejo Nacional de Investigaciones Científicas y Técnicas(CONICET) Buenos Aires C1425FQBArgentina División Paleontología Vertebrados Museo de La Plata-Anexo ⅡFacultad de Ciencias Naturales y MuseoUniversidad Nacional de La PlataCalles 122 y 60La Plata B1900FWAArgentina Instituto de Investigaciones en Biodiversidad y Medioambiente(INIBIOMA) Consejo Nacional de Investigaciones Científicas y Técnicas-Universidad Nacional del ComahueSan Carlos de Bariloche R8400GAMArgentina

The worldwide record of Cretaceous Neornithes and Neornithine-like birds is both controversial and poorly ***,in recent years,the Antarctic continent has yielded a substantial number of Maastrichtian avian specimens,contributing significantly to our understanding of the early evolution of this ***,the keen interest and collaborative efforts of various paleornithologists have resulted in a wealth of knowledge,which we have thoroughly reviewed,updated,and discussed in the context of recent discoveries.

关键词： Maastrichtian Antarctic Peninsula Vega Island Seymour(Marambio)Island Neornithes birds

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Analysis of a passive ankle exoskeleton for reduction of metabolic costs during walking

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Defence Technology（防务技术） 2024年第7期37卷 62-68页

作者： Luís Quinto Pedro Pinheiro Sergio B.Goncalves Ivo Roupa paula Simoes Miguel Tavares da Silva CINAMIL Academia MilitarInstituto Universitario MilitarLisbonPortugal IDMEC Instituto Superior TecnicoUniversidade de LisboaLisbonPortugal

Modern conflicts demand substantial physical and psychological exertion,often resulting in fatigue and diminished combat or operational *** exoskeletons have been developed recently to address these challenges,presenting various limitations that affect their operational or everyday *** article evaluates the performance of a dual-purpose passive ankle exoskeleton developed for the reduction of metabolic costs during walking,seeking to identify a force element that could be applied to the target *** on the 6-min walk test,twenty-nine subjects participated in the study using three different force *** results indicate that it is possible to reduce metabolic expenditure while using the developed ***,the comfort and range of motion results verify the exoskeleton's suitability for use in uneven terrain and during extended ***,the choice of the force element should be tailored to each user,and the control system should be adjustable to optimise the exoskeleton's performance.

关键词： Ankle passive exoskeleton Metabolic cost reduction Dual-use exoskeleton Gait Biomechanics

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