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Hypothalamic circuits and aging:keeping the circadian clock updated

Neural Regeneration Research 2024年第9期19卷 1919-1928页

作者： Rosa Vázquez-Lizarraga Lucia Mendoza-Viveros Carolina Cid-Castro Sareni Ruiz-Montoya Erick Carreño-Vázquez Ricardo Orozco-Solis Instituto Nacional de Medicina Genómica(INMEGEN) México CityMéxico centro de Investigacíon sobre el Envejecimiento Centro de Investigacíon y de Estudios Avanzados(CIE-CINVESTAV)México CityMéxico Instituto de Investigaciones Biomédicas Universidad Nacional Autónoma de México UNAMMéxico CityMéxico

Over the past century,age-related diseases,such as cancer,type-2 diabetes,obesity,and mental illness,have shown a significant increase,negatively impacting overall quality of life.Studies on aged animal models have unveiled a progressive discoordination at multiple regulatory levels,including transcriptional,translational,and post-translational processes,resulting from cellular stress and circadian derangements.The circadian clock emerges as a key regulator,sustaining physiological homeostasis and promoting healthy aging through timely molecular coordination of pivotal cellular processes,such as stem-cell function,cellular stress responses,and inter-tissue communication,which become disrupted during aging.Given the crucial role of hypothalamic circuits in regulating organismal physiology,metabolic control,sleep homeostasis,and circadian rhythms,and their dependence on these processes,strategies aimed at enhancing hypothalamic and circadian function,including pharmacological and non-pharmacological approaches,offer systemic benefits for healthy aging.Intranasal brain-directed drug administration represents a promising avenue for effectively targeting specific brain regions,like the hypothalamus,while reducing side effects associated with systemic drug delivery,thereby presenting new therapeutic possibilities for diverse age-related conditions.

关键词： aging astrocytes cellular stress responses circadian clock hypothalamus intranasal drug administration metabolic control nutrient sensor SIRT1 sleep homeostasis

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Plant cell wall-mediated disease resistance:Current understanding and future perspectives

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Molecular Plant 2024年第5期17卷 699-724页

作者： Antonio Molina Lucıa Jorda Miguel Angel Torres Marina Martın-Dacal Diego Jose Berlanga Patricia Fernandez-Calvo Elena Gomez-Rubio Sonsoles Martın-Santamarıa centro de Biotecnología y Genómica de Plantas Universidad Politécnica de Madrid(UPM)-Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria(INIA/CSIC)Campus de Montegancedo UPMPozuelo de Alarcon(Madrid)Spain departamento de Biotecnologıa-Biología Vegetal Escuela Técnica Superior de Ingenierıa AgronomicaAlimentarıa y de BiosistemasUPMMadridSpain centro de Investigaciones Biologicas Margarita Salas Consejo Superior de Investigaciones Científicas(CSIC)Ramiro de Maeztu 928040 MadridSpain Misión Biológica de Galicia Consejo Superior de Investigaciones Científicas(CSIC)Campus de Montegancedo UPMPozuelo de Alarcón(Madrid)Spain

Beyond their function as structural barriers,plant cell walls are essential elements for the adaptation of plants to environmental conditions.Cell walls are dynamic structures whose composition and integrity can be altered in response to environmental challenges and developmental cues.These wall changes are perceived by plant sensors/receptors to trigger adaptative responses during development and upon stress perception.Plant cell wall damage caused by pathogen infection,wounding,or other stresses leads to the release of wall molecules,such as carbohydrates(glycans),that function as damage-associated molecular patterns(DAMPs).DAMPs are perceived by the extracellular ectodomains(ECDs)of pattern recognition receptors(PRRs)to activate pattern-triggered immunity(PTI)and disease resistance.Similarly,glycans released from the walls and extracellular layers of microorganisms interacting with plants are recognized as microbe-associated molecular patterns(MAMPs)by specific ECD-PRRs triggering PTI responses.The number of oligosaccharides DAMPs/MAMPs identified that are perceived by plants has increased in recent years.However,the structural mechanisms underlying glycan recognition by plant PRRs remain limited.Currently,this knowledge is mainly focused on receptors of the LysM-PRR family,which are involved in the perception of various molecules,such as chitooligosaccharides from fungi and lipo-chitooligosaccharides(i.e.,Nod/MyC factors from bacteria and mycorrhiza,respectively)that trigger differential physiological responses.Nevertheless,additional families of plant PRRs have recently been implicated in oligosaccharide/polysaccharide recognition.These include receptor kinases(RKs)with leucine-rich repeat and Malectin domains in their ECDs(LRR-MAL RKs),Catharanthus roseus RECEPTOR-LIKE KINASE 1-LIKE group(CrRLK1L)with Malectin-like domains in their ECDs,as well as wall-associated kinases,lectin-RKs,and LRR-extensins.The characterization of structural basis of glycans recognition by these new plant receptors will shed light

关键词： Arabidopsis thaliana cell wall damage-associated molecular patterns DAMPs disease resistance glycans oligosaccharides pattern-triggered immunity PTl pattern recognition receptor PRRs

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Insight into endoplasmic reticulum-mitochondria contacts in human amyotrophic lateral sclerosis

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Neural Regeneration Research 2024年第7期19卷 1407-1408页

作者： Naomi Hartopp Andrea Markovinovic Christopher CJ Miller Patricia Gomez-Suaga Sheffield Institute for Translational Neuroscience University of SheffieldSheffieldUK department of Basic and Clinical Neuroscience Institute of PsychiatryPsychology and NeuroscienceLondonUK Universidad de Extremadura.departamento de Bioquímica y Biología Molecular y Genética Facultad de Enfermería y Terapia OcupacionalCáceresSpain centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas-Instituto de Salud Carlos Ⅲ(CIBER-CIBERNED-ISCⅢ) MadridSpain Instituto Universitario de Investigación Biosanitaria de Extremadura(INUBE) CáceresSpain

Amyotrophic lateral sclerosis(ALS) is a fastprogressing fatal neurodegenerative disease and the most common form of motor neuron disease.There is currently no cure and approximately 90% of cases are sporadic.ALS shares genetic causes,clinical and neuropathological features with frontotemporal dementia,the second most common form of presenile dementia.ALS and frontotemporal dementia are therefore considered a disease spectrum(Abramzon et al.,2020).

关键词： senile sclerosis

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Blockade of Rho-associated kinase prevents inhibition of axon regeneration of peripheral nerves induced by anti-ganglioside antibodies

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Neural Regeneration Research 2024年第4期19卷 895-899页

作者： Andrés Berardo Cristian R.Bacaglio Bárbara B.Báez Rubén Sambuelli Kazim A.Sheikh Pablo H.H.Lopez Laboratorio de Neurobiología Instituto de Investigación Médica Mercedes y Martin Ferreyra(INIMEC)-Consejo Nacional de Investigaciones Cientificas y Técnicas(CONICET)Universidad Nacional de Córdoba departamento de Química Biológica-centro de Investigaciones en Química Biológica de Córdoba(CIQUIBIC)-Consejo Nacional de Investigaciones Cientificas y Técnicas(CONICET) Facultad de Cs.QuímicasUniversidad Nacional de Córdoba Servicio de Anatomía Patológica Clínica Universitaria Reina FabiolaUniversidad Católica de Córdoba department of Neurology University of Texas Medical School at Houston

Anti-ganglioside antibodies are associated with delayed/poor clinical recovery in Guillain-Barrèsyndrome,mostly related to halted axon regeneration.Cross-linking of cell surface gangliosides by anti-ganglioside antibodies triggers inhibition of nerve repair in in vitro and in vivo paradigms of axon regeneration.These effects involve the activation of the small GTPase Rho A/ROCK signaling pathways,which negatively modulate growth cone cytoskeleton,similarly to well stablished inhibitors of axon regeneration described so far.The aim of this work was to perform a proof of concept study to demonstrate the effectiveness of y-27632,a selective pharmacological inhibitor of ROCK,in a mouse model of axon regeneration of peripheral nerves,where the passive immunization with a monoclonal antibody targeting gangliosides GD1a and GT1b was previously reported to exert a potent inhibitory effect on regeneration of both myelinated and unmyelinated fibers.Our results demonstrate a differential sensitivity of myelinated and unmyelinated axons to the pro-regenerative effect of y-27632.Treatment with a total dosage of 9 mg/kg of y-27632 resulted in a complete prevention of anti-GD1a/GT1b monoclonal antibody-mediated inhibition of axon regeneration of unmyelinated fibers to skin and the functional recovery of mechanical cutaneous sensitivity.In contrast,the same dose showed toxic effects on the regeneration of myelinated fibers.Interestingly,scale down of the dosage of y-27632 to 5 mg/kg resulted in a significant although not complete recovery of regenerated myelinated axons exposed to anti-GD1a/GT1b monoclonal antibody in the absence of toxicity in animals exposed to only y-27632.Overall,these findings confirm the in vivo participation of Rho A/ROCK signaling pathways in the molecular mechanisms associated with the inhibition of axon regeneration induced by anti-GD1a/GT1b monoclonal antibody.Our findings open the possibility of therapeutic pharmacological intervention targeting Rho A/Rock pathway in immune neuropathies associated wi

关键词： anti-ganglioside antibodies anti-glycan antibodies axon regeneration ganglioside Guillain-Barrésyndrome nerve repair ROCK y-27632

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Differential Expression of Genes Related to Fruit development and Capsaicinoids Synthesis in Habanero Pepper Plants Grown in Contrasting Soil Types

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Phyton-International Journal of Experimental Botany 2024年第2期93卷 151-183页

作者： Eduardo Burgos-Valencia Federico García-Laynes Ileana Echevarría-Machado Fatima Medina-Lara Miriam Monforte-González JoséNarváez-Zapata Manuel Martínez-Estévez Unidad de Bioquímica y Biología Molecular de Plantas Centro de Investigación Científica de YucatánCalle 43#130Chuburnáde HidalgoMéridaYucatán97205México Instituto Politécnico Nacional-centro de Biotecnología Genómica Blvd Del Maestro esq.Elias PiñaReynosaTamaulipas88710México

Habanero pepper(Capsicum chinense Jacq.)is a crop of economic relevance in the Peninsula of yucatan.Its fruits have a high level of capsaicinoids compared to peppers grown in other regions of the world,which gives them industrial importance.Soil is an important factor that affects pepper development,nutritional quality,and capsaicinoid content.However,the effect of soil type on fruit development and capsaicinoid metabolism has been little understood.This work aimed to compare the effect of soils with contrasting characteristics,black soil(BS)and red soil(RS),on the expression of genes related to the development of fruits,and capsaicinoid synthesis using a transcriptomic analysis of the habanero pepper fruits.Plants growing in RS had bigger fruits and higher expression of genes related to floral development,fruit abscission,and softening which suggests that RS stimulates fruit development from early stages until maturation stages.Fruits from plants growing in BS had enrichment in metabolic pathways related to growth,sugars,and photosynthesis.Besides,these fruits had higher capsaicinoid accumulation at 25 days post-anthesis,and higher expression of genes related to the branched-chain amino acids metabolism(ketol-acid reductisomerase KARI),pentose phosphate pathway and production of NADPH(glucose-6-phosphate-1-dehydrogenase G6PDH),and proteasome and vesicular traffic in cells(26S proteasome regulatory subunit T4 RPT4),which suggest that BS is better in the early stimulation of pathways related to the nutritional quality and capsaicinoid metabolism in the fruits.

关键词： Capsicum chinense jacq soil types plant growth environmental conditions fruit quality capsaicinoid metabolism transcriptome

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Exploring multifaceted factors in chronic kidney disease risk: A comprehensive analysis of biochemistry, lifestyle, and inflammation in elderly Chinese individuals

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World Journal of Clinical Cases 2024年第5期12卷 1033-1035页

作者： Fernando Cardona Unitat de Genètica Molecular Instituto de Biomedicina de Valencia–CSICValencia 46010Spain centro de investigación Biomédica en Red Enfermedades Neurodegenerativas(CIBERNED) Instituto de Salud Carlos IIIMadrid 28029Spain departamento de Biotecnología Escuela Técnica Superior de Ingeniería Agronómica y del Medio Natural(ETSIAMN)Univeristat Politècnica de ValenciaValencia 46022Spain

This letter praises a recent article in the World Journal of Clinical Cases(Roles of biochemistry data,lifestyle,and inflammation in identifying abnormal renal function in old Chinese),examining factors affecting abnormal renal function in elderly Chinese using advanced machine learning.It highlights the importance of uric acid,age,hemoglobin,body mass index,sport hours,and systolic blood pressure.The study's holistic approach,integrating lifestyle and inflammation,offers a nuanced understanding of chronic kidney disease risk factors.The letter suggests exploring mechanistic pathways of hyperuricemia,the link between anemia and renal function,and the connection between body mass index and estimated glomerular filtration rate.It advocates investigating physical activity's impact on renal health and the independent effects of blood pressure.The study significantly contributes to chronic kidney disease understanding,proposing avenues for further exploration and interventions.Commendations are extended to the authors and the journal.

关键词： Biochemistry data Lifestyle Machine learning Renal function

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Unilateral rNurr1-V5 transgene expression in nigral dopaminergic neurons mitigates bilateral neuropathology and behavioral deficits in parkinsonian rats withα-synucleinopathy

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Neural Regeneration Research 2024年第9期19卷 2057-2067页

作者： Bismark Gatica-Garcia Michael J.Bannon Irma Alicia Martínez-Dávila Luis O.Soto-Rojas David Reyes-Corona Lourdes Escobedo Minerva Maldonado-Berny ME Gutierrez-Castillo Armando J.Espadas-Alvarez Manuel A.Fernandez-Parrilla Juan U.Mascotte-Cruz CP Rodríguez-Oviedo Irais E.Valenzuela-Arzeta Claudia Luna-Herrera Francisco E.Lopez-Salas Jaime Santoyo-Salazar Daniel Martinez-Fong departamento de Fisiología Biofísica y NeurocienciasCentro de Investigación y de Estudios AvanzadosCiudad de MéxicoMéxico department of Pharmacology Wayne State University School of MedicineDetroitMIUSA Laboratorio de Patogénesis Molecular Carrera Médico CirujanoFacultad de Estudios Superiores IztacalaUniversidad Nacional Autónoma de MéxicoTlalnepantla de BazMéxico Red de Medicina para la Educación y desarrollo y la Investigación Científica de Iztacala(Red MEDICI) Carrera Médico CirujanoFacultad de Estudios Superiores IztacalaUniversidad Nacional Autónoma de MéxicoTlalnepantla de BazMéxico Nanoparticle Therapy Institute AguascalientesMéxico departamento de Biociencias e Ingeniería Centro Interdisciplinario de Investigaciones y Estudios sobre Medio Ambiente y DesarrolloInstituto Politécnico NacionalCiudad de MéxicoMéxico Escuela Nacional de Medicina y Homeopatía Instituto Politécnico NacionalCiudad de MéxicoMéxico departamento de Fisiología Escuela Nacional de Ciencias BiológicasInstituto Politécnico NacionalCiudad de MéxicoMéxico departamento de Biología Molecular y Biotecnología Instituto de Investigaciones BiomédicasUniversidad Nacional Autónoma de MéxicoCiudad de MéxicoMéxico departamento de Física Centro de Investigación y de Estudios AvanzadosCiudad de MéxicoMéxico Programa de Nanociencias y Nanotecnología Centro de Investigación y de Estudios AvanzadosCiudad de MéxicoMéxico

Parkinsonism by unilateral,intranigralβ-sitosterolβ-D-glucoside administration in rats is distinguished in that theα-synuclein insult begins unilaterally but spreads bilaterally and increases in severity over time,thus replicating several clinical features of Parkinson’s disease,a typicalα-synucleinopathy.As Nurr1 repressesα-synuclein,we evaluated whether unilateral transfected of rNurr1-V5 transgene via neurotensin-polyplex to the substantia nigra on day 30 after unilateralβ-sitosterolβ-D-glucoside lesion could affect bilateral neuropathology and sensorimotor deficits on day 30 post-transfection.This study found that rNurr1-V5 expression but not that of the green fluorescent protein(the negative control)reducedβ-sitosterolβ-D-glucoside-induced neuropathology.Accordingly,a bilateral increase in tyrosine hydroxylase-positive cells and arborization occurred in the substantia nigra and increased tyrosine hydroxylase-positive ramifications in the striatum.In addition,tyrosine hydroxylase-positive cells displayed less senescence markerβ-galactosidase and more neuron-cytoskeleton markerβIII-tubulin and brain-derived neurotrophic factor.A significant decrease in activated microglia(positive to ionized calcium-binding adaptor molecule 1)and neurotoxic astrocytes(positive to glial fibrillary acidic protein and complement component 3)and increased neurotrophic astrocytes(positive to glial fibrillary acidic protein and S100 calcium-binding protein A10)also occurred in the substantia nigra.These effects followed the bilateral reduction inα-synuclein aggregates in the nigrostriatal system,improving sensorimotor behavior.Our results show that unilateral rNurr1-V5 transgene expression in nigral dopaminergic neurons mitigates bilateral neurodegeneration(senescence and loss of neuron-cytoskeleton and tyrosine hydroxylase-positive cells),neuroinflammation(activated microglia,neurotoxic astrocytes),α-synuclein aggregation,and sensorimotor deficits.Increased neurotrophic astrocytes and brain-derived neurotrophic factor can mediate t

关键词： A1 astrocytes A2 astrocytes gene therapy microglia motor deficits nanoparticles neurodegeneration neuroinflammation senescence α-synuclein aggregates

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The impact of maternal immune activation on the morphology and electrophysiological properties of postnatally-born neurons in the offspring

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Neural Regeneration Research 2024年第2期19卷 399-400页

作者： Emilio J.Galván Angelica Zepeda departamento de Farmacobiología CINVESTAV Unidad Sur CdMxMéxico、Centro de Investigaciones sobre el EnvejecimientoCIE-CinvestavCdMxMéxico departamento de Medicina Genómica y Toxicología Ambiental Instituto de Investigaciones BiomédicasUniversidad Nacional Autónoma de MéxicoUNAMCdMxMéxico

Pregnancy comes with a combination of physical changes and physiological immunosuppression that increases the susceptibility of women to pathogens and in turn,rises the prevalence of infectious diseases.

关键词： prevalence activation impact

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Gustatory responsiveness in Vespula germanica workers:exploring the interplay between sensory perception and task specialization

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Insect Science 2024年第2期31卷 587-598页

作者： Analia Mattiacci Carolina Mengoni Gonalons MaitéMasciocchi Juan C.Corley Grupo de Ecologia de Poblaciones de Insectos IFAB(CONICETINTA EEA Bariloche)BarilocheArgentina departamento de Ecologia Centro Regional Universitario BarilocheUniversidad Nacional Del ComahueBarilocheArgentina departamento de Biodiversidad y Biologia Experimental Facultad de Ciencias Exactas y NaturalesUniversidad de Buenos AiresBuenos AiresArgentina

Workers'task specialization and division of labor are critical features of social insects'ecological success.It has been proposed that the division of labor relies on response threshold models:individuals varying their sensitivity(and responsiveness)to biologically relevant stimuli and performing a specific task when a stimulus exceeds an internal threshold.In this work,we study carbohydrate and protein responsiveness and their relation to worker task specialization in Vespula germanica,an invasive social wasp.The sucrose and peptone responsiveness of two different subcastes,preforagers and foragers,was determined by stimulating the antenna of the wasps with increasing concentrations of the solution and quantifying whether each concentration elicited a licking response.We studied responsiveness in five different ways:(1)response threshold,(2)concentration 50(concentration to which at least 50%of wasps responded),(3)maximum response,(4)mean scores and(5)median scores.Our results suggest that V germanica foragers are more sensitive to sucrose(lower thresholds)than preforager workers.However,we found no differences for peptone thresholds(i.e.,a protein resource).Nonetheless,this is the first study to investigate response thresholds for protein resources.The intercaste variation in sucrose responsiveness shown in our work contributes to the existing knowledge about response threshold theory as a mechanism for task specialization observed in V germanica.

关键词： carbohydrates responsiveness division of labor protein responsiveness response thresholds models social insect yellow jacket

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genomic selection in plant breeding:Key factors shaping two decades of progress

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Molecular Plant 2024年第4期17卷 552-578页

作者： Admas Alemu Johanna Astrand Osval A.Montesinos-López Julio Isidro y Sanchez Javier Fernandez-Gónzalez Wuletaw Tadesse Ramesh R.Vetukuri Anders S.Carlsson Alf Ceplitis JoséCrossa Rodomiro Ortiz Aakash Chawade department of Plant Breeding Swedish University of Agricultural SciencesAlnarpSweden Lantmannen Lantbruk SvalövSweden Facultad de Telematica University de ColimaColimaColima 28040Mexico centro de Biotecnología y Genómica de Plantas(CBGP UPM-INIA)Universidad Politécnica de Madrid(UPM)-Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria(INIA)Campus de Montegancedo-UPM28223 MadridSpain International Center for Agricultural Research in the Dry Areas(ICARDA) RabatMorocco International Maize and Wheat Improvement Center(CIMMyT) Km 45Carretera México-VeracruzTexcocoMéxico 52640Mexico

genomic selection,the application of genomic prediction(GP)models to select candidate individuals,has significantly advanced in the past two decades,effectively accelerating genetic gains in plant breeding.This article provides a holistic overview of key factors that have influenced GP in plant breeding during this period.We delved into the pivotal roles of training population size and genetic diversity,and their relationship with the breeding population,in determining GP accuracy.Special emphasis was placed on optimizing training population size.We explored its benefits and the associated diminishing returns beyond an optimum size.This was done while considering the balance between resource allocation and maximizing prediction accuracy through current optimization algorithms.The density and distribution of single-nucleotide polymorphisms,level of linkage disequilibrium,genetic complexity,trait heritability,statistical machine-learning methods,and non-additive effects are the other vital factors.Using wheat,maize,and potato as examples,we summarize the effect of these factors on the accuracy of GP for various traits.The search for high accuracy in GP—theoretically reaching one when using the Pearson’s correlation as a metric—is an active research area as yet far from optimal for various traits.We hypothesize that with ultra-high sizes of genotypic and phenotypic datasets,effective training population optimization methods and support from other omics approaches(transcriptomics,metabolomics and proteomics)coupled with deep-learning algorithms could overcome the boundaries of current limitations to achieve the highest possible prediction accuracy,making genomic selection an effective tool in plant breeding.

关键词： genomic selection genetic gain genomic prediction optimization deep learning training population optimization

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