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Hypothalamic circuits and aging:keeping the circadian clock updated

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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

Single atom Cu-n-C catalysts for the electro-reduction of CO_(2) to CO assessed by rotating ring-disc electrode

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Journal of Energy Chemistry 2024年第1期88卷 169-182,I0004页

作者： S.Pérez-Rodríguez M.Gutiérrez-Roa C.Giménez-Rubio D.Ríos-Ruiz P.Arévalo-cid M.V.Martínez-Huerta A.Zitolo M.J.Lázaro D.Sebastián Instituto de Carboquímica(CSIC) Miguel Luesma Castán 450018 ZaragozaSpain Instituto de Catálisis y Petroleoquímica(CSIC) Marie Curie 228049 MadridSpain Synchrotron SOLEIL L’Orme des MerisiersDépartementale 12891190France

The electrochemical CO_(2) reduction reaction(CO_(2)RR) to controllable chemicals is considered as a promising pathway to store intermittent renewable energy. Herein, a set of catalysts based on copper-nitrogendoped carbon xerogel(Cu-n-C) are successfully developed varying the copper amount and the nature of the copper precursor, for the efficient CO_(2)RR. The electrocatalytic performance of Cu-n-C materials is assessed by a rotating ring-disc electrode(RRDE), technique still rarely explored for CO_(2)RR. For comparison, products are also characterized by online gas chromatography in a H-cell. The as-synthesized Cu-nC catalysts are found to be active and highly CO selective at low overpotentials(from -0.6 to -0.8 V vs.RHE) in 0.1 M KHCO_(3), while H_(2) from the competitive water reduction appears at larger overpotentials(-0.9 V vs. RHE). The optimum copper acetate-derived catalyst containing Cu-n_(4) moieties exhibits a CO_(2)-to-CO turnover frequency of 997 h^(-1) at -0.9 V vs. RHE with a H_(2)/CO ratio of 1.8. These results demonstrate that RRDE configuration can be used as a feasible approach for identifying electrolysis products from CO_(2)RR.

关键词： Cu-n-C Carbon xerogel Rotating ring disc electrode Carbon dioxide reduction reaction Carbon monoxide

The computerized LASSI-BC Test versus the Standard LASSI-L Paper-and-Pencil Version in Community-Based-Samples

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Advances in Alzheimer's Disease 2024年第1期13卷 11-25页

作者： Rosie E. Curiel cid Alexandra Ortega Ubbo Visser Marcela Kitaigorodsky D. Diane Zheng Diana Hincapie Kirsten Horne Crenshaw Ashleigh Beaulieu Brooke Bosworth Liz Gallardo Emory neer Sofia Ramirez Elizabeth A. Crocco Mike Georgiou Efrosyni Sfakianaki David A. Loewenstein Center for Cognitive neuroscience and Aging and Department of Psychiatry and Behavioral Sciences Miller School of Medicine University of Miami Miami FL USA Department of Computer Sciences University of Miami Coral Gables FL USA nova Southeastern University Fort Lauderdale FL USA Department of Radiology and nuclear Medicine Miller School of Medicine University of Miami Miami FL USA

Proactive Semantic Interference (PSI) and failure to recover from PSI (frPSI), are novel constructs assessed by the LASSI-L. These measures are sensitive to cognitive changes in early Mild Cognitive Impairment (MCI) and preclinical AD determined by Aβ load using PET. The goal of this study was to compare a new computerized version of the LASSI-L (LASSI-Brief Computerized) to the standard paper-and-pencil version of the test. In this study, we examined 110 cognitively unimpaired (CU) older adults and 79 with amnestic MCI (aMCI) who were administered the paper-and-pencil form of the LASSI-L. Their performance was compared with 62 CU older adults and 52 aMCI participants examined using the LASSI-BC. After adjustment for covariates (degree of initial learning, sex, education, and language of evaluation) both the standard and computerized versions distinguished between aMCI and CU participants. The performance of CU and aMCI groups using either form was relatively commensurate. Importantly, an optimal combination of Cued B2 recall and Cued B1 intrusions on the LASSI-BC yielded an area under the ROC curve of .927, a sensitivity of 92.3% and specificity of 88.1%, relative to an area under the ROC curve of .815, a sensitivity of 72.5%, and a specificity of 79.1% obtained for the paper-and-pencil LASSI-L. Overall, the LASSI-BC was comparable, and in some ways, superior to the paper-and-pencil LASSI-L. Advantages of the LASSI-BC include a more standardized administration, suitability for remote assessment, and an automated scoring mechanism that can be verified by a built-in audio recording of responses.

关键词： Mild Cognitive Impairment Proactive Semantic Interference LASSI-L Computerized Cognitive Assessment

Intertwined leukocyte balances in tumours and peripheral blood as robust predictors of right and left colorectal cancer survival

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World Journal of Gastrointestinal Oncology 2022年第1期14卷 295-318页

作者： Ramón Cantero-cid Karla Marina Montalbán-Hernández Jenny Guevara Alejandro Pascual-Iglesias Elisa Pulido JoséCarlos Casalvilla Cristóbal Marcano Cristina Barragán Serrano Jaime Valentín Gloria Cristina Bonel-Pérez JoséAvendaño-Ortiz Verónica Terrón Roberto Lozano-Rodríguez Alejandro Martín-Quirós Elvira Marín Eva Pena Laura Guerra-Pastrián Eduardo López-Collazo Luis Augusto Aguirre Tumor Immunology Laboratory The Innate Immune Response GroupHospital La Paz Institute for Health Research(IdiPAZ)Madrid 28046Spain Digestive Surgery Service La Paz University HospitalMadrid 28046Spain Emergency Department and Emergent Pathology Research Group Hospital La Paz Institute for Health Research(IdiPAZ)Madrid 28046Spain Pathologic Anatomy Service Hospital La PazMadrid 28046Spain

BACKGROUnD Colorectal cancer(CRC)accounts for 9.4%of overall cancer deaths,ranking second after lung cancer.Despite the large number of factors tested to predict their outcome,most patients with similar variables show big differences in survival.Moreover,right-sided CRC(RCRC)and left-sided CRC(LCRC)patients exhibit large differences in outcome after surgical intervention as assessed by preoperative blood leukocyte status.We hypothesised that stronger indexes than circulating(blood)leukocyte ratios to predict RCRC and LCRC patient outcomes will result from combining both circulating and infiltrated(tumour/peritumour fixed tissues)concentrations of leukocytes.AIM To seek variables involving leukocyte balances in peripheral blood and tumour tissues and to predict the outcome of CRC patients.METHODS Sixty-five patients diagnosed with colon adenocarcinoma by the Digestive Surgery Service of the La Paz University Hospital(Madrid,Spain)were enrolled in this study:43 with RCRC and 22 with LCRC.Patients were followed-up from January 2017 to March 2021 to record overall survival(OS)and recurrence-free survival(RFS)after surgical interventions.Leukocyte concentrations in peripheral blood were determined by routine laboratory protocols.Paraffin-fixed samples of tumour and peritumoural tissues were assessed for leukocyte concentrations by immunohistochemical detection of CD4,CD8,and CD14 marker expression.Ratios of leukocyte concentration in blood and tissues were calculated and evaluated for their predictor values for OS and RFS with Spearman correlations and Cox univariate and multivariate proportional hazards regression,followed by the calculation of the receiver-operating characteristic and area under the curve(AUC)and the determination of Youden’s optimal cutoff values for those variables that significantly correlated with either RCRC or LCRC patient outcomes.RCRC patients from the cohort were randomly assigned to modelling and validation sets,and clinician-friendly nomograms were developed to predict OS and RFS from the

关键词： Left colorectal cancer Leukocyte ratios Prognostic variables Recurrence-free survival Right colorectal cancer Overall survival

Costimulatory molecule programmed death-1 in the cytotoxic response during chronic hepatitis C

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World Journal of Gastroenterology 2009年第41期15卷 5129-5140页

作者： Juan Ramón Larrubia Selma Benito-Martínez Joaquín Miquel Miryam Calvino Eduardo Sanz-de-Villalobos Trinidad Parra-cid Translational Hepatology Unit Guadalajara University Hospital University of Alcalá

Hepatitis C virus (HCV)-specific CD8+ T cells play an important role in the resolution of HCV infection. nevertheless, during chronic hepatitis C these cells lack their effector functions and fail to control the virus. HCV has developed several mechanisms to escape immune control. One of these strategies is the upregulation of negative co-stimulatory molecules such us programmed death-1 (PD-1). This molecule is upregulated on intrahepatic and peripheral HCV-specific cytotoxic T cells during acute and chronic phases of the disease, whereas PD-1 expression is low in resolved infection. PD-1 expressing HCV-specific CD8+ T cells are exhausted with impairment of several effector mechanisms, such as: type-1 cytokine production, expansion ability after antigen encounter and cytotoxic ability. However, PD-1 associated exhaustion can be restored by blocking the interaction between PD-1 and its ligand (PD-L1). After this blockade, HCV-specificCD8+ T cells reacquire their functionality. nevertheless, functional restoration depends on PD-1 expression level. High PD-1-expressing intrahepatic HCV-specific CD8+ T cells do not restore their effector abilities after PD-1/PD-L1 blockade. The mechanisms by which HCV is able to induce PD-1 up-regulation to escape immune control are unknown. Persistent TCR stimulation by a high level of HCV antigens could favour early PD-1 induction, but the interaction between HCV core protein and gC1q receptor could also participate in this process. The PD-1/PD-L1 pathway modulation could be a therapeutic strategy, in conjunction with the regulation of others co-stimulatory pathways, in order to restore immune response against HCV to succeed in clearing the infection.

关键词：共刺激分子程序化死亡丙型肝炎毒性反应慢性细胞

ThMn12-Type Alloys for Permanent Magnets

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Engineering 2020年第2期6卷 141-147页

作者： G.C.Hadjipanayis A.M.Gabay A.M.Schonhobel A.Martin-cid J.M.Barandiaran D.niarchos Department of Physics and Astronomy University of DelawareNewarkDE 19716USA BCMaterials Leioa 48940Spain nCSR Demokritos Agia Paraskevi 15341Greece

Iron-rich compounds with the tetragonal ThMn12-type structure have the potential to meet current demands for rare-earth-lean permanent magnets with high energy density and operating temperatures of 150-200℃.However,while it is normal for magnet technology to lag behind the development of underlying magnetic material,this gap has always been unusually large for ThMn12-type magnets.The gap has widened further in recent years,as excellent combinations of intrinsic magnetic properties have been obtained in compounds synthesized with a smaller amount of structure-stabilizing elements(e.g.,SmFe11V or Sm0.8Zr0.2Fe9.2Co2.3Ti0.5)or with no such elements(i.e.,SmFe9.6Co2.4 thin films).The search for promising compounds continues-with increasing help coming from theoretical calculations.Unfortunately,progress in the development of magnets beyond polymer-bonded interstitially modified powders remains marginal.The introduction of lanthanum(La)was found to stabilize low-meltingtemperature minority phases in Sm(Fe,Ti)12 alloys,thus allowing for liquid-phase sintering for the first time.The high reactivity of La,however,has apparently undermined the development of coercivity(Hc).A controlled crystallization of the initially suppressed ThMn12-type phase makes"bulk"magnetic hardening possible,not only in Sm-Fe-V alloys(in which it has been known since the 1990s),but also is in La-added(Ce,Sm)(Fe,Ti)12 alloys.The properties of the bulk-hardened alloys,however,remain unsatisfactory.Mechanochemically synthesized(Sm,Zr)(Fe,Si)12 and(Sm,Zr)(Fe,Co,Ti)12 powders may become suitable for sintering into powerful fully dense magnets,although not before a higher degree of anisotropy in both alloys and a higher Hc in the latter alloy have been developed.

关键词： Permanent magnets Rare earths permanent magnets ThMn12 structure

Tree encroachment into savannas alters soil microbiological and chemical properties facilitating forest expansion

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Journal of Forestry Research 2016年第5期27卷 1047-1054页

作者： Davi Rodrigo Rossatto Everlon cid Rigobelo Departamento de Biologia Faculdade de Ciencias Agrairias e veterinàrias Univ. Estadual Paulista UNESP Via de Acesso Prof. Paulo Donatto Castellane S/N Vila IndustrialJaboticabal - SP 14884-900 Brazil Departamento de Producao Vegetal Faculdade de Ciencias Agrairias e Veterinarias Univ. Estadual Paulista UNESP Viade Acesso Prof. Paulo Donatto Castellane S/N VilaIndustrial Jaboticabal - SP 14884-900 Brazil

Abstract Forests have been expanding over typical savanna sites for the past 3000 years in the neotropics. Such invasion can produce a series of environmental modifications on typical savanna; however, it remains unclear how modifications in soil properties, caused by the encroachment of woody species, facilitate the expansion of forest ecosystems under dystrophic conditions. Here we examined chemical and microbiological changes associ- ated with tree encroachment in oxisols of a neotropical Savanna at Assis Ecological Station, Southeastern Brazil. We predicted that tree encroachment caused by typical forest species would cause significant changes in the chemical and microbiological properties of savanna soils. Soils were sampled at Assis Ecological Station, from savanna sites differing in tree encroachment （typical, dense and forested savanna） caused by decades of fire exclusion. We analysed vegetation leaf area index and leaf litter volume deposited in the studied plots and chemical （pH,organic matter, P, K, Ca, Mg, A1, nO3-, nH4＋） and microbiological （microbial C biomass and dehydrogenase activity） properties of soils under distinct encroachment conditions. Most soil chemical properties did not change along the tree encroachment gradient; however, total P, soil organic matter, soil microbial C and dehydrogenase activity increased from typical savanna to forested savanna. The changes in soil organic matter and dehydrogenase activity were correlated with the values of leaf area index and litter volume along the encroachment gradient. Our results demonstrate that forest species can increase carbon and phosphorus supplies in tropical savanna soils.

关键词： Dystrophic Encroachment - Forest - Litter Microbiological activity

Alpha2-adrenergic receptor activation reinstates motor deficits in rats recovering from cortical injury

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neural Regeneration Research 2023年第4期18卷 875-880页

作者： Gabriela García-Díaz Laura ERamos-Languren Carmen Parra-cid Joel Lomelí Sergio Montes Camilo Ríos Antonio Bueno-nava Ignacio Valencia-Hernández Rigoberto González-Piña Department of Pharmacology Section of Postgraduate Studies and ResearchHigh Medical SchoolInstituto Politécnico NacionalSalvador Díaz MirónAlcaldía Miguel HidalgoMexico CityMexico Department of neurobiology of Aging and Brain Damage Coordination of Psychobiology and NeurosciencesFaculty of PsychologyNational Autonomous University of MexicoAv.Universidad 3040Col.Copilco UniversidadAlcaldía CoyoacánMexico CityMexico Direction of Research National Institute of Rehabilitation LGIICalz.Mexico-Xochimilco 289Col.Arenal de GuadalupeAlcaldía TlalpanMexico CityMexico Department of Pharmacology Multidisciplinary Academic Unit Reynosa-Aztlan ReynosaAutonomous University of Tamaulipascalle 16 y lago de ChapalaCol.AztlánTamaulipasMexico Department of neurochemistry National Institute of Neurology and Neurosurgery MVSAv.Insurgentes Sur 3877Col.La FamaAlcaldia TlalpanMexico CityMexico Department of Special Education University of the AmericasPuebla 223Col.RomaAlcaldía CuauhtémocMexico CityMexico

norepinephrine plays an important role in motor functional recovery after a brain injury caused by ferrous chloride.Inhibition of norepinephrine release by clonidine is correlated with motor deficits after motor cortex injury.The aim of this study was to analyze the role ofα-adrenergic receptors in the restoration of motor deficits in recovering rats after brain damage.The rats were randomly assigned to the sham and injury groups and then treated with the following pharmacological agents at 3 hours before and 8 hours,3 days,and 20 days after ferrous chloride-induced cortical injury:saline,clonidine,efaroxan(a selective antagonist ofα-adrenergic receptors)and clonidine+efaroxan.The sensorimotor score,the immunohistochemical staining forα-adrenergic receptors,and norepinephrine levels were evaluated.Eight hours post-injury,the sensorimotor score and norepinephrine levels in the locus coeruleus of the injured rats decreased,and these effects were maintained 3 days post-injury.However,20 days later,clonidine administration diminished norepinephrine levels in the pons compared with the sham group.This effect was accompanied by sensorimotor deficits.These effects were blocked by efaroxan.In conclusion,an increase inα-adrenergic receptor levels was observed after injury.Clonidine restores motor deficits in rats recovering from cortical injury,an effect that was prevented by efaroxan.The underlying mechanisms involve the stimulation of hypersensitiveα-adrenergic receptors and inhibition of norepinephrine activity in the locus coeruleus.The results of this study suggest thatαreceptor agonists might restore deficits or impede rehabilitation in patients with brain injury,and therefore pharmacological therapies need to be prescribed cautiously to these patients.

关键词： alpha2-adrenoceptors ambulatory behavior clonidine cortical injury efaroxan functional recovery immunohistochemistry motor deficit norepinephrine sensorimotor score

Daily expression of sodium-dependent glucose cotransporter-1protein in jejunum during rat ontogeny

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Animal nutrition 2019年第3期5卷 290-296页

作者： Juan I.Baston Fabricio D.cid Enrique Caviedes-Vidal Juan G.Chediack Laboratorio de Fisiopatología Endometrial Instituto de Biología y Medicina Experimental(IByME)CONICETCiudad Autoonoma de Buenos AiresC1428ADNArgentina Laboratorio de Biología Integrativa“Prof.E.Caviedes Codelia” Facultad de QuímicaBioquímica y FarmaciaUniversidad Nacional de San LuisSan LuisD5700HHWArgentina Instituto Multidisciplinario de Investigaciones en Biología-San Luis(IMIBIO-SL CCT-SL)CONICETSan Luis D5700HHWArgentina

It is widely known that intestinal capacities such as the enzymatic hydrolysis of carbohydrates,lipids and proteins,and the subsequent absorption of the hydrolyzed products.are evolutionary matched to dietary loads and feeding behaviors.In this study,we demonstrate that the protein expression of apically located sodium-dependent glucose cotransporter-1(SGLT-1)throughout rat ontogeny is daily adjusted to afford glucose uptake when the load of this metabolically essential monosaccharide in the intestinal lumen is maximum.The jejunal expression of SGLT-1 protein in 14 one-day-old suckling pups was found to increase at dark and early light phase(Pn they have a better access to mother milk.In weaning21-d-old and juvenile 28-d-old rats,the cotransporter expression was high throughout the entire day(Pnally,adult 90-d-old rats showed a well-developed circadian rhythm for SGLT-1 protein(Pn increased at late light and dark phase when the highest intestinal glucose load was achieved.To our knowledge,these results are the first reporting the daily profile of SGLT-1 expression during rat early developmental stage and may contribute to understand the biological significance of a well-established molecular capacity to deal with the crucial increase of glucose load in the diet during the weaning process.

关键词： Intestinal SGLT-1 Protein expression Daily rhythms Ontogeny Rat