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Alpha-1 antitrypsin deficiency and pi*z allele as important co-factors in the development of liver fibrosis

World Journal of Hepatology 2024年第8期16卷 1099-1110页

作者： Ana isabel Ferreira Catarina Guimarães Vitor Macedo Silva Sofia Xavier Joana Magalhães JoséCotter Department of Gastroenterology Hospital da Senhora da Oliveira-GuimarãesGuimarães 4835-044Portugal life and Health Sciences Research Institute School of MedicineUniversity of MinhoBraga 4710-057Portugal life and Health Sciences Research Institute/3B’s PT Government Associate LaboratoryBraga 4710-057Portugal Department of pulmonology Hospital Senhora da Oliveira-GuimarãesGuimarães 4835-044Portugal

BACKGROUND Alpha-1 antitrypsin deficiency(AATD)is a codominant autosomal hereditary condition that predisposes patients to the development of lung and/or liver disease,and pi*z allele is the most clinically relevant *** To evaluate the impact of clinical parameters and AATD phenotypes,particularly the pi*z allele,in liver *** Cross-sectional cohort study including consecutive patients with AATD followed in pulmonology or Hepatology *** Included 69 patients,49.3%had pi*Mz phenotype and 10.1%pi**** age≥55 years,age at diagnosis≥41 years and AAT at diagnosisl predicted a nonalcoholic fatty liver disease fibrosis score(NFS)not excluding advanced fibrosis[area under the curve(AUC)=0.840,ppp=0.025].An age≥50 years and age at diagnosis≥41 years predicted a fibrosis-4 index of moderate to advanced fibrosis(AUC=0.831,pppatients with hypertension,type 2 diabetes mellitus(DM),dyslipidaemia,metabolic syndrome,and regular alcohol consumption were more likely to have a NFS not excluding advanced fibrosis(pp=0.002,p=0.008,pp=0.033).patients with at least one pi*z allele and type 2 DM were 8 times more likely to have liver stiffness measurement≥7.1 kpa(p=0.040).CONClUSION Risk factors for liver disease in AATD included an age≥50 years,age at diagnosis≥41 years,metabolic risk factors,regular alcohol consumption,at least one pi*z allele,and AAT value at diagnosislgorithm for liver disease screening in AATD patients to use in primary care,selecting those to be referred to Hepatology consultation.

关键词： Alpha-1 antitrypsin deficiency liver fibrosis Nonalcoholic fatty liver disease fibrosis score Fibrosis-4 index liver stiffness measurement

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Oxidized organic molecules in the tropical free troposphere over Amazonia

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National Science Review 2024年第1期11卷 174-184页

作者： Qiaozhi zha Diego Aliaga Radovan Krejci Victoria A.Sinclair Cheng Wu Giancarlo Ciarelli Wiebke Scholz liine Heikkinen Eva partoll Yvette Gramlich Wei Huang Markus leiminger Joonas Enroth Otso per?kyl? Runlong Cai Xuemeng Chen Alkuin Maximilian Koenig Fernando Velarde isabel Moreno Tuukka pet?j? paulo Artaxo paolo laj Armin Hansel Samara Carbone Markku Kulmala Marcos Andrade Douglas Worsnop Claudia Mohr Federico Bianchi Institute for Atmospheric and Earth System Research/physics University of Helsinki Joint International Research laboratory of Atmospheric and Earth System Sciences Nanjing University Department of Environmental Science & Bolin Centre for Climate Research Stockholm University Department of Chemistry and Molecular Biology University of Gothenburg Institute for Ion and Applied physics University of Innsbruck Ionicon Analytik GmbH laboratory for Atmospheric physics Institute for Physics Research Universidad Mayor de San Andrés Institute of physics University of Sao Paulo Institute for Geosciences and Environmental Research (IGE) University of Grenoble Alpes Agrarian Sciences Institute Federal University of Uberl?ndia Beijing Advanced Innovation Center for Soft Matter Science and Engineering Beijing University of Chemical Technology Department of Atmospheric and Oceanic Sciences University of Maryland Aerodyne Research Inc. Department of Environmental System Science ETH Zürich Switzerland and laboratory of Atmospheric Chemistry Paul Scherrer Institute

New particle formation(NpF) in the tropical free troposphere(FT) is a globally important source of cloud condensation nuclei, affecting cloud properties and climate. Oxidized organic molecules(OOMs)produced from biogenic volatile organic compounds are believed to contribute to aerosol formation in the tropical FT, but without direct chemical observations. We performed in situ molecular-level OOMs measurements at the Bolivian station Chacaltaya at 5240 m above sea level, on the western edge of Amazonia. For the first time, we demonstrate the presence of OOMs, mainly with 4–5 carbon atoms, in both gas-phase and particle-phase(in terms of mass contribution) measurements in tropical FT air from Amazonia. These observations, combined with air mass history analyses, indicate that the observed OOMs are linked to isoprene emitted from the rainforests hundreds of kilometers away. Based on particle-phase measurements, we find that these compounds can contribute to NpF, at least the growth of newly formed nanoparticles, in the tropical FT on a continental scale. Thus, our study is a fundamental and significant step in understanding the aerosol formation process in the tropical FT.

关键词： oxidized organic molecules tropical aerosol formation Amazon free troposphere

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Investigation of normal,lateral,and oblique impact of microscale projectiles into unidirectional glass/epoxy composites

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Defence Technology（防务技术） 2022年第11期18卷 1960-1978页

作者： Christopher S.Meyer isabel G.Catugas John W.Gillespie Jr. Bazle z.Gama Haque University of Delaware Center for Composite Materials(UD-CCM) 101 Academy StreetNewarkDE19716USA

Spacesuits and spacecraft must endure high velocity impacts from micrometeoroids. This work considers the impact of 100 μm diameter projectiles into composite targets at velocities from 0.5 km/s to 2 km/*** work begins by presenting an energy-based theoretical model relating depth of penetration(Do p)and impact force to impact velocity, characteristic time, and threshold velocity and force. Next, this work compares numerical simulations of normal impact on composites to the theoretical model. Numerical simulations are conducted with lS-DYNA and the well-known composite model, MAT-162. The numerical models consider unidirectional S2-glass fiber reinforced SC-15 epoxy composite laminates. The numerical model shows good correlation with the theoretical model. The numerical model also investigates lateral impact, parallel to the fiber direction, and oblique impact at angles from 30°to 82.5°.This work decomposes oblique impact into normal and lateral components, and compares them with normal and lateral impact results. The results show good correlation of the normal component of oblique results with the theoretical model. This numerical and theoretical study focuses on Do p, velocity, and penetration resistance force as functions of time. The theoretical model and numerical simulations are used to determine new Do p parameters: characteristic time of depth of penetration and threshold impact velocity. These models are a first step in developing the capability to predict Do p for oblique,microscale, high-speed impact on composite materials.

关键词： Microscale Hypervelocity impact Composites Erosion penetration

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Functional responses to deforestation in fish communities inhabiting neotropical streams and rivers

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Ecological processes 2023年第1期12卷 716-732页

作者： isabel Cantera Céline Jézéquel Tony Dejean Jérôme Murienne Régis Vigouroux Alice Valentini Sébastien Brosse Department of Environmental Science and policy Universitàdegli Studi di MilanoVia Celoria 2620133 MilanItaly laboratoire Evolution et DiversitéBiologique UMR5174-UniversitéPaul SabatierCNRSIRD118 Route de Narbonne31062 ToulouseFrance SpYGEN Savoie Technolac-BP 27417 Rue du Lac Saint-André73375 Le Bourget-du-Lac CedexFrance HYDRECO Laboratoire Environnement de Petit SautB.P 82397388 Kourou CedexFrench GuianaFrance

Background Deforestation is a widespread disturbance for neotropical freshwater *** biodiversity declines have been associated with deforestation,its functional consequences for stream and river fish faunas remain poorly *** this study,we explored how deforestation affects the different facets of the functional structure of fish communities inventoried using environmental DNA metabarcoding in 64 river and 35 stream sites of French ***,we investigated how functional richness,divergence,evenness and identity of fish faunas are affected by *** We showed that anthropogenic disturbances in French Guiana are modifying the functional diversity of freshwater fish *** disturbances not only affected the amount of functional traits held by the communities but also the identity of the traits and the internal structure of the functional ***,different facets of the functional diversity supported by fish assemblages were *** streams,deforestation did not affect the overall diversity of traits but reduced functional redundancy,underlined by a shift in functional identity towards assemblages dominated by pelagic *** contrast,river fish faunas experienced a decline in functional richness,paired with shifts in functional identity and a loss of fish species with extreme *** The response to deforestation differed between streams and rivers,but it supports the hypothesis that deforestation is linked to functional changes in fish *** diminishing the range of the functions in rivers or by jeopardizing the redundancy of functions in streams,deforestation could severely hamper the functioning and stability of neotropical freshwater ecosystems.

关键词： eDNA Traits Functional space Richness Divergence Evenness Identity Gold mining

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Intraspecific competition in zabrotes subfasciatus： physiological and behavioral adaptations to different amounts of host

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Insect Science 2012年第1期19卷 102-111页

作者： isabel R.V.Teixeira Fernando S.zucoloto Insect Nutrition and Feeding Behavior laboratory Department of BiologyFaculdade de Filosofia Ciencias e Letras de Ribeirao Preto Universidade de Sao PauloSao Paulo epartment of Biology Federal Institute of Sul de Minas-Campus MuzambinhoIFSULDEMINAS MuzambinhoMinas GeraisBrazil

The effects of competition on populations of the bean weevil zabrotes sub- fasciatus were analyzed during 41 generations under different competition levels. Three competition environments were established by maintaining the number of couples （6） and varying the amount of available host seeds： HC, high （limited availability of host： 1.35 g）; IC, intermediate （intermediate availability of host： 6 g）; and lC, low competition （abun- dance of host： 36 g）. It was found that the distribution of the eggs laid on grains was different among treatments： in lC, for example, although females showed high fecundity （35.4 ± 5.6 eggs/female） the number of eggs laid on each grain was small （1.2 ± 0.4 eggs on each seed）, thus avoiding larval competition of their offspring; whereas in HC treatment, females showed low fecundity （27.04 ± 4.5 eggs/female） but laid many eggs on each grain （15.03 ± 4.3 eggs）. There were no changes in the ability to respond to different amounts of host via oviposition behavior （egg distribution） during 41 generations. How- ever, HC females had more offspring than lC females under HC conditions. This suggests that HC insects evolved toward higher fitness in crowded conditions. In addition, after inverting the competition level, insects behaved independently of the treatment conditions they experienced through generations, thus showing that oviposition behavior is flexible. Taken together, our results show that z. subfasciatus presents a broad range of behavioral and physiological responses which allows for quick and reversible adjustments to sudden changes in the amount of resources.

关键词： bean weevil Coleoptera egg distribution oviposition phaseolus vulgaris phenotypic plasticity

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Cell-type-specific memory consolidation driven by translational control

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Signal Transduction and Targeted Therapy 2021年第2期6卷 206-208页

作者： Qing zhang isabel Bestard-lorigados Weihong Song Townsend Family laboratories Department of PsychiatryThe University of British ColumbiaVancouverBCCanada Institute of Aging School of Mental Health and Kangning HospitalThe Second Affiliated Hospital and Yuying Children’s HospitalWenzhou Medical UniversityWenzhouChina

***’s group has significantly contributed to the understanding of translational control in learning and *** a recent Nature article,they further reported the cell-typespecific translational control underlying memory consolidation.1 long-term potentiation(lTp)has been widely acknowledged as one of the main cellular models of learning and ***,there are two components of lTp driven by different stimulations and *** early phase of lTp(E-lTp)and short-term memory(STM)are evoked for short periods and are temporary,relying primarily on modifications of pre-existing *** late phase of lTp(l-lTp)and consequent longterm memory(lTM)are elicited by strong and repetitive stimulation and are long-lasting,requiring new protein synthesis.

关键词： synthesis. translational stimulation

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Host preference of the bean weevil zabrotes subfasciatus

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Insect Science 2008年第4期15卷 335-341页

作者： isabel Ribeiro do Valle Teixeira Angel Roberto Barchuk Fernando Sergio zucoloto Department of Biology Centro Universitario da Fundacao Educacional de Guaxupe Minas Gerais Department of Biology Faculdade de Filosofia Ciencias e Letras de Ribeirao Preto Universidade de Sao Paulo Sao Paulo Department of Biological Sciences Universidade Federal de Alfenas UnifaI-MG Alfenas Minas Gerais Brazil

It is largely known that the range of an insect diet is mostly determined by oviposition behavior, mainly in species with endophytic larvae such as zabrotes subfasciatus. However, the proximate factors determining host choice and the subsequent steps leading to the expansion or reduction of the host number and occasional host shifts are largely unknown. We analyzed various factors determining host preference of z. subfasciatus through the evaluation of：（i） oviposition preference of a wild population of z. subfasciatus on the usual host （bean） and unusual hosts （lentil, chickpea and soy）, and the performance of the offspring; （ii） artificial selection for increasing preference for hosts initially less frequently chosen; （iii） comparison of oviposition behavior between two different populations （reared for -30 generations in beans or chickpeas, respectively）; （iv） oviposition timing on usual and unusual hosts; and （v） identification of preference hierarchies. We found that when using unusual hosts, there is no correlation between performance and preference and that the preference hierarchy changes only slightly when the population passes through several generations on the less frequently accepted host. We also found a positive response to artificial selection for increasing oviposition on the less preferred host; however, when the host-choice experiment involved two varieties of the usual host, the response was faster than when the choice involved usual and unusual hosts. Finally, beetles reared on an unusual host （chickpea） for 26 generations showed similar good fitness on both usual and unusual hosts, indicating that the use of a new host does not necessarily result in the loss of performance on the original host. Nevertheless, this population showed lower fitness on the usual host than that of the original population, suggesting an underlying partial trade-off phenomenon which may contribute to a broadening of diet of this insect species.

关键词： artificial selection evolution phaseolus Cicer plant-insect interaction

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Neuropsychological features of progranulin-associated frontotemporal dementia: a nested case-control study

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Neural Regeneration Research 2021年第5期16卷 910-915页

作者： Marisa lima Miguel Tábuas-pereira Diana Duro João Durães Daniela Vieira Inês Baldeiras Maria Rosário Almeida isabel Santana Neurology Department Centro Hospitalar e Universitário de CoimbraCoimbraPortugal University of Coimbra Faculty of MedicineCoimbraPortugal University of Coimbra Center for Neuroscience and Cell BiologyCoimbraPortugal University of Coimbra Center for Research in Neuropsychology and Cognitive Behavioral Intervention(CINEICC)Faculty of Psychology and Educational SciencesCoimbraPortugal

The distinction between sporadic and genetic behavioural-variant frontotemporal dementia(bvFTD)regarding some neuropsychological(Np)features remains ***,progranulin(GRN)-associated bvFTD frequently presents with early episodic memory impairment and some degree of parietal dysfunction which are supporters of Alzheimer’s disease(AD)*** this context,we aimed to characterize the Np profile of GRN-bvFTD as compared to sporadic-bvFTD and AD in patients with mild dementia(Mini-Mental State Examination score≥17 and Clinical Dementia Rating Scale score≤*** identified 21 patients at Centro Hospitalar e Universitário de Coimbra,portugal with GRN mutations belonging to fifteen different *** our focus was bvFTD variants,FTD-related aphasic forms(3 patients)were *** remaining 18 GRN-bvFTD were further matched with 18 sporadic-bvFTD and 18 AD patients according to disease staging,age and *** patients completed the Mini-Mental State Examination,Montreal Cognitive Assessment(MoCA)and a comprehensive Np assessment *** were converted into *** between groups in individual Np measures and Np domains were assessed through non-parametric tests(Kruskal-Wallis test analysis)and eta squared(ŋ2)was calculated as a measure of effect *** comparisons show that GRN patients have worse performances on verbal retrieval processes(p=0.039,ŋ2=0.110)and visuoconstructive abilities(p=0.039,ŋ2=0.190)than sporadic bvFTD *** compared to AD,GRN patients present a higher impairment in frontal(p=0.001,ŋ2=0.211)and parietal(p=0.041,ŋ2=0.129)measures and a better performance in memory tasks(p=0.020,ŋ2=0.120).Sporadic-bvFTD forms are worse than AD in frontal measures(p=0.032,ŋ2=0.200),being better in both memory(p=0.010,ŋ2=0.131)and visuospatial skills(p=0.023,ŋ2=0.231).Considering these results,we conclude that GRN-bvFTD patients present a Np profile that associates the typical patterns of FTD and AD ***

关键词： Alzheimer’s disease behavioral variant frontotemporal dementia cognitive profile frontotemporal dementia genetics memory neuropsychology progranulin visuoconstructive ability

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Enforced pGC-1α expression promotes CD8 T cell fitness, memory formation and antitumor immunity

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Cellular & Molecular Immunology 2021年第7期18卷 1761-1771页

作者： Nina Dumauthioz Benjamin Tschumi Mathias Wenes Bastien Marti Haiping Wang Fabien Franco Wenhui li isabel Clop.z-Mejia lluis Fajas ping-Chih Ho Alena Donda pedro Romero lianjun zhang Translational Tumor Immunology Group Ludwig Cancer ResearchUniversity of LausanneEpalingesSwitzerland Department of Fundamental Oncology University of LausanneEpalingesSwitzerland Department of Fundamental Oncology University of LausanneEpalingesSwitzerland Ludwig Cancer Research Institute Lausanne BranchEpalingesSwitzerland Center for Systems Medicine Institute of Basic Medical SciencesChinese Academy of Medical Sciences and Peking Union Medical College100005BeijingChina Suzhou Institute of Systems Medicine SuzhouJiangsu215123China Center for Integrative Genomics University of LausanneLausanneSwitzerland

Memory CD8 T cells can provide long-term protection against tumors,which depends on their enhanced proliferative capacity,self-renewal and unique metabolic rewiring to sustain cellular ***,memory CD8 T cells engage oxidative phosphorylation and fatty acid oxidation to fulfill their metabolic *** contrast,tumor-infiltrating lymphocytes(TIls)display severe metabolic defects,which may underlie their functional ***,we show that overexpression of proliferator-activated receptor gamma coactivator 1-alpha(pGC-1α),the master regulator of mitochondrial biogenesis(MB),favors CD8 T cell central memory formation rather than resident memory ***-1α-overexpressing CD8 T cells persist and mediate more robust recall responses to bacterial infection or peptide ***,CD8 T cells with enhanced pGC-1αexpression provide stronger antitumor immunity in a mouse melanoma ***,TIls overexpressing pGC-1αmaintain higher mitochondrial activity and improved expansion when rechallenged in a tumor-free ***,our findings indicate that enforcing mitochondrial biogenesis promotes CD8 T cell memory formation,metabolic fitness,and antitumor immunity in vivo.

关键词： pGC-1α Mitochondria CD8 Memory Anti-tumor immunity

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A Single JAz Repressor Controls the Jasmonate pathway in Marchantia polymorpha

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Molecular plant 2019年第2期12卷 185-198页

作者： isabel Monte Jose M. Franco-zorrilla Gloria Garcia-Casado Angel M. zamarreno Jose M. Garcia-Mina Ryuichi Nishihama Takayuki Kohchi Roberto Solano Department of plant Molecular Genetics Centro Nacional de Biotecnologia Consejo Superior de Investigaciones Cientificas (CNB-CSIC) 28049 Madrid Spain Genomics Unit Centro Nacional de Biotecnologia Consejo Superior de Investigaciones Cientificas (CNB-CSIC) 28049 Madrid Spain Environmental Biology Department University of Navarra Navarre Spain Graduate School of Biostudies Kyoto University Kyoto 606-8502 Japan

JAz proteins are negative regulators of jasm onate responses,acting both as repressors of transcription factors and as co-receptors of JA-lle. The high redundancy of JAz genes in angiosperms has hindered the characterization of a complete depletion of JAz function. Moreover, the recent discovery that dn- OpDA is the jasmonate ligand in Marchantia polymorpha demonstrates that JA-lle is not the sole COI1/ JAz ligand in land plants and highlights the importance of studying JAz co-receptors in bryophytes? Here, we have exploited the low gene redundancy of the liverwort M. polymorpha to characterize the single MpJ4z in this early diverging plant lineage. We clarify the phylogenetic history of the TIFY family, demonstrate that MpJAz is the ortholog of AtJAz with a conserved function, and characterize its repressor activity of dn-OpDA resp on ses. Our results show that, con sistent with previous findings in Arabidopsis, MpJAz represses jasmonates biosynthesis, senescence, and plant defenses, and promotes cell growth and reproductive fitness, highlighting the power of studies in Marchantia.

关键词： Jasmonate repressors Marchantia Hormone signaling evolution gene redundancy

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