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T follicular helper expansion and humoral-mediated rejection are independent of the HVEM/BTLA pathway

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Cellular & Molecular Immunology 2017年第6期14卷 497-510页

作者： Jose-ignacio Rodriguez-Barbosa Carlos Fernandez-Renedo Ana Maria Bravo Moral Leo Biihler Maria-Luisa del Rio Transplantation Immunobiology Section Institute of Biomedicine University of Leon and Castilla and Leon Regional Transplantation Coordination Leon University Hospital Leon Spain Department of Veterinary Clinical Sciences University of Santiago de Compostela Veterinary Faculty Lugo Spain Visceral and Transplantation Surgery Department of Surgery University Hospitals of Geneva and Faculty of Medicine Geneva Switzerland

The molecular pathways contributing to humoral-mediated allograft rejection are poorly defined. In this study, we assessed the role of the herpesvirus entry mediator/B- and T-lymphocyte attenuator （HVEM/BTLA） signalling pathway in the context of antibody-mediated allograft rejection. An experimental setting was designed to elucidate whether the blockade of HVEM/BTLA interactions could modulate de novo induction of host antidonor-specific antibodies during the course of graft rejection. To test this hypothesis, fully allogeneic major histocompatibility complex-mismatched skin grafts were transplanted onto the right flank of recipient mice that were treated with isotype control, anti-CD40L or modulatory antibodies of the HVEM/BTLA signalling pathway. The frequencies of CD4 T follicular helper （Tfh） cells （B220-, CD4＋ CXCR5＋ PD-lhigh）, extrafollicular helper cells （B220-, CD4＋ CXCR5- PD-1＋ and PD-1-） and germinal centre （GC） B cells （B220＋Fas＋ GL7＋） were analysed by flow cytometry in draining and non-draining lymph nodes at day 10 post transplantation during the acute phase of graft rejection. The host antidonor isotype-specific humoral immune response was also assessed. Whereas blockade of the CD40/CD40L pathway was highly effective in preventing the allogeneic humoral immune response, antibody-mediated blockade of the HVEM/BTLA-interacting pathway affected neither the expansion of Tfh cells nor the expansion of GC B cells. Consequently, the course of the host antidonor antibody-mediated response proceeded normally, without detectable evidence of impaired development. In summary, these data indicate that HVEM/BTLA interactions are dispensable for the formation of de novo host antidonor isotype-specific antibodies in transplantation.

关键词： BTLA (CD272) humoral immunity HVEM (TNFRSF14, CD270) T follicular helper cells transplantation

Innate lymphoid cells in tissue homeostasis and diseases

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World Journal of Hepatology 2017年第23期9卷 979-989页

作者： Aline ignacio Cristiane Naffah Souza Breda Niels Olsen Saraiva Camara Laboratory of Transplantation Immunobiology Institute of Biomedical SciencesDepartment of ImmunologyUniversity of Sao PauloSP 05508-900Brazil

Innate lymphoid cells(ILCs) are the most recently discovered family of innate immune cells. They are a part of the innate immune system, but develop from the lymphoid lineage. They lack pattern-recognition receptors and rearranged receptors, and therefore cannot directly mediate antigen specific responses. The progenitors specifically associated with the ILCs lineage have been uncovered, enabling the distinction between ILCs and natural killer cells. Based on the requirement of specific transcription factors and their patterns of cytokine production, ILCs are categorized into three subsets(ILC1, ILC2 and ILC3). First observed in mucosal surfaces, these cell populations interact with hematopoietic and non-hematopoietic cells throughout the body during homeostasis and diseases, promoting immunity, commensal microbiota tolerance, tissue repair and inflammation. Over the last 8 years, ILCs came into the spotlight as an essential cell type able to integrate diverse host immune responses. Recently, it became known that ILC subsets play a key role in immune responses at barrier surfaces, interacting with the microbiota, nutrients and metabolites. Since the liver receives the venous blood directly from the intestinal vein, the intestine and liver are essential to maintain tolerance and can rapidly respond to infections or tissue damage. Therefore, in this review, we discuss recent findings regarding ILC functions in homeostasis and disease, with a focus on the intestine and liver.

关键词： Innate lymphoid cells Intestine Liver Homeostasis Inflammatory diseases

Science Letters:Visual odometry for road vehicles—feasibility analysis

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2007年第12期8卷 2017-2020页

作者： SOTELO Miguel-angel GARCíA Roberto PARRA ignacio FERNNDEZ David GAVILN Miguel LVAREZ Sergio NARANJO José-eugenio Department of Electronics University of Alcalá Alcalá de Henares 28871 Spain Department of Informatics Industrial Automation Institute CSIC Madrid Spain

Estimating the global position of a road vehicle without using GPS is a challenge that many scientists look forward to solving in the near future. Normally, inertial and odometry sensors are used to complement GPS measures in an attempt to provide a means for maintaining vehicle odometry during GPS outage. Nonetheless, recent experiments have demonstrated that computer vision can also be used as a valuable source to provide what can be denoted as visual odometry. For this purpose, vehicle motion can be estimated using a non-linear, photogrametric approach based on RAndom SAmple Consensus (RANSAC). The results prove that the detection and selection of relevant feature points is a crucial factor in the global performance of the visual odometry algorithm. The key issues for further improvement are discussed in this letter.

关键词： 3D visual odometry Ego-motion estimation RAndom SAmple Consensus (RANSAC) Photogrametric approach

Reassessment of Prejanopterus curvirostris, a Basal Pterodactyloid Pterosaur from the Early Cretaceous of Spain

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Acta Geologica Sinica(English Edition) 2012年第6期86卷 1389-1401页

作者： Xabier PEREDA-SUBERBIOLA Fabien KNOLL José ignacio RUIZ-OMEACA Julio COMPANY Fidel TORCIDA FERNNDEZ-BALDOR Universidad del País Vasco/Euskal Herriko Unibertsitatea Facultad de Cienciay TecnologíaDpto.Estratigrafíay Paleontología Departamento de Paleobiología Museo Nacional de Ciencias Naturales-CSIC Museo del Jurásico de Asturias (MUJA) Departamento de Geología Universidad de Oviedo Departamento de Ingeniería del Terreno Universidad Politécnica de Valencia Colectivo Arqueológico-Paleontológico de Salas (C.A.S.) Museo de Dinosaurios

Prejanopterus curvirostra, from the Early Cretaceous of La Rioja province, was the first pterosaur genus and species described from Spain. The material comprises disarticulated cranial and postcranial remains from several individuals. The fossil-bearing bed is assigned to the lacustrine Leza Formation （eastern Cameros Basin, NW margin of the Iberian Range）. This unit is regarded as either Berriasian-Valanginian or Barremian-Aptian. Prejanopterus curvirostris （specific name emended） was originally diagnosed on the basis of several characters of which the most significant was a lateral curvature of the rostrum. Re-examination of the holotype （rostrum） and paratype （partial rostrum with teeth） indicates that there is no genuine sideways bend of the preserved premaxilla-maxilla segments, but a slight dorsal curvature. Prejanopterus is characterized by a unique combination of characters： an emended diagnosis is provided. In contrast with previous estimates, the wing span of Prejanopterus was probably not much （if ever） in excess of 2 m. A phylogenetic analysis suggests that Prejanopterus is a basal pterodactyloid positioned between Pterodactylus and Cycnorhamphus- Gallodactylus. Prejanopterus represents the first evidence of Pterodactylidae in the Early Cretaceous of the Iberian Peninsula.

关键词： Pterosauria Prejanopterus Leza Formation Early Cretaceous La Rioja Spain

Overview of the anterolateral complex of the knee

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World Journal of Clinical Cases 2022年第24期10卷 8474-8481页

作者： ignacio Garcia-Mansilla Juan Pablo Zicaro Ezequiel Fernando Martinez Juan Astoul Carlos Yacuzzi MatiasCosta-Paz Knee Surgery Hospital Italiano de Buenos AiresBuenos Aires 1199Argentina

In the last few years,much more information on the anterolateral complex of the knee has become *** has now been demonstrated how it works in conjunction with the anterior cruciate ligament(ACL)controlling anterolateral rotatory *** studies have shown that the anterolateral complex(ALC)has a role as a secondary stabilizer to the ACL in opposing anterior tibial translation and internal tibial *** is of utmost importance that surgeons comprehend the intricate anatomy of the entire anterolateral aspect of the *** most studies have only focused on the anterolateral ligament(ALL),the ALC of the knee consists of a functional unit formed by the layers of the iliotibial band combined with the anterolateral joint *** interest has also been given to imaging evaluation using magnetic resonance and several studies have targeted the evaluation of the ALC in the setting of ACL *** are inconsistent with a lack of association between magnetic resonance imaging evidence of injury and clinical *** ACL reconstruction may not always reestablish knee rotatory stability in patients with associated ALC *** such cases,additional procedures,such as anterolateral reconstruction or lateral tenodesis,may be *** are several techniques available for ALL *** options include the iliotibial band,gracilis or semitendinosus tendon autograft,or allograft.

关键词： Anterolateral complex Knee instability Anterolateral ligament Anterior cruciate ligament reconstruction

Dissection of miRNA Pathways Using Arabidopsis Mesophyll Protoplasts

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Molecular Plant 2015年第2期8卷 261-275页

作者： Claudia Martinho Ana Confraria Carlos Alexandre Elias Pierre Crozet ignacio Rubio-Somoza Detlef Weigel Elena Baena-Gonzalez Plant Stress Signaling Instituto Gulbenkian de Ciencia Rua da Quinta Grande - 6 2780-156 Oeiras Portugal Department of Molecular Biology Max Planck Institute for Developmental Biology D-72076 Tubingen Germany These authors contributed equally to this article. Present address: Sainsbury Laboratory Cambridge University Bateman Street Cambridge CB2 1LR UK

MicroRNAs （miRNAs） control gene expression mostly post-transcriptionally by guiding transcript cleavage and/or translational repression of complementary mRNA targets, thereby regulating developmental processes and stress responses. Despite the remarkable expansion of the field, the mechanisms underlying miRNA activity are not fully understood. In this article, we describe a transient expression system in Arabidopsis mesophyll protoplasts, which is highly amenable for the dissection of miRNA pathways. We show that by transiently overexpressing primary miRNAs and target mimics, we can manipulate miRNA levels and consequently impact on their targets. Furthermore, we developed a set of luciferase-based sensors for quantifying miRNA activity that respond specifically to both endogenous and overexpressed miRNAs and target mimics. We demonstrate that these miRNA sensors can be used to test the impact of putative components of the miRNA pathway on miRNA activity, as well as the impact of specific mutations, by either overexpression or the use of protoplasts from the corresponding mutants. We further show that our miRNA sensors can be used for investigating the effect of chemicals on miRNA activity. Our cell-based transient expression system is fast and easy to set up, and generates quantitative results, being a powerful tool for assaying miRNA activity in vivo.

关键词： miRNA miRNA activity miRNA sensor protoplasts Arabidopsis thaliana

A single synonymous mutation determines the phosphorylation and stability of the nascent protein

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Journal of Molecular Cell Biology 2019年第3期11卷 187-199页

作者： Konstantinos Karakostis Sivakumar Vadivel Gnanasundram ignacio Lopez Aikaterini Thermou Lixiao Wang Karin Nylander Vanesa Ollvares-Iliana Robin Fahraeus Equipe Labellisee Ligue Contre le Cancer Universite Paris 7INSERM UMR 116227 Rue Juliette DoduParis 75010France Department of Medical Biosciences Umea UniversityUmea SE-90185Sweden Instituto de Ffsica Universidad Autonoma de San Luis Potosi78290 SLPMexico RECAMO Masaryk Memorial Cancer InstituteZluty kopec 7Brno 656 53Czech Republic

p53 is an intrinsically disordered protein with a large number of post-translational modifications and interacting *** hierarchical order and subcellular location of these events are still poorly *** activation of p53 during the DNA damage response(DDR)requires a switch in the activity of the E3 ubiquitin ligase MDM2 from a negative to a positive regulator of *** is mediated by the ATM kinase that regulates the binding of MDM2 to the p53 mRNA facilitating an increase in p53 *** we show that the binding of MDM2 to the p53 mRNA brings ATM to the p53 polysome where it phosphorylates the nascent p53 at serine 15 and prevents MDM2-mediated degradation of p53.A single synonymous mutation in p53 codon 22(L22L)prevents the phosphorylation of the nascent p53 protein and the stabilization of p53 following genotoxic *** ATM trafficking from the nucleus to the p53 polysome is mediated by MDM2,which requires its interaction with the ribosomal proteins RPL5 and *** results show how the ATM kinase phosphorylates the p53 protein while it is bang synthesized and offer a novel mechanism whereby a single synonymous mutation controls the stability and activity of the encoded protein.

关键词： synonymous mutations intrinsically disordered proteins cell signaling MDM2 p53 messenger RNA ATM kinase

Lenvatinib as first-line therapy for recurrent hepatocellular carcinoma after liver transplantation:Is the current evidence applicable to these patients?

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World Journal of Transplantation 2020年第11期10卷 297-306页

作者： Federico Piñero Marcos Thompson Juan ignacio Marín Marcelo Silva Hepatology and Liver Transplant Unit Hospital Universitario AustralBuenos Aires B1629HJArgentina Hospital Universitario Austral Facultad de Ciencias BiomédicasUniversidad AustralBuenos Aires B1629HJArgentina Latin American Liver Research Educational and Awareness Network(LALREAN) Buenos Aires B1629HJArgentina Hepatology and Liver Transplantation Unit Hospital Pablo Tobón UribeMedellín 240Colombia

Liver transplantation(LT)is one of the leading curative therapies for hepatocellular carcinoma(HCC).Despite recent optimization of transplant selection criteria,including alpha-feto protein,HCC recurrence after LT is still the leading cause of death in these *** the last decades,effective systemic treatments for HCC,including tyrosine kinase inhibitors and immunotherapy,have been *** describe the clinical scenario of a patient with recurrence of HCC five years after LT,who received lenvatinib as first-line systemic therapy to introduce systemic treatment options in this clinical *** this opinion review,we detail first and second-line systemic treatment options,focusing on those feasible for patients with recurrent HCC after *** trials have evaluated new drugs to treat HCC patients in first and secondline therapy,but patients with recurrent HCC after LT have been excluded from these ***,most of the evidence comes from observational retrospective *** tyrosine kinase inhibitors will remain the primary therapeutic approach in these patients,due to a relative contraindication for immunotherapy,may be clarified in the near future.

关键词： Liver transplantation Recurrence Systemic therapies Hepatocellular carcinoma

Electrical Noise, Brownian Motion and the Arrow of Time

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Journal of Modern Physics 2015年第2期6卷 131-140页

作者： Jose-ignacio Izpura Department of Aerospace Systems Air Transport and Airports GMME-CEMDATIC Research Group Universidad Politécnica de Madrid (UPM) Madrid Spain

The origin of the Johnson noise of resistors is reviewed by a new model fitting in the Fluctuation-Dissipation framework and compared with the velocity noise in Brownian motion. This new model handling both fluctuations as well as dissipations of electrical energy in the Complex Admittance of any resistor excels current model based on the dissipation in their conductance. From the two orthogonal currents associated to a sinusoidal voltage in an electrical admittance, the new model that also considers the discreteness of the electrical charge shows a Cause-Effect dynamics for electrical noise. After a brief look at systems considered as energy-conserving and deterministic on the microscale that are dissipative and unpredictable on the macroscale, the arrow of time is discussed from the noise viewpoint.

关键词： Electrical Noise Fluctuation-Dissipation Cause-Effect Complex Admittance The Arrow of Time