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Collagen secretion screening in Drosophila supports a common secretory machinery and multiple Rab requirements

Journal of Genetics and Genomics 2018年第6期45卷 299-313页

作者： Hongmei Ke Zhi Feng Min Liu Tianhui Sun Jianli Dai Mengqi Ma Lu-Ping Liu Jian-Quan Ni jos carlos pastor-pareja School of Life Sciences Tsinghua University School of Medicine Tsinghua University

Collagens are large secreted trimeric proteins making up most of the animal extracellular *** of collagen has been a focus of interest for cell biologists in recent years because collagen trimers are too large and rigid to fit into the COPII vesicles mediating transport from the endoplasmic reticulum（ER） to the Golgi. Collagen-specific mechanisms to create enlarged ER-to-Golgi transport carriers have been postulated, including cargo loading by conserved ER exit site（ERES） protein ***, we report an RNAi screening for genes involved in collagen secretion in Drosophila. In this screening, we examined distribution of GFP-tagged Collagen IV in live animals and found 88 gene hits for which the knockdown produced intracellular accumulation of Collagen IV in the fat body, the main source of matrix proteins in the larva. Among these hits, only two affected collagen secretion specifically：PH4 a EFB and Plod, encoding enzymes known to mediate posttranslational modification of collagen in the ER. Every other intracellular accumulation hit affected general secretion, consistent with the notion that secretion of collagen does not use a specific mode of vesicular transport, but the general secretory pathway. Included in our hits are many known players in the eukaryotic secretory machinery, like COPII and COPI components, SNAREs and Rab-GTPase regulators. Our further analysis of the involvement of Rab-GTPases in secretion shows that Rab1, Rab2 and Rab X3, are all required at ERES, each of them differentially affecting ERES morphology. Abolishing activity of all three by Rep knockdown, in contrast,led to uncoupling of ERES and Golgi. We additionally present a characterization of a screening hit we named trabuco（tbc）, encoding an ERES-localized TBC domain-containing Rab-GAP. Finally, we discuss the success of our screening in identifying secretory pathway genes in comparison to two previous secretion screenings in Drosophila S2 cells.

关键词： Collagen Ⅳ COPⅡ vesicles RNAi screening Secretory pathway Rab-GTPases ER exit site

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Nickel-based cerium zirconate inorganic complex structures for CO_(2)valorisation via dry reforming of methane

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Journal of Environmental Sciences 2024年第6期140卷 12-23页

作者： Juan Luis Martín-Espejo Loukia-Pantzechroula Merkouri Jesús Gándara-Loe josé Antonio Odriozola Tomas Ramirez Reina Laura pastor-Pérez Department of Inorganic Chemistry and Material Sciences Institute of Seville University of Seville-CSICSeville 41092Spain Department of Chemical and Process Engineering University of SurreyGuildford GU27XHUnited Kingdom

The increasing anthropogenic emissions of greenhouse gases(GHG)is encouraging extensive research in CO_(2)*** reforming of methane(DRM)depicts a viable strategy to convert both CO_(2)and CH4into syngas,a worthwhile chemical *** the different active phases for DRM,the use of nickel as catalyst is economically favourable,but typically deactivates due to sintering and carbon *** stabilisation of Ni at different loadings in cerium zirconate inorganic complex structures is investigated in this work as strategy to develop robust Ni-based DRM *** and TPR-H2analyses confirmed the existence of different phases according to the Ni loading in these ***,superficial Ni is observed as well as the existence of a CeNiO_(3)perovskite *** catalytic activity was tested,proving that 10 wt.%Ni loading is the optimum which maximises *** catalyst was also tested in long-term stability experiments at 600and 800℃in order to study the potential deactivation issues at two different *** 600℃,carbon formation is the main cause of catalytic deactivation,whereas a robust stability is shown at 800℃,observing no sintering of the active phase evidencing the success of this strategy rendering a new family of economically appealing CO_(2)and biogas mixtures upgrading catalysts.

关键词： CO_(2)conversion Dry reforming of methane Nickel catalysts Pyrochlore Cerium zirconate

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Biomass gasification,catalytic technologies and energy integration for production of circular methanol:New horizons for industry decarbonisation

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Journal of Environmental Sciences 2024年第6期140卷 306-318页

作者： Luis F.Bobadilla Lola Azancot Miriam González-Castañ Estela Ruíz-López Laura pastor-Pérez Francisco J.Durán-Olivencia Runping Ye Katie Chong Paula HBlanco-Sánchez Zenthao Wu Tomás R.Reina joséA.Odriozola Departamento de Química Inorgánica e Instituto de Ciencia de Materiales de Sevilla Centro Mixto CSIC-Universidad de SevillaAvda.Américo Vespucio 49Sevilla 41092Spain Departamento de Ingeniería Universidad Loyola AndalucíaAvda.de Las Universidades s/nSevilla 41704Spain Key Laboratory of Jiangxi Province for Environment and Energy Catalysis School of Chemistry and Chemical EngineeringNanchang UniversityNanchang330031China Energy and Bioproducts Research Institute(EBRI) Aston UniversityBirminghamB47ETUnited Kingdom Department of Chemical and Process Engineering University of SurreyGuildfordGU27XHUnited Kingdom

The Intergovernmental Panel on Climate Change(IPCC)recognises the pivotal role of renewable energies in the future energy system and the achievement of the zero-emission *** implementation of renewables should provide major opportunities and enable a more secure and decentralised energy supply *** fuels provide long-term solutions for the transport sector,particularly for applications where fuels with high energy density are *** addition,it helps reducing the carbon footprint of these sectors in the *** on biomass characteristics feedstock is essential for scaling-up gasification from the laboratory to *** review deals with the transformation biogenic residues into a valuable bioenergy carrier like biomethanol as the liquid sunshine based on the combination of modified mature technologies such as gasification with other innovative solutions such as membranes and microchannel *** abatement is a critical process in product gas upgrading since tars compromise downstream processes and equipment,for this,membrane technology for upgrading syngas quality is discussed in this *** reactor technology with the design of state-of-the-art multifunctional catalysts provides a path to develop decentralised biomethanol synthesis from biogenic ***,the development of a process chain for the production of(i)methanol as an intermediate energy carrier,(ii)electricity and(iii)heat for decentralised applications based on biomass feedstock flexible gasification,gas upgrading and methanol synthesis is analysed.

关键词： Biogenic residues Gasification Biomethanol Circular Economy Microreactors

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The sound of host-SARS-CoV-2 molecular interactions

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The Innovation 2021年第3期2卷 5-6页

作者： joséde la Fuente Juan J.pastor Comín Christian Gortázar SaBio.Instituto de Investigación en Recursos Cinegéticos IREC-CSIC-UCLM-JCCM Ronda de Toledo s/n13005 Ciudad RealSpain Department of Veterinary Pathobiology Center for Veterinary Health SciencesOklahoma State UniversityStillwaterOK 74078USA Centro de Investigación y Documentación Musical CIDoM-UCLM-CSIC Facultad de Educación de Ciudad RealRonda Calatrava 313071 Ciudad RealSpain

Host-and virus-derived factors are key drivers of the COVID-19 pandemic(Gortázar et al.).1 The interaction between the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike glycoprotein(S)and host cell membrane angiotensin I converting enzyme 2(ACE2)receptor is highly dynamic,mediates virus infection,and is the main target for protective antibody response2.

关键词： ACE2 protective acute

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Mesenchymal stem cell therapy in retinal and optic nerve diseases: An update of clinical trials

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World Journal of Stem Cells 2016年第11期8卷 376-383页

作者： Sonia Labrador-Velandia María Luz Alonso-Alonso Sara Alvarez-Sanchez Jorge González-Zamora Irene Carretero-Barrio josé carlos pastor Iván Fernandez-Bueno Girish Kumar Srivastava Instituto Universitario de Oftalmobiología Aplicada Universidad de Valladolid 47011 Valladolid Spain Facultad de Medicina Universidad de Valladolid 47005 Valladolid Spain Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León 47011 Valladolid Spain Red Temática de Investigación Cooperativa Sanitaria del Instituto de Salud carlos Ⅲ. Oftared 28029 Madrid Spain Hospital Clínico Universitario de Valladolid 47003 Valladolid Spain

Retinal and optic nerve diseases are degenerative ocular pathologies which lead to irreversible visual loss. Since the advanced therapies availability, cell-based therapies offer a new all-encompassing approach. Advances in the knowledge of neuroprotection, immunomodulation and regenerative properties of mesenchymal stem cells(MSCs) have been obtained by several preclinical studies of various neurodegenerative diseases. It has provided the opportunity to perform the translation of this knowledge to prospective treatment approaches for clinical practice. Since 2008, several first steps projecting new treatment approaches, have been taken regarding the use of cell therapy in patients with neurodegenerative pathologies of optic nerve and retina. Most of the clinical trials using MSCs are in Ⅰ/Ⅱ phase, recruiting patients or ongoing, and they have as main objective the safety assessment of MSCs using various routes of administration. However, it is important to recognize that, there is still a long way to go to reach clinical trials phase Ⅲ-Ⅳ. Hence, it is necessary to continue preclinical and clinical studies to improve this new therapeutic tool. This paper reviews the latest progress of MSCs in human clinical trials for retinal and optic nerve diseases.

关键词： Mesenchymal stem cells Cell therapy Optic nerve diseases Clinical trials Retinal diseases

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p21 is necessary for the beneficial effects of fasting during chemotherapy

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Cancer Communications 2023年第1期43卷 164-168页

作者： Adrián Plaza Andrés pastor-Fernández joséL.López-Aceituno Marta Barradas Cristina Pantoja Pablo J.Fernandez-Marcos Metabolic Syndrome Group(BIOPROMET) Madrid Institute for Advanced Studies(IMDEA)FoodCEI UAM+CSICMadrid E28049Spain

Dear Editor,Short-term fasting(up to 48 hours)activates strong physiological and molecular responses[1].We and others showed a p53-independent transcriptional activation of the cell cycle inhibitor p21 upon fasting,most strongly in the liver,muscles,and many other tissues[2,3].Studies with mice[4,5]and human patients[6]have shown the beneficial effects of short-term fasting during anti-cancer chemotherapy treatments.

关键词： fasting chemotherapy p21

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Bispecific sigma-1 receptor antagonism and mu-opioid receptor partial agonism:WLB-73502,an analgesic with improved efficacy and safety profile compared to strong opioids

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Acta Pharmaceutica Sinica B 2023年第1期13卷 82-99页

作者： Alba Vidal-Torres Begoña Fernández-pastor Mónica García Eva Ayet Anna Cabot Javier Burgueño Xavier Monroy Bertrand Aubel Xavier Codony Luz Romero Rosalía Pascual Maria Teresa Serafini Gregorio Encina Carmen Almansa Daniel Zamanillo Manuel Merlos joséMiguel Vela WeLab Barcelona Parc Cientific de BarcelonaBarcelona 08028Spain

Opioids are the most effective painkillers,but their benefit-risk balance often hinder their therapeutic ***-73502 is a dual,bispecific compound that binds sigma-1(S1R)and mu-opioid(MOR)***-73502 is an antagonist at the *** behaved as a partial MOR agonist at the G-protein pathway and produced no/unsignificantβ-arrestin-2 recruitment,thus demonstrating low intrinsic efficacy on MOR at both signalling *** its partial MOR agonism,WLB-73502exerted full antinociceptive efficacy,with potency superior to morphine and similar to oxycodone against nociceptive,inflammatory and osteoarthritis pain,and superior to both morphine and oxycodone against neuropathic ***-73502 crosses the blood-brain barrier and binds brain S1R and MOR to an extent consistent with its antinociceptive *** to morphine and oxycodone,tolerance to its antinociceptive effect did not develop after repeated 4-week ***,contrary to opioid comparators,WLB-73502 did not inhibit gastrointestinal transit or respiratory function in rats at doses inducing full efficacy,and it was devoid of proemetic effect(retching and vomiting)in ferrets at potentially effective ***-73502 benefits from its bivalent S1R antagonist and partial MOR agonist nature to provide an improved antinociceptive and safety profile respect to strong opioid therapy.

关键词： WLB-73502 Sigma-1 receptor Mu-opioid receptor Biased agonist Analgesic activity Chronic pain Neuropathic pain Safety

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Modulation of faecal metagenome in Crohn's disease:Role of microRNAs as biomarkers

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World Journal of Gastroenterology 2018年第46期24卷 5223-5233页

作者： María Rojas-Feria Teresa Romero-García jose Angel Fernández Caballero-Rico Helena pastor Ramírez Marta Avilés-Recio Manuel Castro-Fernandez Natalia Chueca Porcuna Manuel Romero-Gomez Federico García Lourdes Grande joséA Del Campo Department of Digestive Diseases Valme University HospitalUGC Digestive Disease and CIBERehdServicio Andaluz de SaludSeville E-41014Spain Complejo Hospitalario Universitario de Granada MicrobiologyGranada E-18016Spain Institute of Biomedicine of Seville Digestive DiseasesHospital Universitario Virgen del Rocío and CIBERehdSeville E-41013Spain Facultad de ciencias de la salud.Universidad Europea Miguel de Cervantes Madrid E-28280Spain

BACKGROUND The gut microbiota plays a key role in the maintenance of intestinal homeostasis and the development and activation of the host immune system. It has been shown that commensal bacterial species can regulate the expression of host genes. 16 S rRNA gene sequencing has shown that the microbiota in inflammatory bowel disease(IBD) is abnormal and characterized by reduced diversity. Micro RNAs(miRNAs) have been explored as biomarkers and therapeutic targets, since they are able to regulate specific genes associated with Crohn's disease(CD). In this work, we aim to investigate the composition of gut microbiota of active treatment-na?ve adult CD patients, with miRNA profile from gut *** To investigate the composition of gut microbiota of active treatment-na?ve adult CD patients, with miRNA profile from gut *** Patients attending the outpatient clinics at Valme University Hospital without relevant co-morbidities were matched according to age and gender. Faecal samples of newonset CD patients, free of treatment, and healthy controls were collected. Faecal samples were homogenized, and DNA was amplified by PCR using primers directed to the 16 S bacterial rRNA gene. Pyrosequencing was performed using GS-Junior platform. For sequence analysis, MGRAST server with the database Ribosomal Project was used. MiRNA profile and their relative abundance were analyzed by quantitative *** Microbial community was characterized using 16 S rRNA gene sequencing in 29 samples(n = 13 CD patients, and n = 16 healthy controls). The mean Shannon diversity was higher in the healthy control population compared to CD group(5.5 vs 3.7). A reduction in Firmicutes and an increase in Bacteroidetes were found. Clostridia class was also significantly reduced in CD. Principal components analysis showed a grouping pattern, identified in most of the subjects in both groups, showing a marked difference between control and CD groups. A functional metabolic study showe

关键词： Crohn’s disease Dysbiosis microRNAs Firmicutes Bacteroidetes

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Comparative effects of idazoxan, efaroxan, and BU 224 on insulin secretion in the rabbit: Not only interaction with pancreatic imidazoline I2 binding sites

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Health 2010年第2期2卷 112-123页

作者： María josé García-Barrado María Francisca pastor María Carmen Iglesias-Osma Christian Carpéné Julio Moratinos 不详

The nature of the binding site(s) involved in the insulin secretory activity of imidazoline compo- unds remains unclear. An imidazoline I2 binding site (I2BS) has been neglected since the classic I2 ligand, idazoxan, does not release insulin. Using the rabbit as an appropriate model for the study of this type of binding sites, we have tried to re-evaluate the effects of idazoxan, the selective I2 compound BU 224, and efaroxan on insulin secretion. Mimicking efaroxan, idazoxan and BU 224 potentiated insulin release from perifused islets in the presence of 8 mM glucose. In static incubation, insulin secretion induced by idazoxan and BU 224 exhibited both dose and glucose dependencies. ATP-sensitive K+ (KATP) channel blockade, though at a different site from the SUR1 receptor, with subsequent Ca2+ entry, mediates the insulin releasing effect of the three ligands. However, additional MAO independent intracellular steps in stimulus- secretion coupling linked to PKA and PKC activation are only involved in the effect of BU 224. Therefore, both an I2 related binding site at the channel level shared by the three ligands and a putative I3-intracellularly located binding site stimulated by BU 224 would be mediating insulin release by these compounds. In vivo experiments reassess the abilities of idazoxan and BU 224 to enhance glucose-induced insulin secretion and to elicit a modest blood glucose lowering response.

关键词： BU 224 Efaroxan Idazoxan Imidazoline Ligands Insulin Secretion IVGTT (Intravenous Glucose Tolerance Test) KATP Channel PK Activity Rabbit Pancreatic Islets

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尼日利亚jos台地前寒武纪基底岩石含锡石的新证据

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地质科技通报 1987年第3期 113-116页

作者： J.pastor A.E.Ogezi 吕宝善

尼日利亚锡石的主要来源是冲积矿床和残积矿床,其母岩是jos台地保罗纪碱性环形杂岩(年轻花岗岩)里的黑云母花岗岩。虽然,从伟晶岩中开采出的锡石不到总产量的5%,这些伟晶岩产于由混合岩、片麻岩、泛非(较老的)花岗岩和伟晶岩所组成的前... 详细信息

尼日利亚锡石的主要来源是冲积矿床和残积矿床,其母岩是jos台地保罗纪碱性环形杂岩(年轻花岗岩)里的黑云母花岗岩。虽然,从伟晶岩中开采出的锡石不到总产量的5%,这些伟晶岩产于由混合岩、片麻岩、泛非(较老的)花岗岩和伟晶岩所组成的前寒武纪基底杂岩内,但随着冲积和残积型矿床储量迅速枯竭,发现新储量的任务就变得十分迫切了。本文对jos附近Gurum地区基底杂岩中的片麻岩、混合岩、伟晶岩和细晶岩内的锡石为一重要的新矿源作了首次报道。这种锡石是由上述岩石遭受淋滤、风化作用后而富集为具有经济意义的矿体的。这类锡石通常比来自侏罗纪黑云母花岗岩的冲积型锡石粒度更细且颜色更深。这一新发现有重要的岩石成因意义和经济意义,它表明基底杂岩可能是年轻花岗岩的母岩,而且可能成为一个在尼日利亚十分重要的潜在锡石来源。

关键词：锡石伟晶岩产状锡矿物脉岩基底岩石 jos 前寒武纪基底尼日利亚

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