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A role for the Tgf-β/Bmp co-receptor Endoglin in the molecular oscillator that regulates the hair follicle cycle

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Journal of Molecular Cell Biology 2019年第1期11卷 39-52页

作者： Maria I.Calvo-sanc.ez sandra Fernandez-Martos Elisa Carrasco gema Moreno-Bueno Carmelo Bernabeu Miguel Quintanilla Jesus Espada Instituto de Investigaciones Biomedicas'Alberto sols' Consejo Superior de Investigaciones Cientificas(CSIC)-Departamento de BioqufmicaUniversidad Autonoma de Madrid(UAM)Madrid 28029Spain Instituto de Investigaciones Biosanitarias Facultad de Ciencias ExperimentalesUniversidad Francisco de Vitoria(UFV)Pozuelo de Alarcon 28223Spain Centro de Investigacion Biomedica en Red de Cancer(CIBEROnc) Spain Centro de Investigaciones Biologicas Consejo Superior de Investigaciones Cientificas(CSIC)and Centro de Investigacion Biomedica en Red de Enfermedades Raras(CIBERER)Madrid 28040Spain Centro Integrativo de Biologfa y Quimica Aplicada Universidad Bernardo O'HigginsSantiago 8370854Chile Instituto Ramon y Cajal de Investigacion sanitaria(IRYCIs) Hospital Universitario Ramon y CajalMadridSpain

The hair follicle is a biological oscillator that alternates growth,regression,and rest phases driven by the sequential activation of the proliferation differentiation programs of resident stem cell *** activation of hair follicle stem cell niches and subsequent entry into the growing phase is mainly regulated by Wnt/β-catenin signalling,while regression and resting phases are mainly regulated by Tgf-β/Bmp/smad activity.A major question still unresolved is the nature of the molecular switch that dictates the coordinated transition between both signalling *** we have focused on the role of Endoglin(Eng),a key co-receptor for members of the Tgf-β/Bmp family of growth *** an Eng haploinsufficient mouse model,we report that Eng is required to maintain a correct follicle cycling pattern and for an adequate stimulation of hair follicle stem cell *** further report thatβ-catenin binds to the Eng promoter depending on Bmp ***,we show thatβ-catenin interacts with smad4 in a Bmp/Eng-dependent context and both proteins act synergistically to activate Eng promoter *** observations point to the existence of a growth/rest switching mechanism in the hair follicle that is based on an Eng-dependent feedback cross-talk between Wnt/β-catenin and Bmp/smad signals.

关键词： Endoglin hair follicle skin stem cells Wnt/β-catenin Tgf-β/Bmp/smad

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多元文化的碰撞米兰VOLGARE零售空间

室内设计与装修 2023年第2期 146-147页

作者：〔西班牙〕gema Gutierrez 西溪(编译) gema Gutiérrez

VOLGARE门店位于米兰一条繁华的街道上,这是一个将时尚元素和摩托车配件相结合的男装品牌。由gemaGu ti rrez领衔的西班牙设计工作室PUNTO FILIPINO完成了此次空间设计。设计师不拘一格的设计手法实现了她的客户——一位摩托车爱好者的... 详细信息

VOLGARE门店位于米兰一条繁华的街道上,这是一个将时尚元素和摩托车配件相结合的男装品牌。由gemaGu ti rrez领衔的西班牙设计工作室PUNTO FILIPINO完成了此次空间设计。设计师不拘一格的设计手法实现了她的客户——一位摩托车爱好者的愿望,创造了一个致力于展现当代男性风格的零售空间。设计师从米兰的创意场景中汲取灵感,同时参考了墨西哥、摩洛哥、西班牙和葡萄牙设计的色彩和形状。

关键词：摩托车配件零售空间摩托车爱好者设计工作室男装品牌时尚元素空间设计门店

Responsible research and innovation training programmes:implementation and evaluation of the HEIRRI project

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Forensic sciences Research 2021年第3期6卷 320-330页

作者： Ružica Tokalić Ivan Buljan Niels Mejlgaard Mar Carrió Alexander Lang gema Revuelta Ana Marušić HEIRRI Consortium Department of research in Biomedicine and health University of split school of Medicinesplitcroatia Danish centre for studies in research and research Policy Department of Political scienceaarhus UniversityaarhusDenmark health sciences education research Group Department of experimental and health sciencesPompeu Fabra UniversityBarcelonaspain Techno-science&societal Transformation research Group institut für höhere studien-institute for advanced studies(i)Viennaaustria estudies centre on science communication and societyDepartment of experimental and health sciencesPompeu Fabra UniversityBarcelonaspain

Responsible research and innovation,or RRI,is a concept that aims to bring together society and science for a better *** are six key elements of RRI:public engagement,gender equality,science education,open access,ethics and *** Education Institutions and Responsible Research and Innovation(HEIRRI)project aimed to bring the concept of RRI into the educational *** state-of-the-art review of good practices,HEIRRI team developed 10 training programmes on RRI for different higher education institution educational levels,including a summer school and a massive open online course(MOOC).We conducted pilot of the trainings and evaluated participants’*** with HEIRRI training programmes on responsible research and innovation was high,both for participants and for the trainers,and trainings raised awareness of ***’feedback was used to identify areas that need improvement and provided for recommendations for final versions of the HEIRRI training *** order to equip researchers with skills to recognize and apply RRI values,RRI should be included in their *** training is suitable for a range of different disciplines,including forensic science,and is free to use and adjust for specific contexts(available from:https://***/heirri-training-programmes).

关键词： Research integrity research ethics responsible research and innovation responsibility societal inclusion higher education institutions RRI teaching

NLRP3 inflammasome blockade reduces adipose tissue inflammation and extracellular matrix remodeling

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Cellular & Molecular Immunology 2021年第4期18卷 1045-1057页

作者： Xabier Unamuno Javier Gomez-Ambrosi Beatriz Ramirez Amaia Rodriguez sara Becerril Victor Valenti Rafael Moncada Camilo silva Javier salvador gema Fruhbeck Victoria Catalan Metabolic Research Laboratory Clfnica Universidad de NavarraPamplonaSpain CIBER Fisiopatologfa de la Obesidad y Nutricion(CIBEROBN) Instituto de Salud Carlos ⅢPamplonaSpain Obesity and Adipobiology Group Instituto de Investigaci6n Sanitaria de Navarra(IdiSNA)PamplonaSpain Department of surgery Clinica Universidad de NavarraPamplonaSpain Department of Anesthesia Clinica Universidad de NavarraPamplonaSpain Department of Endocrinology&Nutrition Clfnica Universidad de NavarraPamplonaSpain

The NLRP3-IL-1β pathway plays an important role in adipose tissue(AT)-induced inflammation and the development of obesityassociated *** aimed to determine the impact of NLRP3 on obesity and its associated metabolic alterations as well as its role in adipocyte inflammation and extracellular matrix(ECM)*** obtained from 98 subjects were used in a case-control *** expression of different components of the inflammasome as well as their main effectors and inflammation-and ECM remodeling-related genes were *** impact of blocking NLRP3 using siRNA in lipopolysaccharide(LPs)-mediated inflammation and ECM remodeling signaling pathways was *** demonstrated that obesity(Psity-associated T2D(Pncreased the expression of different com ponents of the inflammasome as well as the expression and release of IL-1β and IL-18 in *** also found that obese patients with T2D exhibited increased(Pssion levels of NLRP3,IL1B and *** showed that NLRP3,but not NLRP1,is regulated by inflammation and hypoxia in visceral *** revealed that the inhibition of NLRP3 in human visceral adipocytes significantly blocked(Ps-induced inflammation by downregulating the mRNA levels of CCL2,IL1B,IL6,IL8,s100A8,s100A9,TLR4 and TNF as well as inhibiting(Psecretion of IL1-β into the culture ***,blocking NLRP3 attenuated(Ps-induced expression of important molecules involved in AT fibrosis(COL1A1,COL4A3,COL6A3 and MMP2).These novel findings provide evidence that blocking the expression of NLRP3 reduces AT inflammation with significant fibrosis attenuation.

关键词： NLRP3 Inflammasone Inflammation Obesity Type 2 diabetes Nonalcoholic fatty liver disease

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在追逐古老歌曲中绽放青春

China's Tibet 2022年第3期33卷 53-57页

作者： Dawa Yangjen sonam Drolkar gema Tashi Chojor(图) Li Xiaosu(译) 不详

If yuo have ever been to Ngari,Tibet,there is no question that the vast land utterly struck you down with *** the opportunity has never arisen,however,all you would have to do is listen to gema Tashi Chojor’s *** zhanian (the Tibetan six-stringed zither) plucked by this young,millennial musician take you away to that mysterious,remote land.

关键词： string Tibetan struc

FNDC4 and FNDC5 reduce sARs-CoV-2 entry points and spike glycoprotein s1-induced pyroptosis, apoptosis, and necroptosis in human adipocytes

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Cellular & Molecular Immunology 2021年第10期18卷 2457-2459页

作者： gema Frühbeck Victoria Catalán Víctor Valentí Rafael Moncada Javier Gómez-Ambrosi sara Becerril Camilo silva Piero Portincasa Javier Escalada Amaia Rodríguez Metabolic Research Laboratory Clínica Universidad de NavarraPamplonaSpain CIBER Fisiopatología de la Obesidad y Nutrición(CIBEROBN) Instituto de Salud Carlos IIIMadridSpain Obesity and Adipobiology Group Instituto de Investigación Sanitaria de Navarra(IdiSNA)PamplonaSpain Department of Endocrinology and Nutrition Clínica Universidad de NavarraPamplonaSpain Department of surgery Clínica Universidad de NavarraPamplonaSpain Department of Anesthesia Clínica Universidad de NavarraPamplonaSpain Department of Biomedical sciences and Human Oncology Clinica Medica“A.Murri”University of Bari Medical SchoolPoliclinico HospitalBariItaly.

A sedentary lifestyle and obesity are important risk factors for severe COVID-19 complications and death[1,2].Excessive adipose tissue(AT)might contribute to more extensive viral spread with increased shedding,immune activation,and cytokine amplification[3].several factors secreted by contracting muscle,termed myokines,mediate the beneficial effects of exercise in a wide range of diseases,including obesity[4].Thus,we conducted a study to explore the potential role of myokines of the fibronectin type III domain-containing family,FNDC4 and FNDC5,in mechanisms underlying the increased susceptibility to COVID-19 complications in obesity.

关键词： FNDC5 obesity FND

VAMP2 is implicated in the secretion of antibodies by human plasma cells and can be replaced by other synaptobrevins

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Cellular & Molecular Immunology 2018年第4期15卷 353-366页

作者： Laura Gómez-Jaramillo Raquel Romero-García gema Jiménez-Gómez Lisa Riegle Ana Belén Ramos-Amaya JoséAntonio Brieva Marie Kelly-Worden Antonio Campos-Caro Unidad de Investigación Hospital Universitario Puerta del MarCádizSpain Department of Biology Ball State UniversityMuncieINUSA

The production and secretion of antibodies by human plasma cells(PCs)are two essential processes of humoral *** secretion process relies on a group of proteins known as soluble N-ethylmaleimide-sensitive factor attachment protein receptors(sNAREs),which are located in the plasma membrane(t-sNAREs)and in the antibody-carrying vesicle membrane(v-sNARE),and mediate the fusion of both *** have previously shown that sNAP23 and sTX4 are the t-sNAREs responsible for antibody ***,using human PCs and antibody-secreting cell lines,we studied and characterized the expression and subcellular distribution of vesicle associated membrane protein(VAMP)isoforms,demonstrating that all isoforms(with the exception of VAMP1)are expressed by the referenced ***,the functional role in antibody secretion of each expressed VAMP isoform was tested using *** results show that VAMP2 may be the v-sNARE involved in vesicular antibody *** further support this conclusion,we used tetanus toxin light chain to cleave VAMP2,conducted experiments to verify co-localization of VAMP2 in antibody-carrying vesicles,and demonstrated the coimmunoprecipitation of VAMP2 with sTX4 and sNAP23 and the in situ interaction of VAMP2 with *** together,these findings implicate VAMP2 as the main VAMP isoform functionally involved in antibody secretion.

关键词： exocytosis human immunoglobulin plasma cells VAMP proteins

Concomitant visceral and localized cutaneous leishmaniasis in two Moroccan infants

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Infectious Diseases of Poverty 2018年第1期7卷 330-334页

作者： Tarik Mouttaki Hasnaa Maksouri Jilali El Mabrouki gema Merino-Espinosa Hassan Fellah Mohamed Itri Joaquina Martin-sanc.ez Maha soussi-Abdallaoui soumiya Chiheb Myriam Riyad Centre of Doctoral studies on Health sciences(CED.des sciences de la sante) Doctoral School of ImmunopathologyFaculty of Medicine and PharmacyHassan II University of CasablancaCasablancaMorocco Research Team on Immunopathology of Infectious and systemic Diseases Faculty of Medicine and PharmacyHassan II University of CasablancaCasablancaMorocco Laboratory of Parasitology and Mycology University Hospital Ibn Rochd of CasablancaCasablancaMorocco Department of Parasitology Faculty of PharmacyUniversity of GranadaGranadaSpain Children’s Hospital University Hospital Ibn Rochd of CasablancaCasablancaMorocco Laboratory of Parasitology Faculty of Medicine and PharmacyHassan II University of Casablanca19 rue Tarik Ibn ZiadBP.9154 CasablancaMorocco Department of Dermatology University Hospital Ibn Rochd of CasablancaCasablancaMorocco

Background:Leishmaniases are vector-borne diseases caused by the protozoa of the Leishmania *** clinical spectrum of these diseases extends from benign dermal lesions to visceral *** the Mediterranean region,zoonotic visceral leishmaniasis(ZVL)is caused by *** untreated within two years,the disease usually leads to *** Morocco,ZVL is endemic in the north,with a hundred cases notified each year,mostly in children aged below five ***,we report on two clinical observations in infants presenting unusual concomitant VL and cutaneous leishmaniasis(CL)in *** presentation:In this case study,we report on two infants aged nine and 12 months *** both have a history of febrile splenomegaly,anemia,and pallor of mucous *** leishmaniasis was confirmed by parasitological diagnosis(positive bone marrow smear and screening of *** antibodies).However,the clinical examination also showed cutaneous lesions that suggested the presence of *** was reinforced by the patients having a history of living or traveling to endemic ***,direct examination,culture,and PCR-RFLP(ITs1-Hae 3)were carried out on the patients’dermal *** one of the infants,CL was associated with ***,while in the other it was associated with *** infants were treated as according to the recommendations of the Ministry of *** patients were cured in two months;defervescence,reduction of splenomegaly,and healing of cutaneous lesions were all ***:These singular patients illustrate the clinical polymorphism of CL and the necessity of updating the differential diagnosis of leukemia-like syndromes,including VL,in children living in or travelling to known endemic *** observations suggest a change in the Mediterranean VL phenotype that may be associated with CL.

关键词： Visceral leishmaniasis Cutaneous leishmaniasis Leishmania infantum Leishmania tropica Infants Morocco

Use of pocket pulse oximeters for detecting peripheral arterial disease in patients with diabetes mellitus

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Journal of Diabetes Mellitus 2013年第2期3卷 79-85页

作者： Javier Ena Carlos R. Argente Víctor González-sánc.ez Natividad Algado gema Verdú Teresa Lozano Division of Cardiology Hospital Marina Baixa Villajoyosa Alicante Spain Division of Endocrinology and Metabolism Hospital Marina Baixa Villajoyosa Alicante Spain Division of General Internal Medicine Hospital Marina Baixa Villajoyosa Alicante Spain

Recent Aims: New diagnostic methods are needed to detect peripheral arterial disease easier than using the ankle-brachial index measured by Doppler devices. We investigated whether the use of pocket pulse oximeters could meet sensitivity and specificity criteria as screening method to detect significant peripheral arterial perfusion deficits. Methods: We measured oxygen saturation (saO2) at index fingers and great toes (on horizontal and elevated 30°) by a pocket pulse oximeter in 250 subjects with diabetes mellitus attending the outpatient clinic. A finger-to-toe saO2 gradient greater than 2% was considered abnormal. Ankle-brachial index was measured by a hand held Doppler device. Peripheral arterial disease was defined as an ankle-brachial index less than 0.9. Results: A total of 1392 (93%) valid saO2 readings were obtained. Twenty-seven (11%) patients were excluded due to not having measurable saO2 finger-to-toe gradients. A total of 223 patients were analyzed. Peripheral arterial disease was detected in 47 (21%) patients. A finger-to-toe saO2 gradient greater than 2% had sensitivity 42.6% (95% CI 30.0% - 55.3%), specificity 79.1% (95% CI 75.7% - 82.6%), positive predictive value 35.7% (95% CI 25.2% - 46.4%), negative predictive value 83.4% (95% CI 79.8 - 87.1), positive likelihood ratio 2.03 (95% CI 1.23 - 3.17) and negative likelihood ratio 0.73 (95% CI 0.54 - 0.93) to detect peripheral arterial disease. The area under the receiving operating characteristic curve was 0.69 (95% CI 0.62 - 0.77). Conclusion: Pocket pulse oximeters showed insufficient sensitivity as screening method for detecting peripheral arterial disease in patients with diabetes mellitus.

关键词： Ankle-Brachial Pressure Index Doppler Ultrasound Pulse Oximetry Comparative study sensitivity specificity Likelihood Ratio