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The protein-protein interaction landscape of transcription factors during gynoecium development in Arabidopsis

Molecular Plant 2023年第1期16卷 260-278页

作者： Humberto Herrera-Ubaldo Sergio E.Campos Pablo López-Gómez Valentín Luna-García Víctor M.Zúñiga-Mayo Gerardo E.Armas-Caballero Karla L.González-Aguilera Alexander DeLuna Nayelli Marsch-Martínez Carlos Espinosa-Soto Stefan de Folter Unidad de Genómica Avanzada(UGA-LANGEBIO) Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional(CINVESTAV-IPN)IrapuatoGuanajuato 36824México Departamento de Biotecnología y Bioquímica Unidad IrapuatoCINVESTAV-IPNIrapuatoGuanajuato 36824México Instituto de Física Universidad de San Luis PotosíSan Luis PotosíSLP 78290México Present address:Department of Plant Sciences University of CambridgeCambridgeUK Present address:Department of Molecular and Cellular Biology University of California DavisDavisCAUSA Present address:CONACYT Instituto de FitosanidadColegio de PostgraduadosCampus MontecilloTexcocoMéxico

Flowers are composed of organs whose identity is defined by the combinatorial activity of transcription factors(TFs).The interactions between MADS-box TFs and protein complex formation have been schematized in the floral quartet model of flower development.The gynoecium is the flower’s female reproductive part,crucial for fruit and seed production and,hence,for reproductive success.After the establishment of carpel identity,many tissues arise to form a mature gynoecium.TFs have been described as regulators of gynoecium development,and some interactions and complexes have been identified.However,broad knowledge about the interactions among these TFs and their participation during development remains scarce.In this study,we used a systems biology approach to understand the formation of a complex reproductive unit—as the gynoecium—by mapping binary interactions between well-characterized TFs.We analyzed almost 4500 combinations and detected more than 250 protein-protein interactions(PPIs),resulting in a process-specific interaction map.Topological analyses suggest hidden functions and novel roles for many TFs.In addition,we observed a close relationship between TFs involved in auxin and cytokinin-signaling pathways and other TFs.Furthermore,we analyzed the network by combining PPI data,expression,and genetic data,which helped us to dissect it into several dynamic spatio-temporal subnetworks related to gynoecium development processes.Finally,we generated an extended PPI network that predicts new players in gynoecium development.Taken together,all these results serve as a valuable resource for the plant community.

关键词： interactome networks transcription factors gynoecium development

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Two novel mutations in theGAN gene causing giant axonal neuropathy

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World Journal of Pediatrics 2018年第3期14卷 298-304页

作者： Monica Irad Normendez-martínez Lucero Monterde-Cruz Roberto martínez Magdalena Marquez-Harper nayelli Esquitin-Garduno Margarita Valdes-Flores Leonora Casas-Avila Valeria Ponce de Leon-Suarez Viktor Javier Romero-Díaz Alberto Hidalgo-Bravo Medical Specialties Hospital Boulevard Milenio 130San Carlos la Roncha37660 LeonGuanajuatoMexico Department of Gene tics National Institute of R ehabilitationAvenue Mexico-Xochimilco 28914389 Me xico CityMexico Department ofHis tology School ofMedicineAutonomous University oft heS tate ofN uevo LeonMonterreyMexico

Background Giant axonal neuropathy (GAN) is a rare neurodegenerative disease transmitted in an autosomal recessive mode. This disorder presents motor and sensitive symptoms with an onset in early childhood. Progressive neurodegeneration makes the patients wheelchair dependent by the end of the second decade of life. Affected individuals do not survive beyond the third decade of life. Molecular analysis has identified mutations in the gene GAN in patients with this disorder. This gene produces a protein called gigaxonin which is presumably involved in protein degradation via the ubiquitin-proteasome system. However, the underlying molecular mechanism is not clearly understood yet. Methods Here we present the fi rst patient from Mexico with clinical data suggesting GAN. Sequencing of the GAN gene was carried out. Changes in the nucleotide sequence were investigated for their possible impact on protein function and structure using the publicly available prediction tools PolyPhen-2 and PANTHER. Results The patient is a compound heterozygous carrying two novel mutations in the GAN gene. The sequence analy-sis revealed two missense mutations in the Kelch repeats domain. In one allele, a C>T transition was found in exon 9 at the nucleotide position 55393 (g.55393C>T). In the other allele, a transversion G>T in exon 11 at the nucleotide position 67471 (g.67471G>T) was observed. Both of the bioinformatic tools predicted that these amino acid substitutions would have a negative impact on gigaxonin's function. Conclusion This work provides useful information for health professionals and expands the spectrum of disease-causing mutations in the GAN gene and it is the first documented case in Mexican population.

关键词： GAN Genetics Giant axonal neuropathy Incapacity Neurodegenerative

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Secondary sclerosing cholangitis after critical COVID-19:Three case reports

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World Journal of Hepatology 2022年第8期14卷 1678-1686页

作者： Juan M Mayorquín-Aguilar Aldo Lara-Reyes Luis Alberto Revuelta-Rodríguez nayelli C Flores-García Astrid Ruiz-Margáin Marco Antonio Jiménez-Ferreira Ricardo Ulises Macías-Rodríguez Department of Gastroenterology Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico City 14080Mexico Department of Pathology Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico City 14080Mexico

BACKGROUND The global coronavirus disease 2019(COVID-19)pandemic has caused more than 5 million deaths.Multiorganic involvement is well described,including liver disease.In patients with critical COVID-19,a new entity called"post-COVID-19 cholangiopathy"has been described.CASE SUMMARY Here,we present three patients with severe COVID-19 that subsequently developed persistent cholestasis and chronic liver disease.All three patients required intensive care unit admission,mechanical ventilation,vasopressor support,and broad spectrum antibiotics due to secondary infections.Liver transplant protocol was started for two of the three patients.CONCLUSION Severe COVID-19 infection should be considered a potential risk factor for chronic liver disease and liver transplantation.

关键词： SARS-CoV-2 Persistent cholestasis Liver chemistry Hypoxic cholangiopathy Case report

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XAANTAL2 （AGL14） Is an Important Component of the Complex Gene Regulatory Network that Underlies Arabidopsis Shoot Apical Meristem Transitions

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Molecular Plant 2015年第5期8卷 796-813页

作者： Rigoberto V. Perez-R.u.iz Berenice Garcia-Ponce nayelli marsch-martinez Yamel Ugartechea-Chirino Mitzi Villajuana-Bonequi Stefan de Folter Eugenio Azpeitia Jose Davila-Velderrain David Cruz-Sanchez Adriana Garay-Arroyo Maria de la Paz Sanchez Juan M. Estevez-Palmas Elena R. Alvarez-Buylla Instituto de Ecologia Universidad Nacionat Autonoma de Moxico 3er Circuito Exterior s/no Junto al Jardin Bot~nico and Centro de Ciencias de la ComplejidadCiudad Universitaria Coyoacan 04510 Mexico D.F. Mexico Laboratorio Nacional de Genemica para la Biodiversidad (Langebio) Centro de Investigaci6n y de Estudios Avanzados del Instituto Polit~cnico Nacional(CINVESTAV-IPN) Km. 9.6 Carretera Irapuato - Leen AP 629 36821 Irapuato Guanajuato Mexico University of California 431 Koshland Hall Berkeley CA 94720 USA These authors contributed equally to this article. present address: Departamento de Biotecnologia y Biquimica Centro de )nvestigaci6n y de Estudios Avanzados del Instituto Polit6cnico Nacional(CINVESTAV-IPN) Km. 9.6 Libramiento Norte Carr. Irapuato-Leen 36821 Irapuato Guanajuato Mexico present address: Max Planck Institute for Plant Breeding Research D-50829 Cologne Germany Present address: INRIA Project-Team Virtual Plants/CIRAD/INRA UMR AGAP Campus St Priest - BAT 5 CC 05018 860 rue de St Priest 34095 Montpellier Cedex5 France

In Arabidopsis thaliana, multiple genes involved in shoot apical meristem （SAM） transitions have been char- acterized, but the mechanisms required for the dynamic attainment of vegetative, inflorescence, and floral meristem （VM, IM, FM） cell fates during SAM transitions are not well understood. Here we show that a MADS-box gene, XAANTAL2 （XAL2/AGL14）, is necessary and sufficient to induce flowering, and its regula- tion is important in FM maintenance and determinacy, xal2 mutants are late flowering, particularly under short-day （SD） condition, while XAL2 overexpressing plants are early flowering, but their flowers have vege- tative traits. Interestingly, inflorescences of the latter plants have higher expression levels of LFY, AP1, and TFL1 than wild-type plants. In addition we found that XAL2 is able to bind the TFL1 regulatory regions. On the other hand, the basipetal carpels of the 35S：：XAL2 lines lose determinacy and maintain high levels of WUS expression under SD condition. To provide a mechanistic explanation for the complex roles of XAL2 in SAM transitions and the apparently paradoxical phenotypes of XAL2 and other MADS-box （SOCl, AGL24） over- expressors, we conducted dynamic gene regulatory network （GRN） and epigenetic landscape modeling. We uncovered a GRN module that underlies VM, IM, and FM gene configurations and transition patterns in wild- type plants as well as loss and gain of function lines characterized here and previously. Our approach thus provides a novel mechanistic framework for understanding the complex basis of SAM development.

关键词： XAL2/AGL14 MADS-box TFL1 SAM transitions floral reversion gene regulatory networks,epigenetic landscape modeling

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Prognostic performance of an index based on lactic dehydrogenase and transaminases for patients with liver steatosis and COVID-19

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World Journal of Gastroenterology 2022年第37期28卷 5444-5456页

作者： Ricardo Ulises Macías-Rodríguez Alberto Adrián Solís-Ortega Victoria J Ornelas-Arroyo Astrid Ruiz-Margáin Maria Sarai González-Huezo Nestor A Urdiales-Morán Berenice M Román-Calleja Juan M Mayorquín-Aguilar JoséA González-Regueiro Alejandro Campos-Murguía Israel Vicente Toledo-Coronado Mónica Chapa-Ibargüengoitia Bernardo Valencia-Peña Carlos Fernando martínez-Cabrera nayelli C Flores-García Department of Gastroenterology Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico City 14080Mexico Department of Gastroenterology Centro Médico ISSEMYMToluca 52140Mexico Department of Radiology Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico City 14080Mexico

BACKGROUND Metabolic associated fatty liver disease(MAFLD)is associated with complications and mortality in patients with coronavirus disease 2019(COVID-19).However,there are no prognostic scores aimed to evaluate the risk of severe disease specifically in patients with MAFLD,despite its high prevalence.Lactate dehydrogenase,aspartate aminotransferase and alanine aminotransferase have been used as markers of liver damage.Therefore,we propose an index based on lactate dehydrogenase,aspartate aminotransferase and alanine aminotransferase for the prediction of complications and mortality in patients with MAFLD and COVID-19.AIM To evaluate the prognostic performance of an index based on lactate dehydrogenase and transaminases(aspartate aminotransferase/alanine aminotransferase)in patients with COVID-19 and MAFLD[liver fibrosis and nutrition(LNF)-COVID-19 index].METHODS In this retrospective cohort study,two cohorts from two different tertiary centers were included.The first was the derivation cohort to obtain the score cutoffs,and the second was the validation cohort.We included hospitalized patients with severe COVID-19 and MAFLD.Liver steatosis was evaluated by computed tomography scan.Area under the receiver operating characteristic(ROC)curve analysis and survival analysis were used.RESULTS In the derivation cohort,44.6%had MAFLD;ROC curve analysis yielded a LFN-COVID-19 index>1.67 as the best cutoff,with a sensitivity of 78%,specificity of 63%,negative predictive value of 91%and an area under the ROC curve of 0.77.In the multivariate analysis,the LFN-COVID-19 index>1.67 was independently associated with the development of acute kidney injury(odds ratio:1.8,95%confidence interval:1.3-2.5,P<0.001),orotracheal intubation(odds ratio:1.9,95%confidence interval:1.4-2.4,P<0.001),and death(odds ratio:2.86,95%confidence interval:1.6-4.5,P<0.001)in both cohorts.CONCLUSION LFN-COVID-19 index has a good performance to predict prognosis in patients with MAFLD and COVID-19,which could be useful for the MAFLD population.

关键词： COVID-19 Metabolic associated fatty liver disease Lactate dehydrogenase Transaminases Prognosis Nonalcoholic fatty liver disease

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Nutritional therapy for hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2021年第10期13卷 1440-1452页

作者： Astrid Ruiz-Margáin Berenice M Román-Calleja Paulina Moreno-Guillén JoséA González-Regueiro DeyaniraKúsulas-Delint Alejandro Campos-Murguía nayelli C Flores-García Ricardo Ulises Macías-Rodríguez Liver Nutrition Clinic Department of GastroenterologyInstituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico City 14080Mexico Liver Fibrosis and Nutrition Lab MICTLÁN-Network(Mechanisms of Liver InjuryCell Death and Translational Nutrition in Liver Diseases-Research Network)Mexico City 14080Mexico Department of Gastroenterology Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico City 14080Mexico

Hepatocellular carcinoma(HCC)is the most frequent primary liver cancer and presents together with cirrhosis in most cases.In addition to commonly recognized risk factors for HCC development,such as hepatitis B virus/hepatitis C virus infection,age and alcohol/tobacco consumption,there are nutritional risk factors also related to HCC development including high intake of saturated fats derived from red meat,type of cooking(generation of heterocyclic amines)and contamination of foods with aflatoxins.On the contrary,protective nutritional factors include diets rich in fiber,fruits and vegetables,n-3 polyunsaturated fatty acids and coffee.While the patient is being evaluated for staging and treatment of HCC,special attention should be paid to nutritional support,including proper nutritional assessment and therapy by a multidisciplinary team.It must be considered that these patients usually develop HCC on top of long-lasting cirrhosis,and therefore they could present with severe malnutrition.Cirrhosisrelated complications should be properly addressed and considered for nutritional care.In addition to traditional methods,functional testing,phase angle and computed tomography scan derived skeletal muscle index-L3 are among the most useful tools for nutritional assessment.Nutritional therapy should be centered on providing enough energy and protein to manage the increased requirements of both cirrhosis and cancer.Supplementation with branched-chain amino acids is also recommended as it improves response to treatment,nutritional status and survival,and finally physical exercise must be encouraged and adapted to individual needs.

关键词： Sarcopenia Liver Cancer Diet Branched-chain amino acids Nutrition

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Effect of non-alcoholic beer,diet and exercise on endothelial function,nutrition and quality of life in patients with cirrhosis

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World Journal of Hepatology 2020年第12期12卷 1299-1313页

作者： Ricardo U Macias-Rodriguez Astrid Ruiz-Margain Berenice M Roman-Calleja May E Espin-Nasser nayelli CFlores-Garcia Aldo Torre Gretel Galicia-Hernandez Silvia L Rios-Torres Gabriela Fernandez-del-Rivero Arturo Orea-Tejeda Oscar A Lozano-Cruz Department of Gastroenterology Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiranMexico City 14080Mexico Liver Fibrosis and Nutrition Lab(LFN-Lab) MICTLÁN Network:Mechanisms of Liver InjuryCell Death and Translational Nutrition in Liver Diseases-Research NetworkMexico City 14080Mexico Department of Cardiology Instituto Nacional de Enfermedades RespiratoriasMexico City 14080Mexico Department of Internal Medicine Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiranMexico City 14080Mexico

BACKGROUND The implementation of nutritional strategies targeting several variables at once could benefit patients with cirrhosis.Non-alcoholic beer has different compounds that exert antioxidant,anti-inflammatory and nutritional properties.AIM To evaluate the effect of diet+exercise and non-alcoholic beer on nutritional status,endothelial function and quality of life in patients with cirrhosis.METHODS In this randomized open clinical trial,patients with cirrhosis were randomized into two groups:The intervention(non-alcoholic beer+diet+exercise)and control(water+diet+exercise)group.Treatment consisted of 330 mL nonalcoholic beer/day or the same amount of water,plus an individualized dietary plan and an exercise program with a pedometer-based bracelet to reach at least 5000 steps/d and>2500 above the baseline during 8 wk.Endothelial function(flow-mediated dilation,plethysmography),biochemical and nutritional variables and quality of life(CLDQ)were evaluated.RESULTS Forty-three patients were included in the study,21 in the control group and 22 in the intervention group.The mean age was 53.5±7.8 years,60%were women,the median MELD score was 8(7-10)and most patients were Child-Pugh A(88%).Adherence to the interventions was>90%in both groups,there were no adverse events and all biochemical parameters remained stable in both groups.Endothelial function improved in both groups.All measured nutritional parameters improved in the intervention group,compared to only 2 in the control group and quality of life improved in both groups;however,more domains improved in the intervention group.CONCLUSION The intervention consisting of non-alcoholic beer,diet and exercise seems to be safe and well tolerated in patients with cirrhosis,and shows improvement in nutritional status,endothelial function,and quality of life.These results need to be further confirmed.

关键词： Hops Portal hypertension Sarcopenia Diet Cirrhosis Antioxidants

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Clinical perspectives,assessment,and mechanisms of metabolicassociated fatty liver disease in patients with COVID-19

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World Journal of Gastroenterology 2021年第33期27卷 5502-5519页

作者： Alejandro Campos-Murguía Berenice M Román-Calleja JoséA González-Regueiro Ivonne Hurtado-Díaz-de-León Alberto Adrián Solís-Ortega nayelli C Flores-García Ignacio García-Juárez Astrid Ruiz-Margáin Ricardo Ulises Macías-Rodríguez Department of Gastroenterology Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico City 14080Mexico Liver Fibrosis and Nutrition Lab(LFNLab) MICTLÁN-Network(Mechanisms of Liver InjuryCell Death and Translational Nutrition in Liver Diseases-Research Network)Mexico City 14080Mexico

Metabolic diseases are highly prevalent worldwide and have been associated with adverse clinical outcomes,including mortality,in patients developing coronavirus disease(COVID-19).Because of the close relationship between metabolic diseases such as type 2 diabetes mellitus and obesity and the presence of metabolicassociated fatty liver disease(MAFLD),a high number of cases of patients affected by both MAFLD and COVID-19 would be expected,especially in highrisk populations.Some studies have shown an increased risk of adverse clinical outcomes,viral shedding,and deep vein thrombosis,especially in patients with MAFLD-related liver fibrosis.The predisposition to poor outcomes and severe acute respiratory syndrome coronavirus 2 infection in patients with MAFLD could be secondary to mechanisms common to both,including preexisting systemic chronic inflammation,endothelial dysfunction,and involvement of the renin-angiotensin system.Because of the increased risk of adverse outcomes,MAFLD should be screened in all patients admitted for COVID-19.Available computed tomography scans could be of help,assessment of liver fibrosis is also recommended,favoring noninvasive methods to limit the exposure of healthcare workers.Liver involvement in this population ranges from abnormalities in liver chemistry to hepatic steatosis in postmortem biopsies.Finally,preventive measures should be strongly advocated in patients already known to have MAFLD,including the use of telemedicine and vaccination in addition to general measures.

关键词： Metabolic-associated fatty liver disease COVID-19 Mortality Fibrosis Histology Epidemiology

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