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MEP pathway products allosterically promote monomerization of deoxy-D-xylulose-5-phosphate synthase to feedback-regulate their supply

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Plant Communications 2023年第3期4卷 171-182页

作者： supply Xueni Di David Ortega-Alarcon Ramu Kakumanu Javier Iglesias-Fernandez Lucia diaz Edward E.K.Baidoo Adrian Velazquez-Campoy manuel Rodríguez-Concepción Jordi Perez-Gil Institute for Plant Molecular and Cell Biology(IBMCP) CSIC-Universitat Politècnica de València46022 ValenciaSpain 2Centre for Research in Agricultural Genomics(CRAG)CSIC-IRTA-UAB-UBCampus UAB Bellaterra08193 BarcelonaSpain 3Institute for Biocomputation and Physics of Complex Systems(BIFI)Joint Unit GBsC-CSIC-BIFIUniversidad de Zaragoza50009 ZaragozaSpain 4Departamento de Bioquímica y Biología Molecular y CelularUniversidad de Zaragoza50009 ZaragozaSpain 5Joint BioEnergy Institute5885 Hollis StreetEmeryvilleCA 94608USA 6Biological Systems and Engineering DivisionLawrence Berkeley National LaboratoryBerkeleyCA 94720USA 7Nostrum Biodiscovery SL08029 BarcelonaSpain 8Instituto de Investigación Sanitaria de Aragón(IIS Aragon)50009 ZaragozaSpain 9Centro de Investigación Biomédica en Red en elÁrea Temática de Enfermedades Hepáticas y Digestivas(CIBERehd)28029 MadridSpain

Isoprenoids are a very large and diverse family of metabolites required by all living *** isoprenoids derive fromthe double-bond isomers isopentenyl diphosphate(IPP)and dimethylallyl diphosphate(DMAPP),which are produced by the methylerythritol 4-phosphate(MEP)pathway in bacteria and plant *** has been reported that IPP and DMAPP feedback-regulate the activity of deoxyxylulose 5-phosphate synthase(DXS),a dimeric enzyme that catalyzes the main flux-controlling step of the MEP *** we provide experimental insights *** titration calorimetry and dynamic light scattering approaches showed that IPP and DMAPP can allosterically bind to DXS in vitro,causing a size *** silico ligand binding site analysis and docking calculations identified a potential allosteric site in the contact region between the two monomers of the active DXS *** of IPP and DMAPP contents in vivo followed by immunoblot analyses confirmed that high IPP/DMAPP levels resulted in monomerization and eventual aggregation of the enzyme in bacterial and plant *** of the enzymatically active dimeric conformation allows a fast and reversible reduction of DXS activity in response to a sudden increase or decrease in IPP/DMAPP supply,whereas aggregation and subsequent removal of monomers that would otherwise be available for dimerization appears to be a more drastic response in the case of persistent IPP/DMAPP overabundance(e.g.,by a blockage in their conversion to downstream isoprenoids).Our results represent an important step toward understanding the regulation of the MEP pathway and rational design of biotechnological endeavors aimed at increasing isoprenoid contents in microbial and plant systems.

关键词： isoprenoids DXS feedback regulation allosteric monomerization

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Concentrated Extract of Green Tea Polyphenols Enhances the Toxicity of the Elderberry Lectin Nigrin b to Mice

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Food and Nutrition Sciences 2014年第5期5卷 466-471页

作者： Pilar Jiménez Patricia Cabrero Jesús Tejero manuel J. Gayoso manuel Garrosa Damián Cordoba-diaz manuel Cordoba-diaz Tomás Girbés Biología Celular Histología y Farmacología Facul- tad de Medicina and INCYL (Instituto de Neurociencias de Castilla y León) Universidad de Valladolid Valladolid Spain Farmacia y Tecnología Farmacéutica Facultad de Farmacia and IUFI (Instituto Universitario de Farmacia Industrial) Universidad Complu- tense de Madrid Madrid Spain Nutrición y Bromatología Facultad de Medicina and CINAD (Centro de Investigación en Nutrición Alimentación y Dietética Edi- ficio LUCIA-Parque Científico) Universidad de Valladolid Valladolid Spain Nutrición y Bromatología Facultad de Medicina and CINAD (Centro de Investigación en Nutrición Alimentación y Dietética Edi- ficio LUCIA-Parque Científico) Universidad de Valladolid Valladolid Spain

The effect of the administration of large amounts of green tea polyphenols is a matter of controversy. We explored whether a polyphenol mixture from a concentrated green tea extract (Polyphenon 60) could alter the effects on mice of the type 2 (two chains) ribosome-inactivating protein nigrin b isolated from Sambucus nigra L. Nigrin b triggers specific reversible toxic effects on the mouse intestines featured by apoptosis of mice Lieberkühn crypt cells upon parenteral administration of sub-lethal amounts. Independent administration to mice of 30 mg/kg body weight of Polyphenon 60 by oral gavage or 10 mg/kg body weight of nigrin b administered via the intraperitoneal route (i.p.) did not affect survival. In contrast, the simultaneous treatment greatly enhanced nigrin b toxicity leading to the death of some animals. The histological analysis revealed that the most serious injury was inflicted on the small intestine crypts, which disappeared, and on the liver, which evidenced hepatotoxicity showing haemorrhagic areas. These findings raise concerns about the abuse of high concentrations of green tea polyphenols especially when the intestinal mucosa is damaged, for instance by toxins or therapeutic drugs.

关键词： Green Tea Polyphenols Nigrin b Model Ribosome-Inactivating Protein Lectin Small Intestine Liver Apoptosis

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Increased postoperative complications after protective ileostomy closure delay: An institutional study

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World Journal of Gastrointestinal Surgery 2014年第9期6卷 169-174页

作者： Ines rubio-Perez Miguel Leon Daniel Pastor Joaquin diaz Dominguez Ramon Cantero General and Digestive Surgery Department La Paz University Hospital

AIM: To study the morbidity and complications as-sociated to ileostomy reversal in colorectal surgery pa-tients, and if these are related to the time of closure. METHODS: A retrospective analysis of 93 patients, who had undergone elective ileostomy closure between 2009 and 2013 was performed. Demographic, clinical and surgical variables were reviewed for analysis. All complications were recorded, and classified according to the Clavien-Dindo Classification. Statistical univariate and multivariate analysis was performed, setting a P value of 0.05 for ***: The patients had a mean age of 60.3 years, 58% male. The main procedure for ileostomy cre-ation was rectal cancer(56%), and 37% had received preoperative chemo-radiotherapy. The average delay from creation to closure of the ileostomy was 10.3 mo. Postoperative complications occurred in 40% of the pa-tients, with 1% mortality. The most frequent were ileus(13%) and wound infection(13%). Pseudomembra-nous colitis appeared in 4%. Increased postoperative complications were associated with delay in ileostomyclosure(P = 0.041). Male patients had more complica-tions(P = 0.042), mainly wound infections(P = 0.007). Pseudomembranous colitis was also associated with the delay in ileostomy closure(P = 0.003). End-to-end in-testinal anastomosis without resection was significantly associated with postoperative ileus(P = 0.037). CONCLUSION: Although closure of a protective il-eostomy is a fairly common surgical procedure, it has a high rate of complications, and this must be taken into account when the indication is made. The delay in stoma closure can increase the rate of complications in general, and specifically wound infections and colitis.

关键词： Protective ileostomy Stomas Stoma-relat-ed complications Surgical infections Colorectal surgery

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Maternal Response of Perinatally Underfed Wistar Virgin Females Exposed to Newborn Rats

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Journal of Behavioral and Brain Science 2019年第3期9卷 78-89页

作者： manuel Salas Mirelta Regalado Carmen Torrero Minerva Ortiz-Valladares Lorena rubio Department of Developmental Neurobiology and Neurophysiology Institute of Neurobiology National Autonomous University of Mexico Campus UNAM Juriquilla Queretaro Mexico

Nutrition plays a major role in the survival of the progeny, and its perinatal deficiencies delay physical development and interfere with social and cognitive performance later in life. The effects of early undernutrition on maternal social performance of sensitized adult virgin rats were evaluated. Several maternal and non-maternal responses were measured in virgin female Wistar rats randomly divided into two groups, control and early undernourished, during 19 days of chronic daily exposure to fresh foster pups in home-cage conditions. Underfed females (F0) received different percentages of a balanced diet during gestation. After birth, pups were underfed (F1) by alternating every 12 h between litters two lactating dams, one with ligated nipples. Weaning was at 25 days of age followed by an ad lib diet until postpartum day 90, when sensitized virgins were maternally tested daily for seven successive sessions. Significantly (p < 0.05) low body weight scores in UG F1 virgins of five different ages were observed. The UG F1 females expressed significantly (p < 0.05) lower frequency values in sniffing, licking, retrieving, crouching, and handling shavings, with clear prolonged sniffing, retrieving and handling shaving latencies towards the foster pups compared with CG F1 sensitized females. Self-grooming was not affected, whereas exploration was significantly reduced. Current findings suggest that perinatal undernutrition interfered the organization of a core neuronal circuitry underlying the mother-litter interactions involved in social and cognitive performance of sensitized adult virgins. Furthermore, the behavioral maternal alterations in F1 virgins may possibly generate a risky negative social environment to induce cognitive and/or brain disorders in later generations.

关键词： Early Undernutrition Maternal Sensitization Cognitive Development Rats

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Plasma Accumulations of Vitamin B6 from an Oral Dose in a New Reversible Model for Mouse Gut Injury and Regeneration

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Food and Nutrition Sciences 2013年第9期4卷 908-917页

作者： Pilar Jiménez Damián Cordoba-diaz Patricia Cabrero Mónica Aracil manuel J. Gayoso manuel Garrosa manuel Cordoba-diaz Tomás Girbés Biología Celular Histología y Farmacología Facultad de Medicina and INCYL (Instituto de Neurociencias de Castilla y León) Universidad de Valladolid Valladolid Spain. Farmacia y Tecnología Farmacéutica Facultad de Farmacia and IUFI (Instituto Universitario de Farmacia Industrial) Universidad Complutense de Madrid Madrid Spain Nutrición y Bromatología Facultad de Medicina and CINAD (Centro de Investigación en Nutrición Alimentación y Dietética- Edificio LUCIA-Parque Científico) Universidad de Valladolid Valladolid Spain

Chemically based rodent models are used to assess the positive effects promoted by foods and gut microbiota on gut health. Lectins with enzymatic activity, such as type 2 ribosome-inactivating proteins, might also prove useful for exploring these issues. Sub-lethal doses of the lectin nigrin from Sambucus nigra L. to mice promoted reversible derangement of gut epithelium by induction of apoptosis of transit amplifying cells of the small intestine crypts in a time-dependent course. The present work seeks to study vitamin B6 accumulation in plasma from an oral bolus in a mouse nigrin model. 24 h after sub-lethal nigrin b treatment, there was clear body weight reduction associated to a notable increase in Evan’s blue stain accumulation in excised small intestine, an increase in myeloperoxidase activity, and a near 50% reduction in plasma accumulation of vitamin B6. Histological analysis of small intestine sections of nigrin b-treated animals also revealed significant derangement of intestinal crypts. Seventy two hours after nigrin b treatment, stain uptake decreased and vitamin B6 accumulation was almost restored despite villi derangement. Large intestine crypts were scarcely or not at all affected. Eight days after nigrin b treatment, vitamin B6 uptake and intestinal crypt structure had fully recovered. The nigrin b mice model supports the view that, under these conditions, the carrier-mediated vitamin B6 uptake component of the small intestine crypts is probably the most active when the vitamin is administered orally as a bolus. The findings provide insights into the suitability of the present mice model for nutritional or drug absorption studies in conditions of partially altered or injured intestinal mucosa.

关键词： Vitamin B6 Nigrin b Ribosome-Inactivating Protein Sambucus Ricin Intestines Mice Model

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Olfactory Discrimination in Adult Male Rats Undernourished during the Pre- and Neonatal Period

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Journal of Behavioral and Brain Science 2012年第3期2卷 283-290页

作者： Mitzi G. Carreon Carmen Torrero Mirelta Regalado Lorena rubio manuel Salas Developmental Neurobiology and Neurophysiology Department Neurobiology Institute University of Mexico Campus UNAM Juriquilla Queretaro Mexico

In the neonatal rat, the olfactory system is a fundamental channel to locate and recognize the mother, to survive and develop early social behavior, and to distinguish related or unrelated members of a litter. Perinatal undernutrition in rats alters the neuronal organization and functioning of the olfactory system and its ascending relays, possibly affecting odor discrimination. In this study we compared the frequency and time spent visiting the source of urine obtained from unrelated female subjects and amyl acetate odors vs water in adult perinatally underfed rats. Each test initiated with one daily presentation during three consecutive aliquots of deionized water (10 μl) placed on a filter paper for 2 min, separated by 1-min intervals for habituation. The water presentations were followed by three exposures to an odor, all at the same dilution (either 1:1 or 1:80) for dishabituation. Control (C) and undernourished (U) subjects display similar, significant habituation/dishabituation responses, except that the U subjects showed greater increases in the frequency and duration of visits to undiluted and diluted urine and amyl acetate cues compared to the controls. These findings are similar to previous studies showing that adult rats investigate novel odors longer than the familiar ones. Thus, perinatal undernutrition appears to interfere with the foundation of the olfactory development causing long-term olfactory discrimination deficits as revealed by the increased frequency and duration of visits to the source of odors that may be relevant for social behavior.

关键词： Olfactory Discrimination Main Olfactory System Perinatal Undernutrition

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Pathogenesis of glomerular haematuria

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World Journal of Nephrology 2015年第2期4卷 185-195页

作者： Claudia Yuste Eduardo Gutierrez Angel manuel Sevillano Alfonso rubio-Navarro Juan manuel Amaro-Villalobos Alberto Ortiz Jesus Egido manuel Praga Juan Antonio Moreno Department of Nephrology Gregorio Mara?on Hospital Department of Nephrology Renal Vascular and Diabetes Research LabⅡS-Fundación Jiménez Díaz Autonoma University (UAM) Renal Vascular and Diabetes Research LabⅡS-Fundación Jiménez DíazAutonoma University (UAM)

Haematuria was known as a benign hallmark of some glomerular diseases, but over the last decade, new evidences pointed its negative implications on kidneydisease progression. Cytotoxic effects of oxidative stress induced by hemoglobin, heme, or iron released from red blood cells may account for the tubular injury observed in human biopsy specimens. However, the precise mechanisms responsible for haematuria remain unclear. The presence of red blood cells （RBCs） with irregular contours and shape in the urine indicates RBCs egression from the glomerular capillary into the urinary space. Therefore glomerular haematuria may be a marker of glomerular filtration barrier dysfunction or damage. In this review we describe some key issues regarding epidemiology and pathogenesis of haematuric diseases as well as their renal morphological fndings.

关键词： Haematuria Pathogenesis Glomerular filtration barrier Dysmorphic red blood cells Chronic kidney disease Microscopic haematuria

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Telomere function in colorectal cancer

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World Journal of Gastrointestinal Oncology 2009年第1期1卷 3-11页

作者： Cristina Frías Alberto Morán Carmen de Juan Paloma Ortega Tamara Fernández-Marcelo Andrés Sánchez-Pernaute Antonio José Torres Eduardo Díaz-rubio manuel Benito Pilar Iniesta Department of Biochemistry and Molecular Biology Faculty of PharmacyComplutense University Surgery Service San Carlos Hospital Oncology Service San Carlos Hospital

Colorectal cancer is the third most common form of cancer and the second leading cause of cancer-related death in the western *** cells acquire the hallmarks of cancer during the carcinogenic selection *** immortality is one of the principal features acquired during this process which involves the stabilization of telomere *** is achieved mainly,by telomerase ***,the discovery of telomeres and telomerase allowed an understanding of the mechanisms by which cells can become *** studies have shown that tumour cells have shorter telomeres than nontumour cells and have detected telomerase activity in the majority of *** studies have determined that telomere maintenance and telomerase activity are associated with poor *** into account all the results achieved by different groups,quantification and evaluation of telomerase activity and measurement of telomere length may be useful methods for additional biologic and prognostic staging of colorectal carcinoma.

关键词： Colorectal cancer Telomeres Immortality

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Orbital magneto-optical response of periodic insulators from first principles

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npj Computational Materials 2019年第1期5卷 874-882页

作者： Irina V.Lebedeva David A.Strubbe Ilya V.Tokatly Angel rubio Nano-Bio Spectroscopy Group and ETSF Departamento de Física de MaterialesUniversidad del País Vasco UPV/EHU20018 San SebastiánSpain Department of Physics School of Natural SciencesUniversity of CaliforniaMercedCA 95343USA Donostia International Physics Center(DIPC) Manuel de Lardizabal 520018 San SebastiánSpain IKERBASQUE Basque Foundation for Science48011 BilbaoSpain Max Planck Institute for the Structure and Dynamics of Matter and Center for Free-Electron Laser Science Luruper Chaussee 14922761 HamburgGermany

Magneto-optical response,*** response in the presence of a magnetic field,is commonly used for characterization of materials and in optical ***,quantum mechanical description of electric and magnetic fields in crystals is not straightforward as the position operator is ill *** present a reformulation of the density matrix perturbation theory for time-dependent electromagnetic fields under periodic boundary conditions,which allows us to treat the orbital magneto-optical response of solids at the ab initio *** efficiency of the computational scheme proposed is comparable to standard linearresponse calculations of absorption spectra and the results of tests for molecules and solids agree with the available experimental data.A clear signature of the valley Zeeman effect is revealed in the continuum magneto-optical spectrum of a single layer of hexagonal boron *** present formalism opens the path towards the study of magneto-optical effects in strongly driven low-dimensional systems.

关键词： periodic magneto solids

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Differential colorectal carcinogenesis:Molecular basis and clinical relevance

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World Journal of Gastrointestinal Oncology 2010年第3期2卷 151-158页

作者： Alberto Morán Paloma Ortega Carmen de Juan Tamara Fernández-Marcelo Cristina Frías Andrés Sánchez-Pernaute Antonio José Torres Eduardo Díaz-rubio Pilar Iniesta manuel Benito the second Department of Biochemistry and Molecular Biology School of PharmacyComplutense University Surgery Service Ⅱ Clínico San Carlos Hospital Oncology Service Clínico San Carlos Hospital

Colorectal cancer(CCR) is one of the most frequent cancers in developed *** poses a major public health problem and there is renewed interest in understanding the basic principles of the molecular biology of colorectal *** has been established that sporadic CCRs can arise from at least two different carcinogenic *** traditional pathway,also called the suppressor or chromosomal instability pathway,follows the Fearon and Vogelstein model and shows mutation in classical oncogenes and tumour suppressor genes,such as K-ras,adenomatous polyposis coli,deleted in colorectal cancer,or *** in the Wnt pathway are also very common in this type of *** second main colorectal carcinogenesis pathway is the mutator *** pathway is present in nearly 15% of all cases of sporadic colorectal *** is characterized by the presence of mutations in the microsatellite sequences caused by a defect in the DNA mismatch repair genes,mostly in hMLH1 or *** two pathways have clear molecular differences,which will be reviewed in this article,but they also present distinct histopathological *** strikingly,their clinical behaviours are completely different,having the "mutator" tumours a better outcome than the "suppressor" tumours.

关键词： Colorectal cancer Microsatellite instability Clinical outcome

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