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Tres principios de la acción educativa de José Luis González-Simancas y Fernando Carbajo López (2010)

Carlos Daniel Ortiz Caraballo
2017 Praxis & Saber  
En el fondo, el enfoque que proponen González-Simancas y Carbajo López tiene una clara alusión o rescate de la paideia griega.  ...  Reseña del libRo Tres principios de la acción educaTiva de José luis González-simancas y FeRnando caRbaJo lópez(2010)Praxis & Saber -Vol. 8.  ... 
doi:10.19053/22160159.v8.n17.2018.7221 fatcat:7wvkwlxw55ewbpjuy2c2sfirry

A resource for benchmarking the usefulness of protein structure models

Daniel Carbajo, Anna Tramontano
2012 BMC Bioinformatics  
Increasingly, biologists and biochemists use computational tools to design experiments to probe the function of proteins and/or to engineer them for a variety of different purposes. The most effective strategies rely on the knowledge of the three-dimensional structure of the protein of interest. However it is often the case that an experimental structure is not available and that models of different quality are used instead. On the other hand, the relationship between the quality of a model and
more » ... its appropriate use is not easy to derive in general, and so far it has been analyzed in detail only for specific application. Results: This paper describes a database and related software tools that allow testing of a given structure based method on models of a protein representing different levels of accuracy. The comparison of the results of a computational experiment on the experimental structure and on a set of its decoy models will allow developers and users to assess which is the specific threshold of accuracy required to perform the task effectively. Conclusions: The ModelDB server automatically builds decoy models of different accuracy for a given protein of known structure and provides a set of useful tools for their analysis. Pre-computed data for a non-redundant set of deposited protein structures are available for analysis and download in the ModelDB database. Implementation, availability and requirements: Project name: A resource for benchmarking the usefulness of protein structure models. Project home page: http://bl210.caspur.it/MODEL-DB/MODEL-DB_web/MODindex.php.
doi:10.1186/1471-2105-13-188 pmid:22856649 pmcid:PMC3473236 fatcat:ntrr3jy6xzgthi3u43ruboijna

Spontaneous macrocyclization through multiple dynamic cyclic aminal formation

Daniel Carbajo, Antonio Jesús Ruiz-Sánchez, Francisco Nájera Albendín, Ezequiel Perez-Inestrosa, Ignacio Alfonso
2021 Chemical Communications  
The use of aminals in dynamic covalent chemistry is slightly underexplored, probably due to their inherent instability. Here we report the spontaneous [2+2] macrocyclization of tetrakis(aminals). Their unexpected stability and...
doi:10.1039/d0cc07184f pmid:33448267 fatcat:xpyeumplfzgnfmgwr47ht26gwa

Deubiquitinating Enzyme Amino Acid Profiling Reveals a Class of Ubiquitin Esterases [article]

Satpal Virdee, Virginia De Cesare, Daniel Carbajo Lopez, Peter D Mabbitt, Odetta Antico, Nicola T Wood
2020 bioRxiv   pre-print
Acknowledgments We thank Axel Knebel, Richard Ewan, Clare Johnson and Daniel Fountaine from the MRC Protein Production and Assay Development team, and MRC Reagents and Services, who all contributed to  ... 
doi:10.1101/2020.05.11.087965 fatcat:vuczopxvdfbk7cwhqrfuy2lsau

Prostatic tuberculosis: case report

Daniel Sáenz-Abad, Santiago Letona-Carbajo, José Luis de Benito-Arévalo, Isabel Sanioaquín-Conde, Francisco José Ruiz-Ruiz
2008 São Paulo Medical Journal  
CONTEXT: Tuberculosis of the prostate has mainly been described in immunocompromised patients. However, it can exceptionally be found as an isolated lesion in immunocompetent patients. CASE REPORT: We report a case of prostatic tuberculosis in a young, healthy and immunocompetent patient with unremarkable findings from intravenous urographic examination. Computed tomography showed an abscess in the prostate and Mycobacterium tuberculosis was isolated in a urine culture. Treatment with isoniazid, rifampin and pyrazinamide was successful.
doi:10.1590/s1516-31802008000400007 pmid:18853033 fatcat:crojwbww6zg2jogm4jhkwbyqp4

Dynamic Covalent Identification of an Efficient Heparin Ligand

Miriam Corredor, Daniel Carbajo, Cecilia Domingo, Yolanda Pérez, Jordi Bujons, Angel Messeguer, Ignacio Alfonso
2018 Angewandte Chemie  
Miriam Corredor, Daniel Carbajo, Cecilia Domingo, Yolanda Pérez, Jordi Bujons, Angel Messeguer, Ignacio Alfonso* Page No. -Page No.  ... 
doi:10.1002/ange.201806770 fatcat:e3biy76airewnk45cfm5dfknfy

Optimized Stepwise Synthesis of the API Liraglutide Using BAL Resin and Pseudoprolines

Daniel Carbajo, Ayman El-Faham, Miriam Royo, Fernando Albericio
2019 ACS Omega  
The number of peptide-based active pharmaceutical ingredients (APIs) has increased enormously in recent years. Furthermore, the emerging new peptide drug candidates are more complex and larger. For the industrial solid-phase synthesis of C-carboxylic acid peptides, the two main resins available, Wang and chlorotrityl chloride (CTC), have a number of drawbacks. In this context, resins that form an amide bond with the first amino acid are more robust than Wang and CTC resins. Here, we address the
more » ... use of the backbone (BAL) resin for the synthesis of the peptide liraglutide. The BAL resin, in conjunction with the use of pseudoprolines to avoid aggregation, allows the stepwise solid-phase synthesis of this API in excellent purity and yield.
doi:10.1021/acsomega.9b00974 pmid:31459957 pmcid:PMC6648002 fatcat:stkp7txhgnbfbbwygj23gfby5e

Role of VapBC12 Toxin-Antitoxin Locus in Cholesterol-Induced Mycobacterial Persistence

Sakshi Talwar, Manitosh Pandey, Chandresh Sharma, Rintu Kutum, Josephine Lum, Daniel Carbajo, Renu Goel, Michael Poidinger, Debasis Dash, Amit Singhal, Amit Kumar Pandey
2020 mSystems  
The worldwide increase in the frequency of multidrug-resistant and extensively drug-resistant cases of tuberculosis is mainly due to therapeutic noncompliance associated with a lengthy treatment regimen. Depending on the drug susceptibility profile, the treatment duration can extend from 6 months to 2 years. This protracted regimen is attributed to a supposedly nonreplicating and metabolically inert subset of the Mycobacterium tuberculosis population, called "persisters." The mechanism
more » ... g stochastic generation and enrichment of persisters is not fully known. We have previously reported that the utilization of host cholesterol is essential for mycobacterial persistence. In this study, we have demonstrated that cholesterol-induced activation of a RNase toxin (VapC12) inhibits translation by targeting proT tRNA in M. tuberculosis This results in cholesterol-specific growth modulation that increases the frequency of generation of the persisters in a heterogeneous M. tuberculosis population. Also, a null mutant strain of this toxin (ΔvapC12) demonstrated an enhanced growth phenotype in a guinea pig model of M. tuberculosis infection, depicting its role in disease persistence. Thus, we have identified a novel strategy through which cholesterol-specific activation of a toxin-antitoxin module in M. tuberculosis enhances persister formation during infection. The current findings provide an opportunity to target persisters, a new paradigm facilitating tuberculosis drug development.IMPORTANCE The current TB treatment regimen involves a combination of drugs administered for an extended duration that could last for 6 months to 2 years. This could lead to noncompliance and the emergence of newer drug resistance strains. It is widely perceived that the major culprits are the so-called nonreplicating and metabolically inactive "persister" bacteria. The importance of cholesterol utilization during the persistence stage of M. tuberculosis infection and its potential role in the generation of persisters is very intriguing. We explored the mechanism involved in the cholesterol-mediated generation of persisters in mycobacteria. In this study, we have identified a toxin-antitoxin (TA) system essential for the generation of persisters during M. tuberculosis infection. This study verified that M. tuberculosis strain devoid of the VapBC12 TA system failed to persist and showed a hypervirulent phenotype in a guinea pig infection model. Our studies indicate that the M. tuberculosis VapBC12 TA system acts as a molecular switch regulating persister generation during infection. VapBC12 TA system as a drug target offers opportunities to develop shorter and more effective treatment regimens against tuberculosis.
doi:10.1128/msystems.00855-20 pmid:33323416 fatcat:bh7xcsypwrgobpgibg4dae3bwm

Laguerre-Gaussian and beamlet array as second generation laser heater profiles

Nikolas Liebster, Jingyi Tang, Daniel Ratner, Wei Liu, Sharon Vetter, Zhirong Huang, Sergio Carbajo
2018 Physical Review Accelerators and Beams  
The microbunching instability is known to be detrimental to x-ray free electron laser performance. At the Linear Coherent Light Source, the microbunching instability is suppressed with a laser heater, which increases the uncorrelated energy spread of e-beam in the injector. While the current system has been shown to improve x-ray brightness, other laser architectures could further enhance performance. In this study, we model the interaction between a laser and e-beam with arbitrary transverse
more » ... ofiles and examine the effect of various laser designs on the energy distribution of the electrons after the injector and laser heater, as well as their ability to suppress microbunching instability. This simulation incorporates random transverse jitter in order to reproduce physically representative operation of the Linac Coherent Light Source. We compare Gaussian and Laguerre-Gaussian modes, and explore composite beams in the form of an array of Gaussian beamlets. We conclude that the Gaussian laser profile is highly susceptible to e-beam ellipticity and random transverse jitter. The Laguerre-Gaussian profile, a mathematically ideal solution to suppressing microbunching, is less susceptible to these effects and can provide effective suppression even with a distorted e-beam, though performance can be improved by increasing stabilization. The array of beamlets presents a solution that produces consistent and smooth energy distributions with significantly less variance in heating than the Laguerre-Gaussian profile.
doi:10.1103/physrevaccelbeams.21.090701 fatcat:jpnp7yfonvdztae4r5737qavt4

Searching for new cell-penetrating agents: hybrid cyclobutane–proline γ,γ-peptides

Esther Gorrea, Daniel Carbajo, Raquel Gutiérrez-Abad, Ona Illa, Vicenç Branchadell, Miriam Royo, Rosa M. Ortuño
2012 Organic and biomolecular chemistry  
General procedure for 5(6)-Carboxyfluorescein N γ -terminal labeling and Boc group removal of compounds 1-6. Synthesis of peptides 7-12 S2 -Solid phase synthesis: general procedure S2 -Synthesis of compound 14 S3 -Peptide purification and characterization S4 -1 H-NMR and 13 C-NMR spectra for compounds 14, 19, 21, 25, 27, 28, 30, 31, 33, 35 and 37 S17 -Cytotoxicity and cell-uptake properties of peptides 7-12 S28 -Cytotoxicity of peptides, 20, 22, 24, 26, 29, 34, 36, and 38 S28 Electronic
more » ... ntary Material (ESI) compounds 1-6. Synthesis of peptides 7-12. After Cbz removal by H 2 /Pd(C) in peptides 1-6, the unprotected peptide was solved in anhydrous DCM. CF (1.2 eq), PyBOP (1.2 eq) and DIEA (2.4 eq) were solved in minimum amount of NMP and added to the peptide. The reaction was followed by HPLC and 2-4h later, there was no sign of starting material. The reaction mixture was extracted with NaHCO 3 5% aq . The aqueous extracts were mixed together and then lyophilized. After CF-addition, peptide was solved in a TFA / DCM solution (4/6) and it was stirred for 1 h until total conversion. After that, solvent was removed. With the purpose to completely remove all TFA, co-evaporations with toluene (x3) were performed. Then, peptides were purified by semi-preparative HPLC. Solid phase synthesis: general procedure. γ-Hexapeptide backbone was prepared from amino acid (1S,3R)-3-((((9H-fluoren-9yl)methoxy)carbonyl)amino)-2,2-dimethylcyclobutanecarboxylic acid (previously deprotected by reaction of the tert-butyl ester derivative 14 with a 40 % TFA solution in DCM), and the commercially available proline derivative (2S,4S)-4-((9H-fluoren-9-yl)methoxycarbonylamino)-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid, using HBTU and HOBt as coupling agents. MBHA-polystyrene was chosen as the correct solid support to work using Fmoc/Boc chemistry. In order to deprotect the N-terminal group of the methylbenzhydrylamine, the resin was washed for 20 minutes with a 40 % TFA solution in DCM, followed by addition of 20 % DIPEA solution in DCM for 3 minutes. The reaction was monitored by the ninhydrin test. Then, the resin was washed with DMF in order to proceed attaching the first amino acid. All the coupling reactions were carried out for 2 hours approximately using 3 equivalents of the desired amino acid, 3 equivalents of HBTU and HOBT and 9 equivalents of DIPEA, using DMF as solvent and monitored by the ninhydrin test. The resin was washed with DMF (5 x 1 min) and DCM (5 x 1 min) after each coupling. Fmoc deprotection was achieved by washing the resin with a 50 % piperidine solution in DMF (2 x 10 min). For N α -acyl-γ-hexapeptides (33-36), after the N α -Boc groups had been removed, acylation of the αamino groups was carried out using 5-(Boc-amino)valeric acid (Boc-5-Ava-OH) (9 equiv, 3 equiv for each amine), HBTU and HOBt (9 equiv) in the presence of Et 3 N (15 eq) in DMF for 2 h at 25 °C. Proline-cyclobutane γ,γ-hexapeptide 30 The crude peptide was purified by semi-preparative HPLC-MS using a non-linear gradient ( 5 % MeCN for 3 min, increased to 40 % in 1 min, from 40 to 55 % in 8 min, increased to 100 % MeCN in 1 min, and finally the original conditions were re-established) of MeCN (containing 1% of TFA) and H 2 O (containing 1% of TFA). mp 66-69 ºC (from CH 3 CN / H 2 O); [α] D = +10 (c = 0.3, CH 3 OH). Proline-cyclobutane γ,γ-hexapeptide 31 The crude peptide was purified by semi-preparative HPLC-MS using a non-linear gradient ( 5 % MeCN for 3 min, increased to 40 % in 1 min, from 40 to 55 % in 8 min, increased to 100 % MeCN in 1 min, and finally the original conditions were re-established) of MeCN (containing 1% of TFA) and H 2 O (containing 1% of TFA). mp 141-143 ºC (from CH 3 CN / H 2 O); [α] D = +10 (c = 0.3,
doi:10.1039/c2ob25220a pmid:22514076 fatcat:fkfhlzdj2nf5jaxhvqrhao72fu

Host cholesterol dependent activation of VapC12 toxin enriches persister population during Mycobacterium tuberculosis infection [article]

Sakshi Talwar, Manitosh Pandey, Chandresh Sharma, Rintu Kutum, Josephine Lum, Daniel Carbajo, Renu Goel, Michael Poidinger, Debasis Dash, Amit Singhal, Amit Kumar Pandey
2019 bioRxiv   pre-print
Daniel, E. N. Baker, Distant structural homology leads to 528 the functional characterization of an archaeal PIN domain as an exonuclease.  ... 
doi:10.1101/856286 fatcat:utwf5le6z5fg3mkzd2t6fkh52m

Injerto pediculado de asa yeyunal aislada para cubrir perforaciones gástricas experimentales

Carlos Daniel Alberti, Manuel Abella, Humberto Verdinelli, Raúl Mombello, Claudio Fabrizio, Adolfo Barrionuevo, Enrique Travizano, Jorge Carbajo, Eduardo Delgado, Juan Carlos Domínguez
1983 Revista Cirugía del Uruguay  
Basado en la hipótesis de que el corion sumucoso intestinal canino puede resistir la acción clorhidropeptica, en cuarente perros se aplicó un parche de intesti .. no sin mucosa sobre una perforación gástrica observandose a los sesenta días que la mucosa gástrica ha reepitelizado el parche en catorce de veinte perros sacrificados.
doaj:2459d5ae9f324ad0a467b8f1b3e83c4b fatcat:575tjneq4vcmhmv5nmfqztrdua

Retinal isomerization in bacteriorhodopsin captured by a femtosecond X-ray laser

Przemyslaw Nogly, Tobias Weinert, Daniel James, Sergio Carbajo, Dmitry Ozerov, Igor Schapiro, Gebhard Schertler, Richard Neutze, Jürg Standfuss
2018 Acta Crystallographica Section A: Foundations and Advances  
Supplementary Materials for Retinal isomerization in bacteriorhodopsin captured by a femtosecond X-ray laser Przemyslaw Nogly, Tobias Weinert, Daniel James, Sergio Carbajo, Dmitry Ozerov, Antonia Furrer  ... 
doi:10.1107/s2053273318092689 fatcat:idvgevqscnaf5dqxrjmu44w3ya

Copper-Induced Translocation of the Wilson Disease Protein ATP7B Independent of Murr1/COMMD1 and Rab7

Karl Heinz Weiss, Javier Carbajo Lozoya, Sabine Tuma, Daniel Gotthardt, Jürgen Reichert, Robert Ehehalt, Wolfgang Stremmel, Joachim Füllekrug
2008 American Journal of Pathology  
Wilson disease is a genetic disorder of copper metabolism. Impaired biliary excretion results in a gradual accumulation of copper, which leads to severe disease. The specific gene defect lies in the Wilson disease protein, ATP7B, a copper-transporting ATPase that is highly active in hepatocytes. The two major functions of ATP7B in the liver are the copper loading of ceruloplasmin in the Golgi apparatus, and the excretion of excess copper into the bile. In response to elevated copper levels,
more » ... B shows a unique intracellular trafficking pattern that is required for copper excretion from the Golgi apparatus into dispersed vesicles. We analyzed the translocation of ATP7B by both confocal microscopy and RNA interference, testing current models that suggest the involvement of Murr1/COMMD1 and Rab7 in this pathway. We found that although the ATP7B translocation is conserved among nonhepatic cell lines, there is no co-localization with Murr1/COMMD1 or the Rab marker proteins of the endolysosomal system. Consistent with this finding, the translocation of ATP7B was not impaired by the depletion of either Murr1/COMMD1 or Rab7, or by a dominant-negative Rab7 mutant. In conclusion, our data suggest that the translocation of ATP7B takes place independently of Rab7-regulated endosomal traffic events. Murr1/COMMD1 plays a role in a later step of the copper excretion pathway but is not involved in the translocation of the Wilson disease protein.
doi:10.2353/ajpath.2008.071134 pmid:18974300 pmcid:PMC2626389 fatcat:ktrafrv7erbs5hg2wcmgyhyrje

Laguerre-Gaussian Mode Laser Heater for Microbunching Instability Suppression in Free-Electron Lasers

Jingyi Tang, Randy Lemons, Wei Liu, Sharon Vetter, Timothy Maxwell, Franz-Josef Decker, Alberto Lutman, Jacek Krzywinski, Gabriel Marcus, Stefan Moeller, Zhirong Huang, Daniel Ratner (+1 others)
2020 Physical Review Letters  
Microbunching instability (MBI) driven by beam collective effects is known to be detrimental to high-brightness storage rings, linacs, and free-electron lasers (FELs). One known way to suppress this instability is to induce a small amount of energy spread to an electron beam by a laser heater. The distribution of the induced energy spread greatly affects MBI suppression and can be controlled by shaping the transverse profile of the heater laser. Here, we present the first experimental
more » ... ion of effective MBI suppression using a LG_{01} transverse laser mode and compare the improved results with respect to traditional Gaussian transverse laser mode at the Linac Coherent Light Source. The effects on MBI suppression are characterized by multiple downstream measurements, including longitudinal phase space analysis and coherent radiation spectroscopy. We also discuss the role of LG_{01} shaping in soft x-ray self-seeded FEL emission, one of the most advanced operation modes of a FEL for which controlled suppression of MBI is critical.
doi:10.1103/physrevlett.124.134801 pmid:32302180 fatcat:5junzf3mifa4jaqeml77unqmeq
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