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1.
Int J Mol Sci ; 25(2)2024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38255911

RESUMEN

The chorioallantoic membrane (CAM) model, generated during avian development, can be used in cancer research as an alternative in vivo model to perform tumorigenesis in ovo due to advantages such as simplicity, low cost, rapid growth, and being naturally immunodeficient. The aim of this systematic review has been to compile and analyze all studies that use the CAM assay as a tumor induction model. For that, a systematic search was carried out in four different databases: PubMed, Scopus, Cochrane, and WOS. After eliminating duplicates and following the established inclusion and exclusion criteria, a total of 74 articles were included. Of these, 62% use the in ovo technique, 13% use the ex ovo technique, 9% study the formation of metastasis, and 16% induce tumors from patient biopsies. Regarding the methodology followed, the main species used is chicken (95%), although some studies use quail eggs (4%), and one article uses ostrich eggs. Therefore, the CAM assay is a revolutionary technique that allows a simple and effective way to induce tumors, test the effectiveness of treatments, carry out metastasis studies, perform biopsy grafts of patients, and carry out personalized medicine. However, unification of the methodology used is necessary.


Asunto(s)
Neoplasias Experimentales , Animales , Embrión de Pollo , Humanos , Bioensayo , Membrana Corioalantoides , Medicina de Precisión
2.
Support Care Cancer ; 31(2): 105, 2023 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-36625997

RESUMEN

The aim of this study was to investigate mobility, physical functioning, peripheral muscle strength, inspiratory muscle strength and pulmonary function in surgical cancer patients admitted to an intensive care unit (ICU). We conducted a prospective cohort study with 85 patients. Mobility, physical functioning, peripheral muscle strength, inspiratory muscle strength, and pulmonary function were assessed using the following tests: ICU Mobility Scale (IMS); Chelsea Critical Care Physical Assessment (CPAx); handgrip strength and Medical Research Council Sum-Score (MRC-SS); maximal inspiratory pressure (MIP) and S-Index; and peak inspiratory flow, respectively. The assessments were undertaken at ICU admission and discharge. The data were analyzed using the Shapiro-Wilk and Wilcoxon tests and Spearman's correlation coefficient. Significant differences in inspiratory muscle strength, CPAx, grip strength, MRC-SS, MIP, S-Index, and peak inspiratory flow scores were observed between ICU admission and discharge. Grip strength showed a moderate correlation with MIP at admission and discharge. The findings also show a moderate correlation between S-Index scores and both MIP and peak inspiratory flow scores at admission and a strong correlation at discharge. Patients showed a gradual improvement in mobility, physical functioning, peripheral and inspiratory muscle strength, and inspiratory flow during their stay in the ICU.


Asunto(s)
Fuerza de la Mano , Neoplasias , Humanos , Estudios Prospectivos , Fuerza Muscular/fisiología , Unidades de Cuidados Intensivos , Neoplasias/cirugía , Músculos Respiratorios
3.
Inorg Chem ; 61(46): 18590-18600, 2022 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-36346983

RESUMEN

Reduction of nitrous oxide (N2O) with H2 to N2 and water is an attractive process for the decomposition of this greenhouse gas to environmentally benign species. Herein, a series of iridium complexes based on proton-responsive pincer ligands (1-4) are shown to catalyze the hydrogenation of N2O under mild conditions (2 bar H2/N2O (1:1), 30 °C). Among the tested catalysts, the Ir complex 4, based on a lutidine-derived CNP pincer ligand having nonequivalent phosphine and N-heterocyclic carbene (NHC) side donors, gave rise to the highest catalytic activity (turnover frequency (TOF) = 11.9 h-1 at 30 °C, and 16.4 h-1 at 55 °C). Insights into the reaction mechanism with 4 have been obtained through NMR spectroscopy. Thus, reaction of 4 with N2O in tetrahydrofuran-d8 (THF-d8) initially produces deprotonated (at the NHC arm) species 5NHC, which readily reacts with H2 to regenerate the trihydride complex 4. However, prolonged exposure of 4 to N2O for 6 h yields the dinitrogen Ir(I) complex 7P, having a deprotonated (at the P-arm) pincer ligand. Complex 7P is a poor catalytic precursor in the N2O hydrogenation, pointing out to the formation of 7P as a catalyst deactivation pathway. Moreover, when the reaction of 4 with N2O is carried out in wet THF-d8, formation of a new species, which has been assigned to the hydroxo species 8, is observed. Finally, taking into account the experimental results, density functional theory (DFT) calculations were performed to get information on the catalytic cycle steps. Calculations are in agreement with 4 as the TOF-determining intermediate (TDI) and the transfer of an apical hydrido ligand to the terminal nitrogen atom of N2O as the TOF-determining transition state (TDTS), with very similar reaction rates for the mechanisms involving either the NHC- or the P-CH2 pincer methylene linkers.

4.
Int J Mol Sci ; 23(23)2022 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-36499129

RESUMEN

Breast cancer is the most common type of cancer in women, with chemotherapy being the main strategy. However, its effectiveness is reduced by drug resistance mechanisms. miR-21 is upregulated in breast cancer that has been linked to drug resistance and carcinogenic processes. Our aim was to capture miR-21 with a circular sponge (Circ-21) and thus inhibit the carcinogenic processes and drug resistance mechanisms in which it participates. Proliferation, migration, colony formation, cell cycle, and poly [ADP-ribose] polymerase 1 (PARP-1) and vascular endothelial growth factor (VEGF) detection assays were performed with MCF7 breast cancer cells and MCF10A non-tumor cells. In addition, doxorubicin resistance tests and detection of drug resistance gene expression were performed in MCF7 cells. Reduction in proliferation, as well as migration and colony formation, increased PARP-1 expression, inhibition of VEGF expression and cell cycle arrest in G2/M phase were displayed in the Circ-21 MCF7, which were not observed in the MCF10A cells. Furthermore, in the MCF7 cells, the Circ-21 enhanced the antitumor activity of doxorubicin and decreased the expression of resistance genes: ABCA1, ABCC4, and ABCC5. Based on these results, the use of Circ-21 can be considered a first step for the establishment of an effective gene therapy in the treatment of breast cancer.


Asunto(s)
Neoplasias de la Mama , MicroARNs , Femenino , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Regulación Neoplásica de la Expresión Génica , MicroARNs/uso terapéutico , Línea Celular Tumoral , Proliferación Celular , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico
5.
J Community Psychol ; 49(7): 2590-2608, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33881800

RESUMEN

This study highlights the pathways of clients' social service usage through qualitative interviews and visual mapping methodology. Undergraduate students interviewed clients at diverse social service agencies in Los Angeles that include homeless shelters, child welfare organizations, domestic violence organizations, LGBTQIA youth-oriented agencies, nonprofits serving older adults, schools, and organizations serving low-income families. Students used the information gathered from the interviews to visually map their clients' environmental and structural barriers, as well as their pathways to service. The research team then analyzed the students' visual maps to create one cohesive, complex, and multilayered visual map representing clients' overall barriers and pathways to social services in Los Angeles.


Asunto(s)
Personas con Mala Vivienda , Bienestar Social , Adolescente , Anciano , Niño , Humanos , Los Angeles , Organizaciones sin Fines de Lucro , Servicio Social
6.
J Biol Chem ; 294(12): 4538-4545, 2019 03 22.
Artículo en Inglés | MEDLINE | ID: mdl-30696770

RESUMEN

Astrotactin 1 (Astn1) and Astn2 are membrane proteins that function in glial-guided migration, receptor trafficking, and synaptic plasticity in the brain as well as in planar polarity pathways in the skin. Here we used glycosylation mapping and protease protection approaches to map the topologies of mouse Astn1 and Astn2 in rough microsomal membranes and found that Astn2 has a cleaved N-terminal signal peptide, an N-terminal domain located in the lumen of the rough microsomal membranes (topologically equivalent to the extracellular surface in cells), two transmembrane helices, and a large C-terminal lumenal domain. We also found that Astn1 has the same topology as Astn2, but we did not observe any evidence of signal peptide cleavage in Astn1. Both Astn1 and Astn2 mature through endoproteolytic cleavage in the second transmembrane helix; importantly, we identified the endoprotease responsible for the maturation of Astn1 and Astn2 as the endoplasmic reticulum signal peptidase. Differences in the degree of Astn1 and Astn2 maturation possibly contribute to the higher levels of the C-terminal domain of Astn1 detected on neuronal membranes of the central nervous system. These differences may also explain the distinct cellular functions of Astn1 and Astn2, such as in membrane adhesion, receptor trafficking, and planar polarity signaling.


Asunto(s)
Glicoproteínas/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Serina Endopeptidasas/metabolismo , Animales , Biocatálisis , Retículo Endoplásmico/metabolismo , Glicoproteínas/química , Glicosilación , Membranas Intracelulares/metabolismo , Ratones , Microsomas/metabolismo , Proteínas del Tejido Nervioso/química , Proteolisis
7.
Proc Natl Acad Sci U S A ; 113(38): 10559-64, 2016 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-27601675

RESUMEN

Cotranslational translocon-mediated insertion of membrane proteins into the endoplasmic reticulum is a key process in membrane protein biogenesis. Although the mechanism is understood in outline, quantitative data on the energetics of the process is scarce. Here, we have measured the effect on membrane integration efficiency of nonproteinogenic analogs of the positively charged amino acids arginine and lysine incorporated into model transmembrane segments. We provide estimates of the influence on the apparent free energy of membrane integration (ΔGapp) of "snorkeling" of charged amino acids toward the lipid-water interface, and of charge neutralization. We further determine the effect of fluorine atoms and backbone hydrogen bonds (H-bonds) on ΔGapp These results help establish a quantitative basis for our understanding of membrane protein assembly in eukaryotic cells.


Asunto(s)
Aminoácidos/química , Retículo Endoplásmico/metabolismo , Membrana Dobles de Lípidos/metabolismo , Proteínas de la Membrana/metabolismo , Aminoácidos/genética , Retículo Endoplásmico/química , Entropía , Escherichia coli/enzimología , Escherichia coli/genética , Enlace de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Membrana Dobles de Lípidos/química , Proteínas de la Membrana/química , Proteínas de la Membrana/genética , Modelos Moleculares , Estructura Secundaria de Proteína , Serina Endopeptidasas/química , Serina Endopeptidasas/genética , Termodinámica , Agua/química
8.
J Biol Chem ; 292(27): 11349-11360, 2017 07 07.
Artículo en Inglés | MEDLINE | ID: mdl-28512128

RESUMEN

The oligosaccharyltransferase complex, localized in the endoplasmic reticulum (ER) of eukaryotic cells, is responsible for the N-linked glycosylation of numerous protein substrates. The membrane protein STT3 is a highly conserved part of the oligosaccharyltransferase and likely contains the active site of the complex. However, understanding the catalytic determinants of this system has been challenging, in part because of a discrepancy in the structural topology of the bacterial versus eukaryotic proteins and incomplete information about the mechanism of membrane integration. Here, we use a glycosylation mapping approach to investigate these questions. We measured the membrane integration efficiency of the mouse STT3-A and yeast Stt3p transmembrane domains (TMDs) and report a refined topology of the N-terminal half of the mouse STT3-A. Our results show that most of the STT3 TMDs are well inserted into the ER membrane on their own or in the presence of the natural flanking residues. However, for the mouse STT3-A hydrophobic domains 4 and 6 and yeast Stt3p domains 2, 3a, 3c, and 6 we measured reduced insertion efficiency into the ER membrane. Furthermore, we mapped the first half of the STT3-A protein, finding two extra hydrophobic domains between the third and the fourth TMD. This result indicates that the eukaryotic STT3 has 13 transmembrane domains, consistent with the structure of the bacterial homolog of STT3 and setting the stage for future combined efforts to interrogate this fascinating system.


Asunto(s)
Retículo Endoplásmico , Hexosiltransferasas , Membranas Intracelulares , Proteínas de la Membrana , Modelos Moleculares , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Animales , Retículo Endoplásmico/química , Retículo Endoplásmico/genética , Retículo Endoplásmico/metabolismo , Hexosiltransferasas/química , Hexosiltransferasas/genética , Hexosiltransferasas/metabolismo , Membranas Intracelulares/química , Membranas Intracelulares/metabolismo , Proteínas de la Membrana/química , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Dominios Proteicos , Estructura Cuaternaria de Proteína , Saccharomyces cerevisiae/química , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo
9.
Mol Biol Evol ; 34(8): 2041-2056, 2017 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-28505373

RESUMEN

Evolution of the phenolic metabolism was critical for the transition of plants from water to land. A cytochrome P450, CYP73, with cinnamate 4-hydroxylase (C4H) activity, catalyzes the first plant-specific and rate-limiting step in this pathway. The CYP73 gene is absent from green algae, and first detected in bryophytes. A CYP73 duplication occurred in the ancestor of seed plants and was retained in Taxaceae and most angiosperms. In spite of a clear divergence in primary sequence, both paralogs can fulfill comparable cinnamate hydroxylase roles both in vitro and in vivo. One of them seems dedicated to the biosynthesis of lignin precursors. Its N-terminus forms a single membrane spanning helix and its properties and length are highly constrained. The second is characterized by an elongated and variable N-terminus, reminiscent of ancestral CYP73s. Using as proxies the Brachypodium distachyon proteins, we show that the elongation of the N-terminus does not result in an altered subcellular localization, but in a distinct membrane topology. Insertion in the membrane of endoplasmic reticulum via a double-spanning open hairpin structure allows reorientation to the lumen of the catalytic domain of the protein. In agreement with participation to a different functional unit and supramolecular organization, the protein displays modified heme proximal surface. These data suggest the evolution of divergent C4H enzymes feeding different branches of the phenolic network in seed plants. It shows that specialization required for retention of gene duplicates may result from altered protein topology rather than change in enzyme activity.


Asunto(s)
Brachypodium/genética , Transcinamato 4-Monooxigenasa/genética , Secuencia de Aminoácidos , Brachypodium/metabolismo , Sistema Enzimático del Citocromo P-450/genética , Retículo Endoplásmico/metabolismo , Evolución Molecular , Duplicación de Gen/genética , Genes Duplicados/genética , Lignina/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Oxidación-Reducción , Filogenia , Dominios Proteicos/genética , Semillas/metabolismo , Transcinamato 4-Monooxigenasa/metabolismo
10.
J Biol Chem ; 290(28): 17628-41, 2015 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-26041777

RESUMEN

Surfactant protein C (SP-C) is a novel amyloid protein found in the lung tissue of patients suffering from interstitial lung disease (ILD) due to mutations in the gene of the precursor protein pro-SP-C. SP-C is a small α-helical hydrophobic protein with an unusually high content of valine residues. SP-C is prone to convert into ß-sheet aggregates, forming amyloid fibrils. Nature's way of solving this folding problem is to include a BRICHOS domain in pro-SP-C, which functions as a chaperone for SP-C during biosynthesis. Mutations in the pro-SP-C BRICHOS domain or linker region lead to amyloid formation of the SP-C protein and ILD. In this study, we used an in vitro transcription/translation system to study translocon-mediated folding of the WT pro-SP-C poly-Val and a designed poly-Leu transmembrane (TM) segment in the endoplasmic reticulum (ER) membrane. Furthermore, to understand how the pro-SP-C BRICHOS domain present in the ER lumen can interact with the TM segment of pro-SP-C, we studied the membrane insertion properties of the recombinant form of the pro-SP-C BRICHOS domain and two ILD-associated mutants. The results show that the co-translational folding of the WT pro-SP-C TM segment is inefficient, that the BRICHOS domain inserts into superficial parts of fluid membranes, and that BRICHOS membrane insertion is promoted by poly-Val peptides present in the membrane. In contrast, one BRICHOS and one non-BRICHOS ILD-associated mutant could not insert into membranes. These findings support a chaperone function of the BRICHOS domain, possibly together with the linker region, during pro-SP-C biosynthesis in the ER.


Asunto(s)
Precursores de Proteínas/química , Proteína C Asociada a Surfactante Pulmonar/química , Proteínas Amiloidogénicas/química , Proteínas Amiloidogénicas/genética , Proteínas Amiloidogénicas/metabolismo , Animales , Retículo Endoplásmico/metabolismo , Humanos , Técnicas In Vitro , Enfermedades Pulmonares Intersticiales/genética , Enfermedades Pulmonares Intersticiales/metabolismo , Lípidos de la Membrana/metabolismo , Mutagénesis Sitio-Dirigida , Unión Proteica , Pliegue de Proteína , Dominios y Motivos de Interacción de Proteínas , Precursores de Proteínas/genética , Precursores de Proteínas/metabolismo , Proteína C Asociada a Surfactante Pulmonar/genética , Proteína C Asociada a Surfactante Pulmonar/metabolismo , Ratas , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
11.
Chemistry ; 21(48): 17495-502, 2015 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-26481587

RESUMEN

Ru nanoparticles (RuNPs) stabilized by non-isolable chiral N-heterocyclic carbenes (NHCs), namely SIDPhNp ((4S,5S)-1,3-di(naphthalen-1-yl)-4,5-diphenylimidazolidine) and SIPhOH ((S)-3-((1S,2R)-2-hydroxy-1,2-diphenylethyl)-1-((R)-2-hydroxy-1,2-diphenylethyl)-4,5-dihydro-3H-imidazoline), have been synthesized through a new procedure that does not require isolation of the free carbenes. The obtained RuNPs have been characterized by state-of-the-art techniques and their surface chemistry has been investigated by FTIR and solid-state MAS NMR upon the coordination of CO, which indicated the presence of free and reactive Ru sites. Their catalytic activity has been tested in various hydrogenation reactions involving competition between different sites, whereby interesting differences in selectivity were observed, but no enantioselectivity.

12.
Chemistry ; 21(20): 7540-55, 2015 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-25820229

RESUMEN

A series of Ru complexes containing lutidine-derived pincer CNC ligands have been prepared by transmetalation with the corresponding silver-carbene derivatives. Characterization of these derivatives shows both mer and fac coordination of the CNC ligands depending on the wingtips of the N-heterocyclic carbene fragments. In the presence of tBuOK, the Ru-CNC complexes are active in the hydrogenation of a series of imines. In addition, these complexes catalyze the reversible hydrogenation of phenantridine. Detailed NMR spectroscopic studies have shown the capability of the CNC ligand to be deprotonated and get involved in ligand-assisted activation of dihydrogen. More interestingly, upon deprotonation, the Ru-CNC complex 5 e(BF4 ) is able to add aldimines to the metal-ligand framework to yield an amido complex. Finally, investigation of the mechanism of the hydrogenation of imines has been carried out by means of DFT calculations. The calculated mechanism involves outer-sphere stepwise hydrogen transfer to the C-N bond assisted either by the pincer ligand or a second coordinated H2 molecule.

13.
Biochem Biophys Res Commun ; 450(4): 1587-92, 2014 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-25034329

RESUMEN

Experimental tools to determine membrane topology of a protein are rather limited in higher eukaryotic organisms. Here, we report the use of glycosylatable GFP (gGFP) as a sensitive and versatile membrane topology reporter in mammalian cells. gGFP selectively loses its fluorescence upon N-linked glycosylation in the ER lumen. Thus, positive fluorescence signal assigns location of gGFP to the cytosol whereas no fluorescence signal and a glycosylated status of gGFP map the location of gGFP to the ER lumen. By using mammalian gGFP, the membrane topology of disease-associated membrane proteins, URG7, MRP6102, SP-C(Val) and SP-C(Leu) was confirmed. URG7 is partially targeted to the ER, and inserted in Cin form. MRP6102 and SP-C(Leu/Val) are inserted into the membrane in Cout form. A minor population of untargeted SP-C is removed by proteasome dependent quality control system.


Asunto(s)
Proteínas Fluorescentes Verdes/metabolismo , Animales , Células Cultivadas , Retículo Endoplásmico/metabolismo , Citometría de Flujo , Glicosilación , Humanos , Microscopía Fluorescente
14.
Nanoscale ; 15(35): 14488-14495, 2023 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-37606171

RESUMEN

A series of ruthenium nanoparticles (Ru·MIC) stabilized with different mesoionic 1,2,3-triazolylidene (MIC) ligands were prepared by decomposition of the Ru(COD)(COT) (COD = 1,5-cyclooctadiene; COT = 1,3,5-cyclooctatriene) precursor with H2 (3 bar) in the presence of substoichiometric amounts of the stabilizer (0.1-0.2 equiv.). Small and monodisperse nanoparticles exhibiting mean sizes between 1.1 and 1.2 nm were obtained, whose characterization was carried out by means of transmission electron microscopy (TEM), including high resolution TEM (HRTEM), inductively coupled plasma (ICP) analysis and X-ray photoelectron spectroscopy (XPS). In particular, XPS measurements confirmed the presence of MIC ligands on the surfaces of the nanoparticles. The Ru·MIC nanoparticles were used in the isotopic H/D exchange of different hydrosilanes, hydroboranes, hydrogermananes and hydrostannanes using deuterium gas under mild conditions (1.0 mol% Ru, 1 bar D2, 55 °C). Selective labelling of the E-H (E = B, Si, Ge, Sn) bond in these derivatives, with high levels of deuterium incorporation, was observed.

15.
Chem Commun (Camb) ; 58(51): 7176-7179, 2022 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-35670417

RESUMEN

A series of RuSNS nanoparticles, prepared by decomposition of Ru(COD)(COT) with H2 in the presence of an SNS ligand, have been found to catalyse the reduction of the greenhouse gas N2O to N2 employing different hydrosilanes.

16.
FEBS J ; 287(13): 2744-2762, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-31821735

RESUMEN

The malarial parasite Plasmodium exports its own proteins to the cell surfaces of red blood cells (RBCs) during infection. Examples of exported proteins include members of the repetitive interspersed family (RIFIN) and subtelomeric variable open reading frame (STEVOR) family of proteins from Plasmodium falciparum. The presence of these parasite-derived proteins on surfaces of infected RBCs triggers the adhesion of infected cells to uninfected cells (rosetting) and to the vascular endothelium potentially obstructing blood flow. While there is a fair amount of information on the localization of these proteins on the cell surfaces of RBCs, less is known about how they can be exported to the membrane and the topologies they can adopt during the process. The first step of export is plausibly the cotranslational insertion of proteins into the endoplasmic reticulum (ER) of the parasite, and here, we investigate the insertion of three RIFIN and two STEVOR proteins into the ER membrane. We employ a well-established experimental system that uses N-linked glycosylation of sites within the protein as a measure to assess the extent of membrane insertion and the topology it assumes when inserted into the ER membrane. Our results indicate that for all the proteins tested, transmembranes (TMs) 1 and 3 integrate into the membrane, so that the protein assumes an overall topology of Ncyt-Ccyt. We also show that the segment predicted to be TM2 for each of the proteins likely does not reside in the membrane, but is translocated to the lumen.


Asunto(s)
Antígenos de Protozoos/química , Antígenos de Protozoos/metabolismo , Membrana Celular/metabolismo , Proteínas de la Membrana/química , Proteínas de la Membrana/metabolismo , Plasmodium falciparum/fisiología , Proteínas Protozoarias/química , Proteínas Protozoarias/metabolismo , Membrana Celular/química , Retículo Endoplásmico , Células HEK293 , Humanos , Conformación Proteica
17.
Nanoscale ; 12(12): 6821-6831, 2020 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-32182323

RESUMEN

N-Heterocyclic Thiones (NHT) proved to be efficient ligands for the stabilization of small platinum nanoparticles (1.3-1.7 nm), synthesized by decomposition of [Pt(dba)2], under a H2 atmosphere, in the presence of variable sub-stoichiometric amounts of the NHT. Full characterization by means of TEM, HR-TEM, NMR, ICP, TGA and XPS have been carried out, providing information about the nature of the metal nanoparticles and the interaction of the NHT ligands to the metal surface. Importantly, DFT calculations indicate that some NHT ligands interact with the metal through the C[double bond, length as m-dash]C double bond of the imidazole fragment in addition to the sulfur atom, thus providing additional stabilization to the nanoparticles. According to XPS, TGA and ICP techniques, the surface coverage by the ligand increases by decreasing the size of the substituents on the nitrogen atom. The platinum nanoparticles have been used as catalyst in the hydroboration of alkynes. The most active system is that with a less covered surface area lacking an interaction of the ligand by means of the C[double bond, length as m-dash]C double bond. This catalyst hydroborates alkynes with excellent selectivities towards the monoborylated anti-Markovnikov product (vinyl-boronate) when one equiv. of borane is used. Very interestingly, aliphatic alkynes undergo a second hydroborylation process leading to the corresponding 1,1- and 1,2-diboroylated species with good selectivities towards the former.

18.
Chemistry ; 15(36): 9034-45, 2009 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-19658130

RESUMEN

Reaction of the Ir(III) complex [(Tp(Me2))Ir(C(6)H(5))(2)(N(2))] (1N(2)) with ortho-cresol (2-methylphenol) occurs with cleavage of the O-H and two C(sp(3))-H bonds of the phenol and formation of the electrophilic hydride alkylidene derivative [(Tp(Me2))Ir(H){=C(H)C(6)H(4)-o-O}] (2). The analogous reaction of 2-ethylphenol gives a related product 3. Both 2 and 3 have been shown to be identical to the minor, unidentified products of the already reported reactions of 1 with anisole and phenetole, respectively. Thus, in addition to the route that leads to the known heteroatom-stabilized hydride carbene [(Tp(Me2))Ir(H){=C(H)OC(6)H(4)-o-}] (B), anisole can react with 1 with cleavage of the O-CH(3) bond and formation of a new carbon-carbon bond. In contrast, only C-H bond-activation products with structures akin to B result from 1N(2) and 3,5-dimethylanisole (complex 8) or 4-fluoroanisole (9). Using anisole as a model, a computational study of the triple C-H bond activation (two aliphatic C-H bonds plus an ortho-metalation reaction) that is responsible for the formation of these heteroatom-stabilized hydride carbenes has been undertaken.

19.
Chemistry ; 15(36): 9046-57, 2009 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-19670194

RESUMEN

Experimental and theoretical studies on equilibria between iridium hydride alkylidene structures, [(Tp(Me2))Ir(H){=C(CH(2)R)ArO}] (Tp(Me2) = hydrotris(3,5-dimethylpyrazolyl)borate; R = H, Me; Ar = substituted C(6)H(4) group), and their corresponding hydride olefin isomers, [(Tp(Me2))Ir(H){R(H)C=C(H)OAr}], have been carried out. Compounds of these types are obtained either by reaction of the unsaturated fragment [(Tp(Me2))Ir(C(6)H(5))(2)] with o-C(6)H(4)(OH)CH(2)R, or with the substituted anisoles 2,6-Me(2)C(6)H(3)OMe, 2,4,6-Me(3)C(6)H(2)OMe, and 4-Br-2,6-Me(2)C(6)H(2)OMe. The reactions with the substituted anisoles require not only multiple C-H bond activation but also cleavage of the Me-OAr bond and the reversible formation of a C-C bond (as revealed by (13)C labeling studies). Equilibria between the two tautomeric structures of these complexes were achieved by prolonged heating at temperatures between 100 and 140 degrees C, with interconversion of isomeric complexes requiring inversion of the metal configuration, as well as the expected migratory insertion and hydrogen-elimination reactions. This proposal is supported by a detailed computational exploration of the mechanism at the quantum mechanics (QM) level in the real system. For all compounds investigated, the equilibria favor the alkylidene structure over the olefinic isomer by a factor of between approximately 1 and 25. Calculations demonstrate that the main reason for this preference is the strong Ir-carbene interactions in the carbene isomers, rather than steric destabilization of the olefinic tautomers.

20.
Rev Bras Ter Intensiva ; 31(4): 464-473, 2019.
Artículo en Portugués, Inglés | MEDLINE | ID: mdl-31967220

RESUMEN

OBJECTIVE: To evaluate the safety and feasibility of the ultrasound assessment of quadriceps in the emergency setting. To assess the intra- and interrater reliability for the acquisition and analysis of ultrasound images of muscle thickness and echogenicity in critically ill trauma patients between health professionals with different levels of expertise. METHODS: Diagnostic accuracy study. Two examiners (expert and novice) acquired ultrasound images from ten patients; an experienced, blinded analyst quantified the images. In a separate group of ten patients, two analysts (expert and novice) quantified quadriceps muscle thickness and echogenicity (square or trace method) from images acquired by one examiner. RESULTS: Excellent reliability was found for image acquisition and analysis (intraclass correlation coefficients > 0.987; p < 0.001). The standard error of the measurement values ranged from 0.01 - 0.06cm for muscle thickness and from 0.75 - 2.04 arbitrary units for muscle echogenicity. The coefficients of variation were < 6% for thickness and echogenicity. The echogenicity values were higher when using the square technique than when using the tracing technique (p = 0.003). CONCLUSION: Ultrasound is safe, feasible, and reliable for muscle assessment in critically ill trauma patients, regardless of the assessor's level of expertise.


OBJETIVO: Avaliar a segurança e a viabilidade da avaliação por ultrassonografia do quadríceps no pronto-socorro, e avaliar a confiabilidade intra e entre avaliadores para aquisição e análise de imagens de ultrassonografia da espessura e da ecogenicidade muscular em pacientes críticos de trauma. MÉTODOS: Estudo de precisão diagnóstica realizado por meio de exames e avaliações feitos por profissionais de saúde com diferentes níveis de especialização. Dois examinadores (um especialista e um novato) procederam à aquisição de imagens de ultrassom de dez pacientes. Um avaliador experiente, cego quanto aos examinadores, quantificou as imagens obtidas. Em um grupo à parte de dez pacientes, dois avaliadores (um especialista e um novato) quantificaram a espessura do músculo quadríceps femoral, assim como sua ecogenicidade (métodos quadrado ou tracejado) em imagens adquiridas por um examinador. RESULTADOS: Identificou-se excelente confiabilidade quanto à aquisição da imagem e à sua análise (coeficientes de correlação intraclasses > 0,987; p < 0,001). O erro padrão dos valores de mensurações variou de 0,01 a 0,06 cm, para a espessura muscular, e de 0,75 a 2,04 unidades arbitrárias, para ecogenicidade muscular. Os valores de ecogenicidade foram mais elevados quando se utilizou o método quadrado do que quando se utilizou o método tracejado (p = 0,003). CONCLUSÃO: A ultrassonografia é um método seguro, viável e confiável para avaliação muscular em pacientes críticos de trauma, independentemente do nível de especialização do avaliador.


Asunto(s)
Ultrasonografía/métodos , Heridas y Lesiones/complicaciones , Adulto , Enfermedad Crítica , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Músculo Cuádriceps/diagnóstico por imagen , Reproducibilidad de los Resultados , Ultrasonografía/efectos adversos , Adulto Joven
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