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Article: G protein-coupled receptors as therapeutic target.

Alcántara-Hernández, Rocío / Hernández-Espinosa, David A / Medina, Luz Del C / García-Sáinz, Jesús A

2022 Volume 158, Issue 2, Page(s) 98–103

Abstract: ... focuses on the most diverse and abundant family of receptors, G protein-coupled receptors. This family ...

Title translation	Los receptores acoplados a proteínas G como blanco terapéutico.
Abstract	Receptors are proteins coded by DNA, some of which have already been crystalized, thus allowing the details of their structure at the atomic level and some aspects of their function to be known. This review focuses on the most diverse and abundant family of receptors, G protein-coupled receptors. This family of receptors recognizes and mediates the action of several endogenous ligands (hormones, neurotransmitters, growth factors and local hormones) and also intervenes in the pathogenesis of various diseases, which is why they are targeted by approximately 30 to 40% of medications that are used in daily clinical practice and of various illegal drugs as well. X-ray crystallography is one of the essential tools that has allowed to observe the structure of these receptors in the amino acids that participate in this interaction, which allows to know the binding site of the endogenous ligand and of synthetic molecules that act on them to modulate their action. Molecular modeling or "docking" is also a computational bioinformatics tool that supports research on receptor-ligand binding, which allows the design and development of increasingly specific drugs. These developments have brought along significant changes in fundamental pharmacodynamic concepts.
MeSH term(s)	Amino Acids ; Hormones ; Humans ; Ligands ; Models, Molecular ; Receptors, G-Protein-Coupled
Chemical Substances	Amino Acids ; Hormones ; Ligands ; Receptors, G-Protein-Coupled
Language	English
Publishing date	2022-06-23
Publishing country	Mexico
Document type	Journal Article ; Review
ZDB-ID	425456-9
ISSN	0016-3813
ISSN	0016-3813
DOI	10.24875/GMM.M22000648
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Roles of the G protein-coupled receptor kinase 2 and Rab5 in α

Hernández-Espinosa, David A / Reyes-Cruz, Guadalupe / García-Sáinz, J Adolfo

European journal of pharmacology

2019 Volume 867, Page(s) 172846

Abstract: Cells expressing eGFP-tagged Rab5 (wild-type or the GDP-Rab5 mutant) and the DsRed-tagged ... ...

Abstract	Cells expressing eGFP-tagged Rab5 (wild-type or the GDP-Rab5 mutant) and the DsRed-tagged α
MeSH term(s)	Adrenergic alpha-1 Receptor Agonists/pharmacology ; Fluorescence Resonance Energy Transfer ; G-Protein-Coupled Receptor Kinase 2/antagonists & inhibitors ; G-Protein-Coupled Receptor Kinase 2/genetics ; G-Protein-Coupled Receptor Kinase 2/metabolism ; HEK293 Cells ; Humans ; Mutation ; Norepinephrine/pharmacology ; Paroxetine/pharmacology ; Phosphorylation/drug effects ; Receptors, Adrenergic, alpha-1/metabolism ; rab5 GTP-Binding Proteins/genetics ; rab5 GTP-Binding Proteins/metabolism
Chemical Substances	ADRA1B protein, human ; Adrenergic alpha-1 Receptor Agonists ; Receptors, Adrenergic, alpha-1 ; Paroxetine (41VRH5220H) ; GRK2 protein, human (EC 2.7.11.15) ; G-Protein-Coupled Receptor Kinase 2 (EC 2.7.11.16) ; RAB5C protein, human (EC 3.6.1.-) ; rab5 GTP-Binding Proteins (EC 3.6.5.2) ; Norepinephrine (X4W3ENH1CV)
Language	English
Publishing date	2019-12-04
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	80121-5
ISSN	1879-0712 ; 0014-2999
ISSN (online)	1879-0712
ISSN	0014-2999
DOI	10.1016/j.ejphar.2019.172846
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Los receptores acoplados a proteínas G como blanco terapéutico

Rocío Alcántara-Hernández / David A. Hernández-Espinosa / Luz del C. Medina / Jesús A. García-Sáinz

Gaceta Médica de México, Vol 158, Iss

2022 Volume 2

Abstract: ... G. Esta familia de receptores reconoce y media la acción de varios ligandos endógenos (hormonas ...

Abstract	Los receptores son proteínas codificadas por el ADN, algunos de los cuales ya han sido cristalizados, lo que permite conocer los detalles de su estructura a nivel atómico y algunos aspectos de su función. Esta revisión se enfoca en los más diversos y abundantes, los receptores acoplados a la proteína G. Esta familia de receptores reconoce y media la acción de varios ligandos endógenos (hormonas, neurotransmisores, factores de crecimiento y hormonas locales) y también interviene en la patogenia de diversas enfermedades, por lo que son el blanco terapéutico de aproximadamente 30 a 40 % de los medicamentos que se emplean en la práctica clínica cotidiana y de diversas drogas ilegales. La cristalografía de rayos X es una de las herramientas clave que ha permitido observar la estructura de estos receptores en los aminoácidos que participan en esta interacción, lo que posibilita conocer el sitio de unión del ligando endógeno y de moléculas sintéticas que actúan sobre ellos para modular su acción. El modelado molecular es también una herramienta bioinformática computacional que apoya la investigación sobre la unión receptor-ligando, que hace posible el diseño y desarrollo de fármacos cada vez más específicos. A estos desarrollos se suman importantes cambios en los conceptos farmacodinámicos fundamentales.
Keywords	Receptores acoplados a proteínas G. Agonistas sesgados. Proteínas G. β-arrestinas ; Public aspects of medicine ; RA1-1270 ; Internal medicine ; RC31-1245
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	Permanyer
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: The role of β-arrestins in G protein-coupled receptor heterologous desensitization: A brief story.

Carmona-Rosas, Gabriel / Alcántara-Hernández, Rocío / Hernández-Espinosa, David Alejandro

Methods in cell biology

2018 Volume 149, Page(s) 195–204

Abstract: G protein-coupled receptors (GPCRs) are transmembrane proteins that have an important impact ...

Abstract	G protein-coupled receptors (GPCRs) are transmembrane proteins that have an important impact in a myriad of cellular functions. Posttranslational modifications on GPCRs are a key processes that allow these proteins to recruit other intracellular molecules. Among these modifications, phosphorylation is the most important way of desensitization of these receptors. Several research groups have described two different desensitization mechanisms: heterologous and homologous desensitization. The first one involves the phosphorylation of the receptors by protein kinases, such as PKC, following the desensitization and internalization of the receptor, while the second one involves the phosphorylation of the receptors by GRKs, allowing for the receptor to recruit β-arrestins to be desensitized and internalized. Interestingly, a few number of studies have described the participation of β-arrestins during the heterologous desensitization process. Hence, the aim of this review is to briefly explore the role that β-arrestins play during the heterologous desensitization of several GPCRs.
MeSH term(s)	Animals ; Cytological Techniques/methods ; Humans ; Models, Biological ; Receptors, G-Protein-Coupled/metabolism ; beta-Arrestins/metabolism
Chemical Substances	Receptors, G-Protein-Coupled ; beta-Arrestins
Language	English
Publishing date	2018-09-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ISSN	0091-679X
ISSN	0091-679X
DOI	10.1016/bs.mcb.2018.08.004
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: YAP1 nuclear efflux and transcriptional reprograming follow membrane diminution upon VSV-G-induced cell fusion.

Feliciano, Daniel / Ott, Carolyn M / Espinosa-Medina, Isabel / Weigel, Aubrey V / Benedetti, Lorena / Milano, Kristin M / Tang, Zhonghua / Lee, Tzumin / Kliman, Harvey J / Guller, Seth M / Lippincott-Schwartz, Jennifer

Nature communications

2021 Volume 12, Issue 1, Page(s) 4502

Abstract: ... analysis reveals VSV-G-induced cell fusion precedes transcriptional changes. To gain mechanistic insights ...

Abstract	Cells in many tissues, such as bone, muscle, and placenta, fuse into syncytia to acquire new functions and transcriptional programs. While it is known that fused cells are specialized, it is unclear whether cell-fusion itself contributes to programmatic-changes that generate the new cellular state. Here, we address this by employing a fusogen-mediated, cell-fusion system to create syncytia from undifferentiated cells. RNA-Seq analysis reveals VSV-G-induced cell fusion precedes transcriptional changes. To gain mechanistic insights, we measure the plasma membrane surface area after cell-fusion and observe it diminishes through increases in endocytosis. Consequently, glucose transporters internalize, and cytoplasmic glucose and ATP transiently decrease. This reduced energetic state activates AMPK, which inhibits YAP1, causing transcriptional-reprogramming and cell-cycle arrest. Impairing either endocytosis or AMPK activity prevents YAP1 inhibition and cell-cycle arrest after fusion. Together, these data demonstrate plasma membrane diminishment upon cell-fusion causes transient nutrient stress that may promote transcriptional-reprogramming independent from extrinsic cues.
MeSH term(s)	AMP-Activated Protein Kinases/genetics ; AMP-Activated Protein Kinases/metabolism ; Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Biological Transport ; Cell Fusion ; Cell Line ; Cell Line, Tumor ; Cell Membrane/metabolism ; Cell Nucleus/metabolism ; Cells, Cultured ; Giant Cells/metabolism ; HEK293 Cells ; Humans ; Membrane Glycoproteins/genetics ; Membrane Glycoproteins/metabolism ; Mice ; RNA-Seq/methods ; Signal Transduction/genetics ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Transcription, Genetic/genetics ; Viral Envelope Proteins/genetics ; Viral Envelope Proteins/metabolism ; YAP-Signaling Proteins
Chemical Substances	Adaptor Proteins, Signal Transducing ; G protein, vesicular stomatitis virus ; Membrane Glycoproteins ; Transcription Factors ; Viral Envelope Proteins ; YAP-Signaling Proteins ; YAP1 protein, human ; AMP-Activated Protein Kinases (EC 2.7.11.31)
Language	English
Publishing date	2021-07-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-24708-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Gangliosidosis G M1

Juan Pablo Londoño C. / Eugenia Espinosa García / Olga Yaneth Echeverri Peña / Yudy Andrea Ardila / Luis Alejandro Barrera A.

Revista Universitas Medica, Vol 56, Iss 3, Pp 366-

a propósito de un caso clínico

2015 Volume 373

Abstract: La gangliosidosis G M1 es una enfermedad de depósito lisosomal en la cual se acumula gangliósido-G ... se le diagnostica gangliosidosis G M1 tipo 2 o juvenil. ...

Abstract	La gangliosidosis G M1 es una enfermedad de depósito lisosomal en la cual se acumula gangliósido-G M1 y otros compuestos galactoconjugados. La enfermedad es secundaria a la deficiencia de β -galactosidasa, con una afectación multiorgánica, en que predominan las manifestaciones neurológicas progresivas y visceromegalias. Se describe el caso de un niño de 5 años de edad, quien presenta un cuadro de regresión global del neurodesarrollo. Por hallazgos clínicos, de laboratorio y neuroimágenes, se le diagnostica gangliosidosis G M1 tipo 2 o juvenil.
Keywords	Medicine ; R
Language	Spanish
Publishing date	2015-01-01T00:00:00Z
Publisher	Pontificia Universidad Javeriana
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: YAP1 nuclear efflux and transcriptional reprograming follow membrane diminution upon VSV-G-induced cell fusion

Daniel Feliciano / Carolyn M. Ott / Isabel Espinosa-Medina / Aubrey V. Weigel / Lorena Benedetti / Kristin M. Milano / Zhonghua Tang / Tzumin Lee / Harvey J. Kliman / Seth M. Guller / Jennifer Lippincott-Schwartz

Nature Communications, Vol 12, Iss 1, Pp 1-

2021 Volume 17

Abstract: Cells in many tissues fuse into syncytia acquiring new functions. By investigating whether physical remodelling promotes differentiation, here, the authors show that plasma membrane diminution post-fusion causes transient nutrient stress that inhibits ... ...

Abstract	Cells in many tissues fuse into syncytia acquiring new functions. By investigating whether physical remodelling promotes differentiation, here, the authors show that plasma membrane diminution post-fusion causes transient nutrient stress that inhibits YAP1 activity and may reduce proliferation-promoting transcription.
Keywords	Science ; Q
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Mª. J. Villaverde y G. López (eds.)

Francisco Javier Espinosa Antón

Araucaria, Vol 18, Iss 35, Pp 381-

Civilizados y salvajes. La mirada de los ilustrados sobre el mundo no europeo. Madrid: Centro de Estudios Políticos y Constitucionales, 2015. 303 pp.

2016 Volume 386

Keywords	History of scholarship and learning. The humanities ; AZ20-999 ; Political science ; J ; Philosophy (General) ; B1-5802
Language	English
Publishing date	2016-01-01T00:00:00Z
Publisher	Universidad de Sevilla
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Importance of Assessing Compliance with Conservative Treatment of Primary Hyperoxaluria Type 1: A Case Report of a Patient with I244T/c.969-3C>G Mutation.

Medina, Paloma Gutiérrez / Román, Laura Espinosa

The Permanente journal

2019 Volume 24

Abstract: Introduction: Primary hyperoxaluria type 1 (PH1) is an autosomal recessive inherited disorder that progresses to end-stage renal disease. Patients experience excessive urinary oxalate excretion, which causes nephrocalcinosis and recurrent urolithiasis. ... ...

Abstract	Introduction: Primary hyperoxaluria type 1 (PH1) is an autosomal recessive inherited disorder that progresses to end-stage renal disease. Patients experience excessive urinary oxalate excretion, which causes nephrocalcinosis and recurrent urolithiasis. When the glomerular filtration rate declines, calcium oxalate accumulates in extrarenal tissues, causing end-organ damage. More than 190 responsible mutations have been documented, with some genotype-phenotype differences reported. Regardless of the genetic basis, prompt diagnosis and treatment are decisive for the long-term outcome. If the condition advances to chronic kidney disease stage 4 or 5, a combined liver-kidney transplant should be considered. Case presentation: We describe a 5-month-old asymptomatic female patient with bilateral diffuse nephrocalcinosis and nephrolithiasis. Laboratory and genetic findings confirmed PH1. She was promptly administered conservative treatment consisting of high fluid intake, calcium oxalate crystallization inhibitors, and pyridoxine. Nephrocalcinosis and urolithiasis disappeared after 2 years of treatment. As far as we know, this is a unique case of a patient with an I244T/null mutation diagnosed after the neonatal period and with normal renal function, who remained asymptomatic during an 18-year follow-up. This case is also unique because of the long-term therapeutic success. Discussion: Physicians need a high level of suspicion to diagnose this rare disease. It has been previously demonstrated that early conservative treatment improves long-term outcomes, averting preemptive transplant during childhood. This case report emphasizes the importance of encouraging compliance with this approach, reinforces the need for good physician-patient communication, and raises awareness of the problems that might arise during conservative PH1 treatment.
MeSH term(s)	Adolescent ; Calcium Oxalate/antagonists & inhibitors ; Conservative Treatment/methods ; Female ; Fluid Therapy/methods ; Follow-Up Studies ; Guideline Adherence ; Humans ; Hyperoxaluria, Primary/diagnosis ; Hyperoxaluria, Primary/therapy ; Infant ; Mutation ; Pyridoxine/therapeutic use ; Treatment Outcome ; Vitamin B Complex/therapeutic use
Chemical Substances	Vitamin B Complex (12001-76-2) ; Calcium Oxalate (2612HC57YE) ; Pyridoxine (KV2JZ1BI6Z)
Language	English
Publishing date	2019-12-30
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	2062823-7
ISSN	1552-5775 ; 1552-5775
ISSN (online)	1552-5775
ISSN	1552-5775
DOI	10.7812/TPP/19.136
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Redescription of the highly endangered species Scutellastra mexicana (Broderip & G.B. Sowerby I, 1829) (Mollusca, Gastropoda)

Espinosa, F / Carballo, J. L / Bautista-Guerrero, E / Yáñez, B / García-Gómez, J. C / Michel-Morfín, J. E

Journal of natural history. 2020 Apr. 17, v. 54, no. 15-16

2020

Abstract: Broderip & G.B. Sowerby I, 1829) is the largest limpet in the world and a highly ...

Abstract	(Broderip & G.B. Sowerby I, 1829) is the largest limpet in the world and a highly endangered species from the Eastern Pacific that has faced a road to extinction during the last decades. Despite the relevance of S. mexicana, basic data, such as those relevant to its biology and ecology, have not been studied. In addition, previous descriptions of the species were focused only on shell morphology with few details. Very different morphologies between small and large-sized specimens were reported previously, in accordance with the trait already described for specialist species about adult/juvenile differentiation. Here, a new set of data about shell description, soft tissue, radula and genetics are reported in order to make a re-description of the species. Both type of specimens (small and large-sized) genetically belong to S. mexicana with clear traits on shell morphology and soft tissue parts that allow an accurate identification. Considering that small morphology can be found in reproductive specimens, such differences would be caused by shell growth and the erosion provoked by the extreme wave-exposed environment where the species lives. Analyses of the independent COI and 16S datasets revealed that none of the sequences of S. mexicana had any close relationship with other members of Scutellastra; thus, S. mexicana formed an independent and monophyletic clade relative to the other clades.
Keywords	Gastropoda ; adults ; data collection ; ecology ; endangered species ; extinction ; juveniles ; limpets ; monophyly ; natural history ; redescriptions ; tissues
Language	English
Dates of publication	2020-0417
Size	p. 991-1007.
Publishing place	Taylor & Francis
Document type	Article
Note	NAL-AP-2-clean
ZDB-ID	1467695-3
ISSN	1464-5262 ; 0022-2933
ISSN (online)	1464-5262
ISSN	0022-2933
DOI	10.1080/00222933.2020.1777337
Database	NAL-Catalogue (AGRICOLA)

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