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1.
Virology ; 557: 23-33, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33601113

RESUMEN

Herpesviruses encode multiple glycoproteins required for different stages of viral attachment, fusion, and envelopment. The protein encoded by the human cytomegalovirus (HCMV) open reading frame UL116 forms a stable complex with glycoprotein H that is incorporated into virions. However, the function of this complex remains unknown. Herein, we characterize R116, the rat CMV (RCMV) putative homolog of UL116. Two R116 transcripts were identified in fibroblasts with three proteins expressed with molecular weights of 42, 58, and 82 kDa. R116 is N-glycosylated, expressed with late viral gene kinetics, and is incorporated into the virion envelope. RCMV lacking R116 failed to result in productive infection of fibroblasts and siRNA knockdown of R116 substantially reduced RCMV infectivity. Complementation in trans of an R116-deficient virus restored ability of the virus to infect fibroblasts. Finally, UL116 knockdown also decreased HCMV infectivity indicating that R116 and UL116 both contribute to viral infectivity.


Asunto(s)
Citomegalovirus/genética , Fibroblastos/virología , Sistemas de Lectura Abierta/genética , Proteínas del Envoltorio Viral/genética , Virión/química , Animales , Citomegalovirus/química , Glicosilación , Humanos , ARN Bicatenario , Ratas , Acoplamiento Viral , Internalización del Virus
2.
ACS Med Chem Lett ; 11(12): 2446-2454, 2020 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-33335666

RESUMEN

In recent years, novel bacterial topoisomerase inhibitors (NBTIs) have been developed as future antibacterials for treating multidrug-resistant bacterial infections. A series of dioxane-linked NBTIs with an amide moiety has been synthesized and evaluated. Compound 3 inhibits DNA gyrase, induces the formation of single strand breaks to bacterial DNA, and achieves potent antibacterial activity against a variety of Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). Optimization of this series of analogues led to the discovery of a subseries of compounds (22-25) with more potent anti-MRSA activity, dual inhibition of DNA gyrase and topoisomerase IV, and the ability to induce double strand breaks through inhibition of S. aureus DNA gyrase.

3.
Obesity (Silver Spring) ; 22(2): 337-43, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24115765

RESUMEN

OBJECTIVE: Few studies have examined brain changes in response to effective weight loss; none have compared different methods of weight-loss intervention. Functional brain changes associated with a behavioral weight loss intervention to those associated with bariatric surgery were compared. DESIGN AND METHODS: Fifteen obese participants were recruited prior to adjustable gastric banding surgery and 16 obese participants were recruited prior to a behavioral diet intervention. Groups were matched for demographics and amount of weight lost. Functional magnetic resonance imaging scans (visual food motivation paradigm while hungry and following a meal) were conducted before and 12 weeks after surgery/behavioral intervention. RESULTS: When compared to bariatric patients in the premeal analyses, behavioral dieters showed increased activation to food images in right medial prefrontal cortex (PFC) and left precuneus following weight loss. When compared to behavioral dieters, bariatric patients showed increased activation in bilateral temporal cortex following weight loss. CONCLUSIONS: Behavioral dieters showed increased responses to food cues in medial PFC-a region associated with valuation and processing of self-referent information-when compared to bariatric patients. Bariatric patients showed increased responses to food cues in brain regions associated with higher level perception-when compared to behavioral dieters. The method of weight loss determines unique changes in brain function.


Asunto(s)
Gastroplastia , Neuronas/metabolismo , Obesidad Mórbida/cirugía , Obesidad/cirugía , Lóbulo Temporal/metabolismo , Pérdida de Peso , Adulto , Terapia Conductista , Índice de Masa Corporal , Mapeo Encefálico , Señales (Psicología) , Dieta Reductora/efectos adversos , Femenino , Alimentos , Gastroplastia/efectos adversos , Humanos , Hambre , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Comidas , Neuronas/patología , Obesidad/dietoterapia , Obesidad/metabolismo , Obesidad/patología , Obesidad Mórbida/dietoterapia , Obesidad Mórbida/metabolismo , Obesidad Mórbida/patología , Lóbulo Parietal/metabolismo , Lóbulo Parietal/patología , Corteza Prefrontal/metabolismo , Corteza Prefrontal/patología , Lóbulo Temporal/patología
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