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1.
BMC Infect Dis ; 20(1): 111, 2020 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-32039707

RESUMEN

After publication of the original article [1], we were notified that Fig. 3 has "Fig. 1" posted on the top of it and Figs. 4 and 5 have "Genomic Position" in a different spot.

2.
BMC Infect Dis ; 19(1): 1046, 2019 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-31822287

RESUMEN

BACKGROUND: Congenital cytomegalovirus (cCMV) infection is the most common congenital infection and a leading cause of long-term neurological and sensory sequelae, the most common being sensorineural hearing loss (SNHL). Despite extensive research, clinical or laboratory markers to identify CMV infected children with increased risk for disease have not been identified. This study utilizes viral whole-genome next generation-sequencing (NGS) of specimens from congenitally infected infants to explore viral diversity and specific viral variants that may be associated with symptomatic infection and SNHL. METHODS: CMV DNA from urine specimens of 30 infants (17 asymptomatic, 13 symptomatic) was target enriched and next generation sequenced resulting in 93% coverage of the CMV genome allowing analysis of viral diversity. RESULTS: Variant frequency distribution was compared between children with symptomatic and asymptomatic cCMV and those with (n = 13) and without (n = 17) hearing loss. The CMV genes UL48A, UL88, US19 and US22 were found to have an increase in nucleotide diversity in symptomatic children; while UL57, UL20, UL104, US14, UL115, and UL35 had an increase in diversity in children with hearing loss. An analysis of single variant differences between symptomatic and asymptomatic children found UL55 to have the highest number, while the most variants associated with SNHL were in the RL11 gene family. In asymptomatic infants with SNHL, mutations were observed more frequently in UL33 and UL20. CONCLUSION: CMV genomes from infected newborns can be mapped to 93% of the genome at a depth allowing accurate and reproducible analysis of polymorphisms for variant and gene discovery that may be linked to symptomatic and hearing loss outcomes.


Asunto(s)
Infecciones por Citomegalovirus/diagnóstico , Citomegalovirus/genética , ADN Viral/genética , Pérdida Auditiva Sensorineural/diagnóstico , Niño , Citomegalovirus/clasificación , Citomegalovirus/aislamiento & purificación , Infecciones por Citomegalovirus/complicaciones , Infecciones por Citomegalovirus/virología , ADN Viral/metabolismo , ADN Viral/orina , Femenino , Pérdida Auditiva Sensorineural/complicaciones , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Lactante , Recién Nacido , Masculino , Mutación , Filogenia , Análisis de Componente Principal
3.
Antiviral Res ; 203: 105326, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35504491

RESUMEN

Congenital cytomegalovirus (cCMV) infection is the leading non-genetic cause of long-term neurological and sensory sequelae, the most common being sensorineural hearing loss (SNHL). Standard therapy for infants with symptomatic cCMV is valganciclovir for six months. However, little is known about the effects of antiviral therapy on CMV diversity while patients are on treatment. In this study, CMV variation was analyzed from urine specimens isolated from two patients with cCMV shortly after birth and at seven months. One was treated with valganciclovir for six weeks and the other for six months. In order to track these variants a novel bioinformatic approach was employed to analyze changes in low frequency variants over time. In the infant receiving antivirals for only six weeks, there was a fourfold increase in variation in UL97 from the seven month specimen. Furthermore, an eightfold increase in variation was seen in UL83 (pp65) with seven potential escape mutations occurring, and a twofold increase in UL73 (gN). In contrast variation did not increase or was reduced in these coding regions in the infant receiving valganciclovir for six months. However, there were increases in other CMV regions in samples isolated from both patients indicating further longitudinal studies are warranted to better understand the interplay between CMV diversity, antiviral therapy and patient outcome.


Asunto(s)
Infecciones por Citomegalovirus , Pérdida Auditiva Sensorineural , Antivirales/farmacología , Antivirales/uso terapéutico , Citomegalovirus , Pérdida Auditiva Sensorineural/congénito , Humanos , Lactante , Recién Nacido , Valganciclovir/farmacología , Valganciclovir/uso terapéutico
4.
J Mol Neurosci ; 30(1-2): 115-8, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-17192654

RESUMEN

The cytoskeleton plays a vital role in neuromuscular junction (NMJ) formation. It is responsible for shaping synaptic membrane into folds opposed to presynaptic active zones and anchoring acetylcholine receptors (AChRs) to the crest of the junctional folds. Acetylcholine receptors (AChRs) associate with the actin cytoskeleton, the disruption of which affects spontaneous and agrin-induced AChR clusters (Prives et al., 1982; Connolly, 1984; Peng and Phelan, 1984; Bloch, 1986; Dai et al., 2000). How AChRs are tethered to the actin cytoskeleton remains unclear.


Asunto(s)
Citoesqueleto/fisiología , Unión Neuromuscular/fisiología , Actinina/fisiología , Animales , Distroglicanos/fisiología , Proteínas Musculares/fisiología , Utrofina/fisiología
5.
PLoS One ; 10(12): e0145272, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26689910

RESUMEN

Studies have demonstrated that oncolytic adenoviruses based on a 24 base pair deletion in the viral E1A gene (D24) may be promising therapeutics for treating a number of cancer types. In order to increase the therapeutic potential of these oncolytic viruses, a novel conditionally replicating adenovirus targeting multiple receptors upregulated on tumors was generated by incorporating an Ad5/3 fiber with a carboxyl terminus RGD ligand. The virus displayed full cytopathic effect in all tumor lines assayed at low titers with improved cytotoxicity over Ad5-RGD D24, Ad5/3 D24 and an HSV oncolytic virus. The virus was then engineered to deliver immunotherapeutic agents such as GM-CSF while maintaining enhanced heterogenic oncolysis.


Asunto(s)
Adenoviridae , Proteínas E1A de Adenovirus , Inmunoterapia/métodos , Neoplasias/terapia , Viroterapia Oncolítica/métodos , Virus Oncolíticos , Replicación Viral , Proteínas E1A de Adenovirus/genética , Proteínas E1A de Adenovirus/metabolismo , Secuencia de Bases , Línea Celular Tumoral , Humanos , Oligopéptidos/genética , Oligopéptidos/metabolismo , Virus Oncolíticos/genética , Virus Oncolíticos/metabolismo , Eliminación de Secuencia
6.
Mol Brain ; 1: 18, 2008 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-19055765

RESUMEN

AChR is concentrated at the postjunctional membrane at the neuromuscular junction. However, the underlying mechanism is unclear. We show that α-actinin, a protein known to cross-link F-actin, interacts with rapsyn, a scaffold protein essential for neuromuscular junction formation. α-Actinin, rapsyn, and surface AChR form a ternary complex. Moreover, the rapsyn-α-actinin interaction is increased by agrin, a factor known to stimulate AChR clustering. Downregulation of α-actinin expression inhibits agrin-mediated AChR clustering. Furthermore, the rapsyn-α-actinin interaction can be disrupted by inhibiting Abl and by cholinergic stimulation. Together these results indicate a role for α-actinin in AChR clustering.


Asunto(s)
Actinina/metabolismo , Agrina/farmacología , Proteínas Musculares/metabolismo , Receptores Colinérgicos/metabolismo , Animales , Análisis por Conglomerados , Células HEK293 , Humanos , Ratones , Unión Proteica/efectos de los fármacos , Transporte de Proteínas/efectos de los fármacos
7.
J Neurocytol ; 32(5-8): 697-708, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-15034262

RESUMEN

The receptor tyrosine kinase MuSK is activated by agrin, an extracellular matrix protein believed to be utilized by motoneurons to regulate the formation or maintenance of the neuromuscular junction (NMJ). Recent studies have shed light on intracellular signaling mechanisms downstream of MuSK. Agrin enhances the activity of Rho GTPases and PAK, which is required for AChR clustering. Activation of these enzymes requires not only the kinase activity of MuSK, but also its interaction with proteins such as Dishevelled. These results suggest that MuSK may function as a scaffold tyrosine kinase that forms a multi-molecule complex for AChR clustering.


Asunto(s)
Transducción de Señal/fisiología , Sinapsis/metabolismo , Animales , Humanos , Proteínas Tirosina Quinasas Receptoras/química , Proteínas Tirosina Quinasas Receptoras/genética , Proteínas Tirosina Quinasas Receptoras/metabolismo , Receptores Colinérgicos/química , Receptores Colinérgicos/genética , Receptores Colinérgicos/metabolismo , Sinapsis/genética
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