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1.
Sci Adv ; 7(26)2021 06.
Article de Anglais | MEDLINE | ID: mdl-34162536

RÉSUMÉ

The American lobster, Homarus americanus, is integral to marine ecosystems and supports an important commercial fishery. This iconic species also serves as a valuable model for deciphering neural networks controlling rhythmic motor patterns and olfaction. Here, we report a high-quality draft assembly of the H. americanus genome with 25,284 predicted gene models. Analysis of the neural gene complement revealed extraordinary development of the chemosensory machinery, including a profound diversification of ligand-gated ion channels and secretory molecules. The discovery of a novel class of chimeric receptors coupling pattern recognition and neurotransmitter binding suggests a deep integration between the neural and immune systems. A robust repertoire of genes involved in innate immunity, genome stability, cell survival, chemical defense, and cuticle formation represents a diversity of defense mechanisms essential to thrive in the benthic marine environment. Together, these unique evolutionary adaptations contribute to the longevity and ecological success of this long-lived benthic predator.


Sujet(s)
Longévité , Nephropidae , Animaux , Écosystème , Longévité/génétique , Nephropidae/génétique , Nephropidae/métabolisme , Système nerveux
2.
Front Pediatr ; 5: 268, 2017.
Article de Anglais | MEDLINE | ID: mdl-29312906

RÉSUMÉ

Oral feeding competency is a major determinant of length of stay in the neonatal intensive care unit. An infant must be able to consistently demonstrate the ability to take all required enteral nutrition by mouth before discharge home. Most infants born prematurely (<37 weeks) will require days, if not weeks, to master this oral feeding competency skill. Inappropriately timed feeding attempts can lead to acute and long-term morbidities, prolonged hospitalizations, and increased health-care costs. Previously, a panel of five genes involved in essential developmental pathways including sensory integration (nephronophthisis 4, Plexin A1), hunger signaling [neuropeptide Y2 receptor (NPY2R), adenosine-monophosphate-activated protein kinase (AMPK)], and facial development (wingless-type MMTV integration site family, member 3) required for oral feeding success were identified in neonatal saliva. This study aimed to translate these five transcriptomic biomarkers into a rapid proteomic platform to provide objective, real-time assessment of oral feeding skills, to better inform care, and to improve neonatal outcomes. Total protein was extracted from saliva of 10 feeding-successful and 10 feeding-unsuccessful infants matched for age, sex, and post-conceptional age. Development of immunoassays was attempted for five oral feeding biomarkers and two reference biomarkers (GAPDH and YWHAZ) to normalize for starting protein concentrations. Normalized protein concentrations were correlated to both feeding status at time of sample collection and previously described gene expression profiles. Only the reference proteins and those involved in hunger signaling were detected in neonatal saliva at measurable levels. Expression patterns for NPY2R and AMPK correlated with the gene expression patterns previously seen between successful and unsuccessful feeders and predicted feeding outcome. Salivary proteins associated with hunger signaling are readily quantifiable in neonatal saliva and may be utilized to assess oral feeding readiness in the newborn. This study lays the foundation for the development of an informative, rapid, proteomic platform to assess neonatal oral feeding maturation.

3.
J Huntingtons Dis ; 5(4): 347-355, 2016 12 15.
Article de Anglais | MEDLINE | ID: mdl-27983565

RÉSUMÉ

BACKGROUND: Modulation of gene transcription by HDAC inhibitors has been shown repeatedly to be neuroprotective in cellular, invertebrate, and rodent models of Huntington's disease (HD). It has been difficult to translate these treatments to the clinic, however, because existing compounds have limited potency or brain bioavailability. OBJECTIVE: In the present study, we assessed the therapeutic potential of LBH589, an orally bioavailable hydroxamic acid-derived nonselective HDAC inhibitor in mouse models of HD. METHOD: The efficacy of LBH589 is tested in two HD mouse models using various biochemical, behavioral and neuropathological outcome measures. RESULTS: We show that LBH589 crosses the blood brain barrier; induces histone hyperacetylation and prevents striatal neuronal shrinkage in R6/2 HD mice. In full-length knock-in HD mice LBH589-treatment improves motor performance and reduces neuronal atrophy. CONCLUSIONS: Our efficacious results of LBH589 in fragment and full-length mouse models of HD suggest that LBH589 is a promising candidate for clinical assessment in HD patients and provides confirmation that non-selective HDAC inhibitors can be viable clinical candidates.


Sujet(s)
Inhibiteurs de désacétylase d'histone/pharmacologie , Maladie de Huntington/traitement médicamenteux , Acides hydroxamiques/pharmacologie , Indoles/pharmacologie , Neuroprotecteurs/pharmacologie , Animaux , Atrophie/traitement médicamenteux , Atrophie/métabolisme , Atrophie/anatomopathologie , Corps strié/effets des médicaments et des substances chimiques , Corps strié/métabolisme , Corps strié/anatomopathologie , Modèles animaux de maladie humaine , Femelle , Techniques de knock-in de gènes , Inhibiteurs de désacétylase d'histone/pharmacocinétique , Histone/métabolisme , Maladie de Huntington/anatomopathologie , Maladie de Huntington/physiopathologie , Acides hydroxamiques/pharmacocinétique , Indoles/pharmacocinétique , Souris de lignée C57BL , Souris de lignée CBA , Souris transgéniques , Activité motrice/effets des médicaments et des substances chimiques , Neurones/effets des médicaments et des substances chimiques , Neurones/anatomopathologie , Neurones/physiologie , Neuroprotecteurs/pharmacocinétique , Panobinostat
4.
Clin Ther ; 37(3): 498-504, 2015 Mar 01.
Article de Anglais | MEDLINE | ID: mdl-25732629

RÉSUMÉ

Clinical diagnostics can be improved by faster and more accessible disease detection. Our laboratory has developed a point-of-service (POS) device capable of rapid, sensitive, automated, and multiplexed biomarker detection that uses human saliva instead of other biofluids. Here, we review the technology that led to the development of this POS device. This POS technology can advance clinical diagnostics by saving time because of faster diagnosis, saving money because of a shorter hospital stay, and ultimately improving clinical care.


Sujet(s)
Marqueurs biologiques/analyse , Diagnostic , Analyse sur le lieu d'intervention , Salive/composition chimique , Humains , Dosage immunologique/instrumentation , Dosage immunologique/méthodes
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