RESUMO
Mutations in the synaptic scaffolding protein gene SHANK3 are strongly implicated in autism and Phelan-McDermid 22q13 deletion syndrome. The precise location of the mutation within the Shank3 gene is key to its phenotypic outcomes. Here, we report the physiological and behavioral consequences of null and heterozygous mutations in the ankyrin repeat domain in Shank3 mice. Both homozygous and heterozygous mice showed reduced glutamatergic transmission and long-term potentiation in the hippocampus with more severe deficits detected in the homozygous mice. Three independent cohorts were evaluated for magnitude and replicability of behavioral endophenotypes relevant to autism and Phelan-McDermid syndrome. Mild social impairments were detected, primarily in juveniles during reciprocal interactions, while all genotypes displayed normal adult sociability on the three-chambered task. Impaired novel object recognition and rotarod performance were consistent across cohorts of null mutants. Repetitive self-grooming, reduced ultrasonic vocalizations, and deficits in reversal of water maze learning were detected only in some cohorts, emphasizing the importance of replication analyses. These results demonstrate the exquisite specificity of deletions in discrete domains within the Shank3 gene in determining severity of symptoms.
Assuntos
Transtorno Autístico/genética , Proteínas de Transporte/genética , Potenciais Pós-Sinápticos Excitadores/genética , Mutação/genética , Inibição Neural/genética , Fenótipo , Transmissão Sináptica/genética , Fatores Etários , Animais , Transtorno Autístico/psicologia , Feminino , Triagem de Portadores Genéticos , Ácido Glutâmico/genética , Homozigoto , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas dos Microfilamentos , Proteínas do Tecido NervosoRESUMO
Emergency care is in its nascency in most of the world and emergency health systems are developing throughout Africa, including Ethiopia. Ethiopia is a LMIC African nation that has committed to strengthening emergency care systems. A historical perspective provides the background of Ethiopian emergency care with the development of an emergency care taskforce to the first residency program and subsequent development of the Emergency and Critical Care Directorate. The goals of the directorate are discussed as well as their role in the development of the national integrated emergency medicine curriculum. Concurrently the development of multiple residencies as well as a nursing emergency and critical care training increased the human resources for emergency medicine. Recently, the WHO and Ministry of Health-Ethiopia have been working together to roll out an integrated emergency care system development agenda throughout the country bolstered by the recent passing of a world health assembly resolution to strengthen emergency care co-led by Ethiopia. With all the successes of Ethiopia in increasing human resources there have been both triumphs and challenges. The development of human resources for emergency care systems in Ethiopia provides insights and lessons learned to other nations on a similar pathway of strengthening emergency care systems.
RESUMO
Changes to typical procedures in animal husbandry are often necessary to accommodate the needs of behavioral experiments. Two common changes in husbandry for rodents are light chronic food restriction (to motivate animals in reward-association tasks) and social isolation (to accommodate individual feeding schedules or need to reduce interactions because of implants for example). Each of these intervention individually has been shown to modulate behavioral state and with it performance in behavioral tasks. We here systematically test how social isolation and light chronic food restriction modulate olfactory memory in rats. Our results show a strong modulation of olfactory memory after both types of husbandry interventions. These results suggest that common changes in animal husbandry promote distinct and relevant changes in animal behavior.