RESUMEN
The arcuate nucleus is a crucial hypothalamic brain region involved in regulating body weight homeostasis. Neurons within the arcuate nucleus respond to peripheral metabolic signals, such as leptin, and relay these signals via neuronal projections to brain regions both within and outside the hypothalamus, ultimately causing changes in an animal's behaviour and physiology. There is a substantial amount of evidence to indicate that leptin is intimately involved with the postnatal development of arcuate nucleus melanocortin circuitry. Further, it is clear that leptin signalling directly in the arcuate nucleus is required for circuitry development. However, as leptin receptor long isoform (Leprb) mRNA is expressed in multiple nuclei within the developing hypothalamus, including the postsynaptic target regions of arcuate melanocortin projections, this raises the possibility that leptin also signals in these nuclei to promote circuitry development. Here, we used RT-qPCR and RNAscope® to reveal the spatio-temporal pattern of Leprb mRNA in the early postnatal mouse hypothalamus. We found that Leprb mRNA expression increased significantly in the arcuate nucleus, ventromedial nucleus and paraventricular nucleus of the hypothalamus from P8, in concert with the leptin surge. In the dorsomedial nucleus of the hypothalamus, increases in Leprb mRNA were slightly later, increasing significantly from P12. Using duplex RNAscope®, we found Leprb co-expressed with Sim1, Pou3f2, Mc4r and Bdnf in the paraventricular nucleus at P8. Together, these data suggest that leptin may signal in a subset of neurons postsynaptic to arcuate melanocortin neurons, as well as within the arcuate nucleus itself, to promote the formation of arcuate melanocortin circuitry during the early postnatal period.
Asunto(s)
Leptina , Receptores de Leptina , Animales , Ratones , Leptina/metabolismo , Receptores de Leptina/genética , Receptores de Leptina/metabolismo , Hipotálamo/metabolismo , Núcleo Arqueado del Hipotálamo/metabolismo , Melanocortinas/metabolismo , ARN Mensajero/metabolismoRESUMEN
Limb-threatening vascular compromise from an isolated closed clavicle fracture is exceedingly rare. We report a case of a posteriorly angulated, closed clavicle fracture segment causing right upper-extremity ischemia, numbness, and paresis caused by entrapment of the clavicle between the first and second ribs.
Asunto(s)
Clavícula/lesiones , Fracturas Cerradas/complicaciones , Hipoestesia/etiología , Isquemia/etiología , Paresia/etiología , Extremidad Superior/irrigación sanguínea , Accidentes de Tránsito , Adolescente , Arteriopatías Oclusivas/diagnóstico por imagen , Arteriopatías Oclusivas/etiología , Arteriopatías Oclusivas/cirugía , Clavícula/diagnóstico por imagen , Clavícula/cirugía , Fracturas Cerradas/diagnóstico por imagen , Fracturas Cerradas/cirugía , Humanos , Masculino , Peatones , Fracturas de las Costillas/complicaciones , Fracturas de las Costillas/diagnóstico por imagen , Fracturas de las Costillas/cirugía , Arteria Subclavia/diagnóstico por imagen , Arteria Subclavia/cirugíaRESUMEN
The Plasmodium falciparum variant surface antigen PfEMP1 expressed on the surface of infected erythrocytes is thought to play a major role in the pathology of severe malaria. As the sequence pool of the var genes encoding PfEMP1 expands there are opportunities, despite the high degree of sequence diversity demonstrated by this gene family, to reconstruct full-length var genes from small sequence tags generated from patient isolates. To test whether this is possible we have used a set of recently laboratory adapted ICAM-1-binding parasite isolates to generate sequence tags and, from these, to identify the full-length PfEMP1 being expressed by them. In a subset of the strains available we were able to produce validated, full-length var gene sequences and use these to conduct biophysical analyses of the ICAM-1 binding regions.