Recent studies implicate Wnt/beta-catenin signaling in lens differentiation (Stump, R. J., et al., 2003. A role for Wnt/beta-catenin signaling in lens epithelial differentiation. Dev Biol;259:48-61). Beta-catenin is a component of adherens junctions and functions as a transcriptional activator in canonical Wnt signaling. We investigated the effects of Cre/LoxP-mediated deletion of beta-catenin during lens development using two Cre lines that specifically deleted beta-catenin in whole lens or only in differentiated fibers, from E13.5. We found that beta-catenin was required in lens epithelium and during early fiber differentiation but appeared to be redundant in differentiated fiber cells. Complete loss of beta-catenin resulted in an abnormal and deficient epithelial layer with loss of E-cadherin and Pax6 expression as well as abnormal expression of c-Maf and p57(kip2) but not Prox1. There was also disrupted fiber cell differentiation, characterized by poor cell elongation, decreased beta-crystallin expression, epithelial cell cycle arrest at G(1)-S transition and premature cell cycle exit. Despite cell cycle arrest there was no induction of apoptosis. Mutant fiber cells displayed altered apical-basal polarity as evidenced by altered distribution of the tight junction protein, ZO1, disruption of apical actin filaments and abnormal deposition of extracellular matrix, resulting in a deficient lens capsule. Loss of beta-catenin also affected the formation of adhesion junctions as evidenced by dissociation of N-cadherin and F-actin localization in differentiating fiber cells. However, loss of beta-catenin from terminally differentiating fibers had no apparent effects on adhesion junctions between adjacent embryonic fibers. These data indicate that beta-catenin plays distinct functions during lens fiber differentiation and is involved in both Wnt signaling and adhesion-related mechanisms that regulate lens epithelium and early fiber differentiation.
Premature delivery, in the absence of potentiating factors, such as hypoxia or infection, is associated with a decrease in brain growth and the presence of subtle brain injury, which seems to be modified by respiratory therapies with early continuous positive airway pressure being associated with less overall cerebral injury.
Previous studies have shown that individuals with autism spectrum disorder (ASD) demonstrate poorer driving performance than their peers and are less likely to obtain a driver's license. This study aims to examine the relationship between driving performance and executive functioning for novice drivers, with and without ASD, using a driving simulator. Forty-four males (ages 15-23), 17 with ASD and 27 healthy controls, completed paradigms assessing driving skills and executive functioning. ASD drivers demonstrated poorer driving performance overall and the addition of a working memory task resulted in a significant decrement in their performance relative to control drivers. Results suggest that working memory may be a key mechanism underlying difficulties demonstrated by ASD drivers and provides insight for future intervention programs.
This review documents the current status of nerve transfer surgery for upper limb reanimation in tetraplegia and summarizes the functional results in 59 cases with 89 nerve transfers performed, including 15 cases of double-nerve transfer and 1 case of triple-nerve transfer.
A patent ductus arteriosus (PDA) alters pulmonary mechanics and regional blood flow in the preterm infant. Its significance with respect to brain injury and brain development are unclear. We evaluated the effects of surgical ductal ligation on the preterm baboon brain. Baboons were delivered at 125 d of gestation (dg, term approximately 185 dg) and ventilated for 14 d (n ϭ 12). The PDA was ligated 6 d after delivery (n ϭ 7) or left untreated (n ϭ 5). Animals were euthanized at 139 dg and brains compared histologically with gestational control fetuses (n ϭ 7) at 140 dg. Brain and body weights were reduced (p Ͻ 0.05) in both groups of ventilated preterm animals; however, the brain to body weight ratio was increased (p Ͻ 0.01) in ligated, but not unligated newborns compared with gestational controls. No overt lesions were observed in either premature newborn group. Astrocyte density in the neocortex and hippocampus were greatest in the unligated newborns (p Ͻ 0.01). Myelination and oligodendrocytes were reduced (p Ͻ 0.05) in both premature newborn groups. The brain growth and development index was reduced, and the damage index was increased in prematurely delivered baboons. Surgical ligation of the PDA does not increase the incidence of brain injury and may be beneficial if the PDA is contributing to persistent pulmonary and hemodynamic instability. H emodynamic symptoms from a patent ductus arteriosus (PDA) are present in 55-70% of infants delivered below 1000 g or before 28 wk of gestation with the PDA resulting in increased pulmonary blood flow and redistribution of flow to other organs (1). However, the impact of the PDA on the brain remains uncertain. Current therapy for PDA includes medical therapy with indomethacin or ibuprofen and/or surgical ligation. There has been considerable debate about the benefits and risks of surgical ligation for PDA on subsequent neurodevelopmental outcome. Surgery in the neonatal period is associated with a systemic inflammatory response; in addition, the use of sedative and/or anesthetic drugs may adversely impact the immature brain (2). An increased incidence of neurosensory impairment has been observed among infants who underwent ductal ligation (3). On the other hand, in a single center study where infants received prophylactic Indocin and no infant was exposed to patency of the ductus arteriosus for more than 5-7 d, ductal ligation was not associated with abnormal neurodevelopmental outcome (4). No experimental studies have been done to try to answer the impact of ligating a PDA on the developing brain.The premature baboon, delivered at 125 d of gestation (dg; term approximately 185 dg), has a similar neonatal course to the premature human delivered between 26 and 27 wk of gestation: they both develop respiratory distress and fail to close their PDA after birth (5). In addition, despite antenatal glucocorticoids, surfactant treatment, total parenteral nutrition, low tidal volume ventilation, and low supplemental oxygen administration during the first 2 wk after de...
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