The nucleoporin Nup153 is required for nuclear pore basket formation, nuclear pore complex anchoring and import of a subset of nuclear proteins.

The nuclear pore complex (NPC) is a large proteinaceous structure through which bidirectional transport of macromolecules across the nuclear envelope (NE) takes place. Nup153 is a peripheral NPC component that has been implicated in protein and RNP transport and in the interaction of NPCs with the nuclear lamina. Here, Nup153 is localized by immunogold electron microscopy to a position on the nuclear ring of the NPC. Nuclear reconstitution is used to investigate the role of Nup153 in nucleo- cytoplasmic transport and NPC architecture. NPCs assembled in the absence of Nup153 lacked several nuclear basket components, were unevenly distributed in the NE and, unlike wild-type NPCs, were mobile within the NE. Importin alpha/beta-mediated protein import into the nucleus was strongly reduced in the absence of Nup153, while transportin-mediated import was unaffected. This was due to a reduction in import complex translocation rather than to defective receptor recycling. Our results therefore reveal functions for Nup153 in NPC assembly, in anchoring NPCs within the NE and in mediating specific nuclear import events.

The prediction and prevention of intrapartum fetal asphyxia in term pregnancies.

OBJECTIVE: This study was undertaken to examine the roles of clinical risk scoring, electronic fetal heart rate monitoring, and fetal blood gas and acid-base assessment in the prediction and prevention of intrapartum fetal asphyxia in term pregnancies. STUDY DESIGN: The outcomes of 166 term pregnancies with biochemically confirmed fetal asphyxia (umbilical artery base deficit at delivery, >12 mmol/L) were examined. This population included 83 pregnancies delivered abdominally matched with 83 pregnancies delivered vaginally. Antepartum and intrapartum clinical risk factors and neonatal complications were documented. Fetal assessments included fetal heart rate patterns in the fetal heart rate record and fetal capillary blood gas and acid-base assessments. Fetal asphyxia was classified as mild, moderate, or severe on the basis of umbilical artery base deficit (cutoff >12 mmol/L) and neonatal encephalopathy and other organ system complications. RESULTS: Fetal asphyxial exposures were as follows: mild, 140; moderate, 22; and severe, 4. Intervention and delivery during the first or second stage of labor occurred in 98 of the 166 pregnancies. Predictive fetal heart rate patterns were the primary indication leading to intervention and delivery during the first or second stage of labor. Clinical risk factors when present were secondary indications in the clinical decision to intervene. Fetal blood gas and acid-base assessment was a useful supplementary test in 41 pregnancies. Intervention and delivery may have prevented the progression of mild asphyxia in 78 pregnancies and may have modified the degree of moderate or severe asphyxia in 20 pregnancies. CONCLUSION: Although fetal heart rate patterns will not discriminate all asphyxial exposures, continuous fetal heart rate monitoring supplemented by fetal blood gas and acid-base assessment can be a useful fetal assessment paradigm for intrapartum fetal asphyxia. Such an assessment paradigm will not prevent all cases of moderate or severe fetal asphyxia. However, prediction and diagnosis with intervention and delivery during the first or second stage of labor could prevent the progression of mild asphyxia to moderate or severe asphyxia in some cases.