Objective To evaluate associations between neonatal intensive care unit (NICU) room type (open ward and private room) and medical outcomes; neurobehavior, electrophysiology and brain structure at hospital discharge; and developmental outcomes at two years of age. Study design In this prospective longitudinal cohort study, we enrolled 136 preterm infants born <30 weeks gestation from an urban, 75-bed level III NICU from 2007-2010. Upon admission, each participant was assigned to a bedspace in an open ward or private room within the same hospital, based on space and staffing availability, where they remained for the duration of hospitalization. The primary outcome was developmental performance at two years of age (n=86 infants returned for testing, which was 83% of survivors) measured using the Bayley Scales of Infant and Toddler Development, 3rd Edition. Secondary outcomes were 1) medical factors throughout the hospitalization, 2) neurobehavior, and 3) cerebral injury and maturation (determined by magnetic resonance imaging and electroencephalography). Results At term equivalent age, infants in private rooms were characterized by a diminution of normal hemispheric asymmetry and a trend toward having lower amplitude integrated electroencephalography cerebral maturation scores [p= 0.02; β=−0.52 (CI −0.95, −0.10)]. At age two years, infants from private rooms had lower language scores [p= 0.006; β=−8.3 (CI −14.2, −2.4)] and a trend toward lower motor scores [p= 0.02; β=−6.3 (CI −11.7, −0.99)], which persisted after adjustment for potential confounders. Conclusion These findings raise concerns that highlight the need for further research into the potential adverse effects of different amounts of sensory exposure in the NICU environment.

Activation of the serine/threonine kinase Akt/PKB positively impacts on three cellular processes relevant to tumor progression: proliferation, survival, and cell size/growth. Using a three-dimensional culture model of MCF-10A mammary cells, we have examined how Akt influences the morphogenesis of polarized epithelial structures. Activation of a conditionally active variant of Akt elicits large, misshapen structures, which primarily arise from the combined effects of Akt on proliferation and cell size. Importantly, Akt activation amplifies proliferation during the early stages of morphogenesis, but cannot overcome signals suppressing proliferation in late-stage cultures. Akt also cooperates with oncoproteins such as cyclin D1 or HPV E7 to promote proliferation and morphogenesis in the absence of growth factors. Pharmacological inhibition of the Akt effector, mammalian target of rapamycin (mTOR), with rapamycin prevents the morphological disruption elicited by Akt activation, including its effect on cell size and number, and the cooperative effect of Akt on oncogene-driven proliferation, indicating that mTOR function is required for the multiple biological effects of Akt activation during morphogenesis.

Our observations reveal the involvement of PLD1 in mTOR signaling and cell size control, and provide a molecular mechanism for Cdc42 activation of S6K1. A new cascade is proposed to connect mitogenic signals to mTOR through Cdc42, PLD1, and PA.

The inheritance of resistance to Phytophthora capsici Leonian root rot and foliar blight was compared in two different Capsicum annuum L. var. annuum pod types. The seedling was screened for phytophthora root rot, while a genetically identical stem cutting was screened for phytophthora foliar blight to determine if the same gene(s) confer resistance to both disease syndromes. The susceptible parents were `Keystone Resistant Giant #3' (`Keystone'), a bell pepper type, and `Early Jalapeño', while `Criollo de Morelos-334' was the resistant parent. Resistance was observed in both F1 populations screened for phytophthora root and foliar infection indicating dominance for resistance. Reciprocal effects were not detected. To determine if the same gene(s) conferred root rot and foliar resistance, root rot screening results were matched to the corresponding foliar blight stem cutting reaction. The segregation of resistance in the F2 generations was dependent on the susceptible parent. In the F2 generation derived from `Early Jalapeño', root rot resistance and foliar blight resistance segregated in a 9:3:3:1 (root resistant/foliar resistant: root resistant/foliar susceptible: root susceptible/foliar resistant: root susceptible/foliar susceptible) ratio. One independent, dominant gene was necessary for root rot resistance, and a different independent, dominant gene was needed for foliar blight resistance. In the F2 generation derived from `Keystone', root rot and foliar blight resistance segregated in a 7:2:2:5 (root resistant/foliar resistant: root resistant/foliar susceptible: root susceptible/foliar resistant: root susceptible/foliar susceptible) ratio. This segregation ratio is expected when one dominant gene is required for root resistance, and a different dominant gene is required for foliar resistance. In addition to these two genes, at least one dominant allele of a third gene must be present for expression of root rot and foliar blight resistance.

Members of the Rho subfamily of GTP-binding proteins are implicated in the regulation of phospholipase D (PLD). In the present study, we demonstrate a physical association between a Rho family member, Cdc42, and PLD1. Binding of Cdc42 to PLD1 and subsequent activation are GTP-dependent. Although binding of Cdc42 to PLD1 does not require geranylgeranylation, activation of PLD1 is dependent on this lipid modification of Cdc42. Specific point mutations in the switch I region of Cdc42 abolish binding to and, therefore, activation of PLD1 by Cdc42. Deletion of the Rho insert region, which consists of residues 120 -139, from Cdc42 does not interfere with binding to PLD1 but inhibits Cdc42 stimulated PLD1 activity. Interestingly, deletion of the insert region from Cdc42 also inhibits activation of PLD1 by Arf and protein kinase C. With the lack of specific inhibitors of PLD activity, the insert deletion mutant of Cdc42 (designated (⌬L8)Cdc42) is a novel reagent for in vitro studies of PLD1 regulation, as well as for in vivo studies of Cdc42-mediated signaling pathways leading to PLD1 activation. Because the insert region is required for the transforming activity of Cdc42, regulation of PLD1 by this region on Cdc42 is of major interest.