Maturational Changes in Rabbit Renal Brush Border Membrane Vesicle Osmotic Water Permeability

We have recently shown that the osmotic water permeability (P _f ) of proximal tubules from neonatal rabbits is higher than that of adults (AJP 271:F871-F876, 1996). The developmental change in P _f could be due to differences in one or more of the components in the path for transepithelial water transport. The present study examined developmental changes in water transport characteristics of the proximal tubule apical membrane by determining P _f and aquaporin 1 (AQP1) expression in neonatal (10–14 days old) and adult rabbit renal brush border membrane vesicles (BBMV). AQP1 abundance in the adult BBMV was higher than the neonatal BBMV. At 25°C the P _f of neonatal BBMV was found to be significantly lower than the adult BBMV at osmotic gradients from 50 to 250 mOsm/kg water. The activation energy for osmotic water movement was higher in the neonatal BBMV than the adult BBMV (9.19 ± 0.37 vs. 5.09 ± 0.57 kcal · deg⁻¹· mol⁻¹, P < 0.005). Osmotic water movement in neonatal BBMV was inhibited 17.9 ± 1.3% by 1 mm HgCl₂ compared to 34.3 ± 3.8% in the adult BBMV (P < 0.005). These data are consistent with a significantly greater fraction of water traversing the apical membrane lipid bilayer in proximal tubules of neonates than adults. The lower P _f of the neonatal BBMV indicates that the apical membrane is not responsible for the higher transepithelial P _f in the neonatal proximal tubule. Received: 18 December 1997/Revised: 3 April 1998     

Mechanisms of Resilience in Children of Mothers Who Self-Report with Depressive Symptoms in the First Postnatal Year

Background

Symptoms of maternal postnatal depression are associated with an increased risk of adverse effects on child development. However, some children exposed to postnatal depression have outcomes similar to unexposed children, and can be referred to as resilient. This study aimed to determine the mechanisms of resilience in children exposed to depressive symptoms postnatally.

Method

Data are from a prospective cohort study, the Avon Longitudinal Study of Parents and Children. Self-report questionnaire data were collected during pregnancy and the child’s first 2 years regarding maternal views of parenting and her perception of the child. The Edinburgh Postnatal Depression Scale (EPDS) was completed postnatally at 8 months and the Strengths and Difficulties Questionnaire (SDQ) at age 11 years. Exposed children who scored above the median score of non-exposed children were defined as resilient. Structural equation modeling was used to investigate the development of resilience.

Results

From the core ALSPAC cohort, 1,009 children (6.9%) were exposed to maternal depression at 8 months postnatally. The SDQ total difficulties scores at 11 years of age indicated that 325 (32.2%) were resilient, 684 were non-resilient. Maternal positive feelings about parenting and child non-verbal communication at 15 months increased the likelihood of later resilience.

Conclusions

In this study, resilience was associated with two factors: the child’s nonverbal communication at 15 months and by maternal positive feelings about parenting. Early intervention to support mother-child interaction and foster child development in women identified with postnatal depressive symptoms may benefit later child resilience.     

<Emphasis Type="Italic">Hau-Pax6A</Emphasis> expression in the central nervous system of the leech embryo

The leech Helobdella sp. (Austin) has two genes of the Pax6 subfamily, one of which is characterized in detail. Hau-Pax6A was expressed during embryonic development in a pattern similar to other bilaterian animals. RNA was detected in cellular precursors of the central nervous system (CNS) and in peripheral cells including a population associated with the developing eye. The CNS of the mature leech is a ventral nerve cord composed of segmental ganglia, and embryonic Hau-Pax6A expression was primarily localized to the N teloblast lineage that generates the majority of ganglionic neurons. Expression began when the ganglion primordia were four cells in length and was initially restricted to a single cell, n_s.a, whose descendants will form the ganglion’s anterior edge. At later stages, the Hau-Pax6A expression pattern expanded to include additional CNS precursors, including some descendants of the O teloblast. Expression persisted through the early stages of ganglion morphogenesis but disappeared from the segmented body trunk at the time of neuronal differentiation. The timing and iterated pattern of Hau-Pax6A expression in the leech embryo suggests that this gene may play a role in the segmental patterning of CNS morphogenesis.     

Network analysis of skin tumor progression identifies a rewired genetic architecture affecting inflammation and tumor susceptibility

Background  

Germline polymorphisms can influence gene expression networks in normal mammalian tissues and can affect disease susceptibility. We and others have shown that analysis of this genetic architecture can identify single genes and whole pathways that influence complex traits, including inflammation and cancer susceptibility. Whether germline variants affect gene expression in tumors that have undergone somatic alterations, and the extent to which these variants influence tumor progression, is unknown.     

Glucocorticoids increase osmotic water permeability (Pf) of neonatal rabbit renal brush border membrane vesicles

During postnatal maturation, there is an increase in renal brush border membrane vesicle (BBMV) osmotic water permeability and a parallel increase in aquaporin-1 (AQP1) protein abundance. The mechanisms responsible for these changes remain unknown. Because serum glucocorticoid levels rise postnatally and have previously been linked to other maturational changes in renal function, we examined the effects of glucocorticoids on osmotic (Pf) and diffusional (P(DW)) water permeability and AQP1 protein abundance of renal BBMV. Neonatal rabbits were treated with dexamethasone (10 microg/100 g) for three days and compared with control neonates and adults. Pf and P(DW) were measured at 20 degrees C with a stopped-flow apparatus using light-scattering and aminonaphthalene trisulfonic acid (ANTS) fluorescence, respectively. Pf was significantly higher in BBMV from dexamethasone-treated neonates compared with vehicle-treated neonates, but remained lower than in BBMV from adults (P<0.05). P(DW) in dexamethasone and vehicle-treated neonatal BBMV was lower than in adult BBMV. Pf/P(DW) ratio increased from neonate (5.1+/-0.3) to dexamethasone (7.0+/-0.1) and adult BBMV (6.3+/-0.1). AQP1 expression was increased by dexamethasone treatment to adult levels. Membrane fluidity, which is inversely related to generalized polarization (GP) of steady-state laurdan fluorescence, was significantly higher in neonatal BBMV than both dexamethasone and adult BBMV (GP: neonate 0.285+/-0.002, dexamethasone treatment 0.302+/-0.006, and adult 0.300+/-0.005; P<0.05). These combined results show that dexamethasone-treatment during days 4-7 of life increases BBMV water permeability despite a decrease in membrane fluidity. This occurs by increasing channel-mediated water transport, as reflected in an increase in AQP1 protein abundance and a higher Pf/P(DW) ratio. This mimics the maturational changes and suggests a physiological role for glucocorticoids in maturation of proximal tubule water transport.     

Myogenesis in sheep is altered by maternal feed intake during the peri-conception period

The effect of varying short-term maternal feed intake during the peri-conception period on the development of ovine fetal muscle at mid-gestation was investigated. Superovulated donor Merino ewes (n = 24) were fed a roughage/grain pelleted diet (10.1 MJME/kg dry matter) at either 1.5x maintenance (H; high) or 0.5x maintenance (L; low) from 18 days before until 6 days after ovulation. Embryos were transferred to recipient ewes (n = 60) on day 6. Singleton fetuses were collected on day 75 of gestation and placental weights, fetal body dimensions and fetal organ and muscle weights recorded. The number, type and size of muscle fibres and the dry matter, RNA, DNA and protein content in the semitendinosus muscle were determined. Maternal feed intake did not influence body dimensions, organ development or muscle weights in the fetus. However, L feed intake decreased total muscle fibre number in the fetus by approximately 20% (P = 0.06) compared to H feed intake. This resulted from a reduced secondary to primary fibre ratio (P < 0.05) and indicated that secondary fibre formation occurred at a reduced rate in L fetuses. In addition, protein:DNA ratio tended to be lower in muscles of L fetuses (P < 0.1). It is concluded that restricting feed intake over the peri-conception period reduces or delays myogenesis in fetal sheep. The potential mechanisms by which nutritional availability during this period may influence subsequent myogenic development are discussed.     

Physiological routes from intra-uterine seminal contents to advancement of ovulation

Whole boar semen or seminal plasma has been demonstrated to advance the time of ovulation in gilts. As a means of clarifying this influence, the contribution of uterine lymphatics and their white cell populations has been examined. After duct visualisation with Evan's blue, lymph was sampled from a mesometrial vessel in eight pre-ovulatory gilts whose uterine lumen was infused simultaneously with whole semen in one ligated horn and saline in the contralateral ligated horn. Lymph was collected from cannulated vessels for periods of up to four hours under general anaesthesia. Thereafter, mesometrial lymph nodes, utero-tubal junction and uterine wall tissues were sampled. The proportion of nucleated cells in the sampled lymph increased towards the end of the collection period, but erythrocytes were found in all instances preventing a meaningful differentiation and identification of leukocytes. Prominent uterine lymph nodes were present in the mesometrium on both sides of the reproductive tract in 7 of 10 gilts. Differences in cellular contents were demonstrated between the side of the tract infused with semen and that infused with saline control. Two of 4 gilts had lower values for CD4 (Cluster Differentiation) and 3 of 6 gilts higher values for MHC II (Major Histocompatibility Complex) markers on the side challenged with semen. In contrast, values remained constant for CD8 but ranged widely for CD18. Immunohistochemical analysis of uterine tissue samples for MHC II+ cells revealed significant differences (P < 0.05) between the control and semen-treated ligated portions of the horns, as well as between the tissue sample of uterine wall and that from the utero-tubal junction, but there were no significant differences for CD4+ cells. It therefore remains plausible that semen-induced cytokines in the uterine lymph undergo counter-current transfer to the ipsilateral ovary and accelerate the final maturation of pre-ovulatory Graafian follicles.