Experiential and hormonal correlates of maternal behavior in teen and adult mothers

This study explores the role of cortisol and early life experiences in the regulation of maternal behavior and mood in teen and adult mothers. Primiparous mothers (n=119) (teen mothers < 19 years, n=42), young mothers (19-25 years, n= 4), and mature mothers, (>25 years, n=43) were assessed for their maternal behavior, mood, and hormonal profile at approximately 6 weeks postpartum. Outcome measures were analyzed as a function of age and early life experience. Results showed an interaction between age and type of maternal behavior, where teen mothers engaged in more instrumental (e.g. changing diapers, adjusting clothes) less affectionate (e.g., stroking, kissing, patting) behavior, and mature mothers engaged in more affectionate and less instrumental behavior. When groups were reassessed based on early life experience (consistency of care during the first 12 years of life: consistent care; having at least one consistent caregiver, inconsistent care; having multiple and changing caregivers), an interaction was also found between consistency of care and type of behavior shown, where mothers who received inconsistent care engaged in more instrumental and less affectionate behavior. Compared to mature mothers, teen mothers who were breast feeding also had higher salivary cortisol levels, and high cortisol in teen mothers related to decreased fatigue and increased energy. These results suggest that early life experiences are linked to mothering behavior and are consistent with the emerging human and animal literature on intergenerational effects of mothering style.     

Kinetic alterations due to a missense mutation in the Na,K-ATPase alpha2 subunit cause familial hemiplegic migraine type 2

A number of missense mutations in the ATP1A2 gene, which encodes the Na,K-ATPase alpha2 subunit, have been identified in familial hemiplegic migraine with aura. Loss of function and haploinsufficiency have been the suggested mechanisms in mutants for which functional analysis has been reported. This paper describes a kinetic analysis of mutant T345A, recently identified in a detailed genetic analysis of a large Finnish family (Kaunisto, M. A., Harno, H., Vanmolkot, K. R., Gargus, J. J., Sun, G., Hamalainen, E., Liukkonen, E., Kallela, M., van den Maagdenberg, A. M., Frants, R. R., Farkkila, M., Palotie, A., and Wessman, M. (2004) Neurogenetics 5, 141-146). Introducing T345A into the conserved rat alpha2 enzyme does not alter cell growth or catalytic turnover but causes a substantial decrease in apparent K+ affinity (2-fold increase in K0.5(K+)). In view of the location of Thr-345 in the cytoplasmic stalk domain adjacent to transmembrane segment 4, the 2-fold increase in K0.5(K+) is probably due to T345A replacement altering K+ occlusion/deocclusion. Faster K+ deocclusion of the mutant via the E2(K) + ATP --> E1.ATP + K+ partial reaction is evidenced in (i) a marked increase (300%) in K+ stimulation of Na-ATPase at micromolar ATP, (ii) a 4-fold decrease in KATP, and (iii) only a modest increase (approximately 3-fold) in I50 for vanadate, which was used as a probe of the steady state E1/E2 conformational equilibrium. We suggest that the decreased apparent K+ affinity is the basis for a reduced rate of extracellular K+ removal, which delays the recovery phase of nerve impulse transmission in the central nervous system and, thereby, the clinical picture of migraine with aura. This is the first demonstration of a mutation that leads to a disease associated with a kinetically altered but fully functional Na,K-ATPase, refining the molecular mechanism of pathogenesis in familial hemiplegic migraine.     

High-resolution comparative mapping between human chromosomes 4 and 8 and bovine chromosome 27 provides genes and segments serving as positional candidates for udder health in cattle

To get more information about the order of genes located in Bos taurus (BTA) chromosome 27 segments, supposed to harbor loci influencing clinical mastitis and somatic cell count, and to identify genes that serve as positional candidates for the mentioned traits, we constructed a high-resolution, comparative, and comprehensive gene map for BTA27. The map includes 57 loci in a 5000-rad cattle-hamster whole genome radiation hybrid panel supported by 50 syntenic assignments in a cattle-murine somatic hybrid cell panel. Thirty-eight new loci (36 genes, 2 microsatellites) together with repeated mappings of 5 genes and 7 microsatellites and integration of existing data from 7 microsatellites were used to generate a comprehensive RH5000 map. The RH map, constructed at lod score criterion 8 using the software RHMAP v.3.0, consisted of three linkage groups 23, 22, and 590 cR5000 in length. Gene assignments on BTA27 and the localization of 8 more genes on BTA8 and BTA14 previously predicted on BTA8/BTA27 and BTA14/BTA27 narrowed down significantly the chromosome break points between the three cattle chromosomes and segments on Homo sapiens chromosomes HSA4 and HSA8. Defined evolutionary break points increase the accuracy of comparative in silico mapping of further human genes in conserved chromosome segments of BTA27.     

Cell division gene cluster in Spiroplasma kunkelii: functional characterization of ftsZ and the first report of ftsA in mollicutes

Spiroplasma kunkelii is a helical, wall-less bacterium that causes corn stunt disease. In adaptation to its phloem-inhabiting parasitic lifestyle, the bacterium has undergone a reductive evolutionary process and, as a result, possesses a compact genome with a gene set approaching the minimal complement necessary for multiplication and pathogenesis. We cloned a much-reduced cell division gene cluster from S. kunkelii and functionally characterized the key division gene, ftsZ(sk). The 1236-bp open reading frame of ftsZ(sk) is capable of encoding a protein with a calculated molecular mass of 44.1 kDa. Protein sequence alignment revealed that FtsZ(sk) is remarkably similar to FtsZ proteins from other eubacteria, and possesses the conserved GTP-binding and hydrolyzing motifs. We demonstrated that overexpression of ftsZ(sk) in Escherichia coli causes transgression of the host cell division, resulting in a filamentous phenotype. We also report, for the first time, the presence of a ftsA gene in the cell division cluster of a mollicute species.     

The cyclase-associated protein CAP as regulator of cell polarity and cAMP signaling in Dictyostelium

Cyclase-associated protein (CAP) is an evolutionarily conserved regulator of the G-actin/F-actin ratio and, in yeast, is involved in regulating the adenylyl cyclase activity. We show that cell polarization, F-actin organization, and phototaxis are altered in a Dictyostelium CAP knockout mutant. Furthermore, in complementation assays we determined the roles of the individual domains in signaling and regulation of the actin cytoskeleton. We studied in detail the adenylyl cyclase activity and found that the mutant cells have normal levels of the aggregation phase-specific adenylyl cyclase and that receptor-mediated activation is intact. However, cAMP relay that is responsible for the generation of propagating cAMP waves that control the chemotactic aggregation of starving Dictyostelium cells was altered, and the cAMP-induced cGMP production was significantly reduced. The data suggest an interaction of CAP with adenylyl cyclase in Dictyostelium and an influence on signaling pathways directly as well as through its function as a regulatory component of the cytoskeleton.     

DISPERSAL AND POPULATION-GENETIC STRUCTURE OF THE COOPERATIVE SPIDER,AGELENA CONSOCIATA,IN WEST AFRICAN RAINFOREST

Dispersal experiments and gel electrophoresis of allozyme polymorphisms were used to investigate the selective mode underlying cooperative behavior in the rainforest spider, Agelena consociata. Previous work has indicated that individual selection alone does not explain the cooperative and even altruistic behavior noted for this African species, which exists in groups of up to hundreds of adults. We found no evidence for active dispersal by reproductives or any age class of this spider. Nest fragmentation by falling tree limbs and storms is indicated as the cause of new nest formation within local areas, while passive dispersal by vertebrate carriers that either have some association with the nests (bats) or move through them is indicated as the probable mode of longer-distance dispersal. The population-genetic structure observed for A. consociata supports the data obtained on dispersal. Wright's F_ST statistic and G tests for genetic heterogeneity indicate that the populations are subdivided into genetically heterogeneous colonies. Comparisons utilizing Nei's genetic distance show colonies separated by as few as 30 m to be as genetically distinct as are colonies separated by many kilometers. There is also a marked scarcity of heterozygotes, and individuals within nests and associated colonies are genetically related about as much as are full siblings. The results of these analyses indicate that kin selection or some type of family-group selection may have been important in the evolution of cooperative behavior in the species.     

Automated evaluation of autoantibodies on human epithelial-2 cells as an approach to standardize cell-based immunofluorescence tests

Introduction  

Analysis of autoantibodies (AAB) by indirect immunofluorescence (IIF) is a basic tool for the serological diagnosis of systemic rheumatic disorders. Automation of autoantibody IIF reading including pattern recognition may improve intra- and inter-laboratory variability and meet the demand for cost-effective assessment of large numbers of samples. Comparing automated and visual interpretation, the usefulness for routine laboratory diagnostics was investigated.     

The Wilms' tumor suppressor Wt1 is associated with the differentiation of retinoblastoma cells.

We have demonstrated recently that Wilms' tumor suppressor 1 (Wt1),in addition to its role in genitourinary formation,is required for the differentiation of ganglion cells in the developing retina. Here we provide further evidence that Wt1 is associated with neuronal differentiation. Thus, the retinoblastoma-derived human cell line, Y-79, contained robust amounts of Wt1 mRNA and protein. Wt1 expression was down-regulated upon laminin-induced differentiation of Y-79 into neuron-like cells. Inhibition of Wt1 with antisense oligonucleotides dramatically reduced the capacity of undifferentiated Y-79 cells to undergo neuronal differentiation, whereas sense and missense oligonucleotides had no effect. Wt1 immunoreactivity was also detected in solid retinoblastomas, in which it resided mainly in areas with moderate proliferative activity. These findings suggest a role for Wt1 in the differentiation of retinoblastoma cells. Furthermore, Wt1 expression in retinoblastoma may reflect the potential of these tumors to initiate the early steps of neuronal differentiation.