Resemblance for age at menarche in female twins reared apart and together

Menarche is a significant developmental event in the lives of young females. Genetic and family environmental influences on the timing of its occurrence are explored in the first formal analysis using reared-apart and reared-together monozygotic (MZA, MZT) and dizygotic (DZA, DZT) twin pairs. Mean age at menarche was 12.50 years (SD = 1.67) for the reared-apart pairs and 12.86 years (SD = 1.49) for the reared-together pairs. Intraclass correlations for age at menarche were 0.56 for MZA twins, 0.16 for DZA twins, 0.70 for MZT twins, and 0.41 for DZT twins. The mean within-pair difference was 1.07 years (SD = 1.04) for MZA twins, 1.67 years (SD = 1.59) for DZA twins, 0.64 year (SD = 0.86) for MZT twins, and 1.43 years (SD = 1.34) for DZT twins. These results are consistent with genetic influence, although the lower correlations for reared-apart twins and their larger within-pair differences suggest that age at menarche is partly affected by common rearing environments. Feeling understood by one's father during the growing-up years was significantly associated with earlier age at menarche, and a comparable trend was found for feeling understood by one's mother. These findings are considered with reference to current theories of pubertal timing.     

Genetic and environmental correlations among serum lipids and apolipoproteins in elderly twins reared together and apart.

Genetic and environmental correlations among five serum-lipid measures were examined in the Swedish Adoption/Twin Study of Aging. The sample included 302 twin pairs; 146 of these twin pairs were separated at an early age and were reared apart. The lipid measures examined include total cholesterol, HDL-cholesterol, triglycerides, and apolipoproteins A-I and B. Genetic and environmental correlations were evaluated for two different age groups, formed by dividing the sample at the median. The younger group included individuals 41.8-65.4 years of age at the midpoint of testing, although only 24 individuals were < 50 years of age. The older group included all those > 65.4 years of age, up to age 87 years of age. Substantial genetic correlations were found within each age group, although there is no evidence for a single genetic factor common to all five lipids. The comparison of twins reared together with twins reared apart allowed estimation of the effects of shared rearing environment; however, shared rearing environment only appears to be a significant mediator of the phenotypic correlation between apolipoprotein B and cholesterol in the older group. Examination of the genetic and environmental covariances suggests that the relative contributions of genetic factors are lower in the older group. Nonshared environmental factors are relatively more important mediators of phenotypic correlations among the serum lipids in individuals > 65.4 years of age than they are for the younger group. Sex differences in the mediation of these serum lipids were not as clear.     

Genetic and environmental contributions to population group differences on the Raven's Progressive Matrices estimated from twins reared together and apart

We carried out two studies to test the hypothesis that genetic and environmental influences explain population group differences in general mental ability just as they do individual differences within a group. We estimated the heritability and environmentality of scores on the diagrammatic puzzles of the Raven's Coloured and/or Standard Progressive Matrices (CPM/SPM) from two independent twin samples and correlated these estimates with group differences on the same items. In Study 1, 199 pairs of 5- to 7-year-old monozygotic (MZ) and dizygotic (DZ) twins reared together provided estimates of heritability and environmentality for 36 puzzles from the CPM. These estimates correlated with the differences between the twins and 94 Serbian Roma (both rs=0.32; Ns=36; ps<0.05). In Study 2, 152 pairs of adult MZ and DZ twins reared apart provided estimates of heritability and environmentality for 58 puzzles from the SPM. These estimates correlated with the differences among 11 diverse samples including (i) the reared-apart twins, (ii) another sample of Serbian Roma, and (iii) East Asian, White, South Asian, Coloured and Black high school and university students in South Africa. In 55 comparisons, group differences were more pronounced on the more heritable and on the more environmental items (mean rs=0.40 and 0.47, respectively; Ns=58; ps<0.05). After controlling for measurement reliability and variance in item pass rates, the heritabilities still correlated with the group differences, although the environmentalities did not. Puzzles found relatively difficult (or easy) by the twins were those found relatively difficult (or easy) by the others (mean r=0.87). These results suggest that population group differences are part of the normal variation expected within a universal human cognition.     

Atopy and immunoglobulin E concentrations in Hodgkin's disease and other lymphomas.

Serum immunoglobulin E (IgE) concentrations are increased in Hodgkin''s disease (HD) but not in other types of lymphoma. The prevalence of atopic disease is similar to normal in both groups. Patients with high IgE concentrations and HD were separated into atopic and non-atopic groups, which were found to differ clinically. Atopic patients had a significantly lower incidence of night sweats, fever, and weight loss, and treatment had no significant lasting effect on their IgE concentrations. In the non-atopic group there was a striking correlation between high IgE concentrations and a histological appearance of nodular sclerosis, particularly in the presence of night sweats, fever, and weight loss. Successful treatment in the non-atopic group led to a noticeable fall in IgE concentrations, in most cases to normal, though on relapse of the disease they rose again.     

Pulling together and pulling apart: collective cargo movement in eukaryotic cells

To establish and maintain their internal organization, living cells must move molecules to their correct locations. Long-range intracellular movements are often driven by motor molecules moving along microtubules, similarly to trucks driving along a highway. Recent work demonstrates that some randomly dispersed cargos can generate actin filaments that form a connected network whose contraction drives collective cargo movement.     

SMC complexes and topoisomerase II work together so that sister chromatids can work apart

The pairing of sister chromatids in interphase facilitates error-free homologous recombination (HR). Sister chromatids are held together by cohesin, one of three Structural Maintenance of Chromosomes (SMC) complexes. In mitosis, chromosome condensation is controlled by another SMC complex, condensin, and the type II topoisomerase (Top2). In prophase, cohesin is stripped from chromosome arms, but remains at centromeres until anaphase, whereupon it is removed via proteolytic cleavage. The third SMC complex, Smc5/6, is generally described as a regulator of HR-mediated DNA repair. However, cohesin and condensin are also required for DNA repair, and HR genes are not essential for cell viability, but the SMC complexes are. Smc5/6 null mutants die in mitosis, and in fission yeast, Smc5/6 hypomorphs show lethal mitoses following genotoxic stress, or when combined with a Top2 mutant, top2-191. We found these mitotic defects are due to retention of cohesin on chromosome arms. We also show that Top2 functions in the cohesin cycle, and accumulating data suggests this is not related to its decatenation activity. Thus the SMC complexes and Top2 functionally interact, and any DNA repair function ascribed to Smc5/6 is likely a reflection of a more fundamental role in the regulation of chromosome structure.     

Associative interference between cues and between outcomes presented together and presented apart: an integration

In recent years, 'stimulus competition' in the study of acquired behavior has referred exclusively to (a) associative competition between cues trained in compound (e.g. overshadowing and blocking). Rarely cited are older experiments cast in the verbal learning tradition, now complemented with data from humans and rats in Pavlovian preparations, that demonstrate (b) competition between cues separately trained with a common outcome (i.e. proactive and retroactive interference). Similarly neglected are numerous examples of (c) competition between outcomes separately trained with a common cue within the verbal learning literature (also proactive and retroactive interference) as well as within the Pavlovian literature (i.e. counterconditioning). Recent data demonstrate (d) competition between outcomes trained in compound, thereby completing the four cells of a 2x2 matrix (competing stimuli trained together vs. trained apart and the competing stimuli being cues or outcomes) which highlights the ubiquitous nature of associative stimulus interference/competition. Most contemporary theories of acquired behavior can account for the phenomena in one or at most two cells of this matrix. Whether a common mechanism underlies the phenomena in all four cells of the matrix is currently unclear, but until such time as data preclude a common mechanism, parsimony encourages efforts to develop a model that encompasses all four cells. Here we offer a tentative model that addresses all four cells, albeit with two processes.     

T-cell receptor and immunoglobulin genes are rearranged together in Abelson virus-transformed pre-B and pre-T cells.

We have assessed the state of rearrangement and expression of B- and T-cell antigen receptor genes in cells of Abelson murine leukemia virus-transformed thymomas and other tumors. We found that unrearranged TcR gamma genes are expressed, as are unrearranged C mu genes, in pre-T, pre-B, and myeloid cells. We also found TcR gamma genes rearranged and expressed in putative pre-T cells and in cells apparently committed to the B-cell lineage. This is in contrast to the data from more mature T- and B-cell tumors. We conclude that in immature lymphoid cells both immunoglobulin and TcR gamma genes are accessible for rearrangement. We discuss the implications of these observations for an understanding of the B-T lymphoid differentiation event.     

III. Serum and sputum immunoglobulin E levels in respiratory diseases in adults

Using a solid-phase radioimmunoassay, serum IgE level was determined in 46 normal subjects, 53 patients with bronchial asthma, 44 patients with chronic bronchitis and / or emphysema, and 19 patients with restrictive lung disease. Sputum IgE was measured simultaneously in 51 of the subjects. The range of serum IgE concentration in the normal subjects was wide. It varied between 15 and 750 ng/ml with a mean of 135 ng. Asthmatic patients had significantly higher levels of serum IgE with a mean of 579 ng/ml, but only 30% fell outside the normal 95% confidence limits. Patients with chronic bronchitis, emphysema and restrictive lung diseases had normal IgE levels. There was a significant correlation between serum and sputum IgE levels.     

Working together and apart: The twisted relationship of the Mre11 complex and Chk2 in apoptosis and tumor suppression

Central to the DNA damage response (DDR) is the highly conserved Mre11 complex consisting of Mre11, Rad50, and Nbs1. The Mre11 complex acts as a sensor of DNA double-strand breaks (DSBs) and regulates the signal transduction cascades that are triggered following damage detection1. Rare human genetic instability syndromes such as Ataxia-telangiectasia (A-T) and Nijmegen Breakage Syndrome (NBS) have underscored the importance of the DSB response in the suppression of tumorigenesis, as well as other severe pathologies affecting the development of both the immune system and the central nervous system. Using murine models of the human diseases, we have investigated the role of the Mre11 complex, and other modulators of the DSB response, in tumor suppression2, 3. We found that the checkpoint kinase Chk2 is crucial for the suppression of a diverse array of tumor types in Mre11 complex mutants and uncovered multiple roles for the Mre11 complex in apoptotic signaling in parallel to Chk24, 5.     

Taking organelles apart, putting them back together and creating new ones: lessons from the endoplasmic reticulum

The endoplasmic reticulum (ER) is a highly dynamic organelle. It is composed of four subcompartments including nuclear envelope (NE), rough ER (rER), smooth ER (sER) and transitional ER (tER). The subcompartments are interconnected, can fragment and dissociate and are able to reassemble again. They coordinate with cell function by way of protein regulators in the surrounding cytosol. The activity of the many associated molecular machines of the ER as well as the fluid nature of the limiting membrane of the ER contribute extensively to the dynamics of the ER. This review examines the properties of the ER that permit its isolation and purification and the physiological conditions that permit reconstitution both in vitro and in vivo in normal and in disease conditions.     

Membrane organization in immunoglobulin E receptor signaling

The structure and dynamics of the plasma membrane are proposed to be critical for the initial steps of signal transduction by the high-affinity immunoglobulin E receptor. Recent experimental advances indicate that interactions between the high-affinity immunoglobulin E receptor and the tyrosine kinase Lyn with cholesterol- and sphingolipid-rich regions within the plasma membrane are important for receptor function. This accumulating evidence points to spatio-temporal control of immunoglobulin E receptor signaling by the organization of the plasma membrane; an attractive hypothesis is that ligand-dependent receptor aggregation causes the segregation of Lyn-containing ordered regions of the plasma membrane from disordered regions.