A heterogeneity of heterogeneities.
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The structures of new polymeric compounds containing Cu(II) ions and btp (2,6-bis(N'-1,2,4-triazolyl)pyridine) ligands have been determined. The btp ligands bridge Cu(II) ions to form double zigzag chains, [Cu(ClO4)2(btp)2] 3 with perchlorate anions, and form single zigzag chains, [Cu(btp)(H2O)4](SO4).2H2O 4 with sulfate anions. The polymeric compound 3 was found to effectively catalyze the epoxide ring-opening reaction with methanol, while polymeric compound 4 was almost inactive with epoxides under the same conditions. The polymeric compound 3 showed an efficient catalytic activity and regioselective reactivity in the ring opening of epoxides and allowed reuse without a significant loss of activity through three runs with epoxides.
The maintenance of genetic variation is investigated in a finite population where selection at an autosomal locus with two alleles varies temporally between two environments and the heterozygote has an intermediate fitness value. When there is additive gene action and equal selection in both environments, the autocorrelation between subsequent environments must be negative for more maintenance of genetic variation than for neutrality. The maximum maintenance occurs when there is equal selection in the two environments and the autocorrelation approaches -1.0 (for a stochastic model), or when there is short repeating cycle such as one related to seasons. Also comparison of the effects of stochastic variation in selection in finite ans infinite populations is made by using Monte Carlo simulation. One situation was found where temporal environmental variation maintains genetic variation very effectively even in a small population and that is when there is evolution of dominance, i.e., the heterozygote is closer in fitness to the favored homozygote than the other homozygote. An important conclusion is that in a finite population genetic tracing of environmental change, particularly when there is a positive autocorrelation between environments or a long environmental cycle, leads to an increased loss of genetic variation making such a response undesirable in the long term, a result different from that in infinite populations.
Clinical evidence for a physiological impact of luteinizing hormone (LH) isoforms includes their unequal in-vitro bioactivity and altered in-vivo LH kinetics. For example, alkaline LH isospecies emerge in an oestrogen-rich milieu, and show greater bioactivity in vitro along with more rapid metabolic removal in vivo. More acidic LH isotypes are predominant in eugonadal men with end-stage renal failure and in postmenopausal women. The relevance of changes in charge distribution in puberty to sexual maturation is not clear. Molecular LH variants may be associated with decreased testis size and reduced linear growth in boys, menstrual irregularity and/or subfertility in women, and possibly protect against polycystic ovarian syndrome (PCOS). This article summarises the provisional physiological implications of LH isotypes based on current evidence.
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The presence of lecithin:cholesterol acyltransferase (LCAT) deficiency in six probands from five families originating from four different countries was confirmed by the absence or near absence of LCAT activity. Also, other invariate symptoms of LCAT deficiency, a significant increase of unesterified cholesterol in plasma lipoproteins and the reduction of plasma HDL-cholesterol to levels below one-tenth of normal, were present in all probands. In the probands from two families, no mass was detectable, while in others reduced amounts of LCAT mass indicated the presence of a functionally inactive protein. Sequence analysis identified homozygous missense or nonsense mutations in four probands. Two probands from one family both were found to be compound heterozygotes for a missense mutation and for a single base insertion causing a reading frame-shift. Subsequent family analyses were carried out using mutagenic primers for carrier identification. LCAT activity and LCAT mass in 23 genotypic heterozygotes were approximately half normal and clearly distinct from those of 20 unaffected family members. In the homozygous patients no obvious relationship between residual LCAT activity and the clinical phenotype was seen. The observation that the molecular defects in LCAT deficiency are dispersed in different regions of the enzyme suggests the existence of several functionally important structural domains in this enzyme.
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An improvement in the accuracy and specificity of the criteria for identifying people with major depressive disorder would be of great benefit not only in the diagnosis and treatment of patients with depression, but also in research concerning the biological substrates of the emotions. Unfortunately, attempts at developing a biological diagnostic test for depression based on the analysis of major depressive disorder patients identified on the basis of existing diagnostic criteria have not been successful. Undoubtedly, this is due in part to the complexity of the neurochemistry and neuroanatomy of the emotions. But more importantly, it is due to the broad global nature of the criteria used to identify depressed patients. This results in the biological study of patients who are similar in general terms but who differ in specific behavioral symptoms and underlying neurobiology. A detailed analysis of the behavior of depressed people might reveal subtle differences that could be used to separate patients with depression into more homogeneous subgroups for biological study. This would increase the probability of developing biological tests that would lead to further refinement in the diagnosis of depression and in the selection of the most appropriate therapeutic intervention for a particular patient.
Patients with malignant tumors, specifically with metastatic breast carcinoma (BCa), are immunosuppressed and have defective lymphocyte responsiveness to antigenic and mitogenic stimulation. The present study examined the role of perchloric acid (PCA)-soluble glycoproteins and their oligosaccharide moieties from tumor cells and from sera of patients with metastatic BCa. Sera from 15 patients and from age-matched healthy adults were examined for immunoregulatory glycoproteins. BCa tissue was obtained from 9 of the 15 patients. The PCA extracts from tumor tissue were resolved into six (GP-I to GP-VI), and from serum into three (GP-II, GP-IV, and GP-V), BCa-associated glycoproteins. After alkaline borohydride treatment, six groups of BCa-associated oligosaccharides were obtained. Peripheral blood mononuclear (MNC) and natural killer (NK) cells were obtained from patients with metastatic BCa and from age-matched healthy adults. These were used as effector cells in the well-established 4-hr cytotoxicity assay. The results indicated that interleukin 2 (IL-2) significantly (P less than 0.001) enhanced the cytotoxic activities of MNC and NK cells from healthy adults, but it had a nonsignificant effect on MNC and NK cells from patients with metastatic BCa. The BCa-associated glycoproteins and their oligosaccharides varied in their effects on MNC and NK cells from both the healthy adults and the patients with metastatic BCa. IL-2 activated MNC cytotoxic activity against BCa cells. GP-I, GP-II, GP-III, and GP-IV inhibited MNC inherent cytotoxicity and blocked MNC stimulation by IL-2, GP-IV fraction had a statistically nonsignificant effect, whereas GP-V enhanced both MNC inherent and IL-2-activated cytotoxic activities. Oligosaccharides obtained from PCA extracts of BCa tissue and by alkaline borohydride treatment differentially bound and inhibited a series of monoclonal antibodies raised against BCa-associated glycoproteins. These results indicated that the oligosaccharide moieties of the BCa-associated glycoproteins modulate recognition of the BCa cells by the effector cells.
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