The helper and suppressor functions of primate T cells elicited by a 185K streptococcal antigen, as compared with the helper function elicited by a 4K streptococcal antigen

Helper and suppressor functions of human T lymphocytes that act on antibody-forming B cells were elicited by a large 185K streptococcal cell wall antigen. However, a small 4K streptococcal peptide elicited helper but no suppressor function. These differences in the functional activities of the large and small m.w. streptococcal antigens (SA) were confirmed by direct immunisation of rhesus monkeys with the 185K-SA and 4K-SA. Sequential studies have shown that whereas the 185K-SA elicits dose-dependent helper and suppressor activities, the 4K-SA elicits only helper function. Cell-depletion studies with human cells suggest that removal of T8+ cells by killing with OK.T8 and complement leads to a loss of suppressor and a broadening in the concentration of 185K-SA, which elicits helper activity. Because the 4K-SA does not elicit suppression, removal of T8+ cells does not affect this function. However, similar depletion of T4+ cells results in loss of the helper activities, both with the 185K-SA and 4K-SA, and again a broadening in the concentration of the 185K-SA, which elicits suppression. Direct comparison by autoradiography between 125I-labeled 185K-SA and 4K-SA suggests that both antigens can bind directly to monocytes or T8+ VV+ cells. Furthermore, both antigens can induce helper function if T4+ cells are reconstituted with either monocytes or T8+ VV+ cells. Attempts will now be made to sequence the amino acid determinants of the 185K-SA, so as to define the epitopes responsible for the two major regulating functions elicited by this antigen.     

Mitochondria-rough-ER contacts in the liver regulate systemic lipid homeostasis

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A missense variant in the NSDHL gene in a Chihuahua with a congenital cornification disorder resembling inflammatory linear verrucous epidermal nevi

Congenital hemidysplasia with ichthyosiform nevus and limb defects syndrome in humans is a genodermatosis characterized by inflammatory linear verrucous epidermal nevi (ILVEN), often showing a striking lateralization pattern. It is caused by variants in the NSDHL gene encoding a 3β‐hydroxysteroid dehydrogenase involved in the cholesterol biosynthesis pathway. In the present study, we investigated a female Chihuahua, which showed clinical and histological signs of ILVEN. We performed a candidate gene analysis in the affected animal. This analysis revealed a single missense variant in the NSDHL gene in the affected dog (XM_014111859.2:c.700G>A). The variant is predicted to cause a non‐conservative amino acid change from glycine to arginine, XP_013967334.1:p.(Gly234Arg). The mutant allele was absent from WGS data of 594 genetically diverse dogs and eight wolves. Sanger sequencing confirmed that the variant was heterozygous in the affected dog and absent from 22 control Chihuahuas. Based on the knowledge about the functional impact of NSDHL variants in dogs and other species, c.700G>A is probably pathogenic and a convincing candidate causative variant for the observed skin lesions in the affected Chihuahua.     

Initial studies of a phytoestrogen-deoxyribonucleic acid interaction

Molecular modeling studies show that estrogens such as estradiol complement the topography of spaces between base pairs in unwound DNA and simultaneously hydrogen bond phosphate moieties on opposite strands. We demonstrate here that the phytoestrogen coumestrol has this capability, in addition to its documented properties of UV absorbance at lambda greater than 300 nm and fluorescence. The latter properties enable spectroscopic examination of interactions with DNA by methods not possible with estrogenic steroids. On exposure to calf thymus DNA, the UV spectrum of coumestrol displays a bathochromic shift and simultaneous hypochromic effect with an isosbestic point at 370 nm, suggesting a shift between coexisting free and bound states. Similar results are observed with the intercalating agents adriamycin, ethidium bromide, and acridine. The fluorescence spectrum of coumestrol is quenched on exposure to DNA as are those of adriamycin and acridine. Coumestrol differs from the intercalators in that denatured DNA does not affect its UV spectrum or alter its relative fluorescence yield. Unlike classical intercalators, coumestrol has no influence on the thermal stability of calf thymus DNA. Preliminary electrophoretic analysis of DNA plasmid conformers indicates that coumestrol is incapable of significantly altering DNA superhelical density, in contrast to ethidium bromide. These initial physicochemical data provide evidence for the DNA base-estrogen electronic and/or hydrophobic interactions suggested by modeling studies, yet tend to rule out classical intercalation as an explanation for these phenomena.