Genome-Wide Identification of Epigenetic Hotspots Potentially Related to Cardiovascular Risk in Adult Women after a Complicated Pregnancy

Background

The physiological demands of pregnancy on the maternal cardiovascular system can catapult women into a metabolic syndrome that predisposes to atherosclerosis in later life. We sought to identify the nature of the epigenomic changes associated with the increased cardiovascular disease (CVD) risk in adult women following pre-eclampsia.

Findings

We assessed the genome wide epigenetic profile by methyl-C sequencing of monozygotic parous twin sister pairs discordant for a severe variant of pre-eclampsia. In the adult twin sisters at risk for CVD as a consequence of a complicated pregnancy, a set of 12 differentially methylated regions with at least 50% difference in methylation percentage and the same directional change was found to be shared between the affected twin sisters and significantly different compared to their unaffected monozygous sisters.

Conclusion

The current epigenetic marker set will permit targeted analysis of differentially methylated regions potentially related to CVD risk in large cohorts of adult women following complicated pregnancies.     

Observation of mucosal pathology after praziquantel treatment in experimental Fibricola seoulensis infection in rats

It is well known that the duodenum of mice or rats infected with Fibricola seoulensis shows atrophy of villi (shortening, blunting, widening, fusion) and hyperplasia of crypts. This study was performed to observe healing process of these pathological changes after deworming with anthelmintic treatment. Albino rats infected each with 1,000 metacercariae of F. seoulensis were treated with single dose of 10 mg/kg praziquantel on day 15 post-infection. On day 1, 3, 5, 7, 15, 21 and 28 after the treatment, they were sacrificed and their duodenums were histopathologically studied. Control (uninfected) rats showed their normal finger-like projections of duodenal villi and well arranged crypts. In comparison, untreated (infected) controls revealed severe mucosal changes characteristic of villous atrophy and crypt hyperplasia in their duodenum. The damaged duodenal mucosa was found to restore its normal morphology after praziquantel treatment; until day 3 post-treatment the mucosa was severely atrophied; on day 5 long and slender villi sometimes appeared among the fused and stout ones; after day 15 the villi were in their normalizing process. From this experiment, it was shown that the mucosal changes in the duodenum of rats caused by F. seoulensis infection were completely reversible in 21-28 days after anthelmintic treatment.     

Identification of Stictodora lari (Heterophyidae) metacercariae encysted in the brackish water fish, Acanthogobius flavimanus

Metacercariae of the genus Stictodora encysted in the head tissue of Acanthogobius flavimanus (the gobies) caught at Sachun-gun, Kyongnam Province, were identified to be Stictodora lari Yamaguti, 1939 (Trematoda: Heterophyidae), a new parasite fauna in Korea. The metacercariae were 0.39-0.43 mm by 0.32-0.35 mm in size, long elliptical, and with a thin and transparent cyst wall. Total 200 metacercariae were collected from 50 gobies. In order to obtain adult worms two kittens and a puppy were infected each with 34-100 metacercariae, and total 33 adults were recovered between the day 4 and day 8 post-infection. The S. lari adults measured 0.95-1.18 mm long and 0.26-0.32 mm wide and the eggs in uteri 0.028-0.033 mm by 0.017-0.020 mm. The most characteristic morphological feature of these flukes was the presence of a gonotyl and gonotyl spines arranged in two groups; densely crowded group of 30-40 spines and linearly-arranged one of 30-40 spines, together of which made a comma (or reversed comma) shape along the lateral margin of the gonotyl. It has been proved by this study that S. lari is distributed in southern coasts of Korea.     

An examination of proton translocation and energy conservation during heterotrophic nitrification

Whether selected heterotrophic nitrifiers, as do the autotrophs, conserve energy during the oxidation of their nitrogenous substrates was studied. The examination of proton translocation of four different bacterial nitrifiers capable of pyruvic oxime [(PO), CH3-C(NOH)-COOH] nitrification and by an NH4+ oxidizing Arthrobacter sp. was initiated. Three of the PO nitrifying bacteria, all pseudomonads, oxidize hydroxylamine (NH2OH) at a greater rate than PO and yielded only stoichiometric protons when NH2OH was the reductant. The fourth bacterium, Alcaligenes faecalis ATCC 8750, an adept PO oxidizer, does not appreciably oxidize NH2OH. The bacterium displayed----H+NH2OH ratios far less than if NH2OH was stoichiometrically converted to nitrite. When given NH4+, the Arthrobacter sp. yielded proton translocation patterns which were inconsistent with the metabolic data collected concerning NH4+ oxidation. Thus no data was collected which supported energy conservation via proton translocation by these heterotrophic nitrifiers.     

Rat serum albumin synthesis in variant rat hepatoma cells

Variant subclones of the rat hepatoma cell line FU5-5 have been isolated that are altered in their production of rat serum albumin. Three of these variants, isolated in a random screening, have been categorized as high, intermediate, and low producers. They secrete albumin into the culture medium at different rates: 16, 1.7, and 0.3 μg/mg cell protein/48 h. A fourth variant, isolated on the basis of altered morphology, secretes no detectable albumin. Unlike the albumin-producing variants, this null variant is also deficient in the level and inducibility of tyrosine aminotransferase activity. Albumin biosynthesis as determined in pulse-labeling experiments is affected similarly in the four variants, yielding albumin synthetic rates of 0.24, 0.035, 0.006, and < 0.002% of total protein synthesis. The translatable albumin messenger RNA content in these variants was measured using a rabbit reticulocyte lysate system. The null variant contains no detectable mRNA, and the three quantitative variants contain levels of translatable albumin messenger RNA corresponding to 0.07, 0.03, and 0.005% of total stimulated polypeptide synthesis. The highest producing variant contains less translatable albumin mRNA than expected on the basis of cellular biosynthetic measurements, suggesting a translation efficiency difference in this clone. Cell hybrids constructed by fusing the high-producing clone and the null variant produce little or no albumin. This extinction indicates that the null variant contains a diffusible regulatory factor capable of decreasing albumin gene expression. The relatively stable and discrete heritable phenotypic changes exhibited by these clones may serve as a model for similar changes that occur during hepatic differentiation.     

Characteristics of heavily mucoid bacterial isolated from fish pen slime

Weakly gram-positive pleomorphic rods isolated from the slime on the storage pen surfaces of fishing trawlers were found to produce extensive capsular material and intensely mucoid colonies. The isolates studied produced highly pleomorphic club-shaped cells indicative of coryneforms. Their DNA base composition ranged from 64.2 to 68.2 mol% guanine plus cytosine on the basis of melting point determinations.     

Affinity chromatography of aminoacyl-tRNA synthetases on specific tRNA columns without prior purification of tRNA

A method is described for the purification of aminoacyl-tRNA synthetases by affinity chromatography, using a column of tRNA lacking the cognate tRNA, followed by a column of the cognate tRNA. The ability of the enzyme to discriminate between cognate and non-cognate tRNA is exploited in a novel and rapid preparation of the two columns.     

Specific Laboratory Test for Diagnosis of Multiple Sclerosis

Lymphocytes from patients with multiple sclerosis are much more susceptible to the inhibitory activity of linoleic acid (0·08 mg/ml) when tested for sensitization to thyroid by the macrophage electrophoretic mobility test (91% inhibition) than are those from normal subjects (57% inhibition). Cells from patients with a variety of other neurological diseases give 47% inhibition with linoleic acid. These differences are specific for multiple sclerosis and can be used as an in-vitro diagnostic test for the disease. Nearly 43% of clinically normal near relatives of patients with multiple sclerosis show an “anomalous” figure of about 77%; in the remainder the figure is the same as in the general population (57%). An anomalous result is compatible with lifelong freedom from M.S. Possibly a congenital anomalous handling of unsaturated fatty acids is a constant feature of the disease.     

Changes in Membrane Lipid Composition in Exponentially Growing Staphylococcus aureus During the Shift from 37 to 25 C

Lowering the temperature of growth of Staphylococcus aureus from 37 to 25 C decreased the growth rate and induced changes in the composition of the membrane lipids. Changes in lipid composition also occur in the transition between exponential and stationary growth phases at one temperature. To isolate the effects of lowering the temperature, exponentially growing S. aureus was abruptly switched from 37 to 25 C by transfer to cooler medium. Exponential growth continued at 25 C without a lag period but with a threefold increase in doubling time. In the period of exponential growth at suboptimal temperature, there was essentially no change in the fatty acid composition of the lipids, little change in the vitamin K(2) composition with perhaps a slight increase in the total level, and essentially no change in the phospholipid composition, but a marked stimulation of the synthesis of the rubixanthins. Growth of cells at 25 C was much more sensitive to the inhibition of rubixanthin formation by mixed-function oxidase inhibitors than cells growing at 37 C, suggesting some function for the rubixanthins at suboptimal temperatures. The striking increases in the proportions of monoenoic fatty acids observed at lowered growth temperatures in many biological systems are not detected in S. aureus.