EPR study of iron status in human body during intensive physical activity

The iron metabolism was studied in serum blood samples collected from 26 professional sportsmen undergoing intensive physical exercises using EPR combined with hematological and biochemical laboratory tests. Only 23% of EPR spectra (n = 6) were practically normal while in the rest spectra additional abnormal absorption lines were detected. Presumably, the significant portion of new signals may be caused by different cytochromes. Moreover, the anisotropic signals with g ₁ ? 2.02; g ₂ ? 1.94 and g ₃ ? 1.86 registered in some spectra pointed to the sulfur-iron centers. There was nearly linear correlation between the concentration of Fe³⁺ in transferrin (Fe³⁺-Tf) obtained from the EPR spectra and the serum iron concentration measured by absorption photometry both for sportsmen and controls (healthy individuals and patients with different diseases). At equal serum iron concentrations the Fe³⁺-Tf level was higher in sportsmen than that in controls. The Pearson correlation coefficient (r) for Fe³⁺-Tf and serum iron values was equal to 0.89 in sportsmen versus r = 0.97 in controls. Additional new lines in serum EPR spectra of professional sportsmen prove the suitability of EPR assay for scheduled medical exams since routine biochemical and hematological tests are insufficient to discover all abnormalities in iron metabolism under intensive physical exercises.     

Genetic demographic study of an urban sample of Turkmen-teke with behavioral abnormalities

Genetic and demographic studies of urban sample of Turkmen-teke (Ashkhabad city) were performed among probands-36 patients with diagnosis of "schizophrenia" and their 840 relatives. Clinical analysis revealed 27.8% of phenocopies. In other 26 families the genealogical analysis showed autosomal-dominant (12 families), probably, autosomal-dominant (9 families) as well as autosomal-recessive (3 families) types of inheritance of pathology, in two families the type being not established. The empiric risk of affection was determined to be 24.2% for parents, 75.5% for sibs and 33.3% for children. Mean number of children per one woman is 3.53, which is significantly lower than mean populational number (6.17). High level of endogamy of the urban sample tested is established, the total coefficient of inbreeding being 0.009856; grandparents of the probands appeared to be exclusively of rural origin. The negative action of selection (decreased fitness), preferentially monogenic type of heredity and high level of endogamy are discussed as factors providing broad hereditary heterogeneity of schizophrenia.     

A strategy for construction of industrial strains of distiller's yeast

A procedure was developed for construction of industrial strains of distiller's yeast (Saccharomyces cerevisiae). It includes several steps: construction of congenic genetically marked haploid strains of opposite mating types starting from an industrial strain of hybrid nature, integrative transformation of the above haploid strains with a DNA fragment containing an expression cassette responsible for new technological facilities, and hybridization of transformants and isolation of final industrial homozygous strains under experimental conditions simulating commercial fermentation processes. This strategy permits the generation of strains that have desirable characteristics of traditional races of distiller's yeast along with new technological facilities determined by the particular expression cassette. Using this procedure, we have constructed an industrial strain with improved amylolytic activity. (c) 1995 John Wiley & Sons, Inc.     

Changes in Lipid Peroxidation under Exposure to Electromagnetic Radiation of Nonthermal Intensity in the Prenatal Period

Biophysics - This study focused on the redox homeostasis in the lenses of 20- and 30-day-old chinchilla rabbit kits exposed to a combination of hypoxia and electromagnetic radiation at a nonthermal...     

Aberrant promoter hypermethylation of PBRM1, BAP1, SETD2, KDM6A and other chromatin-modifying genes is absent or rare in clear cell RCC

Recent sequencing studies of clear cell (conventional) renal cell carcinoma (ccRCC) have identified inactivating point mutations in the chromatin-modifying genes PBRM1, KDM6A/UTX, KDM5C/JARID1C, SETD2, MLL2 and BAP1. To investigate whether aberrant hypermethylation is a mechanism of inactivation of these tumor suppressor genes in ccRCC, we sequenced the promoter region within a bona fide CpG island of PBRM1, KDM6A, SETD2 and BAP1 in bisulfite-modified DNA of a representative series of 50 primary ccRCC, 4 normal renal parenchyma specimens and 5 RCC cell lines. We also interrogated the promoter methylation status of KDM5C and ARID1A in the Cancer Genome Atlas (TCGA) ccRCC Infinium data set. PBRM1, KDM6A, SETD2 and BAP1 were unmethylated in all tumor and normal specimens. KDM5C and ARID1A were unmethylated in the TCGA 219 ccRCC and 119 adjacent normal specimens. Aberrant promoter hypermethylation of PBRM1, BAP1 and the other chromatin-modifying genes examined here is therefore absent or rare in ccRCC.     

Driver Mutations in Acute Myeloid Leukemia with Inversion of Chromosome 16

Molecular Biology - Certain subtypes of acute myeloid leukemia occur as a result of the cooperation of several events these are, the formation of fusion genes as a result of chromosomal...     

Mutational Profiling of Pediatric Myeloid Leukemia Subtypes without Clinically Significant Chromosomal Aberrations

Molecular Biology - The discovery of novel significant molecular and genetic markers is important for the diagnostics, prognosis, and therapy selection in hematological malignancies. Distinct...     

In vitro and ex vivo EPR investigation of metabolic changes in blood under the action of radiotoxins obtained from irradiated potato tubers

The effect of radiotoxin (RT) obtained from y-irradiated potato tubes on blood of sheep and mice has been investigated by using in vitro and ex vivo EPR. In experiments in vitro, the action of different preparations (RT, extract from unirradiated potato tubers, 1%-HCl or 30%-hydrogen peroxide) on sheep blood has been compared. It has been established that RT is an effective oxidant (like 1%-HCl) of haem iron that leads to an increase of the methemoglobin concentration. The specific peculiarity of RT effect on blood in vitro is an appearance of two well-resolved lines from methemoglobin belonging, probably, to different paramagnetic centers. The signal from nonspecific complexes of Fe3+ has been also observed. Ex vivo EPR spectra markedly differ from these obtained in experiments in vitro. An additional line with g approximately 2.005 and width 6 G in 30 minutes after intraperitoneal RT injection in the lethal dose (0.2 ml of preparation containing of 2 mg RT) has been revealed. Subsequent intoxication of mice is accompanied by the appearance of the signal from nitrosyl complexes in EPR spectra. These differences in experimental results of in vitro and ex vivo EPR can be explained by launch of compensatory adaptive response of organism on the action of highly toxic preparation.     

Structure and stability of the spinach aquaporin SoPIP2;1 in detergent micelles and lipid membranes

Background

SoPIP2;1 constitutes one of the major integral proteins in spinach leaf plasma membranes and belongs to the aquaporin family. SoPIP2;1 is a highly permeable and selective water channel that has been successfully overexpressed and purified with high yields. In order to optimize reconstitution of the purified protein into biomimetic systems, we have here for the first time characterized the structural stability of SoPIP2;1.

Methodology/Principal Finding

We have characterized the protein structural stability after purification and after reconstitution into detergent micelles and proteoliposomes using circular dichroism and fluorescence spectroscopy techniques. The structure of SoPIP2;1 was analyzed either with the protein solubilized with octyl-β-D-glucopyranoside (OG) or reconstituted into lipid membranes formed by E. coli lipids, diphytanoylphosphatidylcholine (DPhPC), or reconstituted into lipid membranes formed from mixtures of 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPE), 1-palmitoyl-2oleoyl-phosphatidylethanolamine (POPE), 1-palmitoyl-2-oleoyl-phosphatidylserine (POPS), and ergosterol. Generally, SoPIP2;1 secondary structure was found to be predominantly α-helical in accordance with crystallographic data. The protein has a high thermal structural stability in detergent solutions, with an irreversible thermal unfolding occurring at a melting temperature of 58°C. Incorporation of the protein into lipid membranes increases the structural stability as evidenced by an increased melting temperature of up to 70°C.

Conclusion/Significance

The results of this study provide insights into SoPIP2;1 stability in various host membranes and suggest suitable choices of detergent and lipid composition for reconstitution of SoPIP2;1 into biomimetic membranes for biotechnological applications.