The spectrum of spontaneous mutations caused by deficiency in proteasome maturase Ump1 in Saccharomyces cerevisiae

Ump1 is responsible for maturation of the catalytic core of the 26S proteasome. Dysfunction of Ump1 causes an increase in the frequency of spontaneous mutations in Saccharomyces cerevisiae. In this study we analyze the spectrum of mutations occurring spontaneously in yeast deficient in Ump1 by use of the SUP4-o system. Single base substitutions predominate among the mutations analyzed (73 of the 91 alterations examined). Two major classes are GC to TA transversions and GC to AT transitions ( approximately 50 and approximately 30% of base substitutions, respectively). Besides base substitutions, almost all the major types of sequence alterations are represented. The specificity and distribution of mutations occurring in the ump1 strain are unique compared to the spectra previously established for other yeast mutators. However, the profile of mutations arising in this strain is similar to that observed in wild type. The same similarity has previously been reported for yeast deficient in Mms2, a protein involved in Rad6-dependent postreplication DNA repair (PRR). The specificity of the mutator effect caused by ump1 is discussed in light of the proposed role of the proteasome activity in the regulation of the PRR mechanisms.     

Serological and structural characterization of the O-antigens of the unclassified <Emphasis Type="Italic">Proteus mirabilis</Emphasis> strains TG 83, TG 319, and CCUG 10700 (OA)

INTRODUCTION: Lipopolysaccharide (endotoxin, LPS) is an important potential virulence factor of Proteus rods. The serological specificity of the bacteria is defined by the structure of the O-polysaccharide chain (O-antigen) of the LPS. Until now, 76 O-serogroups have been differentiated among Proteus strains. MATERIALS AND METHODS: LPSs were isolated from Proteus mirabilis TG 83, TG 319, and CCUG 10700 (OA) strains by phenol/water extraction. Antisera were raised by immunization of rabbits with heat-killed bacteria. Serological investigations were performed using enzyme immunosorbent assay, passive immunohemolysis, inhibition of both assays, absorption of antisera, and Western blot. RESULTS: The cross-reactive epitope shared by these strains and P. penner O72a,O72b is located on the O-polysaccharide and is most likely associated with an alpha-D-Glcp-(1-->6)-beta-D-GalpNAc disaccharide fragment. The serological data indicated the occurrence of two core types in the LPSs studied, one characteristic for P. mirabilis TG 319 and CCUG 10700 (OA) and the other for P. mirabilis TG 83 and O57. CONCLUSIONS: The serological and structural data showed that P. mirabilis TG 83, TG 319, CCUG 10700 (OA), and O57 have the same O-antigen structure and could be qualified to the Proteus O57 serogroup.     

Genetic and environmental influences on plasma homocysteine: results from a Danish twin study

BACKGROUND: Increased plasma homocysteine has been linked to many clinical conditions including atherosclerosis and ischemic stroke. We assessed the genetic and environmental influences on homocysteine in adult twins and tested the influence of 3 candidate polymorphisms. METHODS: Homocysteine was analyzed in 1206 healthy twins, who were genotyped for 3 polymorphisms: MTHFR 677C>T, MTR 2756A>G, and NNMT (dbSNP: rs694539). To perform quantitative trait linkage analysis of the MTHFR locus, the genotyping was supplemented with 2 genetic markers localized on each site of the MTHFR locus. The twin data were analyzed using biometric structural equation models as well as a combined association and linkage analysis in 2 age cohorts. RESULTS: Age, sex, and MTHFR genotype have a significant impact on homocysteine concentrations, whereas the other genotypes were not associated with homocysteine concentrations. The variance in homocysteine could be solely ascribed to additive genetic and nonshared environmental factors, with an estimated additive genetic proportion of total variation at age 18-39 years of 0.63 (95% CI, 0.53-0.71) and at age 40-65 years of 0.27 (95% CI, 0.10-0.41). The impact of the MTHFR locus is estimated to explain 53% (95% CI, 0.07-0.67) of the total phenotypic variation in persons 18-39 years old and 24% (95% CI, 0.00-0.39) in persons 40-65 years old, i.e., almost all additive genetic variance. CONCLUSIONS: Homocysteine concentrations have a high heritability that decreases with age. The MTHFR gene locus is responsible for almost all the variation attributable to genetic factors, leaving very little influence of other genetic variations.     

Effect of long-term administration of ranitidine,a histamine H2 receptor antagonist,on bone metabolism in young growing rats

Background

Histamine regulates function of osteoclasts and osteoblasts, however data regarding the influence of histamine H2 receptors antagonists on bone tissue are ambiguous. Factors that influence growing skeleton may have an important impact on the peak bone mass and future risk of fractures. The aim of our study was the assessment of influence of ranitidine, on growing bones.

Exploring the motives of Israeli Jews who were living kidney donors to strangers

Non-directed living donors are individuals who donate a kidney to a recipient with whom they have neither a genetic nor emotional relationship. Israel legalized this type of donation in 2008. After this law was implemented, living donations significantly expanded. The aim of this article was to determine the motivations, characteristics, and perioperative experiences of non-directed living donors in Israel. Three online questionnaires (own questionnaire, Rosenberg Self-Esteem Scale (RSES), Rushton Self-Report Altruism Scale) were distributed to 180 Jewish kidney donors with the help of Matnat Chaim organization. One hundred and fifteen responses were received (69.3% response rate). The motivation for most donors (60%) was a strong willingness to help and a desire to do good. The majority of donors (78.3%) reported their health status as unchanged after donation; however, 16.5% experienced clinical problems (eg, wound infection, more pain than expected), and 5.2% experienced psychological complications. About 18% reported their health to improve after donation. Most (80%) inspired someone else to also become a kidney donor. This study breaks the myth that Jews do not support organ donation. In fact, their high level of altruism and their positive experience with donation has propelled the practice of non-directed donation in Israel.     

Renal anaemia treatment in haemodialysis patients in the Central and Eastern European countries in everyday clinical practice follow-up

Background

Chronic kidney disease is almost always accompanied by anaemia. Erythropoietin-stimulating agents (ESA) can increase haemoglobin concentration and thus reduce the frequency of anaemia-related complications including the cardiovascular events.

Aim

The aim of the study was to collect prospective data on 12-month standard ESA therapy used in haemodialyzed patients in selected CEE countries as well as on cardiovascular complications, iron status and anaemia treatment.

Patients and methods

Fifty centres in 3 countries participated in the study. A group of 398 haemodialysed stable patients (M-231, F-167) aged 19–90 years (57.5 ± 14.7) on standard ESA therapy for chronic renal anaemia were recruited. Twelve-month prospective data on iron parameters, ESA therapy and cardiovascular events were collected. The use of iron, folic acid and blood transfusions were also assessed. Patient were divided into three groups according to ESA therapy start: group A—patients who received ESA after start of haemodialysis, group B—patients who received ESA within 3 months from the day of first haemodialysis and group C—patients who had received ESA more than 3 months before haemodialysis. Chi² test for qualitative data and Kruskall–Wallis test for quantitative data with p < 0.05 were used in statistical analysis.

Results

At prestudy period, the mean weekly dose of ESA in group C was statistically lower than in the remaining two groups (3,823 ± 3,169 vs. 5,276 ± 2,915 and 6,427 ± 3,441 units/week, p < 0.001), but during prospective phase of the study the doses did not differ among groups A, B and C. No major fluctuation of ESA administration schedule was observed during the study in the groups; however, at majority of visits, the mean frequency of ESA administration in group C was statistically higher than in groups A and B. At baseline visit, the haemoglobin concentration in group A patients (10.86 ± 1.34 g/dL) was slightly lower than in group B (11.26 ± 1.43 g/dL) and group C (10.98 ± 1.35 g/dL) (p = 0.025), but at subsequent visits these differences disappeared and mean haemoglobin concentration was stable around 11 g/dL. Ferritin concentration increased from 280 ± 241 at baseline to 506 ± 405 at month 12, and no important differences in the groups were observed. The other haematological parameters (haematocrit, iron concentration) remained stable during the entire study. The frequency of blood transfusion and total volume of blood in group C were lower than in groups A and B. During the prospective 12-month follow-up, 23 (5.8 %) of the patients died and 35 (8.8 %) were transplanted. No differences in death or transplantation rate were observed among groups A, B and C. The number of patients with adverse events, serious adverse events or drug-related adverse events in all groups was similar. In conclusion, ESA therapy increased haemoglobin concentration and no major differences in haematological parameters among the groups were observed during the entire study irrespective of early versus late start. Mortality, cardiovascular events or other adverse events were similar among the groups during the observation period; however, the limitation of the study is the sample size.     

Review of the Applications of Biomedical Compositions Containing Hydroxyapatite and Collagen Modified by Bioactive Components

Regenerative medicine is becoming a rapidly evolving technique in today’s biomedical progress scenario. Scientists around the world suggest the use of naturally synthesized biomaterials to repair and heal damaged cells. Hydroxyapatite (HAp) has the potential to replace drugs in biomedical engineering and regenerative drugs. HAp is easily biodegradable, biocompatible, and correlated with macromolecules, which facilitates their incorporation into inorganic materials. This review article provides extensive knowledge on HAp and collagen-containing compositions modified with drugs, bioactive components, metals, and selected nanoparticles. Such compositions consisting of HAp and collagen modified with various additives are used in a variety of biomedical applications such as bone tissue engineering, vascular transplantation, cartilage, and other implantable biomedical devices.