Co-segregation and heteroplasmy of two coding-region mtDNA mutations within a matrilineal pedigree

The ENG1 Lebers hereditary optic neuropathy (LHON) family spans six generations and comprises more than 90 maternally related individuals. In this pedigree, the G:A LHON mutation at nucleotide position 11778 shows a complex pattern of segregation in which it is homoplasmic mutant in two branches, homoplasmic wildtype in another, and heteroplasmic in a fourth branch. In addition, there is co-segregation of the 11778 mutant allele and of a G:A silent polymorphism at nucleotide position 5471 in 18 of 19 family members. This co-segregation indicates that the two substitutions arose either simultaneously, or nearly so, in the same founder mtDNA molecule. However, the highly divergent mitochondrial allele ratios in the one family member suggest that there has been a complex origin and segregation history of these two substitutions. Taking all of the results into consideration, the evidence supports sequential single mutations at sites 5471 and 11778, in close temporal proximity, with subsequent segregation of the intermediate mutational genotype to high levels in one branch of the ENG1 LHON family. In other branches, either the double wildtype or double mutant genotype has become essentially homoplasmic.     

Endomorphins interact with tachykinin receptors

Soon after the discovery of endomorphins several studies indicated differences between pharmacological effects of endomorphins and other MOR selective ligands, as well as differences between the effects of endomorphin I and endomorphin II. We now propose that these differences are the result of an additional non-opioid property of endomorphins, namely, their weak antagonist properties with respect to tachykinin NK1 and NK1 receptors.     

AMP-deaminase from hen stomach smooth muscle--physico-chemical properties of the enzyme

AMP-deaminase from hen stomach smooth muscle was isolated and physico-chemical properties of the purified enzyme were investigated. The enzyme had an activity optimum at pH 6.5, and poorly deaminated the substrate analogues tested. At optimum pH (6.5), in the absence of regulatory ligands (control conditions), the enzyme manifested hyperbolic substrate-saturation kinetics with half-saturation constant (S(0.5)) of about 4.5 mM. Additions of adenine nucleotide effectors (ATP, ADP) activated the enzyme strongly at all the concentrations tested, diminishing significantly the value of S(0.5) constant. In contrast, the regulatory effect of orthophosphate was variable, and depended on the orthophosphate concentration used. The molecular mass of the enzyme subunit determined in SDS/PAG electrophoresis was about of 37kDa. The obtained results suggest that in different types of hen muscle, similarly as in humans and rats, expression of AMP-deaminase is under the control of independent genes.     

Can inhibition of angiogenesis and stimulation of immune response be combined into a more effective antitumor therapy?

Cancer initiation and progression is strongly influenced by the tumor microenvironment consisting of various types of host cells (inflammatory cells, vascular cells and fibroblasts), extracellular matrix and non-matrix molecules. Host cells play a defining role in two major processes crucial for tumor growth: angiogenesis and escape from immune surveillance. The interdependence of these processes resemble the principles of Yin and Yang, as the stimulation of tumor angiogenesis inhibits effective immune responses, while angiogenesis inhibition may have the opposite effect. These considerations may be useful in developing anticancer strategies based on the potentially synergistic combinations of antiangiogenic and immunostimulatory drugs.     

Evaluation of genetic biodiversity in farm-bred and wild raccoon dogs in Poland

The aim of the study was to analyze the intra- and inter-group diversity in farm-raised and wild raccoon dogs with the use of molecular markers. Genetic differences between the particular raccoon dog groups were observed, accompanied by a relatively high intra-group genetic variation. It was noted that the wild raccoon dogs were characterized by the highest genetic diversity, compared to the three study groups of farm-bred raccoon dogs. Wild raccoon dogs and farm-bred raccoon dogs constitute separate phylogenetic groups. The results obtained suggest that farm breeding may lead to differentiation into a different phylogenetic lineage than that of the wild raccoon dogs. In each case, the genetic distance between the animals bred on the individual farms was lower than the distances between the farm-raised and wild animals. Since the Polish farm breeding is based entirely on phenotype ranking, the genotype of "native" animals is still closely related to that of wild animals.     

4-Substituted boro-proline dipeptides: Synthesis, characterization, and dipeptidyl peptidase IV, 8, and 9 activities

The boroProline-based dipeptidyl boronic acids were among the first DPP-IV inhibitors identified, and remain the most potent known. We introduced various substitutions at the 4-position of the boroProline ring regioselectively and stereoselectively, and incorporated these aminoboronic acids into a series of 4-substituted boroPro-based dipeptides. Among these dipeptidyl boronic acids, Arg-(4S)-boroHyp (4q) was the most potent inhibitor of DPP-IV, DPP8 and DPP9, while (4S)-Hyp-(4R)-boroHyp (4o) exhibited the most selectivity for DPP-IV over DPP8 and DPP9.     

Main dietary compounds and pancreatic cancer risk. The quantitative analysis of case-control and cohort studies

Objective: Estimation of the role of main dietary compounds in the risk of developing pancreatic cancer. Research methods and procedures: Literature published till 2010 was reviewed and selected for further analysis. The used terms were: red meat, minced meat, ham, bacon, sausages, white meat, poultry, vegetables, fish, eggs, fruits, lifestyle, diet, pancreatic cancer and pancreatic neoplasm. The collected data were meta-analysed with calculation of combined relative risk and 95% confidence interval as well as studies heterogeneity. Results: A meta-analysis of 11 case–control studies indicates that red meat ingestion elevates pancreatic cancer risk by 48% (95% CI = 1.25–1.76). The vegetables and fruit reduce the risk by 38% (95% CI = 0.54–0.73) and 29% (95% CI = 0.59–0.84), respectively. The pooled analyses of 10 cohort studies do not show significant relations between main dietary compound ingestion and pancreatic cancer risk. Conclusion: The red meat intake is associated with elevated risk of pancreatic cancer in contrast to vegetables and fruit ingestion. The ingestion of red meat, vegetables and fruit in cohort studies was not influenced on pancreatic cancer risk. The role of fish, poultry and eggs was not significant in both case–control and cohort studies, thus further studies were needed.