Carboxylate-induced degradation of poly(3-hydroxybutyrate)s

This communication shows that thermal degradation of poly(3-hydroxybutyrate)s (PHBs) is induced by carboxylate groups via a newly proposed E1cB mechanism. In PHBs with end groups in the form of carboxylic acid salts with Na+, K+, and Bu4N+ counterions, the proposed mechanism explains the dependence of thermal stability on the size of the counterion. The degradation via intermolecular alpha-deprotonation by carboxylate is suggested to be the main PHB decomposition pathway at moderate temperatures. The results of the present study show the ability to control the degradation and stability of poly(3-hydroxybutyrate)s as well as of their blends via chemical structure and concentration of the carboxylate polymer end groups.     

The posttranslational modification of thyrotropin receptor and thyroid diseases

The thyrotropin receptor (TSHR), lutropin receptor, and follitropin receptor are related members of the superfamily of leucine-rich repeats containing adenylate cyclase stimulating receptors. The unique posttranslational modification of the TSHR leads to the transformation of its monomeric form to the subunit structure where the subunits A and B are connected by disulphide bonds. This natural processing occurs with the release from the receptor of a short peptide C, and is followed by the release of the subunit A. Both monomeric and dimeric forms of the receptor are stimulated by TSH, so no clear functional significance of TSHR modifications have been found. We can speculated that the processing of TSHR with the release of its large fragments contributes to the development of autoimmune diseases and production anti-TSH receptor autoantibodies. The extrathyroidal manifestations of Graves disease may also be related to metastasis of the autoimmune reaction to extrathyroidal sites via the released A subunit. The TSHR processing may, to some extent, be connected to the hyperthyroidism since the release of the subunit A from the receptor augmented the adenylate cyclase activity in the absence of TSH. According to the recent model of receptors action the TSHR is in equilibrium between the inactive (closed) and active (opened) conformations. In opened conformation it can associate with Gs protein and trigger the intracellular signal. TSH and stimulating autoantibodies preferentially bind to opened receptors and stabilizes them.     

New derivatives of picolinic acid and nicotinic acid with anticonvulsant activity

Previously obtained Pic-BZA is a potent anticonvulsant with low neurotoxicity, but its half-time of action is only about 15 min. In search for equally effective anticonvulsants but with a longer time of action fourteen Pic-BZA analogs were obtained. The compounds were evaluated in the Anticonvulsant Screening Project (ASP) of Antiepileptic Drug Development Program (ADDP) of NIH. Picolinic acid 2-fluorobenzylamide (Pic-2-F-BZA, 7) appeared to be the most effective compound of the series.     

Multidrug resistance phosphoglycoprotein (ABCB1) in the mouse placenta: fetal protection

The multidrug resistance phosphoglycoprotein ATP-binding cassette subfamily B (ABCB1) actively extrudes a range of structurally and functionally diverse xenobiotics as well as glucocorticoids. ABCB1 is present in many cancer cell types as well as in normal tissues. Although it has been localized within the mouse placenta, virtually nothing is known about its regulation. In the mouse, two genes, Abcb1a and Abcb1b, encode ABCB1. We hypothesized that there are changes in placental Abcb1a and Abcb1b gene expression and ABCB1 protein levels during pregnancy. Using in situ hybridization, we demonstrated that Abcb1b mRNA is the predominant placental isoform and that there are profound gestational changes in the expression of both Abcb1a and Abcb1b mRNA. Placentas from pregnant mice were analyzed between Embryonic Days (E) 9.5 and 19 (term approximately 19.5d). Abcb1b mRNA was detected in invading trophoblast cells by E9.5, peaked within the placental labyrinth at E12.5, and then progressively decreased toward term (P < 0.0001). Abcb1a mRNA, although lower than that of Abcb1b at midgestation, paralleled changes in Abcb1b mRNA. Changes in Abcb1 mRNA were reflected by a significant decrease in ABCB1 protein (P < 0.05). A strong correlation existed between placental Abcb1b mRNA and maternal progesterone concentrations, indicating a potential role of progesterone in regulation of placental Abcb1b mRNA. In conclusion, there are dramatic decreases in Abcb1a and Abcb1b mRNA and in ABCB1 at the maternal-fetal interface over the second half of gestation, suggesting that the fetus may become increasingly susceptible to the influences of xenobiotics and natural steroids in the maternal circulation.     

Urban and rural differences in mortality and causes of death in historical Poland

The purpose of this paper is to document and interpret urban-rural differences in mortality in the past. To this end, we used data on mortality in Wielkopolska, Poland, in the 19th century and at the beginning of the 20th century. The data on mortality in rural areas (N = 1,173,910 deceased), small towns (N = 573,903 deceased), and Poznań, the capital of the Wielkopolska region (N = 86,352 deceased), were gathered from original Prussian statistical yearbooks (Preussische Statistik). Causes of death were also analyzed (rural areas, N = 449,576 deceased; small towns, N = 238,365 deceased; Poznań, N = 61,512 deceased). Mortality measures such as crude death rate (CDR), infant death rate (IDR), and neonatal and postneonatal death rates were calculated. Life tables were constructed for both stationary and stable population models and measures of the opportunity for natural selection calculated (Crow's index I(m), potential gross reproduction rate R(pot), and biological state index I(bs)). Relative frequencies of leading causes of death were computed. Stratification depending on the place of residence was evident in all mortality measures as well as in the values of the life tables and the measures of the opportunity for natural selection, but it was reverse of what is observed today in developed countries. In Poznań (a large industrial city), the mortality situation was the least favorable. It was caused by large population density, lack of water supply and sewage systems (up to 1896), and bad working conditions. The values of CDR ranged between 26.89-31.46, and IDR between 190.6-280.5. Newborn life expectancy (for a stable population model) was 31.6 years, I(m) = 0.79, R(pot) = 0.85, and I(bs) = 0.47. The most common causes of death were tuberculosis, other diseases of the respiratory and circulatory systems, dysentery and diarrhea, and cancer. These diseases were less common in rural areas, so they had the most favorable values of mortality measures (CDR between 22.87-27.32, IDR between 181.8-219.4, life expectancy of newborn e(0) = 42.12, I(m) = 0.55, R(pot) = 0.93, I(bs) = 0.60). Infectious diseases (other than tuberculosis), frailty at birth, and frailty in old age were the most frequent causes of death in rural areas. Small towns (population <20,000) had a mortality intermediate between city and rural areas.     

Application of biochemical markers for identification of biological properties of animal semen

The use of biochemical markers for identification of biological properties of semen will help to develop new criteria that are accurate and objective in predicting and improving male fertility. Understanding and controlling the mechanisms involved in fertility is a key challenge, which is of fundamental importance in successful animal reproductive performance. Moreover, unraveling the unique molecular mechanism associated with sperm function might have considerable diagnostic value in the evaluation of male infertility. This review offered insights into some recent achievements and provided perspectives for possible applications of the biochemical markers of semen.     

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.     

Brain-derived heat shock protein 70-peptide complexes induce NK cell-dependent tolerance to experimental autoimmune encephalomyelitis

Heat shock proteins (Hsp) are markedly up-regulated at sites of inflammation during autoimmune diseases like experimental autoimmune encephalomyelitis (EAE). In this study, we show that Hsp70-peptide complexes (pc) isolated from brains of mice with EAE prevented the development of EAE clinically and pathologically when administered before proteolipid protein 139-151 (PLP139-151) immunization. In contrast, pure Hsp70 or Hsp70-pc derived from brains of healthy mice or other inflamed tissue did not modulate the expression of EAE. In animals in which EAE had been suppressed by Hsp70-pc, lymphocytes showed increased cell death in response to PLP139-151 that correlated with elevated IFN-gamma and NO production. Coculture of spleen cells from Hsp70-pc immunized mice with spleen cells from untreated EAE mice, in addition to depletion experiments, showed that NK cells reduced reactivity to PLP139-151. Transfer of NK cells from Hsp70-pc-immunized mice to recipients sensitized for EAE abolished disease development. Thus, we propose that Hsp70 demonstrate the ability to bind to peptides generated during brain inflammation and to induce a regulatory NK cell population that is capable of preventing subsequent autoimmunization for EAE.