Role of the guanidine group in the N-terminal fragment of PTH(1–11)

A series of PTH hybrids containing a diamine [NH₂(CH₂) _n NH₂; n = 4, 5, 6] in the C-terminal position was synthesized based on the H-Aib-Val-Aib-Glu-Ile-Gln-Leu-Nle-His-Gln-Har-NH₂ (Har = homoarginine) template. The compounds were pharmacologically characterized at PTH1R receptors for agonist activity.     

Upregulation of 11β-hydroxysteroid dehydrogenase 1 in lymphoid organs during inflammation in the rat

Glucocorticoids exert anti-inflammatory and immunomodulatory effects that may be regulated in part by the activities of the glucocorticoid-activating and -inactivating enzymes, 11β-hydroxysteroid dehydrogenase type 1 (11HSD1) and type 2 (11HSD2), respectively. Previous studies have demonstrated that inflammatory bowel diseases in humans and experimental animals upregulate 11HSD1 and downregulate 11HSD2. We investigated whether proinflammatory cytokines modulate colonic 11HSDs as well as whether lymphoid organs exhibit any 11HSD response to inflammation. Colon tissue explants exposed to tumor necrosis factor α exhibited an upregulation of 11HSD1 mRNA whereas interleukin 1β downregulated 11HSD2 mRNA. Experimental colitis induced by the intracolonic administration of 2,4,6-trinitrobenzenesulfonic acid stimulated 11HSD1 activity not only in the colon but also in mesenteric lymph nodes and the spleen. Analysis of mRNA for 11HSD1 in colon-draining lymph nodes and the spleen showed that inflammation upregulates the expression of this enzyme in mobile lymphoid cells similar to the intraepithelial and lamina propria leukocytes isolated from the colon. It is inferred that inflammation stimulates the reactivation of glucocorticoids in lymphoid organs and in gut-associated lymphoid tissue.     

Localization of the β-globin gene to 11p15 by in situ hybridization: Utilization of chromosome 11 rearrangements

Summary Chromosome preparations from four subjects, one normal 46,XY male and three patients with different rearrangements of chromosome 11:46,XX,del(11)(p11.2p15.1), 46,XY,inv(11)(p13q24.2), and 46,XY,rec(11)inv(11)(p13q24.2) pat, were utilized for in situ hybridization studies with a tritium-labeled cDNA probe containing a -globin insert. Using the hybridization technique described by Harper and Saunders (1981), there were 1–2 grains over each labeled metaphase. Of 360 cells scored, 88 were labeled over chromosome 11, band p15 (24%). Approximately half of the chromosome 11s labeled from the abnormal patients were the del(11) or inv(11). These results exclude the -globin locus from 11p11p14, since these bands were not present in the recent 11, and assign it to 11p15. This is in agreement with the recent exclusion data of de Martiville and Francke (1984) and Junien (1984), and suggestive assignment data of Morton et al. (1984).     

The topology of the mitochondrial 11β-hydroxylase system in bovine adrenal cortex

Binding of deoxycorticosterone to cytochrome P-450 of the 11β-hydroxylase system in adrenal cortex mitochondria was inhibited by the nonpenetrating protein reagent diazobenzenesulfonate in damaged but not in intact mitochondria. The slowly penetrating hydrophilic substrate deoxycorticosterone 21-sulfate showed a slow binding to cytochrome P-450 as compared to the hydrophobic nonesterified steroid. In contrast, the esterified and nonesterified steroids bound equally fast in sonicated, aged or lysolecithin-treated mitochondria. These data imply that the steroid substrates must penetrate the inner mitochondrial membrane to interact with the 11β-hydroxylase system.     

Variation in the cell cycle time in the crypts of lieberkühn of the mouse

The durations of the phases of the cell cycle were measured at different levels in the jejunal crypts of male Balb/c mice. A mean cell cycle time of 12.3 h was found for the whole crypt. In cell positions 1 and 2, the cell cycle time was 16.7 h, and this time steadily decreased to a value of between 10 and 11 h for cell positions above 11. It is concluded that basally situated crypt cells in the mouse are cycling relatively slowly, and that they form the functional stem cell pool for the crypt. These cells may also compose the potential stem cell pool which repopulates the crypt after death of proliferative cells.     

Regeneration of the progesterone 11α-hydroxylase of Rhizopus nigricans by the use of periodate

Summary The cell-free progesterone 11-hydroxylase enzyme of Rhizopus nigricans can be directly regenerated by periodate oxidation. This permits action of the enzyme over a period of hours with an activity similar to that in the presence of an NADPH generating system.     

Change in the power of EEG activity in the α range in response to tonic nociceptive stimulation of the distal joint of the little finger

Examination of 12 healthy volunteers aged 20–56 years was performed to study the EEG changes caused by a tonic squeeze of the distal joint of the little finger of the left and then the right hand. This stimulation caused painful sensations of different intensity (pain on the right was stronger). Spectral power was measured in the ( ₁ (8–10.5 Hz) and (₂ ranges (10.5–13 Hz) under different conditions. Weak pain led to an increase in the power of the (₁ and ₂ ranges in the occipital regions. With strong pain, the power of ₁ waves increased bilaterally in the posterior regions (O ₁, O ₂, T ₆), as well as in the left frontal region (F ₃, F ₇). The powers of the ₁ and ₂ ranges substantially increased relative to the background level after the strong nociceptive stimulation ceased. This finding testified to a latent and inertial character of its effect on the -wave parameters.Translated from Fiziologiya Cheloveka, Vol. 31, No. 2, 2005, pp. 77–84.Original Russian Text Copyright © 2005 by Garkavenko, Gorkovenko, Mankovskaya, Shevko, Lyskov, Kostyukov.     

Localization of the LDHA gene to 11p14→11p15 by in situ hybridization of an LDHA cDNA probe to two translocations with breakpoints in 11p13

Summary Lymphoblastoid cell lines established from two individuals with apparently balanced translocations involving 11p13 were used for LDHA regional localization. The karyotypes were 46,XY,t(4;11)(q21;p13) and 46,XY,t(1;11) (p22;p13). In situ hybridization of a human LDHA cDNA probe to chromosome preparations from these cell lines resulted in specific labeling over bands p14p15 of the normal chromosomes 11 and over bands 11p1411p15 of the derivative chromosomes 4 and 1. These results exclude LDHA from any region proximal to 11p13 and localize the gene to 11p1411p15.     

Zooplankton in the ponds with tropical plants in the greenhouses of the Botanical Garden of the Jagiellonian University in Kraków

The presence of P. tetraurelia was found in the pond in "The Palm-House" greenhouse.     

Methylation of the ß-positions of the furan ring in F-acids

Major incubation products in feeding experiments with the sodium salt of 7-(5-butyl-furan-2-yl)heptanoic acid (3) on suspension cultures of Saccharum spec. are the unusual F-acids (4a) and (4b). They possess in contrast to natural monomethyl substituted F-acids a methyl substituent in the 4-position of the furan ring. Unexpectedly, the dimethyl substituted F-acids (4c) and (4d) were found only in very small amounts. The detection and structure elucidation of the methylation products (4a)–(4d) was achieved predominantly by GC-MS analysis of the corresponding tetrahydrofuran derivatives (5a)–(5d).     

Role of the hydrophobic and charged residues in the 218–226 region of apoA-I in the biogenesis of HDL

We investigated the significance of hydrophobic and charged residues 218–226 on the structure and functions of apoA-I and their contribution to the biogenesis of HDL. Adenovirus-mediated gene transfer of apoA-I[L218A/L219A/V221A/L222A] in apoA-I^−/− mice decreased plasma cholesterol and apoA-I levels to 15% of wild-type (WT) control mice and generated pre-β- and α4-HDL particles. In apoA-I^−/− × apoE^−/− mice, the same mutant formed few discoidal and pre-β-HDL particles that could not be converted to mature α-HDL particles by excess LCAT. Expression of the apoA-I[E223A/K226A] mutant in apoA-I^−/− mice caused lesser but discrete alterations in the HDL phenotype. The apoA-I[218–222] and apoA-I[E223A/K226A] mutants had 20% and normal capacity, respectively, to promote ABCA1-mediated cholesterol efflux. Both mutants had ∼65% of normal capacity to activate LCAT in vitro. Biophysical analyses suggested that both mutants affected in a distinct manner the structural integrity and plasticity of apoA-I that is necessary for normal functions. We conclude that the alteration of the hydrophobic 218–222 residues of apoA-I disrupts apoA-I/ABCA1 interactions and promotes the generation of defective pre-β particles that fail to mature into α-HDL subpopulations, thus resulting in low plasma apoA-I and HDL. Alterations of the charged 223, 226 residues caused milder but discrete changes in HDL phenotype.     

Localization of the antigen for the monoclonal antibody ②9F11-B-E4 interspecific cross-reaction in the freshwater triclads

The localization of the antigen for monoclonal antibody 9F11-B-E₄ was clarified by immuno-electron microscopy. The antigens were localized on the mitochondria and Golgi bodies in the male germ cells and on the secretory granules of various glands cells in the penis bulb and subepidermal parenchymal tissue of Phagocata vivida. The results of the interspecific cross-reaction tests with seven other freshwater triclads showed that these secretory granules are species-specific. A positive interspecific reaction was showed with Dugesia (family Dugesiidae), but not with Polycelis within the same family Planariidae which suggests the position of Phagocata within the Planariidae needs to be reassesed.     

Involvement of binding lipoproteins in the absorption and transport of α-tocopherol in the rat

1. Specific lipoproteins binding alpha-tocopherol but not its known metabolites have been isolated and identified from cytosol of rat intestinal mucosa and from serum. 2. A timestudy of the appearance of the orally administered alpha-[(3)H]tocopherol with these lipoproteins indicates that very-low-density lipoprotein of serum acts as a carrier of the vitamin. 3. The involvement of the mucosal lipoprotein in the absorption of the vitamin from the intestine has been inferred from observations on the amounts of alpha-tocopherol in serum of orotic acid-fed rats where release of lipoproteins from the liver to serum is completely inhibited. A considerable decrease in the association of alpha-tocopherol with serum very-low-density lipoprotein under this condition is interpreted to mean that serum lipoproteins are limiting factors for the transport of the vitamin across the intestine and that this is possibly effected by exchange of alpha-tocopherol between serum very-low-density lipoprotein and mucosal lipoprotein.     

Common chaperone activity in the G-domain of trGTPase protects L11�CL12 interaction on the ribosome

Translational GTPases (trGTPases) regulate all phases of protein synthesis. An early event in the interaction of a trGTPase with the ribosome is the contact of the G-domain with the C-terminal domain (CTD) of ribosomal protein L12 (L12-CTD) and subsequently interacts with the N-terminal domain of L11 (L11-NTD). However, the structural and functional relationships between L12-CTD and L11-NTD remain unclear. Here, we performed mutagenesis, biochemical and structural studies to identify the interactions between L11-NTD and L12-CTD. Mutagenesis of conserved residues in the interaction site revealed their role in the docking of trGTPases. During docking, loop62 of L11-NTD protrudes into a cleft in L12-CTD, leading to an open conformation of this domain and exposure of hydrophobic core. This unfavorable situation for L12-CTD stability is resolved by a chaperone-like activity of the contacting G-domain. Our results suggest that all trGTPases—regardless of their different specific functions—use a common mechanism for stabilizing the L11-NTD•L12-CTD interactions.     

Identification of novel proteins in culture filtrates of Mycobacterium bovis bacillus Calmette-Guérin in the isoelectric point range 6-11

Two-dimensional gel electrophoresis and mass spectrometry were used to identify proteins in the isoelectric point range 6-11 in culture filtrates of Mycobacterium bovis bacillus Calmette-Guérin (BCG). Twelve proteins were identified, three of which had not been described previously. The expression of the identified proteins was comparatively analyzed in culture filtrates of BCG in different growth phases and culture conditions. For some of these proteins, the relative protein abundance in the different culture filtrate preparations was significantly different. The differential expression of the identified proteins is discussed in relation to their putative localization and/or biological function.     

Modeling the Role of TGF-β in Regulation of the Th17 Phenotype in the LPS-Driven Immune System

Airway exposure levels of lipopolysaccharide (LPS) are known to determine type I versus type II helper T cell induced experimental asthma. While low doses of LPS derive Th2 inflammatory responses, high (and/or intermediate) LPS levels induce Th1- or Th17-dominant responses. The present paper develops a mathematical model of the phenotypic switches among three Th phenotypes (Th1, Th2, and Th17) in response to various LPS levels. In the present work, we simplify the complex network of the interactions between cells and regulatory molecules. The model describes the nonlinear cross-talks between the IL-4/Th2 activities and a key regulatory molecule, transforming growth factor β (TGF-β), in response to high, intermediate, and low levels of LPS. The model characterizes development of three phenotypes (Th1, Th2, and Th17) and predicts the onset of a new phenotype, Th17, under the tight control of TGF-β. Analysis of the model illustrates the mono-, bi-, and oneway-switches in the key regulatory parameter sets in the absence or presence of time delays. The model also predicts coexistence of those phenotypes and Th1- or Th2-dominant immune responses in a spatial domain under various biochemical and bio-mechanical conditions in the microenvironment.     

Analysis of the long-term stability of the output of electron beams generated by the Novac11™ IORT accelerator

Aim

The aim of the study was to analyze the long-term stability of electron beams generated by the Novac11? IORT accelerator.