Covalent binding of reactive estrogen metabolites to microtubular protein as a possible mechanism of aneuploidy induction and neoplastic cell transformation.

Neoplastic cell transformation induced by estrogens and some other carcinogens such as benzene appears to involve the induction of mitotic aneuploidy rather than DNA damage and point mutations. As metabolic activation may also play an important role in the mechanism of carcinogenesis of these nongenotoxic compounds, we have studied the interaction of reactive quinone metabolites of various estrogens and of benzene with the major microtubular protein, tubulin, in a cell-free system. Covalent binding of the radioactively labeled metabolites to the alpha- and beta-subunit of tubulin was found to depend on the structure of the metabolite. When the adducted tubulins were tested in vitro for their ability to polymerize to microtubules, inhibition of microtubule assembly was observed in every case, although to varying extents. It is proposed that the formation of covalent tubulin adducts may impair the formation of mitotic spindles and thus contribute to chromosomal nondisjunction and aneuploidy induction

Theoretical characterization of a model of aragonite crystal orientation in red abalone nacre

Nacre, commonly known as mother-of-pearl, is a remarkable biomineral that in red abalone consists of layers of 400-nm thick aragonite crystalline tablets confined by organic matrix sheets, with the $(001)$ crystal axes of the aragonite tablets oriented to within $\pm$ 12 degrees from the normal to the layer planes. Recent experiments demonstrate that this orientational order develops over a distance of tens of layers from the prismatic boundary at which nacre formation begins. Our previous simulations of a model in which the order develops because of differential tablet growth rates (oriented tablets growing faster than misoriented ones) yield patterns of tablets that agree qualitatively and quantitatively with the experimental measurements. This paper presents an analytical treatment of this model, focusing on how the dynamical development and eventual degree of order depend on model parameters. Dynamical equations for the probability distributions governing tablet orientations are introduced whose form can be determined from symmetry considerations and for which substantial analytic progress can be made. Numerical simulations are performed to relate the parameters used in the analytic theory to those in the microscopic growth model. The analytic theory demonstrates that the dynamical mechanism is able to achieve a much higher degree of order than naive estimates would indicate.Comment: 20 pages, 3 figure

Directed motion emerging from two coupled random processes: Translocation of a chain through a membrane nanopore driven by binding proteins

We investigate the translocation of a stiff polymer consisting of M monomers through a nanopore in a membrane, in the presence of binding particles (chaperones) that bind onto the polymer, and partially prevent backsliding of the polymer through the pore. The process is characterized by the rates: k for the polymer to make a diffusive jump through the pore, q for unbinding of a chaperone, and the rate q kappa for binding (with a binding strength kappa); except for the case of no binding kappa=0 the presence of the chaperones give rise to an effective force that drives the translocation process. Based on a (2+1) variate master equation, we study in detail the coupled dynamics of diffusive translocation and (partial) rectification by the binding proteins. In particular, we calculate the mean translocation time as a function of the various physical parameters.Comment: 22 pages, 5 figures, IOP styl

Differences in intestinal size, structure, and function contributing to feed efficiency in broiler chickens reared at geographically distant locations

The contribution of the intestinal tract to differences in residual feed intake (RFI) has been inconclusively studied in chickens so far. It is also not clear if RFI-related differences in intestinal function are similar in chickens raised in different environments. The objective was to investigate differences in nutrient retention, visceral organ size, intestinal morphology, jejunal permeability and expression of genes related to barrier function, and innate immune response in chickens of diverging RFI raised at 2 locations (L1: Austria; L2: UK). The experimental protocol was similar, and the same dietary formulation was fed at the 2 locations. Individual BW and feed intake (FI) of chickens (Cobb 500FF) were recorded from d 7 of life. At 5 wk of life, chickens (L1, n = 157; L2 = 192) were ranked according to their RFI, and low, medium, and high RFI chickens were selected (n = 9/RFI group, sex, and location). RFI values were similar between locations within the same RFI group and increased by 446 and 464 g from low to high RFI in females and males, respectively. Location, but not RFI rank, affected growth, nutrient retention, size of the intestine, and jejunal disaccharidase activity. Chickens from L2 had lower total body weight gain and mucosal enzyme activity but higher nutrient retention and longer intestines than chickens at L1. Parameters determined only at L1 showed increased crypt depth in the duodenum and jejunum and enhanced paracellular permeability in low vs. high RFI females. Jejunal expression of IL1B was lower in low vs. high RFI females at L2, whereas that of TLR4 at L1 and MCT1 at both locations was higher in low vs. high RFI males. Correlation analysis between intestinal parameters and feed efficiency metrics indicated that feed conversion ratio was more correlated to intestinal size and function than was RFI. In conclusion, the rearing environment greatly affected intestinal size and function, thereby contributing to the variation in chicken RFI observed across locations

Effects of bovine colostrum on performance, survival, and immunoglobulin status of suckling piglets during the first days of life

Supplementation of bovine colostrum (BC) has shown to improve growth performance, intestinal development, and immune response in early-weaned pigs. Little is known about whether BC may have similar effects in neonatal piglets. In the present study, the effect of BC supplementation on mortality, growth performance, and blood parameters (plasma proteins and white blood count) of suckling piglets in the first 10 days of life was investigated under practical conditions with special emphasis on low birth weight piglets. In total, 258 newborn piglets from 30 multiparous sows in a commercial breeding unit were randomly assigned to two different treatment groups. Piglets received either 1 ml of BC orally on days 1-3 of life (group BC, n = 128) or 1 ml of saline (0.9%) (control (CON) group; n = 130). Body weight was measured on days 1, 4, and 10 of life. Blood was collected on days 1 and 4 from 60 piglets per group. No differences in mortality, body weight, and average daily weight gain were observed between treatment groups in days 1-10. However, compared to CON, particularly in low birth weight piglets the administration of BC supported (P < 0.01) their survival. Group BC exhibited lower plasma total protein (P = 0.03) and beta-globulin (P = 0.02) concentrations compared to group CON. In conclusion, BC improved low and normal birth weight piglets' survival during their first 10 days of life. Further research is needed to clarify whether the survival rate is related to earlier gut closure indicated by lower plasma protein levels, which might be beneficial due to a lower uptake of potential antigenic substances

Effects of bovine colostrum on performance, survival, and immunoglobulin status of suckling piglets during the first days of life

Supplementation of bovine colostrum (BC) has shown to improve growth performance, intestinal development, and immune response in early-weaned pigs. Little is known about whether BC may have similar effects in neonatal piglets. In the present study, the effect of BC supplementation on mortality, growth performance, and blood parameters (plasma proteins and white blood count) of suckling piglets in the first 10 days of life was investigated under practical conditions with special emphasis on low birth weight piglets. In total, 258 newborn piglets from 30 multiparous sows in a commercial breeding unit were randomly assigned to two different treatment groups. Piglets received either 1 ml of BC orally on days 1-3 of life (group BC, n = 128) or 1 ml of saline (0.9%) (control (CON) group; n = 130). Body weight was measured on days 1, 4, and 10 of life. Blood was collected on days 1 and 4 from 60 piglets per group. No differences in mortality, body weight, and average daily weight gain were observed between treatment groups in days 1-10. However, compared to CON, particularly in low birth weight piglets the administration of BC supported (P < 0.01) their survival. Group BC exhibited lower plasma total protein (P = 0.03) and beta-globulin (P = 0.02) concentrations compared to group CON. In conclusion, BC improved low and normal birth weight piglets' survival during their first 10 days of life. Further research is needed to clarify whether the survival rate is related to earlier gut closure indicated by lower plasma protein levels, which might be beneficial due to a lower uptake of potential antigenic substances

Translocation of structured polynucleotides through nanopores

We investigate theoretically the translocation of structured RNA/DNA molecules through narrow pores which allow single but not double strands to pass. The unzipping of basepaired regions within the molecules presents significant kinetic barriers for the translocation process. We show that this circumstance may be exploited to determine the full basepairing pattern of polynucleotides, including RNA pseudoknots. The crucial requirement is that the translocation dynamics (i.e., the length of the translocated molecular segment) needs to be recorded as a function of time with a spatial resolution of a few nucleotides. This could be achieved, for instance, by applying a mechanical driving force for translocation and recording force-extension curves (FEC's) with a device such as an atomic force microscope or optical tweezers. Our analysis suggests that with this added spatial resolution, nanopores could be transformed into a powerful experimental tool to study the folding of nucleic acids.Comment: 9 pages, 5 figure

Fractional transport equations for Levy stable processes

The influence functional method of Feynman and Vernon is used to obtain a quantum master equation for a Brownian system subjected to a Levy stable random force. The corresponding classical transport equations for the Wigner function are then derived, both in the limit of weak and strong friction. These are fractional extensions of the Klein-Kramers and the Smoluchowski equations. It is shown that the fractional character acquired by the position in the Smoluchowski equation follows from the fractional character of the momentum in the Klein-Kramers equation. Connections among fractional transport equations recently proposed are clarified.Comment: 4 page

Dietary calcium concentration and cereals differentially affect mineral balance and tight junction proteins expression in jejunum of weaned pigs

Ca plays an essential role in bone development; however, little is known about its effect on intestinal gene expression in juvenile animals. In the present study, thirty-two weaned pigs (9·5 (sem 0·11) kg) were assigned to four diets that differed in Ca concentration (adequate v. high) and cereal composition (wheat–barley v. maize) to assess the jejunal and colonic gene expression of nutrient transporters, tight junction proteins, cytokines and pathogen-associated molecular patterns, nutrient digestibility, Ca balance and serum acute-phase response. To estimate the impact of mucosal bacteria on colonic gene expression, Spearman's correlations between colonic gene expression and bacterial abundance were computed. Faecal Ca excretion indicated that more Ca was available along the intestinal tract of the pigs fed high Ca diets as compared to the pigs fed adequate Ca diets (P0·35; P< 0·05) indicated an association between operational taxonomic units assigned to the phyla Bacteroidetes, Firmicutes and Proteobacteria and bacterial metabolites and mucosal gene expression in the colon. The present results indicate that high Ca diets have the potential to modify the jejunal and colonic mucosal gene expression response which, in turn, interacts with the composition of the basal diet and mucosa-associated bacteria in weaned pigs