Endothelial Nitric Oxide Genotypes and Haplotypes Are Not Associated with End-Stage Renal Disease

The identification of genetic markers associated with chronic kidney disease (CKD) may help to predict its development. Because reduced nitric oxide (NO) bioavailability and endothelial dysfunction are involved in CKD, genetic polymorphisms in the gene encoding the enzyme involved in NO synthesis (endothelial NO synthase [eNos]) may affect the susceptibility to CKD and the development of end-stage renal disease (ESRD). We compared genotype and haplotype distributions of three relevant eNOS polymorphisms (T(-786) C in the promoter region, Glu298Asp in exon 7, and 4b/4a in intron 4) in 110 healthy control subjects and 127 ESRD patients. Genotypes for the T(-786) C and Glu298Asp polymorphisms were determined by TaqMan (R) Allele Discrimination assay and real-time polymerase chain reaction. Genotypes for the intron 4 polymorphism were determined by polymerase chain reaction and fragment separation by electrophoresis. The software program PHASE 2.1 was used to estimate the haplotypes frequencies. We considered significant a probability value of p < 0.05/number of haplotypes (p < 0.05/8 = 0.0063). We found no significant differences between groups with respect to age, ethnicity, and gender. CKD patients had higher blood pressure, total cholesterol, and creatinine levels than healthy control subjects (all p < 0.05). Genotype and allele distributions for the three eNOS polymorphisms were similar in both groups (p > 0.05). We found no significant differences in haplotype distribution between groups (p > 0.05). The lack of significant associations between eNOS polymorphisms and ESRD suggests that eNOS polymorphisms may not be relevant to the genetic component of CKD that leads to ESRD.

Multi-trait and random regression mature weight heritability and breeding value estimates in Nelore cattle

Mature weight breeding values were estimated using a multi-trait animal model (MM) and a random regression animal model (RRM). Data consisted of 82 064 weight records from 8 145 animals, recorded from birth to eight years of age. Weights at standard ages were considered in the MM. All models included contemporary groups as fixed effects, and age of dam (linear and quadratic effects) and animal age as covariates. In the RRM, mean trends were modelled through a cubic regression on orthogonal polynomials of animal age and genetic maternal and direct and maternal permanent environmental effects were also included as random. Legendre polynomials of orders 4, 3, 6 and 3 were used for animal and maternal genetic and permanent environmental effects, respectively, considering five classes of residual variances. Mature weight (five years) direct heritability estimates were 0.35 (MM) and 0.38 (RRM). Rank correlation between sires' breeding values estimated by MM and RRM was 0.82. However, selecting the top 2% (12) or 10% (62) of the young sires based on the MM predicted breeding values, respectively 71% and 80% of the same sires would be selected if RRM estimates were used instead. The RRM modelled the changes in the (co) variances with age adequately and larger breeding value accuracies can be expected using this model.

A simplified minimal residual disease polymerase chain reaction method at early treatment points can stratify children with acute lymphoblastic leukemia into good and poor outcome groups

Background Minimal residual disease is an important independent prognostic factor in childhood acute lymphoblastic leukemia. The classical detection methods such as multiparameter flow cytometry and real-time quantitative polymerase chain reaction analysis are expensive, time-consuming and complex, and require considerable technical expertise. Design and Methods We analyzed 229 consecutive children with acute lymphoblastic leukemia treated according to the GBTLI-99 protocol at three different Brazilian centers. Minimal residual disease was analyzed in bone marrow samples at diagnosis and on days 14 and 28 by conventional homo/heteroduplex polymerase chain reaction using a simplified approach with consensus primers for IG and TCR gene rearrangements. Results At least one marker was detected by polymerase chain reaction in 96.4%, of the patients. By combining the minimal residual disease results obtained on days 14 and 28, three different prognostic groups were identified: minimal residual disease negative on days 14 and 28, positive on day 14/negative on day 28, and positive on both. Five-year event-free survival rates were 85%, 75.6%,, and 27.8%, respectively (p<0.0001). The same pattern of stratification held true for the group of intensively treated children. When analyzed in other subgroups of patients such as those at standard and high risk at diagnosis, those with positive B-derived CD10, patients positive for the TEL/AML1 transcript, and patients in morphological remission on a day 28 marrow, the event-free survival rate was found to be significantly lower in patients with positive minimal residual disease on day 28. Multivariate analysis demonstrated that the detection of minimal residual disease on day 28 is the most significant prognostic factor. Conclusions This simplified strategy for detection of minimal residual disease was feasible, reproducible, cheaper and simpler when compared with other methods, and allowed powerful discrimination between children with acute lymphoblastic leukemia with a good and poor outcome.

RNA interference-mediated knockdown of CD49e (alpha 5 integrin chain) in human thymic epithelial cells modulates the expression of multiple genes and decreases thymocyte adhesion

Background: The thymus is a central lymphoid organ, in which bone marrow-derived T cell precursors undergo a complex process of maturation. Developing thymocytes interact with thymic microenvironment in a defined spatial order. A component of thymic microenvironment, the thymic epithelial cells, is crucial for the maturation of T-lymphocytes through cell-cell contact, cell matrix interactions and secretory of cytokines/chemokines. There is evidence that extracellular matrix molecules play a fundamental role in guiding differentiating thymocytes in both cortical and medullary regions of the thymic lobules. The interaction between the integrin alpha 5 beta 1 (CD49e/CD29; VLA-5) and fibronectin is relevant for thymocyte adhesion and migration within the thymic tissue. Our previous results have shown that adhesion of thymocytes to cultured TEC line is enhanced in the presence of fibronectin, and can be blocked with anti-VLA-5 antibody. Results: Herein, we studied the role of CD49e expressed by the human thymic epithelium. For this purpose we knocked down the CD49e by means of RNA interference. This procedure resulted in the modulation of more than 100 genes, some of them coding for other proteins also involved in adhesion of thymocytes; others related to signaling pathways triggered after integrin activation, or even involved in the control of F-actin stress fiber formation. Functionally, we demonstrated that disruption of VLA-5 in human TEC by CD49e-siRNA-induced gene knockdown decreased the ability of TEC to promote thymocyte adhesion. Such a decrease comprised all CD4/CD8-defined thymocyte subsets. Conclusion: Conceptually, our findings unravel the complexity of gene regulation, as regards key genes involved in the heterocellular cell adhesion between developing thymocytes and the major component of the thymic microenvironment, an interaction that is a mandatory event for proper intrathymic T cell differentiation.

Effects of polymorphisms of LHR and FSHR genes on sexual precocity in a Bos taurus x Bos indicus beef composite population

The purpose of the present research was to investigate the effects of polymorphisms of luteinizing hormone receptor (LHR) and follicle-stimulating hormone receptor (FSHR) genes, evaluated by polymerase chain reaction-restriction fragment length polymorphism in European-Zebu composite beef heifers from six different breed compositions. The polymorphism site analysis from digestion with HhaI and AluI restriction endonucleases allowed the genotype identification for LHR (TT, CT and CC) and FSHR (GG, CG and CC) genes. A high frequency of heterozygous animals was recorded in all breed compositions for both genes, except in two compositions for LHR. The probability of pregnancy (PP) at first breeding was used to evaluate the polymorphism effect on sexual precocity. The PP was analyzed as a binary trait, with a value of 1 (success) assigned to heifers that were diagnosed pregnant by rectal palpation and a value of 0 (failure) assigned to those that were not pregnant at that time. Heterozygous heifers showed a higher pregnancy rate (67 and 66% for LHR and FSHR genes, respectively), but no significant effects were observed for the genes studied (P=0.9188 and 0.8831 for LHR and FSHR, respectively) on the PP. These results do not justify the inclusion of LHR and FSHR restriction fragment length polymorphism markers in selection programs for sexual precocity in beef heifers. Nevertheless, these markers make possible the genotype characterization and may be used in additional studies to evaluate the genetic structure in other bovine populations.

Comparison of a PCR assay in whole blood and serum specimens for canine brucellosis diagnosis

The performance of a serum PCR assay was compared with that of a blood PCR assay for the diagnosis of canine brucellosis caused by Brucella canis in 72 dogs. The dogs were classified into three groups (infected, non-infected and suspected brucellosis) according to the results of blood culture and serological tests. The sensitivities of blood PCR and serum PCR were, respectively, 97.14 per cent and 25.71 per cent. The specificities of both were 100 per cent. In the group of dogs with suspected brucellosis, three were positive by blood PCR and none was positive by serum PCR. Serum PCR showed little value for the direct diagnosis of canine brucellosis as the assay had low diagnostic sensitivity and fewer positive dogs were detected by this test than by blood culture, blood PCR, rapid slide agglutination test (RSAT) and RSAT with 2-mercaptoethanol.

Chain motifs: The tails and handles of complex networks

A great part of the interest in complex networks has been motivated by the presence of structured, frequently nonuniform, connectivity. Because diverse connectivity patterns tend to result in distinct network dynamics, and also because they provide the means to identify and classify several types of complex network, it becomes important to obtain meaningful measurements of the local network topology. In addition to traditional features such as the node degree, clustering coefficient, and shortest path, motifs have been introduced in the literature in order to provide complementary descriptions of the network connectivity. The current work proposes a different type of motif, namely, chains of nodes, that is, sequences of connected nodes with degree 2. These chains have been subdivided into cords, tails, rings, and handles, depending on the type of their extremities (e.g., open or connected). A theoretical analysis of the density of such motifs in random and scale-free networks is described, and an algorithm for identifying these motifs in general networks is presented. The potential of considering chains for network characterization has been illustrated with respect to five categories of real-world networks including 16 cases. Several interesting findings were obtained, including the fact that several chains were observed in real-world networks, especially the world wide web, books, and the power grid. The possibility of chains resulting from incompletely sampled networks is also investigated.

Determination of the minimum value of the safety factor from geodesic Alfven eigenmodes in Joint European Torus

An analysis of the experimental conditions under which low-frequency (70-150 kHz) Alfven eigertmodes (AE) are excited during the monster sawtooth in Joint European Torus [F Romanelli et al, Proceedings of the 22nd IAEA Fusion Energy Conference, Geneva, Switzerland, 2008] is presented for the specific case of a discharge with ion cyclotron heating (5 MW) Using a simplified AE model for modes excited at the Alfven wave continuum maximum with geodesic corrections taken into account, the temporal evolution of the value of the safety factor q(0) at the magnetic axis is determined We describe a new scheme to determine the time variation of q(0) that works under conditions in which other standard diagnostics, such as the motional Stark effect do not give reliable results such as during a monster sawtooth [doi 10 1063/1 3494212]

Power-law creep behavior of a semiflexible chain

Rheological properties of adherent cells are essential for their physiological functions, and microrheological measurements on living cells have shown that their viscoelastic responses follow a weak power law over a wide range of time scales. This power law is also influenced by mechanical prestress borne by the cytoskeleton, suggesting that cytoskeletal prestress determines the cell's viscoelasticity, but the biophysical origins of this behavior are largely unknown. We have recently developed a stochastic two-dimensional model of an elastically joined chain that links the power-law rheology to the prestress. Here we use a similar approach to study the creep response of a prestressed three-dimensional elastically jointed chain as a viscoelastic model of semiflexible polymers that comprise the prestressed cytoskeletal lattice. Using a Monte Carlo based algorithm, we show that numerical simulations of the chain's creep behavior closely correspond to the behavior observed experimentally in living cells. The power-law creep behavior results from a finite-speed propagation of free energy from the chain's end points toward the center of the chain in response to an externally applied stretching force. The property that links the power law to the prestress is the chain's stiffening with increasing prestress, which originates from entropic and enthalpic contributions. These results indicate that the essential features of cellular rheology can be explained by the viscoelastic behaviors of individual semiflexible polymers of the cytoskeleton.

Unusual magneto-optical phenomenon reveals low energy spin dispersion in the spin-1 anisotropic Heisenberg antiferromagnetic chain system NiCl(2)-4SC(NH(2))(2)

Electron paramagnetic resonance measurements of NiCl(2)-4SC(NH(2))(2) reveal the low-energy spin dispersion, including a magnetic-field interval in which the two-magnon continuum is within k(B)T of the ground state, allowing a continuum of excitations over a range of k states, rather than only the k=0 single-magnon excitations. This produces a novel Y shape in the frequency-field EPR spectrum measured at T >= 1.5 K. Since the interchain coupling J(perpendicular to)< k(B)T, this shape can be reproduced by a single S=1 antiferromagnetic Heisenberg chain with a strong easy-plane single-ion anisotropy. Importantly, the combination of experiment and modeling we report herein demonstrates a powerful approach to probing spin dispersion in a wide range of interacting magnetic systems without the stringent sample requirements and complications associated with inelastic scattering experiments.

f t value of the 0(+)-> 0(+) beta(+) decay of (32)Ar: A measurement of isospin symmetry breaking in a superallowed decay

We determined the absolute branch of the T=2 superallowed decay of (32)Ar by detecting the beta(+)-delayed protons and gamma decays of the daughter state. We obtain b(SA)(beta)=(22.71 +/- 0.16)%, which represents the first determination of a proton branch to better than 1%. Using this branch along with the previously determined (32)Ar half-life and energy release, we determined ft=(1552 +/- 12) s for the superallowed decay. This ft value, together with the corrected Ft value extracted from previously known T=1 superallowed decays, yields a measurement of the isospin symmetry breaking correction in (32)Ar decay delta(exp)(C)=(2.1 +/- 0.8)%. This can be compared to a theoretical calculation delta(C)=(2.0 +/- 0.4)%. As by-products of this work, we determined the gamma and proton branches for the decay of the lowest T=2 state of (32)Cl, made a precise determination of the total proton branch and relative intensities of proton groups that leave (31)S in its first excited state and deduced an improved value for the (32)Cl mass.

Random perturbations of stochastic processes with unbounded variable length memory

We consider binary infinite order stochastic chains perturbed by a random noise. This means that at each time step, the value assumed by the chain can be randomly and independently flipped with a small fixed probability. We show that the transition probabilities of the perturbed chain are uniformly close to the corresponding transition probabilities of the original chain. As a consequence, in the case of stochastic chains with unbounded but otherwise finite variable length memory, we show that it is possible to recover the context tree of the original chain, using a suitable version of the algorithm Context, provided that the noise is small enough.

Beta-2 adrenergic receptor gene polymorphisms Gln27Glu, Arg16Gly in patients with heart failure

Background -: Beta-2 adrenergic receptor gene polymorphisms Gln27Glu, Arg16Gly and Thr164Ile were suggested to have an effect in heart failure. We evaluated these polymorphisms relative to clinical characteristics and prognosis of alarge cohort of patients with heart failure of different etiologies. Methods -: We studied 501 patients with heart failure of different etiologies. Mean age was 58 years (standard deviation 14.4 years), 298 (60%) were men. Polymorphisms were identified by polymerase chain reaction-restriction fragment length polymorphism. Results -: During the mean follow-up of 12.6 months (standard deviation 10.3 months), 188 (38%) patients died. Distribution of genotypes of polymorphism Arg16Gly was different relative to body mass index (chi(2) = 9.797; p = 0.04). Overall the probability of survival was not significantly predicted by genotypes of Gln27Glu, Arg16Gly, or Thr164Ile. Allele and haplotype analysis also did not disclose any significant difference regarding mortality. Exploratory analysis through classification trees pointed towards a potential association between the Gln27Glu polymorphism and mortality in older individuals. Conclusion -: In this study sample, we were not able to demonstrate an overall influence of polymorphisms Gln27Glu and Arg16Gly of beta-2 receptor gene on prognosis. Nevertheless, Gln27Glu polymorphism may have a potential predictive value in older individuals.

Analytical calculation of the transition to complete phase synchronization in coupled oscillators

Here we present a system of coupled phase oscillators with nearest neighbors coupling, which we study for different boundary conditions. We concentrate at the transition to the total synchronization. We are able to develop exact solutions for the value of the coupling parameter when the system becomes completely synchronized, for the case of periodic boundary conditions as well as for a chain with fixed ends. We compare the results with those calculated numerically.

A Markovian model market-Akerlof`s lemons and the asymmetry of information

In this work we study an agent based model to investigate the role of asymmetric information degrees for market evolution. This model is quite simple and may be treated analytically since the consumers evaluate the quality of a certain good taking into account only the quality of the last good purchased plus her perceptive capacity beta. As a consequence, the system evolves according to a stationary Markov chain. The value of a good offered by the firms increases along with quality according to an exponent alpha, which is a measure of the technology. It incorporates all the technological capacity of the production systems such as education, scientific development and techniques that change the productivity rates. The technological level plays an important role to explain how the asymmetry of information may affect the market evolution in this model. We observe that, for high technological levels, the market can detect adverse selection. The model allows us to compute the maximum asymmetric information degree before the market collapses. Below this critical point the market evolves during a limited period of time and then dies out completely. When beta is closer to 1 (symmetric information), the market becomes more profitable for high quality goods, although high and low quality markets coexist. The maximum asymmetric information level is a consequence of an ergodicity breakdown in the process of quality evaluation. (C) 2011 Elsevier B.V. All rights reserved.