The effect of high protein diet on urea and guanidino compound levels in renal insufficient mice

Summary. Nephrectomy in mice provokes a decrease in creatinine clearance (CTN_Cl) and an increase in urea and specific guanidino compound (GC) concentrations in blood and other tissues. Our purpose was to investigate the influence of high protein diet (HPD) on CTN_Cl, urea and GC levels in NX mice. Mice were nephrectomized or sham-operated and subdivided in groups to study five diet conditions. At the end of each experiment, 10 days and 30 days postsurgery, urine and blood were collected for determination of urea and GCs, including creatinine. HPD resulted in significantly higher CTN_Cl values in sham-operated mice than those observed in mice under normal protein diet, 10 days as well as 30 days postnephrectomy. HPD induced significant increases in plasma urea, guanidinosuccinic acid, argininic acid and α-keto-δ-guanidinovaleric acid concentration 10 days postsurgery but not 30 days postsurgery. HPD coincided with significantly higher excretion of urea, guanidinosuccinic acid, α-keto-δ-guanidinovaleric acid, creatine, argininic acid and γ-guanidinobutyric acid in sham-operated and nephrectomized mice 10 days postsurgery. Our results show that HPD induces supplementary (to nephrectomy) increases of urea and GCs in the early postsurgery period but not in the later phase. Received June 13, 2000 Accepted January 9, 2001     

Populational Heritability: Extending Punnett Square Concepts to Evolution at the Metapopulation Level

In a previous study, using experimental metapopulations of the flour beetle, Tribolium castaneum, we investigated phase III of Wright's shifting balance process (Wade and Griesemer 1998). We experimentally modeled migration of varying amounts from demes of high mean fitness into demes of lower mean fitness (as in Wright's characterization of phase III) as well as the reciprocal (the opposite of phase III). We estimated the meta-populational heritability for this level of selection by regression of offspring deme means on the weighted parental deme means.Here we develop a Punnett Square representation of the inheritance of the group mean to place our empirical findings in a conceptual context similar to Mendelian inheritance of individual traits. The comparison of Punnett Squares for individual and group inheritance shows how the latter concept can be rigorously defined and extended despite the lack of explicitly formulated, simple Mendelian laws of inheritance at the group level. Whereas Wright's phase III combines both interdemic selection and meta-populational inheritance, our formulation separates the issue of meta-populational heritability from that of interdemic selection. We use this conceptual context to discuss the controversies over the levels of selection and the units of inheritance.     

Behaviour of interleukin-2 serum levels in advanced non-small-cell lung cancer patients: relationship with response to therapy and survival

 Interleukin(IL)-2 is a T helper (Th) 1 type cytokine that has been shown to play an important role in antitumour immune responses. In this study, the prognostic significance of serum IL-2 levels was investigated in 60 advanced non-small-cell lung cancer (NSCLC) patients. IL-2 serum levels were determined before chemotherapy, at the end of chemotherapy and during follow-up, using a commercially available enzyme-linked immunoadsorbent assay kit. The results were analysed according to the response to therapy and were used to generate a model predicting overall survival and time to treatment failure. All 60 patients were shown to have higher IL-2 serum levels than controls (P < 0.0001). Stage IV patients had significantly lower IL-2 levels than stage III patients (P < 0.0001), although they were still significantly higher than controls (P < 0.0001). It is interesting that, when patients were divided into responders and non-responders according to the response to therapy, the former were shown to have significantly higher pre-chemotherapy levels than the latter (P < 0.0001). Moreover, a further significant increase in IL-2 serum levels (P=0.004) and a significant decrease (P < 0.0001) were shown in responders and non-responders, respectively at the end of the therapy. Using univariate and multivariate analyses, both overall survival and time to treatment failure were shown to be affected by the mean pathological levels of IL-2. Furthermore, the prognostic significance of the serum level of IL-2 was confirmed by the stepwise regression analysis. In conclusion, determination of pre-treatment IL-2 serum levels was shown to be of independent prognostic utility in patients with advanced NSCLC; therefore, its possible use for prediction of outcome is proposed. Received: 16 March 2000 / Accepted: 27 July 2000     

Light‐dependent changes of tomato glutamine synthetase in response to Pseudomonas syringae infection or phosphinothricin treatment

Glutamine synthetase (GS, EC 6.3.1.2), a key enzyme in nitrogen assimilation, was investigated in tomato ( Lycopersicon esculentum Mill. cv. Hellfrucht Frühstamm) leaves infected with Pseudomonas syringae pv. tomato (Pst) or treated with the herbicide phosphinothricin (PPT), an irreversible inhibitor of GS. GS activity decreased markedly when Pst infection occurred in illuminated leaves, but only a slight decrease in relation to control leaves was observed under non‐photosynthetic conditions. In leaves treated with PPT, a rapid inhibition of GS activity was observed under all experimental conditions. When bacterial infection or herbicide treatment was carried out in the light, cytosolic GS (GS1) appeared as the predominant GS polypeptide; however, under non‐photosynthetic conditions GS2 remained the most abundant molecular GS species as occurs in non‐stressed plants. These results suggest a close correlation between the photosynthetic process and changes in the relative proportions of GS polypeptides during infection or herbicide treatment. Ammonium has been described as an inducer of GS genes, but as ammonium accumulated during all treatments, other light‐dependent factors could be involved in GS regulation of stressed leaves.     

Comparison of Linear,Nonlinear and Semiparametric Mixed‐effects Models for Estimating HIV Dynamic Parameters

The potency of antiretroviral agents in AIDS clinical trials can be assessed on the basis of an early viral response such as viral decay rate or change in viral load (number of copies of HIV RNA) of the plasma. Linear, parametric nonlinear, and semiparametric nonlinear mixed‐effects models have been proposed to estimate viral decay rates in viral dynamic models. However, before applying these models to clinical data, a critical question that remains to be addressed is whether these models produce coherent estimates of viral decay rates, and if not, which model is appropriate and should be used in practice. In this paper, we applied these models to data from an AIDS clinical trial of potent antiviral treatments and found significant incongruity in the estimated rates of reduction in viral load. Simulation studies indicated that reliable estimates of viral decay rate were obtained by using the parametric and semiparametric nonlinear mixed‐effects models. Our analysis also indicated that the decay rates estimated by using linear mixed‐effects models should be interpreted differently from those estimated by using nonlinear mixed‐effects models. The semiparametric nonlinear mixed‐effects model is preferred to other models because arbitrary data truncation is not needed. Based on real data analysis and simulation studies, we provide guidelines for estimating viral decay rates from clinical data. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Bayesian Methods for Examining Hardy–Weinberg Equilibrium

Summary .  Testing for Hardy–Weinberg equilibrium is ubiquitous and has traditionally been carried out via frequentist approaches. However, the discreteness of the sample space means that uniformity of  p -values under the null cannot be assumed, with enumeration of all possible counts, conditional on the minor allele count, offering a computationally expensive way of  p -value calibration. In addition, the interpretation of the subsequent  p -values, and choice of significance threshold depends critically on sample size, because equilibrium will always be rejected at conventional levels with large sample sizes. We argue for a Bayesian approach using both Bayes factors, and the examination of posterior distributions. We describe simple conjugate approaches, and methods based on importance sampling Monte Carlo. The former are convenient because they yield closed-form expressions for Bayes factors, which allow their application to a large number of single nucleotide polymorphisms (SNPs), in particular in genome-wide contexts. We also describe straightforward direct sampling methods for examining posterior distributions of parameters of interest. For large numbers of alleles at a locus we resort to Markov chain Monte Carlo. We discuss a number of possibilities for prior specification, and apply the suggested methods to a number of real datasets.     

Intraspecific genome size variation and morphological differentiation of Ranunculus parnassifolius (Ranunculaceae), an Alpine–Pyrenean–Cantabrian polyploid group

The aim of this study was to assess genome size variation and multivariate morphometric analyses to ascertain cytotype distribution patterns and the morphological differentiation within the Ranunculus parnassifolius group in the Pyrenees and the Alps. Although divergences in nuclear DNA content among different species within a genus are widely acknowledged, intraspecific variation is still a somewhat controversial issue. Holoploid and monoploid genome sizes (C‐ and Cx‐values) were determined using propidium iodide flow cytometry in 125 plants of R. parnassifolius s.l. distributed across four European countries. Three different DNA ploidy levels were revealed in the study area: diploid (2n ～ 2x, 57.14%), triploid (2n ～ 3x, 1.19%), and tetraploid (2n ～ 4x, 41.67%). The mean population 2C‐values ranged from 8.15 pg in diploids to 14.80 pg in tetraploids, representing a ratio of 1 : 1.8. Marked intraspecific/interpopulation differences in nuclear DNA content were found. Diploid populations prevail in the Pyrenees, although tetraploid cytotypes were reported throughout the distribution area. In general, mixed‐cytotype populations were not found. The Spearman correlation coefficient did not reveal significant correlations between genome size and altitude, longitude, or latitude. Morphometric analyses and cluster analyses based on genome size variation revealed the presence of three major groups, which exhibited a particular biogeographical pattern. A new cytotype, DNA triploid, was found for the first time. Tetraploid populations showed constant nuclear DNA levels, whereas diploid populations from the Pyrenees, in which introgressive hybridization is suggested as a presumable trigger for genome size variation, did not. Scenarios for the evolution of geographical parthenogenesis in R. parnassifolius s.l. are discussed. Finally, the different levels of effectiveness between plant and animal reference standards are analysed. © 2010 The Linnean Society of London, Biological Journal of the Linnean Society, 2010, 101 , 251–271.     

微囊藻毒素在滇池鱼体内的积累水平及分布特征

为了解富营养化水体中鱼体内微囊藻毒素(MC)的积累水平及其分布特征,2003年4月和9月份两次在滇池试验区采集了鲢、鳙和草鱼等鱼种,用ELISA方法对鱼体中肝、肾、空肠、胆、肌肉等不同组织中MC的含量进行了检测。结果表明,MC在所有样品中均能检测到,且主要分布在鱼体的肝肾脏和消化道等器官,而肌肉和非消化道器官中毒素含量相对较低。不同鱼种不同组织对MC的富集程度也明显不同,鲢鳙中肝脏和肾脏这两个主要的靶器官对MC的蓄积能力就远高于草鱼。同时,不同季节MC在鱼体内的积累水平也明显不同,4月份鱼样中MC的含量普遍低于9月份鱼样中MC的含量。最后按照WHO生活饮用水安全标准的建议进行推算,所有鱼肉中的MC均没有超过其推荐的人体每日可允许摄入量(≤0.04μg/kg人体重),初步推断鱼肉中MC暂时还未危及到人体健康,但仍具有潜在的风险性。     

Levels of endemism are not necessarily biased by the co-presence of species with different range sizes: a case study of Vilenkin and Chikatunov's models

Aim  To illustrate problems in the methods proposed by B. Vilenkin and V. Chikatunov to study levels of endemism and species–area relationships.
Location  The study used data on the distribution of tenebrionid beetles (Coleoptera, Tenebrionidae) on the Aegean Islands (Greece).
Methods  A total of 32 islands and 170 taxa (species and subspecies) were included in this study. Levels of endemism were evaluated both as the proportion of endemic taxa, and according to the methods proposed by Vilenkin and Chikatunov, which are based on the number of non-endemic taxa and various relationships with area. A model of the species–area relationship proposed by these authors was also analysed.
Results  The number of endemic taxa was positively correlated with the number of taxa with different distribution types, but this positive correlation did not influence the estimation of the level of endemism. In fact, the commonly used estimate of endemicity as a percentage was strongly correlated with the endemism values calculated according to the method of Vilenkin and Chikatunov. The usual power function fitted the species–area relationship as well as the most complicated method of Vilenkin and Chikatunov.
Main conclusions  As hypothesized by Vilenkin and Chikatunov, the number of endemic taxa was influenced both by the number of taxa of other biogeographical ranks, and by an island's area. However, explanations for the positive relationship between the number of endemic taxa and taxa of different biogeographical ranks are equivocal. Importantly, this relationship did not necessarily influence the level of endemism, which could be expressed adequately by percentages. The method proposed by Vilenkin and Chikatunov to estimate the species–area relationship cannot be clearly justified on theoretical grounds and is of questionable practical utility.