丙型肝炎病毒感染实验动物模型的研究进展

丙型肝炎病毒（HCV）感染是导致人类慢性病毒性肝炎、肝硬化和肝癌的最主要病因之一。由于缺乏合适的HCV感染实验动物模型,使得针对HCV感染更为有效的疗法及疫苗的研发滞后。黑猩猩是HCV感染研究的最佳实验动物,但由于其来源有限、价格昂贵及临床症状等诸多问题,其应用受限,因此发展新的实验动物模型用于HCV感染相关的基础和应用研究迫在眉睫。近年来,以啮齿类等动物为替代模型取得了不少进展,应用转基因等实验技术使替代动物感染了HCV,并成功应用于多个学科领域的研究。本文分析了HCV自然感染的实验动物、自然感染和非自然感染的替代实验动物在致病机制研究、药物评价和疫苗研发应用中的优缺点及未来研究趋势。     

The rhizosphere and plant nutrition: a quantitative approach

The role of the rhizosphere in relation to mineral nutrition is discussed within a quantitative framework using the Barber-Cushman model as a starting point. The uptake or release of nutrients by roots growing in soil leads to concentration gradients forming in the soil: the zone so affected is termed the rhizosphere. The nature of these gradients depends on three factors: the rate of uptake/release; the mobility of the nutrient in soil; and the rate of conversion between available and unavailable forms. The interplay between these factors determines the amount of mineral nutrients acquired by the plant and it is the complexity of the interplay which demands the use of mathematical models in order to understand which factors most limit uptake. Despite extensive experimental evidence of root-mediated changes to the physical, chemical and biological status of rhizosphere soil, the quantitative significance of these changes for mineral nutrition has not been assessed. The problems of making this quantitative transition are reviewed.     

Rhabdomyosarcomas: an overview on the experimental animal models

Rhabdomyosarcomas (RMS) are aggressive childhood soft-tissue malignancies deriving from mesenchymal progenitors that are committed to muscle-specific lineages. Despite the histopathological signatures associated with three main histological variants, termed embryonal, alveolar and pleomorphic, a plethora of genetic and molecular changes are recognized in RMS. Over the years, exposure to carcinogens or ionizing radiations and gene-targeting approaches in vivo have greatly contributed to disclose some of the mechanisms underlying RMS onset. In this review, we describe the principal distinct features associated with RMS variants and focus on the current available experimental animal models to point out the molecular determinants cooperating with RMS development and progression.     

A porcine animal model to mimic the restart of enteral nutrition (refeeding-model)

With the aim towards establishing an animal model of total parenteral nutrition (TPN), 12 piglets aged 9 weeks (mean body weight 21 kg) were surgically provided with central venous catheters. Six piglets were nourished parenterally with the objective to reach a 14-d period of TPN; the other six piglets served as control and were fed normally. Only one animal from each group could be monitored over the whole period. Nine piglets were euthanised on d 13 and one on d 12. No animal showed fever or signs of septicaemia during the study. The levels of Ca, Mg, Na and P in the blood were within the normal range as were those for blood glucose and plasma creatinine. Symptoms of the TPN included: transient diarrhoea, occasional appearance of faecal blood and occasional absence of defecation. A reduced small intestine length and altered mucosal morphology and function were observed. One animal showed bile stasis at the end of the study. All TPN animals showed a remarkably high level of blood urea early in the morning. The intestinal symptoms observed may resemble the human situation during TPN. However, due to the fast growth rate, pigs aged 9 weeks have higher nutrient requirements per kg body weight. Consequently, the osmolality of the nutrient solution was necessarily high. Whether the significantly higher blood urea observed in the TPN group reflected a catabolic metabolism during the starving period at night-time could not be conclusively shown. Alternatively, it could reflect a slower growth rate and a resulting quantitative excess of amino acids (AA), or could have been the consequence of a suboptimal AA composition. A permanent infusion would be favourable in order not to overcharge the capacity for glucose uptake and amino acid metabolism during the infusion.     

Evaluation of nutrition models to estimate performance of young dairy calves: a meta-analytical study under tropical conditions

Mathematical models are important tools to estimate nutritional requirements and animal growth. Very few calf models generated from other countries with different feeding programs, environment and production systems have been evaluated. The objective of this paper is to evaluate two calf models: (i) the National Research Council (NRC) in 2001 and (ii) the updates published by Van Amburgh and Drackley in 2005 and inputted into Agricultural Modeling and Training Systems (AMTS, version 3.5.8). Data from 16 previous studies involving 51 diets for dairy calves under tropical conditions (n=485 calves, initial BW 37.5±4.35 kg and weaning weight of 62.0±10.16 kg) were used. The calves were fed with whole milk, milk replacer or fermented colostrum, plus starter (20.9±1.78% of CP). The accuracy of the average daily gain (ADG) prediction was evaluated by mean bias, mean square prediction error (MSPE), concordance correlation coefficient, bias correction factor (Cb), and regression between the observed and predicted values. The ADG observed from birth to weaning was 0.452±0.121 kg/day. Calves fed with whole milk had greater ADG compared with calves fed milk replacer (0.477 v. 0.379 kg/day) during the milk-feeding period. When all data were pooled (n=51 diets), predictions had a mean bias of −0.019 and 0.068 kg/day for energy-allowable gain using NRC and AMTS models, respectively. The regression equation between observed and predicted values obtained from energy of diets showed an intercept different from zero (P<0.0001) and slope that differed from unity (P<0.0001). In a second evaluation, when calves were fed only milk replacer, the energy-allowable gain from AMTS showed the lowest mean bias (0.008 kg/day) and 82.1% of the MSPE value originated from random errors. The lowest MSPE, the higher Cb value and no significant slope bias (P>0.05) indicate that the AMTS growth model resulted in accurate predictions for calves fed with milk replacer. However, within these latter two approaches, the goodness of fit (R²) was low, representing low precision. The weight gain estimated by the energy available from the diet was overestimated by 19 g/day when calculated by the NRC and underestimated by 68 g/day when calculated by AMTS. The reasons for this discrepancy need to be understood, for only then new models could be developed and parameterized to estimate animal performance in tropical conditions more accurately and precisely.     

The “ideal protein” concept is not ideal in animal nutrition

Amino acids (AAs) are required for syntheses of proteins and low-molecular-weight substances with enormous physiological importance. Since 1912, AAs have been classified as nutritionally essential amino acids (EAAs) or nonessential amino acids (NEAAs) for animals. EAAs are those AAs that are either not synthesized or insufficiently synthesized de novo in the organisms. It was assumed that all NEAAs (now known as AAs that are synthesizable in animal cells de novo [AASAs]) were formed sufficiently in animals and were not needed in diets. However, studies over the past three decades have shown that sufficient dietary AASAs (e.g. glutamine, glutamate, glycine, and proline) are necessary for the maximum growth and optimum health of pigs, chickens, and fish. Thus, the concept of “ideal protein” (protein with an optimal EAA pattern that precisely meets the physiological needs of animals), which was originally proposed in the 1950s but ignored AASAs, is not ideal in animal nutrition. Ideal diets must provide all physiologically and nutritionally essential AAs. Improved patterns of AAs in diets for swine and chickens as well as zoo and companion animals have been proposed in recent years. Animal-sourced feedstuffs supply abundant EAAs and AASAs (including glutamate, glutamine, glycine, proline, 4-hydroxyproline, and taurine) for diets of swine, poultry, fish, and crustaceans to improve their growth, development, reproduction, and health, while sustaining global animal production. Nutritionists should move beyond the “ideal protein” concept to consider optimum ratios and amounts of all proteinogenic AAs in diets for mammals, birds, and aquatic animals, and, in the case of carnivores, also taurine.     

Gamma generalized linear models for pharmacokinetic data

Summary .   This article considers the modeling of single-dose pharmacokinetic data. Traditionally, so-called compartmental models have been used to analyze such data. Unfortunately, the mean function of such models are sums of exponentials for which inference and computation may not be straightforward. We present an alternative to these models based on generalized linear models, for which desirable statistical properties exist, with a logarithmic link and gamma distribution. The latter has a constant coefficient of variation, which is often appropriate for pharmacokinetic data. Inference is convenient from either a likelihood or a Bayesian perspective. We consider models for both single and multiple individuals, the latter via generalized linear mixed models. For single individuals, Bayesian computation may be carried out with recourse to simulation. We describe a rejection algorithm that, unlike Markov chain Monte Carlo, produces independent samples from the posterior and allows straightforward calculation of Bayes factors for model comparison. We also illustrate how prior distributions may be specified in terms of model-free pharmacokinetic parameters of interest. The methods are applied to data from 12 individuals following administration of the antiasthmatic agent theophylline.     

植物硅营养的研究进展

阐述了植物吸收硅的机理、硅与其它营养元素的关系及其对非胁迫和胁迫条件下植物生长发育的有益作用 .植物吸收硅的机制目前尚不是很清楚 ,不同植物吸收硅的方式不同 .硅可影响植物中其它营养元素的含量 .在非胁迫条件下 ,硅可促进植物的生长 ;硅也参与了植物抗病、抗虫等生物胁迫 ,以及抗金属毒害、盐害、温度胁迫、干旱、抗倒伏等非生物胁迫的反应 .目前 ,应从多种植物上深入研究硅的吸收方式与机理 ;同时 ,应该改变硅在细胞壁的沉积仅仅起增强组织机械强度作用的观点 ,而应从生理代谢调控的角度进行硅作用机制的研究 ,为生产实践中硅肥的应用奠定理论基础     

Overdispersed fungus germination data: statistical analysis using R

ABSTRACT

Proportion data from dose-response experiments are often overdispersed, characterised by a larger variance than assumed by the standard binomial model. Here, we present different models proposed in the literature that incorporate overdispersion. We also discuss how to select the best model to describe the data and present, using R software, specific code used to fit and interpret binomial, quasi-binomial, beta-binomial, and binomial-normal models, as well as to assess goodness-of-fit. We illustrate applications of these generalized linear models and generalized linear mixed models with a case study from a biological control experiment, where different isolates of Isaria fumosorosea (Hypocreales: Cordycipitaceae) were used to assess which ones presented higher resistance to UV-B radiation. We show how to test for differences between isolates and also how to statistically group isolates presenting a similar behaviour.     

Boron in human and animal nutrition

This review describes the findings from human and animal studies indicating that B is a dynamic trace element which, in physiological amounts, can affect the metabolism or utilisation of numerous other substances involved in life processes including macrominerals, energy substrates such as triglycerides and glucose, nitrogen containing substances such as amino acids and proteins, reactive oxygen species, and estrogen. Through these effects, B can affect the function or composition of several body systems, including the brain, skeleton and immune system, generally in a beneficial fashion. Moreover, homeostatic mechanisms apparently exist for B because it is rapidly excreted in the urine, does not accumulate in tissues, and is maintained in a relatively narrow range of concentrations in blood of healthy individuals. Thus, even though B has not been conclusively established as essential because a biochemical function for it has not been identified, its beneficial actions suggest that an intake of over 1 mg day^-1 (but probably not more than 13 mg day^-1) is desirable; diets low in fruits, vegetables, legumes and nuts may not provide this amount of B. Boron may be of more practical nutritional importance than currently acknowledged.     

植物钾营养性状的遗传潜力v

钾是植物生长发育所必需的大量元素,是与氮、磷并列的植物营养的“三大要素”之一。不同植物种类或同种类植物的不同品种之间钾营养效率的差异非常显著,这为植物钾营养性状的遗传改良提供了科学依据     

Analysis of clustered and longitudinal binary data subject to response misclassification

Misclassified clustered and longitudinal data arise in studies where the response indicates a condition identified through an imperfect diagnostic procedure. Examples include longitudinal studies that use an imperfect diagnostic test to assess whether or not an individual has been infected with a specific virus. This article presents methods to implement both population-averaged and cluster-specific analyses of such data when the misclassification rates are known. The methods exploit the fact that the class of generalized linear models enjoys a closure property in the case of misclassified responses. Data from longitudinal studies of infectious disease will illustrate the findings.     

Mesenchymal stem cells in the treatment of inflammatory and autoimmune diseases in experimental animal models

Multipotent mesenchymal stromal cells [also known as mesenchymal stem cells(MSCs)] are currently being studied as a cell-based treatment for inflammatory disorders. Experimental animal models of human immune-mediated diseases have been instrumental in establishing their immunosuppressive properties. In this review, we summarize recent studies examining the effectiveness of MSCs as immunotherapy in several widely-studied animal models, including type 1 diabetes, experimental autoimmune arthritis, experimental autoimmune encephalomyelitis, inflammatory bowel disease, graft-vs-host disease, and systemic lupus erythematosus. In addition, we discuss mechanisms identified by which MSCs mediate immune suppression in specific disease models, and potential sources of functional variability of MSCs between studies.