International recommendations for training future toxicologic pathologists participating in regulatory-type, nonclinical toxicity studies

The International Federation of Societies of Toxicologic Pathologists (IFSTP) proposes a common global framework for training future toxicologic pathologists who will support regulatory-type nonclinical toxicology studies. Trainees optimally should undertake a scientific curriculum of at least 5 years at an accredited institution leading to a clinical degree (veterinary medicine or medicine). Trainees should then obtain 4 or more years of intensive pathology practice during a residency and/or on-the-job "apprenticeship," at least 2 years of which must be focused on regulatory-type toxicologic pathology topics. Possession of a recognized pathology qualification (i.e., certification) is highly recommended. A non-clinical pathway (e.g., a graduate degree in medical biology or pathology) may be possible if medically trained pathologists are scarce, but this option is not optimal. Regular, lifelong continuing education (peer review of nonclinical studies, professional meetings, reading, short courses) will be necessary to maintain and enhance one's understanding of current toxicologic pathology knowledge, skills, and tools. This framework should provide a rigorous yet flexible way to reliably train future toxicologic pathologists to generate, interpret, integrate, and communicate data in regulatory-type, nonclinical toxicology studies.     

Contribution of toxicologic pathologists for the safety of human health in biomedical research—past,present, and future of the JSTP

The research field of “Toxicologic Pathology” evaluates potentially toxic chemical exposures and chemically mediated illnesses in humans and experimental animals. Comparative studies of chemical exposures between model organisms and humans are essential for the risk assessment of chemicals and human health. Here we review the development and activities of the Japanese Society of Toxicologic Pathology (JSTP) during its 37-year history. Toxicological pathology studies provide many interesting and valuable findings. Rodent cancer bioassay data demonstrate the importance of dose levels, times, and duration of exposures to chemicals that possibly cause human cancers. Studies of toxic injuries in the nasal cavity demonstrate that specific chemical compounds affect different target cells and tissues. These observations are relevant for current air pollution studies in the preventive medicine field. Future toxicological pathology studies will be enhanced by applying molecular pathology with advanced observation techniques. In addition to the nasal cavity, another sense organ such as the tongue should be a potential next program of our mission for risk assessment of inhaled and ingested chemicals. As a message to the younger members of the JSTP, interdisciplinary and global cooperation should be emphasized. Elucidating the mechanisms of toxicologic pathology with a combination of advanced expertise in genetics and molecular biology offers promise for future advances by JSTP members.     

代谢组学在奶牛营养与牛奶质量安全方面的研究进展

代谢组学是检测低分子质量(通常分子质量小于1 000u)代谢物的变化,并以此来研究生物体受到病理/生理刺激或基因改变后所产生代谢产物的构成及其变化规律的学科。它是后基因时代发展起来的一门新的学科,是系统生物学的重要组成部分。代谢组学已经广泛应用于生理学、病理学、药理学、动物营养学、动物学和植物学等各个领域,但代谢组学在奶牛营养与牛奶质量安全研究中的应用还比较少。本文从代谢组学的基本概念、研究思路和方法等入手,综述了目前代谢组学在奶牛营养、疾病、热应激、牛奶质量与奶品安全中的应用。     

Molecular pathology in the cancer clinic – where are we now and where are we headed?

Molecular pathology is a developing sub-microscopic discipline of pathology that studies the effects of molecular variations and mutations on disease processes. The ultimate goal of molecular pathology in cancer is to predict risk, facilitate diagnosis and improve prognostication based on a complete understanding of the biological impact of specific molecular variations, mutations and dysregulations. This knowledge will provide the basis for customised cancer treatment, so-called precision medicine. Rapid developments in genomics have placed this field at the forefront of clinical molecular pathology and there are already a number of well-established genetic tests available for clinical use including PCR of antigen receptor rearrangement and KIT mutational analysis. Moving beyond tests assessing a single gene, there are significant research efforts utilising genomics to predict cancer risk, forecast aggressive behaviour and identify druggable mutations and therapeutic biomarkers. Researchers are also investigating the use of circulating cells and nucleic acid for clinically useful low morbidity genomic assessments. If we are to realise the full potential of molecular pathology and precision medicine there are a number of challenges to overcome. These include developing our understanding of the underlying biology (in particular intra-tumoural heterogeneity), methodological standardisation of assays, provision of adequate infrastructure and production of novel therapeutics backed by high-quality clinical data supporting the precision medicine approach. The era of molecular pathology holds the potential to revolutionise veterinary cancer care, but its impact on clinical practice will depend upon the extent to which the inherent challenges can be overcome.     

动物体内微生物的宏基因组学分析

随着分子生物学技术的快速发展及其在微生物研究中的广泛应用,宏基因组学分析方法得到了快速发展。宏基因组学通过直接从动物体内的微生物中提取总DNA,构建宏基因组文库,利用基因组学的研究方法研究样品所包含的全部微生物的遗传组成及其群落功能。作者综述了一些研究基因组组成和动物体内细菌物种的数据库和试验技术,以及肠道微生物的宏基因组学分析。     

猪重大育种价值基因及挖掘技术研究进展

随着分子生物学和动物遗传育种技术的快速发展,对于畜禽优良性状的研究已从对表型选育进入到对单个或多个重要性状关联基因的分子选育,如对猪肉质性状的相关研究,在影响猪背膘厚、肌内脂肪含量、火腿重量等方面筛选到许多关键基因。近年来,非洲猪瘟肆虐,对猪抗病的研究再次成为热点,也发现了众多关键基因,如CD163直接参与了猪呼吸与繁殖综合征病毒的侵入机制。除了疾病的影响外,繁殖性状对养猪业的发展也起着至关重要的作用。随着研究人员对各重要性状研究的不断深入,现已积累了大量重要育种价值基因的多维数据,且由此开发出了多种基因筛选技术,尤其是CRISPR-Cas9基因编辑技术的发现及其作为全基因组筛选工具的成功应用,以及在后基因组时代功能基因组筛选与多组学的联合应用等,进一步推动了遗传育种领域的发展。作者系统总结了猪肉质、抗病及繁殖性状相关的重要育种价值基因及其挖掘技术,以期为猪的遗传改良提供指导性建议和参考。     

代谢组学分析技术在动物营养学研究中的应用进展

代谢组学是系统生物学的重要分支,因其可通过研究生物过程的终端代谢产物来考察生物过程的整体变化及代谢轮廓特征而使其成为现代科学研究的热点,代谢组学在医学、药理学、病理学、毒理学、食品科学、营养学等领域均有较多研究和应用,但其在动物营养与饲料科学领域的研究和应用还较为欠缺。本文就代谢组学分析技术及其在动物营养学中的应用研究进行综述。     

Update on molecular techniques for diagnostic testing of infectious disease.

The era of diagnostic molecular biology has arrived for small animal clinicians, and it is a near certainty that assays such as the PCR and RT-PCR will become more widely available for a wider array of infectious agents. Already there is an extensive list of infectious diseases of dogs and cats that have been investigated with molecular tools. A partial list is included in box 1. An understanding of the advantages and disadvantages of the molecular techniques and some of the questions these techniques can answer for clinicians can serve practitioners well in their approach to the diagnosis of infectious diseases in dogs and cats. It is likely that additional applications of these tools to small animal medicine will become apparent as investigators use and refine them for their research purposes, or as new uses emerge from human medical applications. Clinicians also are likely to reap the benefits of this knowledge. Because samples often are acquired easily from clinical patients in most practice settings, access to these tools puts all clinicians in the group of discoverers of new, or variations of, infectious diseases and their clinical manifestations.     

Alpharma Beef Cattle Nutrition Symposium: nutrition and the genome

It has long been appreciated that animals fed the same diet may perform differently. This is due to the ability of nutrients to interact with and affect molecular pathways that result in differences in BW gain, production performance, or disease resistance. To understand these effects, studies are being undertaken to discover how the differential expression and function of genes occur with different diets. These studies are using new technologies, genomic resources, and analysis techniques that have recently become available for domestic animals. Nutrigenomics and nutrigenetics are new research approaches that strive to optimize health by looking beyond the diet to understand the effects of food at the genetic and epigenetic levels. Nutrigenomics is focused on the effects of diet on health through an understanding of how bioactive chemicals in foods and supplements alter gene expression or the structure of the genome of an animal. Nutrigenetics focuses on how the genetic composition (i.e., genetic variation) of an animal influences their response to a given diet. Results from these studies will aid in formulating nutritionally appropriate diets that may be optimized for animals based on their genomic underpinnings. Nutrigenomics and nutrigenetics unite many fields: nutrition, bioinformatics, molecular biology, genomics, functional genomics, epidemiology, and epigenomics. The use of multi-disciplinary tools promises new opportunities to investigate the complex interactions of the genome and the diet of an animal. Through these new approaches, the partnerships of the genome and nutrition will be revealed resulting in improved efficiency of diets, enhanced sustainability of animals as a protein source, and improved methods for preventing illnesses.     

动物转录因子相关数据库研究进展

转录因子是真核生物中调控基因转录的一类重要的反式作用因子。目前,对动物群体的转录因子已经开展了较为深入的研究,科研人员不仅通过实验证实而且利用生物信息技术预测了全基因组范围内的转录因子,并基于上述数据构建了多个专用的二级数据库。概述了8个应用于动物群体的转录因子数据库,以期为进一步探明转录因子调控动物相关基因转录的分子机制提供理论基础。     

ASAS centennial paper: Future needs in animal breeding and genetics

The past century has seen animal breeding and genetics evolve and expand from definition and validation of basic population genetics theory to development of selection index theory to today's relatively sophisticated genetic prediction systems enabling industry genetic improvement. The end of the first century of the American Society of Animal Science coincides with the rapid movement of the field into the era of genome-enabled genetic improvement and precision management systems. Led by recent research infrastructure investments by the United States and international partners to develop chicken, bovine, swine, ovine, and equine "genomic toolboxes," the animal breeding community is poised to play a crucial role in the century to come. These genomic toolboxes provide the needed platforms for developing whole-genome selection programs based on linkage disequilibrium for a wide spectrum of traits; allow the opportunity to redefine genetic prediction based on allele sharing as opposed to traditional pedigree relationships; and provide for the first time simultaneous information upon which to practice genetic selection and plan precision management of specific genotypes, all early in the life of the animal. An area of major focus will be mining of the genomes through systems biology approaches to better understand gene and metabolic networks--what has previously been lumped into poorly understood genotype by environment and genotype by genotype interactions. Perhaps the greatest obstacle to the successful merger of genomic and quantitative approaches will be the lack of necessary animal resource populations to appropriately define and measure phenotypes (i.e., the so-called phenomic gap) for difficult-to-measure traits such as resistance to disease and stress, adaptability, longevity, and efficiency of nutrient utilization. Additionally, because of de-emphasis of quantitative genetics and animal breeding programs in academia over the past quarter century, a dearth of qualified young scientists to effectively mine the genomes must immediately be addressed. Although the motivating factors may have changed, the need for high-quality animal breeding and genetics research and education has never been greater.     

The potential of organoids in toxicologic pathology: role of toxicologic pathologists in in vitro chemical hepatotoxicity assessment

The development of in vitro toxicity assessment methods using cultured cells has gained popularity for promoting animal welfare in animal experiments. Herein, we briefly discuss the current status of hepatoxicity assessment using human- and rat-derived hepatocytes; we focus on the liver organoid method, which has been extensively studied in recent years, and discuss how toxicologic pathologists can use their knowledge and experience to contribute to the development of in vitro chemical hepatotoxicity assessment methods for drugs, pesticides, and chemicals. We also propose how toxicological pathologists should assess toxicity regarding the putative distribution of undifferentiated and differentiated cells in the organoid when liver organoids are observed in hematoxylin and eosin–stained specimens. This was done while considering the usefulness and limitations of in vitro studies for toxicologic pathology assessment.     

Molecular tools for the characterisation of antibiotic-resistant bacteria.

This review will discuss a number of molecular tools which are currently used as well as some innovative approaches for the characterisation of antibiotic-resistant bacterial strains. Various methods involved in the detection and characterisation of genes and mutations associated with antibiotic resistance and that are used for strain typing as part of epidemiological studies, are described. Furthermore, a few examples are discussed in which the results of both gene and strain characterisation are combined to investigate the underlying mechanism of the spread of antibiotic resistance. Some of the available molecular techniques are heavily supported by the existence of databases on the Internet. These databases either contain a fast growing amount of sequence information or a large number of allelic or fingerprint profiles. The current progress in applied DNA technology and the ongoing projects on the elucidation of the whole genomic sequence of bacterial species have lead and will further lead to the development and application of sophisticated new strategies for the analysis of antibiotic resistant bacterial strains.     

The place of the post-mortem room in the training of the small animal veterinarian

The post-mortem room can be an important focal point in the training of the small animal veterinarian. Repetitive necropsy demonstrations are necessary to provide a firm foundation of gross pathology for the clinician. More importantly, collaborative post-mortem demonstration/discussions involving clinicians, pathologist and laboratory diagnosticians are necessary to develop understanding of clinico-pathological correlation and this has an important function in developing clinical diagnostic skills and confidence.     

功能基因组学研究进展

2 1世纪是生物时代和信息时代 ,基因组学的研究已从结构基因组学转向功能基因组学 ,对于基因功能的研究也由单一基因转向大规模、批量分析。文章对功能基因组学及相关学科的概念作了概述 ,介绍了功能基因组学的研究内容与研究方法 ,主要包括应用差异显示反转录 PCR、基因表达序列分析 (SAGE)、微点阵、蛋白质组学和生物信息学等研究基因组表达概况、基因组多样性和模式生物学等。     

Diagnostic sampling and establishing a minimum database in exotic animal toxicology.

A toxicologic diagnosis is based on knowledge of the circumstances surrounding a particular case, knowledge of the clinical symptomatology, receipt and evaluation of proper specimens by a qualified laboratory, and judicious interpretation of the laboratory results. Failure to have all necessary ingredients can result in a wrong or missed diagnosis. Many veterinary toxicology laboratories can detect suspected toxicants in feed, tissue, and environmental samples at extremely low concentrations. The ability to detect toxicants at such low levels has often outpaced the ability of the diagnostician to interpret the analytic findings. This article provides guidelines for acquiring a good history, collecting appropriate samples for analysis, and selecting a veterinary analytic laboratory to maximize the probability of making a correct toxicologic diagnosis.     

Brucella proteomes--a review

The proteomes of selected Brucella spp. have been extensively analyzed by utilizing current proteomic technology involving 2-DE and MALDI-MS. In Brucella melitensis, more than 500 proteins were identified. The rapid and large-scale identification of proteins in this organism was accomplished by using the annotated B. melitensis genome which is now available in the GenBank. Coupled with new and powerful tools for data analysis, differentially expressed proteins were identified and categorized into several classes. A global overview of protein expression patterns emerged, thereby facilitating the simultaneous analysis of different metabolic pathways in B. melitensis. Such a global characterization would not have been possible by using time consuming and traditional biochemical approaches. The era of post-genomic technology offers new and exciting opportunities to understand the complete biology of different Brucella species.     

分子生物学技术在反刍动物营养中的应用

本文对利用分子生物学技术改造或生产动物性营养物质；在分子水平上研究营养与基因表达、调控的关系，以从根本上阐明营养对机体的作用机制；利用基因工程技术开发饲料资源等三个方面进行了综述。最后探讨了分子生物学在动物营养中的存在问题及应用前景。     

Swine as models in biomedical research and toxicology testing

Swine are considered to be one of the major animal species used in translational research, surgical models, and procedural training and are increasingly being used as an alternative to the dog or monkey as the choice of nonrodent species in preclinical toxicologic testing of pharmaceuticals. There are unique advantages to the use of swine in this setting given that they share with humans similar anatomic and physiologic characteristics involving the cardiovascular, urinary, integumentary, and digestive systems. However, the investigator needs to be familiar with important anatomic, histopathologic, and clinicopathologic features of the laboratory pig and minipig in order to put background lesions or xenobiotically induced toxicologic changes in their proper perspective and also needs to consider specific anatomic differences when using the pig as a surgical model. Ethical considerations, as well as the existence of significant amounts of background data, from a regulatory perspective, provide further support for the use of this species in experimental or pharmaceutical research studies. It is likely that pigs and minipigs will become an increasingly important animal model for research and pharmaceutical development applications.