The absence of one class of virus-induced protein in arginine-deprived cells infected with pig herpesvirus.

C57BL/6 mice responded to immunization with purified gp71 of Friend murine leukemia virus by mounting both humoral and cell-mediated responses. As measured by a number of tests, the responses were generally stronger than those obtained in BALB/c mice. However, in contrast to the BALB/c mice, immunization of C57BL/6 mice with gp71 did not result in the development of cytotoxic lymphocytes, although spleen lymphocytes were capable of undergoing blastogenesis when incubated with purified gp71. As in the BALB/c mice, the humoral response was type-specific.A unique feature of the response in gp71-immunized C57BL/6 mice was the accelerated activation of the endogenous virus as measured by the development of an immune response to its distinct envelope antigens. This resulted in the production of three distinguishable antibody populations: (1) type-specific antibodies to FLV gp71; (2) type-specific antibodies reacting with AKR gp71 (AKR virus being related to the endogenous virus of C57BL/6 mice); and (3) antibodies directed against p15 (E) which reacted both with AKR and Friend-Moloney-Rauscher viruses and are therefore considered group-specific in the murine system. The possible significance of the activation of the endogenous virus subsequent to gp71 immunization of C57BL/6 mice is discussed.     

SPF级BALB/c裸小鼠的生产管理与质量控制

SPF级裸小鼠的饲养及质量控制涉及多方面的环节和工作。生产管理及质量控制效果,直接影响动物的数量和质量。我中心2007年开始,逐步建立了规范的SPF级BALB/c裸小鼠生产繁育体系。裸小鼠生产繁育至今,数量和质量得到较好的保证。本文通过介绍我中心SPF级BALB/c裸小鼠的设施、种群、饲养管理及质量控制的具体做法和经验体会,为SPF级BALB/c裸小鼠相关繁育和研究提供参考和借鉴。     

Towards a universal vaccine for avian influenza: Protective efficacy of modified Vaccinia virus Ankara and Adenovirus vaccines expressing conserved influenza antigens in chickens challenged with low pathogenic avian influenza virus

Current vaccines targeting surface proteins can drive antigenic variation resulting either in the emergence of more highly pathogenic viruses or of antigenically distinct viruses that escape control by vaccination and thereby persist in the host population. Influenza vaccines typically target the highly mutable surface proteins and do not provide protection against heterologous challenge. Vaccines which induce immune responses against conserved influenza epitopes may confer protection against heterologous challenge. We report here the results of vaccination with recombinant modified Vaccinia virus Ankara (MVA) and Adenovirus (Ad) expressing a fusion construct of nucleoprotein and matrix protein (NP + M1). Prime and boost vaccination regimes were trialled in different ages of chicken and were found to be safe and immunogenic. Interferon-γ (IFN-γ) ELISpot was used to assess the cellular immune response post secondary vaccination. In ovo Ad prime followed by a 4 week post hatch MVA boost was identified as the most immunogenic regime in one outbred and two inbred lines of chicken. Following vaccination, one inbred line (C15I) was challenged with low pathogenic avian influenza (LPAI) H7N7 (A/Turkey/England/1977). Birds receiving a primary vaccination with Ad-NP + M1 and a secondary vaccination with MVA-NP + M1 exhibited reduced cloacal shedding as measured by plaque assay at 7 days post infection compared with birds vaccinated with recombinant viruses containing irrelevant antigen. This preliminary indication of efficacy demonstrates proof of concept in birds; induction of T cell responses in chickens by viral vectors containing internal influenza antigens may be a productive strategy for the development of vaccines to induce heterologous protection against influenza in poultry.     

饲料灭菌不当引起的实验大鼠脱毛病例观察研究

目的探讨SPF级实验用大鼠脱毛病例的病因，为其科学饲养管理提供依据。方法试验选择在屏障系统人工饲养过程中40只脱毛SD大鼠，分为5组，进行真菌、寄生虫检测以及营养方面的病因分析和治疗试验。结果经皮肤真菌和体表寄生虫检测结果为阴性，排除以上病因；通过调整饲料灭菌方法及氨基酸、微量元素和维生素的强化治疗，结果为氨基酸、微量元素和维生素强化治疗各组被毛生长得到显著改善。结论该批实验用SD大鼠脱毛病因为饲料经脉动真空蒸汽灭菌后氨基酸、微量元素和维生素成分破坏严重。     

Assessment and control of exposures to polymeric methylene diphenyl diisocyanate (pMDI) in spray polyurethane foam applicators

In this work we characterize personal inhalation and dermal exposures to diphenyl methane diisocyanate (MDI) and other species in polymeric MDI (pMDI) formulations during spray polyurethane foam (SPF) insulation at 14 sites in New England. We further assess the adequacy of current workplace practices and exposure controls via comparative urinary biomonitoring of the corresponding methylene diphenyl diamine (MDA) pre- and post-shift. MDI and pMDI are potent dermal and respiratory sensitizers and asthmagens, strong irritants of the skin, eyes, and the respiratory tract, and may cause skin burns. This study is the first comprehensive report to-date on the work practices, inhalation and dermal exposures to isocyanates and effectiveness of existing controls during SPF applications.Breathing zone exposures to 4,4′ MDI (n = 31; 24 sprayers, 7 helpers) ranged from 0.9 to 123.0 μg/m3 and had a geometric mean (GM) of 13.8 μg/m3 and geometric standard deviation (GSD) of 4.8. Stationary near field area samples (n = 15) were higher than personal exposures: GM, 40.9 (GSD, 3.9) μg/m3, range 1.4–240.8 μg/m3. Sixteen percent of personal air samples and 35% of area samples exceeded the National Institute for Occupational Health and Safety's (NIOSH) full shift recommended exposure limit (REL) of 50 μg/m3, assuming zero exposure for the unsampled time. 4,4′ MDI load on the glove dosimeters had a GM of 11.4 (GSD 2.9) μg/glove pair/min, suggesting high potential for dermal exposures. Urinary MDA had a GM of 0.7 (GSD, 3.0) μmol MDA/mol creatinine (range, nd-14.5 μmol MDA/mol creatinine). Twenty-five % of urine samples exceeded the Health and Safety Executive (HSE) biological monitoring guidance value (BMGV) of 1 μmol MDA/mol creatinine. We further report on field observations regarding current exposure controls, discuss implications of these findings and opportunities for improving work practices to prevent isocyanate exposures during SPF insulation.     

Expressing cytotoxic compounds in Escherichia coli Nissle 1917 for tumor-targeting therapy

Abnormal blood vessels and hypoxic and necrotic regions are common features of solid tumors and related to the malignant phenotype and therapy resistance. Certain obligate or facultative anaerobic bacteria exhibit inherent ability to colonize and proliferate within solid tumors in vivo. Escherichia coli Nissle 1917 (EcN), a non-pathogenic probiotic in European markets, has been known to proliferate selectively in the interface between the viable and necrotic regions of solid tumors. The objective of this study was to establish a tumor-targeting therapy system using the genetically engineered EcN for targeted delivery of cytotoxic compounds, including colibactin, glidobactin and luminmide. Biosynthetic gene clusters of these cytotoxic compounds were introduced into EcN and the corresponding compounds were detected in the resultant recombinant EcN strains. The recombinant EcN showed significant cytotoxic activity in vitro and in vivo as well, and significantly suppressed the tumor growth. Together, this study confirmed efficient tumor-targeting colonization of EcN and demonstrated its potentiality in the tumor-specific delivery of cytotoxic compounds as a new tumor-targeting therapy system.     

Genetic dissection of dietary restriction in mice supports the metabolic efficiency model of life extension

Dietary restriction (DR) has been used for decades to retard aging in rodents, but its mechanism of action remains an enigma. A principal roadblock has been that DR affects many different processes, making it difficult to distinguish cause and effect. To address this problem, we applied a quantitative genetics approach utilizing the ILSXISS series of mouse recombinant inbred strains. Across 42 strains, mean female lifespan ranged from 380 to 1070 days on DR (fed 60% of ad libitum [AL]) and from 490 to 1020 days on an AL diet. Longevity under DR and AL is under genetic control, showing 34% and 36% heritability, respectively. There was no correlation between lifespans on DR and AL; thus different genes modulate longevity under the two regimens. DR lifespans are significantly correlated with female fertility after return to an AL diet after various periods of DR (R = 0.44, P = 0.006). We assessed fuel efficiency (FE, ability to maintain growth and body weight independent of absolute food intake) using a multivariate approach and found it to be correlated with longevity and female fertility, suggesting possible causality. We found several quantitative trait loci responsible for these traits, mapping to chromosomes 7, 9, and 15. We present a metabolic model in which the anti-aging effects of DR are consistent with the ability to efficiently utilize dietary resources.