Complement activation by both classical and alternative pathways is critical for the effector phase of arthritis

To analyze the role of the classical and alternative pathways of complement activation in the effector phase of arthritis, we have induced arthritis in C3- and factor B (FB)-deficient (C3(-/-) and FB(-/-)) DBA/1J mice using well-defined monoclonal IgG2b and IgG2a antibodies to type II collagen. In control DBA/1J mice, severe swelling of the joints, destruction of cartilage and erosion of bone developed very rapidly with a 100% incidence and a peak on days 7-10. Although 75% of C3(-/-) mice developed arthritis, the clinical severity was very mild and the onset was delayed. Severity of arthritis in FB(-/-) mice ranked intermediate in comparison with C3(-/-) and control mice with an incidence of 100%. Immunohistochemical analysis of the inflamed joints demonstrated substantial reduction in macrophage and neutrophilic leukocyte infiltration in both C3(-/-) and FB(-/-) mice, thereby confirming the clinical findings. We conclude that both the classical and the alternative pathways of complement activation are involved in the effector phase of arthritis.     

Human defensive behaviors to threat scenarios show parallels to fear- and anxiety-related defense patterns of non-human mammals

Defense patterns of rats and mice have been characterized in terms of the relationships between the type of defensive behavior (e.g. flight, freezing, hiding, defensive threat/attack, and risk assessment) and particular features of the eliciting (threat) stimulus and the situation in which it is encountered. Because the defense systems of rodents serve as major models for investigating and understanding both the physiology and the behavioral expression of emotional response to aversive stimuli, it is essential to evaluate whether these systems show strong parallels in human responsivity to threat.

One hundred and sixty male and female undergraduate students read a set of 12 scenarios involving a present or potential threatening conspecific, and chose a primary defensive response to each. These scenarios were designed to vary features known to influence defensive responding in rodents: magnitude of threat; escapability of the situation; ambiguity of the threat stimulus; distance between the threat and the subject; presence of a hiding place. Male and female responses to the various scenarios were highly correlated, except for yell, scream, or call for help which was frequent for females, rare for males. However, a combination of this response category with ‘attack’ showed a highly positive (+0.96) male–female correlation, across scenarios.

Correlations between manipulated (and rated) features of the threat stimulus and situation, and type of defensive behavior chosen, strongly supported a view that the patterning of defensive behavior is similar for humans and non-human mammals. Significant correlations were obtained relevant to eight specific hypotheses derived from the animal literature, with some support for two additional hypotheses (non-significant correlations averaging 0.4 or more in expected direction). While three predicted correlations were not supported in these findings, only a single significant correlation was obtained that had not been predicted on the basis of the animal literature. Although the scenario approach, and this application, have specific limitations, these results provide substantial suggestion of congruence between human and non-human mammal defense systems.     

城市残存鼠的分布特点及防制措施的研究

对上海市大规模灭鼠达标巩固一年后的连片居民住宅区、不同地带的宾馆、现代化建筑物和一些行业中的所谓残存鼠,从分布、行为特点和防制措施等方面作了广泛调查和研究分析。观察到:①目前上海地区住宅内主要残存鼠是小家鼠,厨房是残存鼠的主要活动和觅食场所;②残存鼠的分布和种类数量组成与环境关系密切;③防灭残存鼠应根据鼠改变着的习性,采取有针对性的措施。同时强调指出,灭鼠除害是一项系统工程,全社会都应重视、配合。     

流行性出血热疫区鼠类监测分析

目的：了解、掌握流行性出血热疫区鼠类的密度构成与种群分布；方法：夹日法，村内、村外同时布夹，每次布夹不应少于2昼夜；结果：村内密度为20．16％，村外密度为10．21％，村内鼠种较村外丰富，黑线姬鼠为优秀种，褐冢鼠、小家鼠、大仓鼠为常见种；结论：防制流行性出血热发生的最佳灭鼠时机应在每年的3月和10月进行。     

An overview of maternal separation effects on behavioural outcomes in mice: Evidence from a four-stage methodological systematic review

Early life stress (ELS) developmental effects have been widely studied by preclinical researchers. Despite the growing body of evidence from ELS models, such as the maternal separation paradigm, the reported results have marked inconsistencies. The maternal separation model has several methodological pitfalls that could influence the reliability of its results. Here, we critically review 94 mice studies that addressed the effects of maternal separation on behavioural outcomes. We also discuss methodological issues related to the heterogeneity of separation protocols and the quality of reporting methods. Our findings indicate a lack of consistency in maternal separation effects: major studies of behavioural and biological phenotypes failed to find significant deleterious effects. Furthermore, we identified several specific variations in separation methodological procedures. These methodological variations could contribute to the inconsistency of maternal separation effects by producing different degrees of stress exposure in maternal separation-reared pups. These methodological problems, together with insufficient reporting, might lead to inaccurate and unreliable effect estimates in maternal separation studies.     

Genotoxic evaluation of pirfenidone using erythrocyte rodent micronucleus assay

Pirfenidone is a non-steroidal antifibrotic compound that has been proposed in clinical protocols and experimental studies as a pharmacological treatment for fibroproliferative diseases. The objective of this study was to determine the genotoxicity or cytotoxicity of three doses of pirfenidone using the micronuclei test in peripheral blood erythrocytes of rodent models. Pirfenidone was administered orally to Balb-C mice for 3 days, and also was administered topically to hairless Sprague Dawley rats during the final stage of gestation. Mice were sampled every 24 h over the course of 6 days; pregnant rats were sampled every 24 h during the last 6 days of gestation, and pups were sampled at birth. Blood smears were analyzed and the frequencies of micronucleated erythrocytes (MNEs), micronucleated polychromatic erythrocytes (MNPCEs), and the proportion of polychromatic erythrocytes (PCEs), were recorded in samples from mice, pregnant rats and rat neonates. Increases in MN frequencies (p < 0.03) were noted only in the positive control groups. No genotoxic effects or decreased PCE values were observed neither in newborn rats transplacentally exposed to pirfenidone, or in two adult rodent models when pirfenidone was administered orally or topically.     

An expanded clade of rodent Trim5 genes

Trim5α from primates (including humans), cows, and rabbits has been shown to be an active antiviral host gene that acts against a range of retroviruses. Although this suggests that Trim5α may be a common antiviral restriction factor among mammals, the status of Trim5 genes in rodents has been unclear. Using genomic and phylogenetic analyses, we describe an expanded paralogous cluster of at least eight Trim5-like genes in mice (including the previously described Trim12 and Trim30 genes), and three Trim5-like genes in rats. Our characterization of the rodent Trim5 locus, and comparison to the Trim5 locus in humans, cows, and rabbits, indicates that Trim5 has undergone independent evolutionary expansions within species. Evolutionary analysis shows that rodent Trim5 genes have evolved under positive selection, suggesting evolutionary conflicts consistent with important antiviral function. Sampling six rodent Trim5 genes failed to reveal antiviral activities against a set of eight retroviral challenges, although we predict that such activities exist.     

Mucosal immunotherapy for protection from pneumonic infection with Francisella tularensis

Previous studies have demonstrated that systemically administered immunotherapy can protect mice from systemic challenge with the bacterial pathogen Francisella tularensis. However, for protection from inhalational challenge with this bacterium, we wondered if mucosally administered immunotherapy might be more effective. Therefore, we administered cationic liposome–DNA complexes (CLDC), which are potent activators of innate immunity, intranasally (i.n.) and assessed the effectiveness of protection from lethal inhalational challenge with F. tularensis. We found that pretreatment by i.n. administration of CLDC 24 h prior to bacterial challenge elicited nearly complete protection of BALB/c mice from lethal challenge with F. tularensis LVS strain. We also observed that mucosal CLDC immunotherapy provided a statistically significant increase in survival time in mice challenged with the highly virulent F. tularensis Schu4 strain. Protection was associated with a significant reduction in bacterial burden in the lungs, liver, and spleen. Mucosal administration of CLDC elicited significantly increased expression of IL-12, IFN-γ, TNF-α, IFN-β and IFN-α genes in the lung as detected by real-time quantitative PCR. In vitro treatment of F. tularensis infected macrophages with CLDC-elicited cytokines also significantly suppressed intracellular replication of F. tularensis in infected macrophages. In vivo, depletion of NK cells prior to administration of CLDC completely abolished the protective effects of CLDC immunotherapy. CLDC-elicited protection was also dependent on induction of IFN-γ production in vivo. We conclude therefore that activation of local pulmonary innate immune responses is capable of eliciting significant protection from inhalational exposure to a virulent bacterial pathogen.