Laboratory Infection of Novel Akhmeta Virus in CAST/EiJ Mice

Akhmeta virus is a zoonotic Orthopoxvirus first identified in 2013 in the country of Georgia. Subsequent ecological investigations in Georgia have found evidence that this virus is widespread in its geographic distribution within the country and in its host-range, with rodents likely involved in its circulation in the wild. Yet, little is known about the pathogenicity of this virus in rodents. We conducted the first laboratory infection of Akhmeta virus in CAST/EiJ Mus musculus to further characterize this novel virus. We found a dose-dependent effect on mortality and weight loss (p < 0.05). Anti-orthopoxvirus antibodies were detected in the second- and third-highest dose groups (5 × 10⁴ pfu and 3 × 10² pfu) at euthanasia by day 10, and day 14 post-infection, respectively. Anti-orthopoxvirus antibodies were not detected in the highest dose group (3 × 10⁶ pfu), which were euthanized at day 7 post-infection and had high viral load in tissues, suggesting they succumbed to disease prior to mounting an effective immune response. In order of highest burden, viable virus was detected in the nostril, lung, tail, liver and spleen. All individuals tested in the highest dose groups were DNAemic. Akhmeta virus was highly pathogenic in CAST/EiJ Mus musculus, causing 100% mortality when ≥3 × 10² pfu was administered.     

蜡皮整粒毒饵对小家鼠和褐家鼠杀灭效果研究

目的观察蜡皮整粒毒饵对小家鼠与褐家鼠的杀灭效果。方法选择济南市历城区张马村,放0．05％敌鼠钠蜡皮玉米粒毒饵、蜡皮小麦粒毒饵与对照毒饵。结果蜡皮玉米粒、蜡皮小麦粒毒饵对小家鼠的灭效分别为99．47％、100．00％,二者比较差异无统计学意义（u=1．84,P〉0．05）,对褐家鼠分别为92．44％、96．59％。二者比较差异具有统计学意义（u=8．14,P〈0．01）。蜡皮玉米粒毒饵、对照普通玉米粒毒饵对褐家鼠的灭效分别为92．44％、92．74％,二者比较差异无统计学意义（u=0．42,P〉0．01）,对小家鼠分别为99．47％、98．34％,二者比较差异具有统计学意义（u=4．57,P〈0．01）。蜡皮小麦粒毒饵与对照普通小麦粒毒饵对褐家鼠的灭效分别为96．59％、100．00％,二者比较差异具有统计学意义（u=7．69,P〈0．01）;对小家鼠分别为100．00％、98．58％,二者比较差异具有统计学意义（u=3．84,P〈0．01）。结论蜡皮整粒毒饵对小家鼠与褐家鼠的杀灭效果很好,证明其接受性良好。     

Crystal structure of the Mus81-Eme1 complex

The Mus81-Eme1 complex is a structure-specific endonuclease that plays an important role in rescuing stalled replication forks and resolving the meiotic recombination intermediates in eukaryotes. We have determined the crystal structure of the Mus81-Eme1 complex. Both Mus81 and Eme1 consist of a central nuclease domain, two repeats of the helix-hairpin-helix (HhH) motif at their C-terminal region, and a linker helix. While each domain structure resembles archaeal XPF homologs, the overall structure is significantly different from those due to the structure of a linker helix. We show that a flexible intradomain linker that formed with 36 residues in the nuclease domain of Eme1 is essential for the recognition of DNA. We identified several basic residues lining the outer surface of the active site cleft of Mus81 that are involved in the interaction with a flexible arm of a nicked Holliday junction (HJ). These interactions might contribute to the optimal positioning of the opposite junction across the nick into the catalytic site, which provided the basis for the "nick and counternick" mechanism of Mus81-Eme1 and for the nicked HJ to be the favored in vitro substrate of this enzyme.     

Dissecting innate immunity by germline mutagenesis

The innate arm of our immune system is the first line of defence against infections. In addition, it is believed to drive adaptive immune responses, which help fight pathogens and provide long-term memory. As such, the innate immune system is instrumental for protection against pathogens that would otherwise destroy their host. Although our understanding of the innate immune components involved in pathogen sensing and fighting is improving, it is still limited. This is particularly exemplified by increased documentation of innate immune deficiencies in humans that often result in high and recurrent susceptibility to infections or even death, without the genetic cause being evident. To provide further insight into the mechanisms by which pathogen sensing and eradication occur, several strategies can be used. The current review focuses on the forward genetic approaches that have been used to dissect innate immunity in the fruit fly and the mouse. For both animal models, forward genetics has been instrumental in the deciphering of innate immunity and has greatly improved our understanding of how we respond to invading pathogens.     

城市特殊环境与居民环境鼠类生态比较研究

本文首次对城市特殊环境与居民环境鼠类生态作了比较研究。结果发现,物种构成、鼠类群落多样性和均匀度因地区、环境不同而异,但褐家鼠(Rattus norvegicus)、小家鼠(Mus musculus)是共同的优势种。鼠密度总体水平在两种环境的差异亦因地区不同而异,如吉林省和内蒙包头市的特殊环境鼠密度显著低于居民环境(P<0.001),湖北省则相反(P<0.001);吉林省特殊环境与居民环境鼠密度基本呈同步起伏,湖北省两者很不相同。不同鼠种在不同地区、环境的密度水平及时间变动曲线也不一致。吉林省特殊环境与居民环境的褐家鼠密度水平相近,基本呈同步起伏;湖北省特殊环境显著高于居民环境,二者时间变动曲线很不相同。吉林省居民环境小家鼠密度显著高于特殊环境(P<0.001),二者基本呈同步起伏;湖北省恰恰相反。两省特殊环境的褐家鼠、小家鼠密度变异性均比居民环境大。褐家鼠、小家鼠性比在不同地区各异,总体上雌性比越高则鼠密度水平越高,小家鼠雌性比与密度总体上呈显著正相关(r=0.563,P<0.05),而褐家鼠无显著相关性。本文还报道了包头市特殊环境鼠类分类调查等结果。特殊环境建筑面积与居民环境比为1∶13;居民环境鼠类分布特点:凉房鼠密度为住房的11倍。