Large animal models for Huntington's disease research

Huntington'sdisease(HD)isahereditary neurodegenerative disorder for which there is currently no effectivetreatmentavailable.Consequently,the development of appropriate disease models is critical to thoroughly investigate disease progression.The genetic basis of HD involves the abnormal expansion of CAG repeats in the huntingtin(HTT)gene,leading to the expansion of a polyglutamine repeat in the HTT protein.Mutant HTT carrying the expanded polyglutamine repeat undergoes misfolding and forms aggregates in the brain,which precipitate selective neuronal loss in specific brain regions.Animal models play an important role in elucidating the pathogenesis of neurodegenerative disorders such as HD and in identifying potential therapeutic targets.Due to the marked species differences between rodents and larger animals,substantial efforts have been directed toward establishing large animal models for HD research.These models are pivotal for advancing the discovery of novel therapeutic targets,enhancing effective drug delivery methods,and improving treatment outcomes.We have explored the advantages of utilizing large animal models,particularly pigs,in previous reviews.Since then,however,significant progress has been made in developing more sophisticated animal models that faithfully replicate the typical pathology of HD.In the current review,we provide a comprehensive overview of large animal models of HD,incorporating recent findings regarding the establishment of HD knock-in(KI)pigs and their genetic therapy.We also explore the utilization of large animal models in HD research,with a focus on sheep,non-human primates(NHPs),and pigs.Our objective is to provide valuable insights into the application of these large animal models for the investigation and treatment of neurodegenerative disorders.

Effect of amino acid mutation at position 127 in 3A of a rabbitattenuated foot-and-mouth disease virus serotype Asia1 on viral replication and infection

An amino acid mutation(R127→I) in the 3A non-structural protein of an FMDV serotype Asia1 rabbit-attenuated ZB strain was previously found after attenuation of the virus. To explore the effects of this mutation on viral replication and infection, the amino acid residue isoleucine(I) was changed to arginine(R) in the infectious cDNA clone of the rabbit-attenuated ZB strain by sitedirected mutagenesis, and the R127-mutated virus was rescued. BHK monolayer cells and suckling mice were inoculated with the R127-mutated virus to test its growth property and pathogenicity, respectively. The effects of the R127 mutation on viral replication and virulence were analyzed. The data showed that there was a slight difference in plaque morphology between the R127-mutated and wild-type viruses. The growth rate of the mutated virus was lower in BHK-21 cells and its virulence in suckling mice was also attenuated. This study indicates that the R127 mutation in 3A may play an important role in FMDV replication in vitro and in pathogenicity in suckling mice.

The Complete Genomic Sequence of a Foot-and-Mouth Disease Virus Isolated from the Swine

The complete genomic sequence of foot-and-mouth disease virus (FMDV) Chinese strain OH/CHA/99 was determined. The 8040 nt sequence and the deduced amino acid sequence werecompared with FMDV sequences published. The results showed that OH/CHA/99 shared highersequence homology with OTYTW/97, indicating their close genetic relationship. However,the strain had lower sequence identity with O1/Kaufbeuren/66 strain. Besides, largedeletions in 3A coding region were observed in OH/CHA/99. It was shown that the poly (A)tail of OH/CHA/99 had 56 As at least.

Comparison of Three ELISA Kits for the Differentiation of Foot-and-mouth Disease Virus-infected from Vaccinated Animals

研究被执行验证工具包为 FMDV 的区别在中国开发了的 3 FMDV 3ABC-I-ELISA 感染并且种牛痘的动物。从天真、种牛痘的牛以及从被感染了的牛的 sera 的集合被商业诊断工具包对 FMDV 的 nonstructural 蛋白质(NSP ) 为抗体测试， Ceditest 吗？FMDV-NS (Ceditest？工具包) ， UBI？FMDV NONSTRUCTURAL 蛋白质 ELISA 方向插入(UBI？工具包) 并且一个 FMDV 3ABC-I-ELISA 工具包在 Lanzhou 发展了兽医研究院。三个工具包的测试参数(敏感和特性) 被决定，并且从 FMD 3ABC-I-ELISA 工具包获得的结果与从二个外国工具包获得了那相比。结果显示巧合在 FMDV 3ABC-I-ELISA 和 Ceditest 之间评价吗？工具包 98.05% 是，并且在 FMDV 3ABC-I-ELISA 和 UBI 之间的巧合率？工具包是 94.4% ；两 Ceditest 的敏感？并且 FMDV 3ABC-I-ELISA 工具包是 100% 。然而， UBI 的敏感？工具包仅仅是 81.8% 。与从天真或种牛痘的非感染的动物的 sera，所有测试的特性超过了 90% 。关键词 Foot-and-mouth 疾病病毒(FMDV )- 非结构的蛋白质 3ABC - ELISA CLC 数字 S852.65 基础项目：国家鈥 ? 73 鈥 ? 研究工程(G199901190， 2005CB23201 ) ；国际原子能机构(国际原子能机构)(10697/R2 )

Adverse Effects of Inactivated Foot-and-Mouth Disease Vaccine—Possible Causes Analysis and Countermeasures

Foot-and-mouth disease (FMD) is an infectious and sometimes fatal viral disease that affects cloven-hoofed animals, and Chinese government adopts compulsory immunization measures for FMD. The adverse effects of FMD vaccine to pigs, cattle and goats have been reported increasingly frequent during the spring and autumn seasons when large numbers of farm livestock are vaccinated. The financial losses caused by vaccine adverse effects have been a serious concern for both farmers and primary prevention personnel. There are various causative factors reported to involve into adverse effect of FMD vaccine, including the inappropriate vaccine production, transportation and storage, livestock poor tolerance, and unqualified vaccinating manipulations. Symptomatic treatment and early drug prevention have a certain effect on the adverse effects. To analyze causes and propose countermeasures, in the current study possible reasons during the production and processing procedures of inactivated FMD vaccine were reviewed and corresponding countermeasures were recommended. The review may provide references for better use of vaccine to prevent FMD.

Review of Air Dispersion Modelling Approaches to Assess the Risk of Wind-Borne Spread of Foot-and-Mouth Disease Virus

Foot-and-mouth disease virus (FMDV) is one of the most economically serious veterinary pathogens due to its negative effects on livestock and its highly infectious nature via a variety of transmission paths through oral and inhalation routes. Measures to enhance outbreak management can be designed according to analytical results predicted by mathematical models for wind-borne dispersion, an important path of virus transmission. Accurate atmospheric dispersion models are useful tools for properly determining risk management plans, while inaccurate models may conversely lead to accidental loss in two possible ways. Overly strict measures, e.g., slaughter for too wide an area, can cause severe economic difficulties, including irreversible loss of business operations for a number of farms. On the contrary, inestimable loss potentially caused by lax controls is a persistent threat. In this paper, available modelling procedures for forecasting the spread of FMDV, which have been used since the 1970s, each having its advantages and limitations, are reviewed for the purpose of ensuring suitable application in various conditions of any future emergency cases.

Assessment of immunization procedures for foot-and-mouth disease in large-scale pig farms in China based on actual data and dynamics

Foot-and-mouth disease(FMD)is an acute,highly infectious and pathogenic animal disease.In recent years,with the rapid development of the swine breeding industry in China,pig farms have shown a trend of larger-scale development.Large-scale pig farms employ standardized management,a high level of automation,and a strict_system.However,these farms have a large trading volume,and increased transmission intensity of FMD is noted inside the farm.At present,the main control measure against FMD is pig vaccination.However,a standard for immunization procedures is not available,and currently adopted immunization procedures have not been effectively and systematically evaluated.Taking a typical large-scale pig farm in China as the research subject and considering the breeding pattern,piggery structure,age structure and immunization procedures,an individual-based state probability model is established to evaluate the effectiveness of the immune procedure.Based on numerical simulation,it is concluded that the optimal immunization program involves primary immunization at 40 days of age and secondary immunization at 80 days of age for commercial pigs.Breeding boars and breeding sows are immunized 4 times a year,and reserve pigs are immunized at 169 and 259 days of age.According to the theoretical analysis,the average control reproduction number of individuals under the optimal immunization procedure in the farm is 0.4927.In the absence of immunization,the average is 1.7498,indicating that the epidemic cannot be controlled without immunization procedures.

Effect of Attenuated Highly Pathogenic Pig Reproductive and Respiratory Syndrome(HP-PRRS) TJM-F92 Strain Vaccine on Immune Antibody Levels against Classical Swine Fever(CSF) and Foot-and-Mouth Disease(FMD)

Effects of attenuated highly pathogenic pig reproductive and respiratory syndrome（HP-PRRS）TJM-F92 strain vaccine on immune antibody level against classical swine fever（CSF）and foot-and-mouth disease（FMD）were studied from October 8 to November 12 in 2014,in order to optimize vaccination program of CSF,HP-PRRS and FMD and to provide scientific guidance for animal disease control and prevention work.The results showed that attenuated HP-PRRS（TJMF92 strain）vaccine had no significant effect on immune antibody level of hog cholera lapinized virus（HCLV,ST passage cell vaccine）attenuated vaccine and FMD-O inactivated vaccines（OZK/93 strain）,and single or combined use of three vaccines received good immunization effects.

Sequence Analysis of Attachment Gene of Lumpy Skin Disease and Sheep Poxviruses

In Egypt,protection of cattle against lumpy skin disease (LSD) was carried out using a sheep poxvirus (Kenyan strain) vaccination strategy.In the present study 15 skin nodules from LSD suspected cows and 5 scab samples from sheep pox (SP) suspected sheep were collected.Hyperimmune rabbit sera to Lumpy skin disease virus (LSDV)/Ismailyia88 strain and sheep pox virus (SPV)/ Kenyan vaccinal strain were prepared.The causative agent in the collected samples was identified using immunoflourescence (IF) and immunoperoxidase techniques.Of the 15 skin nodules suspected of LSD,10 showed a positive reaction and 3 out of 5 skin scabs suspected of sheeppox were found to be positive.An antigenic correlation between field skin isolate of LSDV,tissue culture adapted LSDV/Ismailyia88 strain,field skin isolate of SPV and SPV/Kenyan vaccinal strain was studied using prepared hyperimmune sera.Also,nucleotide sequence of the PCR amplified attachment gene fragments of field skin isolate of LSDV,tissue culture adapted LSDV/Ismailyia88 strain,field skin isolate of SPV and SPV /Kenyan vaccinal strain were compared.The results revealed that the four used viruses were antigenically identical.Sequence analysis indicated that field skin LSDV isolate is more related to tissue culture adapted LSDV/Ismailyia88 strain than to vaccinal SPV/ Kenyan strain and the skin isolate of SPV is more closely related to field skin isolate of LSDV than to SPV/Kenyan vaccinal strain.Thus,further study should be applied on the advantage of a LSD vaccine prepared from LSDV in protection of cattle against LSD compared to the commonly used sheep pox vaccine.

Foot-and-Mouth Disease Outbreak at Bageshwori Gaushala,Chitwan,Nepal

Cow being the national animal of Nepal has special place in the society.Religious institutions have since prehistoric time reared and cared for cattle herds and the tradition still continues.The Bageshwori Gaushala(cow shelter),initiated by the Hindu Rastraguru Yogi Narhaharinath in mid-1990s is one of the largest of such nucleus indigenous cattle herds in Nepal.Indigenous cattle conservation strategy of Nepal has recognized the importance of this nucleus herd,kept by grazing in the surrounding forest.Ethnoveterinary approaches of managing the herd health is in practice and vaccination was never done.Occasional outbreak did happen in past but overall the herd never suffered severe impact.In April 2018,an outbreak of foot-and-mouth disease(FMD)occurred at Bageshwori,Gaushala,Devghat,Bharatpur Metropolitan-1,Chitwan district of Nepal.In the bovine herd studied,80(53.33%)out of 150 affected animals presented characteristics FMD symptoms as vesicular lesions,drooling salivation,foot lameness,high fever and weakness.Following prompt supportive treatment,the condition improved.The complete recovery of infected herd was observed after 45 d.Laboratory analysis showed the presence of Aphthovirus serotype O in the clinical sample.The present study attempts to provide fresh insights into the recent FMD outbreak,clinical signs,their effective treatment protocol and preventive measures that must be practiced following FMD outbreak.

Expression,Purification and Activity Detection of Structural Protein VP1 of Foot-and-Mouth Disease Virus Serotype A

The paper was to obtain the VP1 protein of FMDV serotype A with high activity. With recombinant plasmid pMD19A-T-vp1 as the tem- plate, vpl gene fragment amplified by PCR was connected into prokaryotic expression vector pET28a to construct recombinant plasmid pET-A-vpl. The E. coli BL21 （DE3） strain containing recombinant plasmid pET-A-vpl were induced by IPTG. SDS-PAGE showed that VP1 protein was ex- pressed in the form of inclusion body, and its molecular weight was about 29 ku. Based on the optimizing IPTG concentration and expression time, the largest expression of VP1 protein was induced by 0.3 mmol/L IPTG for 6 h at 37 ℃. Western-Blot analysis indicated that the expression of VP1 protein could be specifically recognized by positive serum of FMDV serotype A. ELISA test showed that VP1 inclusion body protein had high activity after purification by washing and renaturation by urea concentration gradient dialysis.

Geographic Information System to Monitor and Forecast the Influence of Foot-and-Mouth Disease of Poultry and Cattle

The paper introduces the origin,technical features,scale,application efficiency of geographic information system(GIS)to monitor the situation and forecast the spread of foot-and-mouth disease of poultry and cattle—a technological product of Vietnam Software Academy for Water.Application of the system will help the producers and managers to quickly capture the situation of raising poultry and cattle,vaccination results in the related territory,flu outbreaks,epidemic foot-and-mouth disease,and the spread of these two dangers as they arise,resulting in appropriate decisions and solutions in order to prevent,minimize the risk effectively.

Molecular and Serological Epidemiology of Foot-and-Mouth Disease Virus in North Region of Cameroon

The serological prevalence of foot and mouth disease virus (FMDV) among the cattle population in the North region of Cameroon was determined using ELISA (Enzyme Linked Immunosorbent Assays) serological tests for structural as well as non-structural proteins. In these cattle, FMDV RNA was identified, amplified, sequenced and the sequences were used to construct a phylogenetic tree. A sedentary cattle population randomly selected from six veterinary centres in the North region was sampled twice, six months apart. High prevalence of FMDV antibody was recorded in the first (402/466 (85.84%)) and second (358/411 (86.90%)) sampling periods. There was no significant difference (P > 0.05) in prevalence of FMDV antibody between the two sampling periods. Goudali and Peulh breeds of cattle and animals of three to five years old were the most infected with FMDV and mostly in the months of May and August. A seroprevalence of 100% (n = 14) of FMDV against serotypes A and O was observed in sera from convalescent animals in the study area. FMDV antigen detection ELISA showed a prevalence of 18/37 (48.65%) for serotypes SAT1 (8.1%), SAT2 (35.1%), A (10.8%) and O (2.7%) among the clinically infected animals. There was no significant difference (P > 0.05) in prevalence of FMDV RNA between the sampling periods. A prevalence of FMDV RNA (17.5% (n = 120) and 16.7% (n = 240)) was observed among the sedentary animals that were sampled four to five months apart. FMDV RNA prevalence of 28/37 (75.6%) among clinically infected animals was also observed, thus confirming all the 12 outbreaks investigated. Sequence analysis of VP1 coding gene of the SAT2 serotype showed that it was homologous to the Libyan isolates (that caused epidemics in northern Africa in 2012) and also clustered with the serotypes isolated from both Nigeria and Sudan in 2007.

Space-Time Analysis of Foot-and-Mouth Disease from 2005 to 2014 among Cattle Populations in Benin:A Retrospective Study

Many cases of foot-and-mouth disease (FMD) are reported every year in Benin. In order to elucidate the epidemiology of this disease, a space-time analysis was carried out in all the 77 municipalities of the country aiming to identify high risk areas as well as risk factors such as season and transhumance on the period of 2005 to 2014. Data were collected retrospectively from the Directory of Animal Production of Benin. The method of Kulldorff was used with the software SaTScanTM for the space-time analysis while a script was designed in the software R to generate new sizes with three different models of transhumance. From 2005 to 2014, 434 foci were recorded. Many outbreaks occurred in August, September and October. This period corresponds to the small rainy season in the South and the rainy season of the North. The municipality of Parakou was regarded as the source FMD outbreaks in Benin because it hosts one of the largest livestock markets in the country and many rivers. It was the municipality at the highest risk. The other municipalities at risk were Nikki, Pèrèrè and Kalaléas well as Karimama (hosting the national parkW), Kouandé and Toucountouna located nearby Pendjari’s national park. This study revealed that the space-time configuration is real and the main factors of persistence and dissemination of FMD virus were national parks, classified forests and the livestock market of Parakou all located in the North. The variation of the number of cattle due to their transhumance from the North to the South did not influence the zones at risk. Therefore, Northern Benin is probably at high risk of FMD.

Diagnostic assays developed for the control of foot-andmouth disease in India

Foot-and-mouth disease(FMD) is a highly contagious and economically devastating disease of livestock, primarily affecting cattle, buffalo and pigs. FMD virus serotypes O, A and Asia1 are prevalent in India and systematic efforts are on to control and eventually eradicate the disease from the country. FMD epidemiology is complex due to factors like co-circulation, extinction, emergence and re-emergence of genotypes/lineages within the three serotypes, animal movement, diverse farm practices and large number of susceptible livestock in the country. Systematic vaccination, prompt diagnosis, strict biosecurity measures, and regular monitoring of vaccinal immunity and surveillance of virus circulation are indispensible features for the effective implementation of the control measures. Availability of suitable companion diagnostic tests is very important in this endeavour. In this review, the diagnostic assays developed and validated in India and their contribution in FMD control programme is presented.

Selection of Highly Susceptible Cell Lines to Foot and Mouth Disease Virus Infection

Different non-established cultures were examined to find those that showed high sensitivity to Foot and Mouth Disease Virus (FMDV). Ovine kidney cultures showed high sensitivity to types A, O and C, and were suitable to detect viral infection in samples of animal, as well as cell culture origin. The level of detection in this system was up to ten times higher than in BHK21 cells, which were commonly used for FMDV isolation and production. Viral production levels in ovine kidney cultures ranged from similar to twice as high as in BHK21. Ovine kidney cultures maintained these characteristics for at least 18 passages, allowing their use as an alternative system for FMDV diagnoses.

新疆阿克苏地区部分养殖场户绵羊体表硬蜱种类鉴定及携带病原检测

为了解新疆阿克苏地区绵羊体表硬蜱种类及携带病原情况,从5个养殖场户的168只绵羊体表采集硬蜱,采用形态学及分子生物学方法进行蜱种鉴定,同时应用PCR方法对硬蜱中携带的泰勒虫、巴贝斯虫、无浆体及立克次体等进行检测并构建遗传进化树。结果显示:共采集硬蜱630只,其中504只为图兰扇头蜱,126只为小亚璃眼蜱,2种硬蜱与GenBank上已发表的哈萨克斯坦序列MN853166、MN853167相似性分别高达98.30%、99.00%;硬蜱的立克次体、泰勒虫、无浆体及巴贝斯虫携带率分别为64.29%(405/630)、29.52%(186/630)、25.71%(162/630)、0(0/630);遗传进化树显示,泰勒虫与伊拉克株(MN712508)同源性最高(99.61%),位于同一分支上,立克次体与我国民丰县虫株(KU645284)同源性达100%,无浆体与西班牙株(HQ014384)同源性最高(99.62%),位于同一分支上。结果说明:图兰扇头蜱为新疆阿克苏地区绵羊体表优势蜱种,存在携带传播立克次体、泰勒虫及无浆体的风险,建议加强硬蜱驱虫及蜱传疫病监测。

牛结节性皮肤病免疫抗体监测的Meta分析

疫苗接种是预防牛结节性皮肤病(lumpy skin disease,LSD)的重要措施,但是疫苗接种后诱导的体液免疫应答水平参差不齐,目前尚缺乏评价疫苗免疫效果的有效手段。本文使用R软件利用Meta分析对已发表的LSD免疫抗体监测结果进行统计,并进行亚组分析,综合评价免疫抗体监测的意义。通过计算机分别检索中国知网、万方数据知识服务平台、维普中文科技期刊数据库、PubMed、Web of science等中英文数据库,检索时限截止至2023年7月,收集LSD免疫抗体监测的相关文献,根据制定的文献纳入与排除标准,共纳入符合筛选条件的文献24篇,涉及羊痘疫苗的文献共有13篇,涉及LSD疫苗的文献共有13篇,其中2篇文献同时涉及羊痘疫苗和LSD疫苗,包含8638例样本,其中阳性样本2782份,结局指标为免疫抗体阳性率。Meta分析结果显示,羊痘疫苗的免疫抗体水平为41%(95%CI:27%~55%),LSD疫苗的免疫抗体水平为73%(95%CI:64%~86%),各文献间的同质性较低,两种疫苗之间无显著性差异(P=0.59>0.05),与羊痘疫苗接种(P=0.12>0.05)和LSD疫苗接种(P=0.077>0.05)相关的文献均提示未存在明显发表偏移;按养殖环境和检测方法分类进行亚组分析,不同养殖环境(P=0.84>0.05)和检测方法(P=0.40>0.05)均无显著性差异,两亚组均非异质性的主要来源。本文结果提示,使用免疫抗体监测方法评价免疫效果存在较大的不确定性,在实际工作中需要综合分析研判。

青海部分地区藏羊高效养殖场主要动物疫病的检测与分析

为了解青海部分地区高效养殖环境下藏羊主要疫病的感染和流行情况,本研究通过双抗体夹心法酶联免疫吸附试验,对青海省7个地区藏羊高效养殖场的277份血清样品分别进行了羊传染性胸膜肺炎、羊蓝舌病、羊传染性脓疱、羊衣原体病和羊包虫病等5种主要动物疫病的ELISA检测。结果显示,在277份血清样本中,5种疫病的阳性率分别为4.7%(13/277)、6.5%(18/277)、2.5%(7/277)、7.6%(21/277)和6.9%(19/277)。其中,都兰县羊传染性胸膜肺炎的阳性率最高,为14.3%(2/14);贵德县羊蓝舌病的阳性率最高,为18.2%(2/11);共和县羊传染性脓疱的阳性率最高,为9.7%(7/72);共和县羊衣原体病的阳性率最高,为19.4%(14/72);都兰县羊包虫病的阳性率最高,为14.3%(2/14)。5种疫病在乐都区和湟源县均未检出。研究结果可为当地藏羊高效养殖场主要动物疫病防控决策、疾病净化及后期无规定动物疫病区建设提供相应的科学依据。

山东省羊产业现状、优势特点与建议

山东省是全国养羊大省,羊存栏量、出栏量及羊肉产量连续多年位列全国前五、农区前二。该文系统分析了山东省羊产业的发展现状,全面总结了山东省羊产业在品种资源、饲草料生产和产业化发展等方面存在的优势特点,指出了山东省羊产业在现有品种利用、规模化生产技术配套、疫病防治和应对市场挑战等方面存在的问题,并对各个问题提出了针对性的对策和建议,以期为羊产业的健康、稳定和可持续发展提供参考。