Mink IgG-allotypes and Aleutian disease

IgG polymorphism (allotypes H3, H4, H6 and H8 of constant region of the gamma-chain) was investigated in healthy and affected with Aleutian disease (AD) minks from two Siberian and one Danish populations. In all three populations, the expression of H3 and H4 allotypes was strongly associated with AD. Among the AD minks the frequency of H6, H8 phenotype was found to be decreased, whereas the frequency of H3, H4, H6, H8 phenotype was significantly increased. At the same time, the populational distribution of the rest phenotypes was similar among healthy and AD minks. The H3, H4, H6, H8 minks showed the highest pathomorphological characteristics of AD. Based on the data concerning mink H3 and H4, and human Gm allotypes, their role as possible genetic markers for hereditary susceptibility to distinct disease is discussed.     

Development of a Peptide ELISA for the Diagnosis of Aleutian Mink Disease

Aleutian disease (AD) is a common immunosuppressive disease in mink farms world-wide. Since the 1980s, counterimmunoelectrophoresis (CIEP) has been the main detection method for infection with the Aleutian Mink Disease Virus (AMDV). In this study, six peptides derived from the AMDV structural protein VP2 were designed, synthesized, and used as ELISA antigens to detect anti-AMDV antibodies in the sera of infected minks. Serum samples were collected from 764 minks in farms from five different provinces, and analyzed by both CIEP (a gold standard) and peptide ELISA. A peptide designated P1 (415 aa–433 aa) exhibited good antigenicity. A novel ELISA was developed using ovalbumin-linked peptide P1 to detect anti-AMDV antibodies in mink sera. The sensitivity and specificity of the peptide ELISA was 98.0% and 97.5%, respectively. Moreover, the ELISA also detected 342 early-stage infected samples (negative by CIEP and positive by PCR), of which 43.6% (149/342) were true positives. These results showed that the peptide ELISA had better sensitivity compared with CIEP, and therefore could be preferable over CIEP for detecting anti-AMDV antibodies in serological screening.     

DNA and antibodies to DNA in Aleutian mink disease]

Free DNA and various types of antibodies to DNA were determined in the blood serum and plasma of minks which contracted Aleutian disease (AD) spontaneously and of minks experimentally infected with this disease. Healthy minks and other animals served as controls. It was found that a higher incidence of antibodies to DNA of the 2nd and 3rd types in high titres (1: 80-1: 2560) was characteristic of the experimental group of animals. Besides, a free polymeric DNA was more frequently revealed in the experimental group of animals.     

Activation of the antioxidant system as a factor in increasing the body resistance during combined adaptation

In semi-aquatic mammals (minks and muskrats) significant changes were found to occur in the leukocyte formula during adaptation to hypoxia, as compared with non-adapted rats and mice, although no increase in lipid peroxidation was found in any of their organs. This latter finding seems to be due to simultaneously enhanced activities of superoxide dismutase and catalase. In humans under professional stress, treatment with combined technology of adaptation: cold-and-hypoxic exposure, yields a positive therapeutic result accompanied by a decrease in lipid peroxidation and increase in superoxide dismutase and catalase activities in the blood. The data obtained suggest that the strategy of formation of protection against hypoxia and toxic free radical oxidation is common for the animals and humans.     

Immunoglobulin (IgG) allotypes of the American mink with Aleutian disease

Mink Aleutian disease (AD) is characterized by intensive proliferation of B-lymphocytes and hypergammaglobulinemia. Populational distribution of five genetic immunoglobulin markers (light chain allotype L1 and C gamma-allotypes H2, H3, H6 and H8) in minks of different coat color (Sapphire, Standard and Topaz) was studied. The groups of infected minks differed significantly from healthy ones in the distribution of the H3 allotype: the frequencies of some phenotypes--H3, H6, H8 and L1, H3, H6, H8 (Sapphire, Standard). H2, H3, H6, H8 and L1, H2, H3, H6, H8 (Sapphire) were increased significantly. At the same time, the frequencies of H6, H8; L1, H6, H8 and H2, H6, H8; L1, H2, H6, H8 were decreased in the AD population. The preferential stimulation of proliferation of the H3 + B-lymphocyte clones is suggested.     

Effect of coat color mutations on behavioral polymorphism in farm populations of american minks (Mustela vison Schreber, 1777) and sables (Martes zibellina Linnaeus, 1758)

Behavioral polymorphism estimated by the expression of the defensive reaction towards humans has been studied in farm-bred American minks and sables with different color types. Most animals (both minks and sables) from farm populations displayed passive defensive behavior towards humans in the standard hand catch test. Coat color genes have been found to have pleiotropic effects; they influence both the penetrance and expressivity of domestication behavior: in animals with aberrant color types (both sapphire minks and white-and-black sables), the proportion of animals with domestication behavior and the expressivity of this behavior are significantly higher (p <0.01 and p < 0.001, respectively).     

Effect of coat color mutations on behavioral polymorphism in farm populations of American minks (<Emphasis Type="Italic">Mustela vison</Emphasis> Schreber, 1777) and sables (<Emphasis Type="Italic">Martes zibellina</Emphasis> Linnaeus, 1758)

Behavioral polymorphism estimated by the expression of the defensive reaction towards humans has been studied in farm-bred American minks and sables with different color types. Most animals (both minks and sables) from farm populations displayed passive defensive behavior towards humans in the standard hand catch test. Coat color genes have been found to have pleiotropic effects; they influence both the penetrance and expressivity of domestication behavior: in animals with aberrant color types (both sapphire minks and white-and-black sables), the proportion of animals with domestication behavior and the expressivity of this behavior are significantly higher (p < 0.01 and p < 0.001, respectively).     

水貂自咬症个体分子鉴定引物的开发与应用

<正>自咬症是危害笼养水貂(Mustla vison)的一种慢性疾病,其特征是阵发性神经高度兴奋、反复自咬身体后躯和尾部、对外界刺激敏感。常因外界刺激引起高度兴奋发作,干扰兽群繁殖。若咬伤部     

Review: SARS-CoV-2 infection in farmed minks – an overview of current knowledge on occurrence,disease and epidemiology

Coronaviruses (CoVs), which are enveloped, positive-sense RNA viruses, may cause infections in mammals and birds. Apart from the respiratory manifestations, CoVs are also responsible for infections of the gastrointestinal tract and nervous systems. Their propensity to recombine allows them to easily transmit and adapt to new hosts. The emergence of a new CoV in humans, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is attributed to a zoonotic origin, has provoked numerous studies to assess its pathogenicity for different animal species (pets, farm and wild animals). Available results indicate that numerous animal species are susceptible to infection with SARS-CoV-2. From April 2020, when the first SARS-CoV-2 infection in minks was reported in the Netherlands, to the end of January 2021, further outbreaks have been confirmed in Denmark, Italy, Spain, Sweden, the United States, Greece, France, Canada, Lithuania and Poland. It has also been established that human-to-minks and minks-to-human transmission may occur. The results obtained to date indicate that the virus was originally introduced into the minks population by humans, possibly at the start of the pandemic and had been circulating in the population for several weeks before detection. Recent data indicate that minks are highly susceptible to SARS-CoV-2 infection, but the route or routes of virus transmission between farms, other than by direct contact with infected humans, have not been identified. In minks, infection can occur in clinical and subclinical form, making it possibly difficult to detect. Therefore, minks could represent potentially dangerous, not always recognized, animal reservoir for SARS-CoV-2. The current data indicate that further studies on minks and other Mustelidae are needed to clarify whether they may be a potential reservoir for SARS-CoV-2, and if so, how and whether this can be prevented.     

Generation of antibodies specific for beta-amyloid by vaccination of patients with Alzheimer disease

To characterize antibodies produced in humans in response to Abeta42 vaccination, we carried out immunohistochemical examinations of the brains of both transgenic mice and human patients with beta-amyloid pathology. We collected sera from patients with Alzheimer disease who received a primary injection of pre-aggregated Abeta42 followed by one booster injection in a placebo-controlled study. Antibodies in immune sera recognized beta-amyloid plaques, diffuse Abeta deposits and vascular beta-amyloid in brain blood vessels. The antibodies did not cross-react with native full-length beta-amyloid precursor protein or its physiological derivatives, including soluble Abeta42. These findings indicate that vaccination of AD patients with Abeta42 induces antibodies that have a high degree of selectivity for the pathogenic target structures. Whether vaccination to produce antibodies against beta-amyloid will halt the cognitive decline in AD will depend upon clinical assessments over time.     

Autoantibody-catalyzed hydrolysis of amyloid beta peptide

We describe IgM class human autoantibodies that hydrolyze amyloid beta peptide 1-40 (Abeta40). A monoclonal IgM from a patient with Waldenstr?m's macroglobulinemia hydrolyzed Abeta40 at the Lys-28-Gly-29 bond and Lys-16-Ala-17 bonds. The catalytic activity was inhibited stoichiometrically by an electrophilic serine protease inhibitor. Treatment with the catalytic IgM blocked the aggregation and toxicity of Abeta40 in neuronal cell cultures. IgMs purified from the sera of patients with Alzheimer disease (AD) hydrolyzed Abeta40 at rates superior to IgMs from age-matched humans without dementia. IgMs from non-elderly humans expressed the least catalytic activity. The reaction rate was sufficient to afford appreciable degradation at physiological Abeta and IgM concentrations found in peripheral circulation. Increased Abeta concentrations in the AD brain are thought to induce neurodegenerative effects. Peripheral administration of Abeta binding antibodies has been suggested as a potential treatment of AD. Our results suggest that catalytic IgM autoantibodies can help clear Abeta, and they open the possibility of using catalytic Abs for AD immunotherapy.     

Concentration of monoamines in the brain of minks differing in their reaction to man

Content of dopamine in the striatum; of serotonin, 5-hydroxyindolacetic acid and noradrenaline in the hypothalamus, striatum and midbrain was studied in three groups of minks from population of an animal farm, differing by their reaction to humans (cowardly, calm, aggressive). The reaction to humans was estimated by a system of marks at the attempt to catch the mink with a mitten. Aggressive animals had a lowered level of serotonin in the hypothalamus and striatum, a lesser content of serotonin metabolite--5-hydroxyindolacetic acid in the striatum. Minks of different groups did not differ by noradrenaline content, but dopamine level in the striatum of cowardly minks was higher than in calm and aggressive animals. Conclusion is made that polymorphism of behaviour corresponds to polymorphism of the state of monoaminergic systems.     

Genotype analysis of Malassezia restricta as the major cutaneous flora in patients with atopic dermatitis and healthy subjects

Lipophilic yeasts of the genus Malassezia colonize the skin surface of humans and are an exacerbating factor in atopic dermatitis (AD). Two species, M. restricta and M. globosa are major cutaneous microflora in both AD patients and healthy subjects. We compared the DNA sequences of the intergenic spacer (IGS) region, located between the 26S and 5S rRNA genes of M. restricta colonizing the skin surfaces of 13 AD patients and 12 healthy subjects, and of three CBS stock strains as references. The IGS 1 sequences were divided into two major groups, corresponding to AD patients and healthy subjects. These findings suggest that a specific genotype of M. restricta plays a significant role in AD, although M. restricta commonly colonizes both AD patients and healthy subjects.     

Synthetic peptides define the fine specificity of the human immunodeficiency virus (HIV) gp160 humoral immune response in HIV type 1-infected chimpanzees

The fine specificities of antibodies produced against human immunodeficiency virus type 1 (HIV-1) gp160 were examined in sera from 23 HIV-1-infected chimpanzees. These animals had been infected with one of six isolates of HIV-1. Sera were screened by enzyme-linked immunosorbent assay for reactivity against seven synthetic peptides corresponding to regions of gp160. Chimpanzees appear to remain healthy after infection with HIV-1, suggesting that these animals may prevent extensive spread of the virus in vivo through immunologic mechanisms. Antibody specificity to gp160 epitopes may play a key role in the defense against HIV-1-related disease. Approximately one-half of all chimpanzee sera contained antibodies reactive with peptide 846-860, which corresponds to the carboxyl terminus of gp41. Less than 10% of sera from HIV-1-infected humans that were examined contained antibodies reactive with peptide 846-860, suggesting that this region is not highly immunogenic in humans. Of the human sera containing antibodies reactive with this peptide, all were from individuals classified as Walter Reed stages 1 to 3. No sera from humans with advanced stages of the disease contained antibodies reactive with peptide 846-860. Peptide 600-611, which reportedly reacts with nearly all sera from HIV-infected humans, was reactive with less than one-half of sera from HIV-1-infected chimpanzees. The observed differences in antibody reactivity to gp160 peptides in sera from HIV-1-infected chimpanzees and humans suggest that each may generate antibodies against differing sets of HIV-1 epitopes. These differences may contribute to the lack of disease progression in chimpanzees after infection with HIV-1.     

Preparation of Type 2 Herpes Simplex Virus Complement-Fixing Antigen

Comparable complement-fixing antigens of type 1 and type 2 herpes simplex virus were produced by extraction of infected African green monkey cells with 0.85% NaCl which was buffered at pH 9.0 with 0.05 m glycine-NaOH. The optimal antigen dilutions were higher in titrations against hyperimmune animal sera than in titrations against human sera. Complement-fixing antibody to type 2 herpes antigen was detected in 5 of 17 sera from healthy humans.     

Interplay between aggression,brain monoamines and fur color mutation in the American mink

Domestication of wild animals alters the aggression towards humans, brain monoamines and coat pigmentation. Our aim is the interplay between aggression, brain monoamines and depigmentation. The Hedlund white mutation in the American mink is an extreme case of depigmentation observed in domesticated animals. The aggressive (?2.06 ± 0.03) and tame (+3.5 ± 0.1) populations of wild‐type dark brown color (standard) minks were bred during 17 successive generations for aggressive or tame reaction towards humans, respectively. The Hedlund mutation was transferred to the aggressive and tame backgrounds to generate aggressive (?1.2 ± 0.1) and tame (+3.0 ± 0.2) Hedlund minks. Four groups of 10 males with equal expression of aggressive (?2) or tame (+5) behavior, standard or with the Hedlund mutation, were selected to study biogenic amines in the brain. Decreased levels of noradrenaline in the hypothalamus, but increased concentrations of the serotonin metabolite, 5‐hydroxyindoleacetic acid and dopamine metabolite, homovanillic acid, in the striatum were measured in the tame compared with the aggressive standard minks. The Hedlund mutation increased noradrenaline level in the hypothalamus and substantia nigra, serotonin level in the substantia nigra and striatum and decreased dopamine concentration in the hypothalamus and striatum. Significant interaction effects were found between the Hedlund mutation and aggressive behavior on serotonin metabolism in the substantia nigra (P < 0.001), dopamine level in the midbrain (P < 0.01) and its metabolism in the striatum (P < 0.05). These results provide the first experimental evidence of the interplay between aggression, brain monoamines and the Hedlund mutation in the American minks.     

Docosahexaenoic acid homeostasis,brain aging and Alzheimer's disease: Can we reconcile the evidence?

A crossroads has been reached on research into docosahexaenoic acid (DHA) and Alzheimer's disease (AD). On the one hand, several prospective observational studies now clearly indicate a protective effect of higher fish and DHA intake against risk of AD. On the other hand, once AD is clinically evident, supplementation trials demonstrate essentially no benefit of DHA in AD. Despite apparently low DHA intake in AD, brain DHA levels are frequently the same as in controls, suggesting that low DHA intake results in low plasma DHA but does not necessarily reduce brain DHA in humans. Animal models involving dietary omega-3 fatty acid deficiency to deplete brain DHA may therefore not be appropriate in AD research. Studies in the healthy elderly suggest that DHA homeostasis changes during aging. Tracer methodology now permits estimation of DHA half-life in the human brain and whole body. Apolipoprotein E alleles have an important impact not only on AD but also on DHA homeostasis in humans. We therefore encourage further development of innovative approaches to the study of DHA metabolism and its role in human brain function. A better understanding of DHA metabolism in humans will hopefully help explain how higher habitual DHA intake protects against the risk of deteriorating cognition during aging and may eventually give rise to a breakthrough in the treatment of AD.     

Identification of a Novel Human Polyomavirus in Organs of the Gastrointestinal Tract

Polyomaviruses are small, non-enveloped viruses with a circular double-stranded DNA genome. Using a generic polyomavirus PCR targeting the VP1 major structural protein gene, a novel polyomavirus was initially identified in resected human liver tissue and provisionally named Human Polyomavirus 12 (HPyV12). Its 5033 bp genome is predicted to encode large and small T antigens and the 3 structural proteins VP1, VP2 and VP3. Phylogenetic analyses did not reveal a close relationship to any known human or animal polyomavirus. Investigation of organs, body fluids and excretions of diseased individuals and healthy subjects with both HPyV12-specific nested PCR and quantitative real-time PCR revealed additional virus-positive samples of resected liver, cecum and rectum tissues and a positive fecal sample. A capsomer-based IgG ELISA was established using the major capsid protein VP1 of HPyV12. Seroprevalences of 23% and 17%, respectively, were determined in sera from healthy adults and adolescents and a pediatric group of children. These data indicate that the virus naturally infects humans and that primary infection may already occur in childhood.     

Diagnosis of Alzheimer's disease based on disease-specific autoantibody profiles in human sera

After decades of Alzheimer's disease (AD) research, the development of a definitive diagnostic test for this disease has remained elusive. The discovery of blood-borne biomarkers yielding an accurate and relatively non-invasive test has been a primary goal. Using human protein microarrays to characterize the differential expression of serum autoantibodies in AD and non-demented control (NDC) groups, we identified potential diagnostic biomarkers for AD. The differential significance of each biomarker was evaluated, resulting in the selection of only 10 autoantibody biomarkers that can effectively differentiate AD sera from NDC sera with a sensitivity of 96.0% and specificity of 92.5%. AD sera were also distinguishable from sera obtained from patients with Parkinson's disease and breast cancer with accuracies of 86% and 92%, respectively. Results demonstrate that serum autoantibodies can be used effectively as highly-specific and accurate biomarkers to diagnose AD throughout the course of the disease.     

Neuronal protection by sirtuins in Alzheimer's disease

Silent information regulator 2, a member of NAD+-dependent histone deacetylase in yeast, and its homologs in mice and humans, participate in numerous important cell functions, including cell protection and cell cycle regulation. The sirtuin family members are highly conserved evolutionarily, and are predicted to have a role in cell survival. The science of sirtuins is an emerging field and is expected to contribute significantly to the role of sirtuins in healthy aging in humans. The role of sirtuins in neuronal protection has been studied in lower organisms, such as yeast, worms, flies and rodents. Both yeast Sir2 and mammalian sirtuin proteins are up-regulated under calorie-restricted and resveratrol treatments. Increased sirtuin expression protects cells from various insults. Caloric restriction and antioxidant treatments have shown useful effects in mouse models of aging and Alzheimer's disease (AD) and in limited human AD clinical trials. The role sirtuins may play in modifying and protecting neurons in patients with neurodegenerative diseases is still unknown. However, a recent report of Huntington's disease revealed that Sirtuin protects neurons in a Huntington's disease mouse model, suggesting that sirtuins may protect neurons in patients with neurodegenerative diseases, such as AD. In this review, we discuss the possible mechanisms of sirtuins involved in neuronal protection and the potential therapeutic value of sirtuins in healthy aging and AD.