RESUMO
BACKGROUND: In the spring of 2020 during the first wave of the pandemic an above-average number of residents and staff in nursing homes fell ill and accounted for the highest number of incidences. Due to the pandemic, managers in nursing homes had to make new decisions on a daily basis as well as interpret and integrate decisions made by higher level authorities. AIM OF THE STUDY: The aim was to describe the decisions that had to be made by the managers of nursing homes in dealing with the COVID-19 pandemic and related consequences. MATERIAL AND METHODS: A qualitative multicentre cross-sectional design was chosen. Data collection was conducted with semi-structured telephone interviews. The recorded audio data were transcribed, analyzed using the framework analysis method and reflected in peer debriefings. RESULTS: A total of 78 interviews were conducted in 43 nursing homes and 3 main themes with 10 subthemes emerged: decisions about social participation, decisions on quarantine and isolation and staff adjustments. DISCUSSION: Clearer information and directives for the implementation of measures are needed, e.g. through standardized guidelines nationwide. Additionally, public health departments should play a stronger and more responsible role in a pandemic situation. The consequences of their decisions were hardly foreseeable for the managers and were marked by uncertainty. Responsibilities for and consequences of pandemic-related decisions should be further evaluated to empower managers in times of crises.
Assuntos
COVID-19 , Pandemias , COVID-19/epidemiologia , Estudos Transversais , Humanos , Assistência de Longa Duração , SARS-CoV-2RESUMO
1. Ascarids (Ascaridia galli and Heterakis spp.) are highly prevalent in free-range laying hens. Ascarid eggs survive for long periods in soil, and one preventive measure is to add litter material to areas close to the henhouse. In this study, recovery rates of ascarid eggs from three common litter materials, namely pea gravel, beech (Fagus sylvatica) and spruce (Picea abies) wood chips were compared to recovery rates from soil. 2. Materials were mixed with faeces containing 1,408 ascarid eggs per g of faeces, placed in plastic fruit boxes and exposed to natural weather conditions in a randomised block design with six replicates per treatment. 3. Numbers of ascarid eggs were quantified at 28 time points over 3.5 years. Ascarid eggs were recovered for over three years from all materials and completely disappeared during the fourth winter of exposure. Time needed to get to a 50% reduction in ascarid eggs did not differ between litter materials and soil (242 to 269 days). A 99% reduction was reached significantly (P < 0.001) earlier in pea gravel (548 days) than in the three other materials, and earlier in the two wood chips (day 682 for beech, day 692 for spruce, P < 0.05) than in soil (1,277 days). 4. Accumulation of ascarid eggs in the area close to the henhouse can be reduced by any of the tested litter materials compared to bare soil. Adding litter to this area is highly recommended for free-range layer farmers in order to reduce numbers of infective ascarid eggs.
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Galinhas , Doenças das Aves Domésticas , Animais , Feminino , Óvulo , Solo , MadeiraRESUMO
Objectives: To identify correlates of self-rated and proxy-rated quality of life (QoL) in people with dementia on (i) a dementia-specific and (ii) a capability-wellbeing QoL measure at baseline and 12-month follow-up, and to consider such factors in the context of QoL intervention development.Method: Prospective clinical and demographic data were collected from 451 community-dwelling dyads (mild-moderate dementia) across eight European countries. QoL was measured using the QOL-AD and the ICECAP-O. Multivariate modelling identified correlates of self- and proxy-rated QoL at baseline and at 12-month follow-up.Results: Carer's proxy-ratings of QoL were significantly lower than self-ratings at all time-points for both measures. Proxy-ratings declined over time, but self-ratings remained stable. Baseline predictors of greater self-rated QoL were education, and greater functional ability and relationship quality. Greater proxy-rated QoL was associated with education and greater functional ability, relationship quality, carer social support and carer QoL, lower carer anxiety/depression and less severe neuropsychiatric symptoms in people with dementia. At follow-up, greater self-rated QoL was predicted by greater functional ability, relationship quality, carer social support and having a spousal carer. Greater proxy-rated QoL at follow-up was associated with the same factors as at baseline; however, the dyad living together was an additional predictive factor.Conclusion: Both proxy-ratings and self-ratings of QoL should be interpreted with caution and in the context of each individual caregiving relationship. Different functional, psychosocial, relational and contextual factors influence self- and proxy-ratings, and both sets of factors should be considered in the context of QoL intervention development for the dyad.
Assuntos
Cuidadores/psicologia , Demência/psicologia , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Europa (Continente) , Feminino , Humanos , Vida Independente , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Procurador , Inquéritos e QuestionáriosRESUMO
BACKGROUND: People with dementia and their informal carers often do not receive appropriate professional support or it is not received at the right time. OBJECTIVES: Description and comparison of common pathways to formal community dementia care in eight European countries as a part of the transnational Actifcare project. MATERIALS AND METHODS: The German team was responsible for creating an individual case scenario as a starting point. The research teams in Ireland, Italy, the Netherlands, Norway, Portugal, Sweden, and the United Kingdom were then asked to describe a common pathway to formal dementia care by writing their own vignette using the provided individual case scenario. RESULTS: A transnational qualitative content analysis was used to identify the following categories as being the most important: involved professionals, dementia-specific and team-based approaches, proactive roles, and financial aspects. General practitioners (GPs) are described as being the most important profession supporting the access to formal care in all the involved countries. In some countries other professionals take over responsibility for the access procedure. Dementia-specific approaches are rarely part of standard care; team-based approaches have differing significances in each of the countries. Informal carers are mainly proactive in seeking formal care. The Nordic countries demonstrate how financial support enhances access to the professional system. CONCLUSION: Enhanced cooperation between GPs and other professions might optimize access to formal dementia care. Team-based approaches focusing on dementia care should be developed further. Informal carers should be supported and relieved in their role. Financial barriers remain which should be further investigated and reduced.
Assuntos
Cuidadores/psicologia , Demência/terapia , Acessibilidade aos Serviços de Saúde , Adulto , Idoso , Idoso de 80 Anos ou mais , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação das Necessidades , Qualidade de VidaRESUMO
In this study, direct genomic values for the functional traits general temperament, milking temperament, aggressiveness, rank order in herd, milking speed, udder depth, position of labia, and days to first heat in Brown Swiss dairy cattle were estimated based on ~777,000 (777 K) single nucleotide polymorphism (SNP) information from 1,126 animals. Accuracy of direct genomic values was assessed by a 5-fold cross-validation with 10 replicates. Correlations between deregressed proofs and direct genomic values were 0.63 for general temperament, 0.73 for milking temperament, 0.69 for aggressiveness, 0.65 for rank order in herd, 0.69 for milking speed, 0.71 for udder depth, 0.66 for position of labia, and 0.74 for days to first heat. Using the information of ~54,000 (54K) SNP led to only marginal deviations in the observed accuracy. Trying to predict the 20% youngest bulls led to correlations of 0.55, 0.77, 0.73, 0.55, 0.64, 0.59, 0.67, and 0.77, respectively, for the traits listed above. Using a novel method to estimate the accuracy of a direct genomic value (defined as correlation between direct genomic value and true breeding value and accounting for the correlation between direct genomic values and conventional breeding values) revealed accuracies of 0.37, 0.20, 0.19, 0.27, 0.48, 0.45, 0.36, and 0.12, respectively, for the traits listed above. These values are much smaller but probably also more realistic than accuracies based on correlations, given the heritabilities and samples sizes in this study. Annotation of the largest estimated SNP effects revealed 2 candidate genes affecting the traits general temperament and days to first heat.
Assuntos
Bovinos/fisiologia , Indústria de Laticínios , Estudo de Associação Genômica Ampla/veterinária , Genoma , Polimorfismo de Nucleotídeo Único , Animais , Cruzamento , Bovinos/genética , Feminino , Masculino , Reprodutibilidade dos Testes , TemperamentoRESUMO
The aim of this study was to estimate genetic parameters and accuracies of breeding values for milk content traits of individual udder quarters in Brown Swiss cattle. Data of 1,799 phenotyped cows from 40 Swiss dairy herds were analyzed, taking the complete pedigree into account. Fat, protein, lactose, and urea contents, somatic cell score (SCS), and information about hyperkeratosis were available for each udder quarter. The milk of rear udder quarters was found to have significantly higher lactose content and significantly lower fat content than milk of the front udder quarters. The same trend found for fat content was observed for protein content, whereas no differences between the udder quarters were observed for urea content, SCS, or hyperkeratosis. Heritabilities for each udder quarter were in the following ranges: fat content 0.09±0.06 to 0.14±0.06, protein content 0.20±0.09 to 0.33±0.07, lactose content 0.04±0.03 to 0.16±0.07, urea content 0.13±0.07 to 0.22±0.08, SCS 0.18±0.06 to 0.32±0.07, and hyperkeratosis 0.12±0.04 to 0.26±0.05. In our study, hyperkeratosis, protein content, and SCS showed higher heritabilities in the front udder quarters, fat content had higher heritabilities in the rear udder quarters, and no systematic pattern in heritability was observed for lactose content or urea content. Additive genetic correlations between all udder quarters were >0.90 for protein and urea contents, whereas they were remarkably low (<0.60) for SCS. For fat and lactose contents, the genetic correlations between the 2 front or between the 2 rear quarters, respectively, were notably higher than correlations between 1 front and 1 rear quarter, suggesting that the front and the rear udders could be considered as partly genetically different organs. The variability within the udder as such was found to be of low heritability (<0.10) in general, but repeatability was moderate to high for some traits (lactose content: 0.33±0.05, protein content: 0.53±0.05). Some of these findings can be explained by differences in the physiological background of the traits.
Assuntos
Bovinos/genética , Glândulas Mamárias Animais/anatomia & histologia , Característica Quantitativa Herdável , Animais , Bovinos/anatomia & histologia , Contagem de Células/veterinária , Gorduras/análise , Feminino , Lactação/genética , Lactose/análise , Leite/química , Leite/citologia , Proteínas do Leite/análise , Fenótipo , Ureia/análiseRESUMO
The aim of this study was to estimate genetic parameters and accuracies of breeding values for a set of functional, behavior, and conformation traits in Brown Swiss cattle. These traits were milking speed, udder depth, position of labia, rank order in herd, general temperament, aggressiveness, milking temperament, and days to first heat. Data of 1,799 phenotyped Brown Swiss cows from 40 Swiss dairy herds were analyzed taking the complete pedigree into account. Estimated heritabilities were within the ranges reported in literature, with results at the high end of the reported values for some traits (e.g., milking speed: 0.42±0.06, udder depth: 0.42±0.06), whereas other traits were of low heritability and heritability estimates were of low accuracy (e.g., milking temperament: 0.04±0.04, days to first heat: 0.02±0.04). For most behavior traits, we found relatively high heritabilities (general temperament: 0.38±0.07, aggressiveness: 0.12±0.08, and rank order in herd: 0.16±0.06). Position of labia, arguably an indicator trait for pathological urovagina, was genetically analyzed in this study for the first time, and a moderate heritability (0.28±0.06) was estimated.
Assuntos
Bovinos/genética , Característica Quantitativa Herdável , Animais , Bovinos/anatomia & histologia , Feminino , Lactação/genética , Glândulas Mamárias Animais/anatomia & histologia , Gravidez/genética , Fatores de TempoRESUMO
Data from breeder hens and chicks are particularly critical for the development of vitamin B2 recommendations for organic poultry. To test safe thresholds of supplementation, 100 breeder hens (Hubbard JA 57â¯K) and ten cockerels were allocated to ten housing groups, with each receiving supplementation of either 4.0 (treatment CON) or 2.5â¯mg (treatment RED) riboflavin per kg feed. After 15â¯weeks of experimental feeding, 256 eggs were incubated. From the hatched chicks (Hubbard S757), 192 were allocated to four treatments based on their parents' treatment (CON- or RED-) and on their own supplementation of either 4.0 (-CON) or 2.5â¯mg (-RED) riboflavin per kg feed. Two groups of each combination (CON-CON, CON-RED, RED-CON, RED-RED), each with 24 chicks of both sexes, were fattened for nine weeks and slaughtered. Analysis of total riboflavin (sum of native concentrations and supplements) in the parent's feeds revealed an average, over the 15â¯weeks, of 7.8 and 5.8â¯mg per kg feed for CON and RED, respectively. Body weight, plumage integrity, gait appearance, footpad, claw and keel bone integrity, lesion scores, laying performance, and egg mass were found to be of similarly high levels for all hens without any treatment effects. Performance traits of the hens in both treatments reached the specifications of the producer for this genotype. Yolk and albumen riboflavin concentrations were not affected although yolk colour in the RED treatment group became darker. Fertility was not affected, and hatchability was 100 per cent. Total riboflavin concentrations in the broiler diets were on average, over 9 weeks, 8.2 and 6.1 mg/kg for CON and RED, respectively. In chicks, RED treatment of their parents led to significant depressions of feed intake and growth. The RED treatment of the chicks themselves also impaired growth. Growth rates of the CON-CON treatment were in line with the specifications of the producer for this genotype. Plumage scores, footpad integrity and walking appearance of the broilers, and dressing percentage of the carcasses were not affected by treatment. The RED treatment of chicks caused lower spleen and heart weights, while pancreas and liver weights, and liver riboflavin concentrations were not affected. In conclusion, supplementation of 4.0â¯mg/kg to organic diets did not evoke any health or performance problems for breeder hens or broiler chicks, while a supplementation level of 2.5â¯mg per kg feed led to reduced weight gains, although without any other riboflavin deficiency symptoms.
Assuntos
Ração Animal , Galinhas , Ração Animal/análise , Animais , Dieta/veterinária , Suplementos Nutricionais , Feminino , Fertilidade , Masculino , RiboflavinaRESUMO
Although it is still most common to rear dairy calves separately from adult cattle, the interest in prolonged contact between dairy calves and lactating cows during early life is increasing. Previous research has documented positive effects of cow-calf contact (CCC) on for example early calf growth and udder health of suckled cows, but also negative effects such as increased separation distress and reduced weight gains after weaning. The aim of this study was to use information from European farms with prolonged cow-calf contact to identify innovative solutions to common challenges for CCC farms. Commercial dairy farms that kept calves with adult lactating cows for seven days or more after birth were invited to participate, and interviews were performed with 104 farmers from six countries. During interviews, information about farm management, calf rearing, farmers' perception of animal health on their farm, and farmers' drivers and barriers for implementing CCC were collected. We found that CCC was practised in a large variety of housing and management systems, and that calves could be reared together with their dam, with foster cows, or using a combination of the two. The contact period varied considerably (7-305 days) between farms and about 25% of the farms manually milk fed the calves during parts of the milk feeding period. Daily contact time varied between farms, from 30 minutes per day to permanent contact except at milking. Behaviours indicative of separation distress, most commonly vocalisation in cows and calves, were reported by 87% of the farmers. Strategies to alleviate separation distress, for example simultaneous gradual weaning and separation, were used on some farms. Building constraints were most often mentioned as a barrier for implementing CCC. Our findings suggest that CCC is practised in a variety of commonly used husbandry systems. Reported challenges were primarily related to weaning and separation, and to building constraints; these aspects should be areas of future research.
Assuntos
Indústria de Laticínios , Lactação , Animais , Bovinos , Estudos Transversais , Fazendas , Feminino , Leite , DesmameRESUMO
Although the use of local breeds is recommended by organic regulations, breed comparisons performed under organic production conditions with similar production intensities are scarce. Therefore, we compared data of local and widely used Holstein dairy cattle breeds from 2011 to 2015 regarding production, fertility and health from German and Swedish organic farms with similar management intensities within country. In Germany, the energy-corrected total milk yield tended to be lower in the local breed Original Angler Cattle (AAZ, 5193 kg) compared to the modern German Holstein Friesian breed (HO, 5620 kg), but AAZ showed higher milk fat and protein contents (AAZ v. HO: 5.09% v. 4.18% and 3.61% v. 3.31%, respectively). In Sweden, the widely used modern Swedish Holstein (SH) breed had the highest milk yield (9209 kg, fat: 4.10%, protein: 3.31%), while the local Swedish Polled (SKB) showed highest milk fat and protein contents (6169 kg, 4.47%, 3.50%, respectively), followed by the local breed Swedish Red (SRB, 8283 kg, 4.33%, 3.46%, respectively). With regard to fertility characteristics, the German breeds showed no differences, but AAZ tended to have less days open compared to HO (-17 days). In Sweden, breeds did not differ with regard to calving interval, but both local breeds showed a lower number of days open (-10.4 in SRB and -24.1 in SKB compared to SH), and SKB needed fewer inseminations until conception (-0.5 inseminations) compared to SH. Proportion of test day records with a somatic cell count content of ≥100 000 cells per ml milk did not reveal breed differences in any of the two countries. German breeds did not differ regarding the proportion of cows with veterinary treatments. In Sweden, SRB showed the lowest proportion of cows with general veterinary treatment as well as specific treatment due to udder problems (22.8 ± 6.42 and 8.05 ± 2.18, respectively), but the local breed SKB did not differ from SH in either of the two traits. In Sweden, we found no breed differences regarding veterinary treatments due to fertility problems or diagnosis of claw or leg problems during claw trimming. Our results indicate a stronger expression of the antagonism between production and functional traits with increasing production intensity. Future breed comparisons, therefore, need to consider different production intensities within organic farming in order to derive practical recommendations as to how to implement European organic regulations with regard to a suitable choice of breeds.
Assuntos
Cruzamento , Lactação , Animais , Bovinos/genética , Feminino , Alemanha , Leite , SuéciaRESUMO
Myelin repair (remyelination) following the demyelination of central nervous system (CNS) axons in diseases such as multiple sclerosis plays a critical role in determining the level of accompanying neurologic disability. While remyelination can be quite robust, in multiple sclerosis it often fails. Understanding and stimulating the remyelination process are therefore important goals in MS research. Remyelination is a complex cellular process that involves an intimate interplay between the myelin-producing cells of the CNS (oligodendrocytes), the axons to be myelinated, as well as CNS-infiltrating immune cells. Genetic analysis can be a powerful tool for the functional analysis of complex cellular processes and has recently been applied to the problem of remyelination failure during disease. This chapter reviews the recent use of genetic approaches for the study of CNS remyelination in mouse models of demyelinating disease.
Assuntos
Doenças do Sistema Nervoso Central/genética , Doenças do Sistema Nervoso Central/patologia , Doenças Desmielinizantes/genética , Doenças Desmielinizantes/patologia , Bainha de Mielina/fisiologia , Regeneração Nervosa/fisiologia , Animais , Infecções por Cardiovirus/genética , Infecções por Cardiovirus/patologia , Infecções por Cardiovirus/fisiopatologia , Doenças do Sistema Nervoso Central/fisiopatologia , Doenças Desmielinizantes/fisiopatologia , Modelos Animais de Doenças , Humanos , Camundongos , Bainha de Mielina/patologia , TheilovirusRESUMO
Fasciclin I is a membrane-associated glycoprotein that is regionally expressed on a subset of fasciculating axons during neuronal development in insects; it is expressed on apposing cell surfaces, suggesting a role in specific cell adhesion. In this paper we show that Drosophila fasciclin I is a novel homophilic cell adhesion molecule. When the nonadhesive Drosophila S2 cells are transfected with the fasciclin I cDNA, they form aggregates that are blocked by antisera against fasciclin I. When cells expressing fasciclin I are mixed with cells expressing fasciclin III, another Drosophila homophilic adhesion molecule, the mixture sorts into aggregates homogeneous for either fasciclin I- or fasciclin III-expressing cells. The ability of these two novel adhesion molecules to mediate cell sorting in vitro suggests that they might play a similar role during neuronal development.
Assuntos
Moléculas de Adesão Celular Neuronais , Moléculas de Adesão Celular Neuronais/fisiologia , Drosophila/crescimento & desenvolvimento , Animais , Anticorpos , Cálcio/fisiologia , Adesão Celular/fisiologia , Moléculas de Adesão Celular Neuronais/biossíntese , Agregação Celular/fisiologia , Células Cultivadas , Drosophila/citologia , Proteínas de Drosophila , TransfecçãoRESUMO
The assignment of specific roles to cell-surface proteins by standard methods can be a major problem. In the technique described below, Schneider-2 (S2) cells, an established Drosophila cell line, have been used in cell transfection and aggregation experiments. As such, they have proved to be a useful tool for the functional characterization of putative cell-adhesion molecules.
Assuntos
Moléculas de Adesão Celular/fisiologia , Animais , Moléculas de Adesão Celular/genética , Linhagem Celular , Clonagem Molecular , DNA/genética , Drosophila melanogasterRESUMO
We report the crystal structure of two adjacent fibronectin type III repeats from the Drosophila neural cell adhesion molecule neuroglian. Each domain consists of two antiparallel beta sheets and is folded topologically identically to single fibronectin type III domains from the extracellular matrix proteins tenascin and fibronectin. beta bulges and left-handed polyproline II helices disrupt the regular beta sheet structure of both neuroglian domains. The hydrophobic interdomain interface includes a metal-binding site, presumably involved in stabilizing the relative orientation between domains and predicted by sequence comparision to be present in the vertebrate homolog molecule L1. The neuroglian domains are related by a near perfect 2-fold screw axis along the longest molecular dimension. Using this relationship, a model for arrays of tandem fibronectin type III repeats in neuroglian and other molecules is proposed.
Assuntos
Drosophila/química , Fibronectinas/química , Neuroglia/química , Sequência de Aminoácidos , Animais , Sequência de Bases , Sítios de Ligação , Moléculas de Adesão Celular Neuronais/química , Cristalização , Cristalografia por Raios X , Endopeptidases/metabolismo , Proteínas da Matriz Extracelular/química , Fibronectinas/genética , Metais/metabolismo , Modelos Moleculares , Dados de Sequência Molecular , Fragmentos de Peptídeos/química , Estrutura Secundária de Proteína , Sequências Repetitivas de Ácido Nucleico , TenascinaRESUMO
We recently described the characterization and cloning of Drosophila neuroglian, a member of the immunoglobulin superfamily. Neuroglian contains six immunoglobulin-like domains and five fibronectin type III domains and shows strong sequence homology to the mouse neural cell adhesion molecule L1. Here we show that the neuroglian gene generates at least two different protein products by tissue-specific alternative splicing. The two protein forms differ in their cytoplasmic domains. The long form is restricted to the surface of neurons in the CNS and neurons and some support cells in the PNS; in contrast, the short form is expressed on a wide range of other cells and tissues. Thus, whereas the mouse L1 gene appears to encode only one protein that functions largely as a neural cell adhesion molecule, its Drosophila homolog, the neuroglian gene, encodes at least two protein forms that may play two different roles, one as a neural cell adhesion molecule and the other as a more general cell adhesion molecule involved in other tissues and imaginal disc morphogenesis.
Assuntos
Moléculas de Adesão Celular Neuronais/genética , DNA Recombinante/genética , Drosophila/genética , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais/imunologia , Sequência de Bases , Moléculas de Adesão Celular Neuronais/imunologia , Moléculas de Adesão Celular Neuronais/metabolismo , Sistema Nervoso Central/citologia , Sistema Nervoso Central/metabolismo , Clonagem Molecular , Citoplasma/metabolismo , DNA Recombinante/metabolismo , Proteínas de Drosophila , Embrião não Mamífero/metabolismo , Epitopos/imunologia , Regulação da Expressão Gênica , Imunoglobulinas/genética , Imunoglobulinas/metabolismo , Imuno-Histoquímica , Larva/metabolismo , Larva/fisiologia , Dados de Sequência Molecular , Neuroglia/citologia , Neuroglia/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Nervos Periféricos/citologia , Nervos Periféricos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transcrição GênicaRESUMO
Autoimmune responses directed against the central nervous system (CNS) have generally been considered pathogenic in nature. Although there are several well understood conditions in which this is the case, there is also a growing body of experimental evidence to show that both the cellular and humoral immune responses can promote tissue repair following CNS injury and disease. Our laboratory has used a mouse model of chronic demyelinating disease to characterize a class of polyreactive IgM autoantibodies that react with oligodendrocyte surface antigens and promote myelin repair. By screening a large number of human monoclonal antibodies, we have found that IgM antibodies that react with CNS tissue are relatively common. Autoreactive IgM antibodies might constitute an endogenous system for tissue repair, and therefore these antibodies could be of value as therapeutic reagents.
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Formação de Anticorpos/fisiologia , Autoimunidade/fisiologia , Doenças do Sistema Nervoso Central/imunologia , Regeneração Nervosa/imunologia , Animais , Humanos , Bainha de Mielina/imunologiaRESUMO
CD44 is a cell surface adhesion molecule and its principal ligand is hyaluronic acid (HA), a key component of the brain's extracellular matrix. CD44 levels are decreased in the cerebrospinal fluid (CSF) of depressed individuals, and the CD44 gene has been identified in genome wide association study as a possible risk gene in suicidal behavior. In order to define the pathobiological mechanisms by which CD44 may affect behavior, we investigated the role of CD44 using male CD44 knockout (CD44KO) and wild-type mice that underwent chronic mild stress (CMS). Behavior was characterized using the sucrose preference and forced swim tests, open field, novel object recognition, social preference, and the elevated plus maze tests. Gene expression in hippocampus was evaluated using quantitative real-time PCR. Brain monoamines and their metabolites were assessed by high-performance liquid chromatography and serum HA and IL-1ß levels were measured using ELISA and electrochemiluminescence assays. CD44KO mice were more susceptible to stress-induced anxiety-like behavior and displayed increased anhedonia and despair than the wild-type controls. The behavioral phenotype of stressed CD44KO mice was associated with reduced cortical serotonergic and striatal dopaminergic turnover. The hippocampal expression of the receptor for HA-mediated motility (RHAMM) was reduced in the non- stressed CD44KO mice compared with WT mice, in a value similar to that observed in WT mice following exposure to stress. Taken together, our experiments suggest that CD44 plays a key role in stress response in mice.
Assuntos
Ansiedade/genética , Receptores de Hialuronatos/genética , Estresse Psicológico/genética , Animais , Ansiedade/etiologia , Ansiedade/metabolismo , Dopamina/metabolismo , Deleção de Genes , Hipocampo/metabolismo , Hipocampo/fisiologia , Ácido Hialurônico/sangue , Interleucina-1beta/sangue , Masculino , Camundongos , Camundongos Endogâmicos DBA , Fenótipo , Serotonina/metabolismo , Estresse Psicológico/complicações , Estresse Psicológico/metabolismoRESUMO
A major lethal protein was isolated from the venom of Mojave rattlesnake (Crotalus scutulatus) by successive purification in DEAE column chromatography and isoelectric focusing. This homogeneous and monomeric form of toxin is designated as "Mojave toxin". Unlike basic neurotoxins or cytotoxins isolated from venoms of cobras, kraits and sea snakes, the Mojave toxin is an acidic protein with an isoelectric point of 4.7. The toxin is also different from crotoxin (from Crotalus durissus terrificus) which consists of both acidic and basic components. The molecular weight determined by Sephadex G-75 column chromatography resulted in a value of about 22 000. A singel protein band with a molecular weight of about 12 000, was observed after sodium dodecyl sulfate gel electrophoresis of the reduced Mojave toxin. Isoelectric focusing gel in the presence of 8 M urea also showed a single protein band, suggesting that the toxin is composed of subunits. Unlike the neurotoxic nature of the basic proteins from the venoms of Elapidae and sea snakes (Hydrophiidae) and crotoxin, Mojave toxin is cardiotoxic rather than neurotoxic. It is very likely that venoms of all rattlesnakes from North and Central America contain Mojave toxin as the common toxin.
Assuntos
Proteínas , Venenos de Serpentes/análise , Toxinas Biológicas , Toxinas Biológicas/isolamento & purificação , Peçonhas/análise , Aminoácidos/análise , Animais , Bioensaio , Pressão Sanguínea/efeitos dos fármacos , Carboidratos/análise , Cromatografia por Troca Iônica , Eletroforese em Gel de Poliacrilamida , Coração/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Focalização Isoelétrica , Camundongos , Proteínas/isolamento & purificação , Respiração/efeitos dos fármacos , Temperatura , Fatores de Tempo , Toxinas Biológicas/farmacologia , Toxinas Biológicas/toxicidadeRESUMO
The 400 MHz 1H-NMR spectrum of myotoxin a from the venom of Crotalus viridis viridis is described. The identification of spin systems in the aromatic region corresponding to the six aromatic residues of myotoxin a was completed using both one- and two-dimensional NMR spectroscopy and the pH dependence of chemical shifts. Assignments of these spin systems to specific residues was possible for the singly occurring amino acids Tyr-1 and Phe-12. Resonances from Tyr-1, His-5 and His-10 were shifted significantly from their random coil values in a pH-dependent manner. These shift perturbations were deemed evidence of a helical arrangement of the amino terminal region which placed these residues in close proximity to each other.