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1.
J Dairy Sci ; 104(6): 6897-6908, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33685702

RESUMO

The addition of cattle health and immunity traits to genomic selection indices holds promise to increase individual animal longevity and productivity, and decrease economic losses from disease. However, highly variable genomic loci that contain multiple immune-related genes were poorly assembled in the first iterations of the cattle reference genome assembly and underrepresented during the development of most commercial genotyping platforms. As a consequence, there is a paucity of genetic markers within these loci that may track haplotypes related to disease susceptibility. By using hierarchical assembly of bacterial artificial chromosome inserts spanning 3 of these immune-related gene regions, we were able to assemble multiple full-length haplotypes of the major histocompatibility complex, the leukocyte receptor complex, and the natural killer cell complex. Using these new assemblies and the recently released ARS-UCD1.2 reference, we aligned whole-genome shotgun reads from 125 sequenced Holstein bulls to discover candidate variants for genetic marker development. We selected 124 SNPs, using heuristic and statistical models to develop a custom genotyping panel. In a proof-of-principle study, we used this custom panel to genotype 1,797 Holstein cows exposed to bovine tuberculosis (bTB) that were the subject of a previous GWAS study using the Illumina BovineHD array. Although we did not identify any significant association of bTB phenotypes with these new genetic markers, 2 markers exhibited substantial effects on bTB phenotypic prediction. The models and parameters trained in this study serve as a guide for future marker discovery surveys particularly in previously unassembled regions of the cattle genome.


Assuntos
Complexo Antígeno-Anticorpo , Genoma , Animais , Bovinos/genética , Feminino , Estudo de Associação Genômica Ampla/veterinária , Genômica , Genótipo , Masculino , Polimorfismo de Nucleotídeo Único/genética
2.
Br J Dermatol ; 182(3): 729-737, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31168818

RESUMO

BACKGROUND: Recessive forms of congenital ichthyosis encompass a group of rare inherited disorders of keratinization leading to dry, scaly skin. So far, 13 genes have been implicated, but there is a paucity of data on genotype-phenotype correlation in some populations. OBJECTIVES: We compiled an English cohort of 146 individuals with recessive ichthyosis and assessed genotype-phenotype correlation. METHODS: Deep phenotyping was undertaken by history-taking and clinical examination. DNA was screened for mutations using a next-generation sequencing ichthyosis gene panel and Sanger sequencing. RESULTS: Cases were recruited from 13 National Health Service sites in England, with 65% of patients aged < 16 years at enrolment. Pathogenic biallelic mutations were found in 83% of cases, with the candidate gene spread as follows: TGM1 29%, NIPAL4 12%, ABCA12 12%, ALOX12B 9%, ALOXE3 7%, SLC27A4 5%, CERS3 3%, CYP4F22 3%, PNPLA1 2%, SDR9C7 1%. Clinically, a new sign, an anteriorly overfolded ear at birth, was noted in 43% of patients with ALOX12B mutations. The need for intensive care stay (P = 0·004), and hand deformities (P < 0·001), were associated with ABCA12 mutations. Self-improving collodion ichthyosis occurred in 8% of the cases (mostly TGM1 and ALOX12B mutations) but could not be predicted precisely from neonatal phenotype or genotype. CONCLUSIONS: These data refine genotype-phenotype correlation for recessive forms of ichthyosis in England, demonstrating the spectrum of disease features and comorbidities, as well as the gene pathologies therein. Collectively, the data from these patients provide a valuable resource for further clinical assessment, improving clinical care and the possibility of future stratified management. What's already known about this topic? Recessive forms of ichthyosis are rare but often difficult to diagnose. Mutations in 13 genes are known to cause recessive forms of ichthyosis: ABCA12, ALOX12B, ALOXE3, CERS3, CYP4F22, LIPN, NIPAL4, PNPLA1, SDR9C7, SLC27A4, SULT2B1, ST14 and TGM1. Some phenotypic features may associate with certain gene mutations, but paradigms for genotype-phenotype correlation need refining. What does this study add? The genotypic spectrum of recessive ichthyosis in England (based on 146 cases) comprises TGM1 (29%), NIPAL4 (12%), ABCA12 (12%), ALOX12B (9%), ALOXE3 (7%), SLC27A4 (5%), CERS3 (3%), CYP4F22 (3%), PNPLA1 (2%) and SDR9C7 (1%). New or particular phenotypic clues were defined for mutations in ALOX12B, ABCA12, CYP4F22, NIPAL4, SDR9C7 and TGM1, either in neonates or in later life, which allow for greater diagnostic precision. In around 17% of cases, the molecular basis of recessive ichthyosis remains unknown.


Assuntos
Ictiose Lamelar , Ictiose , Transportadores de Cassetes de Ligação de ATP/genética , Adolescente , Criança , Pré-Escolar , Inglaterra/epidemiologia , Proteínas de Transporte de Ácido Graxo , Genes Recessivos , Estudos de Associação Genética , Humanos , Ictiose/genética , Ictiose Lamelar/genética , Lactente , Recém-Nascido , Lipase , Mutação/genética , Oxirredutases
3.
Anim Genet ; 49(2): 103-109, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29368428

RESUMO

Genetic selection of cattle more resistant to bovine tuberculosis (bTB) may offer a complementary control strategy. Hypothesising underlying non-additive genetic variation, we present an approach using genome-wide high density markers to identify genomic loci with dominance effects on bTB resistance and to test previously published regions with heterozygote advantage in bTB. Our data comprised 1151 Holstein-Friesian cows from Northern Ireland, confirmed bTB cases and controls, genotyped with the 700K Illumina BeadChip. Genome-wide markers were tested for associations between heterozygosity and bTB status using marker-based relationships. Results were tested for robustness against genetic structure, and the genotypic frequencies of a significant locus were tested for departures from Hardy-Weinberg equilibrium. Genomic regions identified in our study and in previous publications were tested for dominance effects. Genotypic effects were estimated through ASReml mixed models. A SNP (rs43032684) on chromosome 6 was significant at the chromosome-wide level, explaining 1.7% of the phenotypic variance. In the controls, there were fewer heterozygotes for rs43032684 (P < 0.01) with the genotypic values suggesting that heterozygosity confers a heterozygote disadvantage. The region surrounding rs43032684 had a significant dominance effect (P < 0.01). SNP rs43032684 resides within a pseudogene with a parental gene involved in macrophage response to infection and within a copy-number-variation region previously associated with nematode resistance. No dominance effect was found for the region on chromosome 11, as indicated by a previous candidate region bTB study. These findings require further validation with large-scale data.


Assuntos
Bovinos/genética , Resistência à Doença/genética , Genética Populacional , Tuberculose Bovina/genética , Animais , Bovinos/microbiologia , Indústria de Laticínios , Estudo de Associação Genômica Ampla/veterinária , Genótipo , Heterozigoto , Irlanda , Modelos Genéticos , Polimorfismo de Nucleotídeo Único
4.
BMC Genomics ; 18(1): 477, 2017 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-28646863

RESUMO

BACKGROUND: Susceptibility to Mycobacterium bovis infection in cattle is governed in part by host genetics. However, cattle diagnosed as infected with M. bovis display varying signs of pathology. The variation in host response to infection could represent a continuum since time of exposure or distinct outcomes due to differing pathogen handling. The relationships between host genetics and variation in host response and pathological sequelae following M. bovis infection were explored by genotyping 1966 Holstein-Friesian dairy cows at 538,231 SNPs with three distinct phenotypes. These were: single intradermal cervical comparative tuberculin (SICCT) test positives with visible lesions (VLs), SICCT-positives with undetected visible lesions (NVLs) and matched controls SICCT-negative on multiple occasions. RESULTS: Regional heritability mapping identified three loci associated with the NVL phenotype on chromosomes 17, 22 and 23, distinct to the region on chromosome 13 associated with the VL phenotype. The region on chromosome 23 was at genome-wide significance and candidate genes overlapping the mapped window included members of the bovine leukocyte antigen class IIb region, a complex known for its role in immunity and disease resistance. Chromosome heritability analysis attributed variance to six and thirteen chromosomes for the VL and NVL phenotypes, respectively, and four of these chromosomes were found to explain a proportion of the phenotypic variation for both the VL and NVL phenotype. By grouping the M. bovis outcomes (VLs and NVLs) variance was attributed to nine chromosomes. When contrasting the two M. bovis infection outcomes (VLs vs NVLs) nine chromosomes were found to harbour heritable variation. Regardless of the case phenotype under investigation, chromosome heritability did not exceed 8% indicating that the genetic control of bTB resistance consists of variants of small to moderate effect situated across many chromosomes of the bovine genome. CONCLUSIONS: These findings suggest the host genetics of M. bovis infection outcomes is governed by distinct and overlapping genetic variants. Thus, variation in the pathology of M. bovis infected cattle may be partly genetically determined and indicative of different host responses or pathogen handling. There may be at least three distinct outcomes following M. bovis exposure in dairy cattle: resistance to infection, infection resulting in pathology or no detectable pathology.


Assuntos
Mapeamento Cromossômico , Indústria de Laticínios , Variação Genética , Mycobacterium bovis/fisiologia , Tuberculose Osteoarticular/genética , Animais , Bovinos , Cromossomos de Mamíferos/genética , Feminino , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único
5.
Rev Sci Tech ; 34(3): 673-88, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27044144

RESUMO

The World Organisation for Animal Health (OIE) is the global standard-setting organisation for animal health and these standards are references for the World Trade Organization legal framework. In 2002, noting the relationship between animal health and welfare, the OIE accepted the mandate to develop animal welfare standards. These standards were subsequently adopted by Member Countries and have been included in the TerrestrialAnimal Health Code and the Aquatic Animal Health Code. The implementation of the OIE standards by Member Countries is continually promoted. National OIE Delegates are encouraged to nominate National Focal Points for key topics, including animal welfare. In 2012, the OIE Regional Commission of the Americas adopted a Regional Animal Welfare Strategy (Regional Strategy) to promote a coordinated approach to the implementation of the OIE animal welfare standards by the 29 Member Countries in the region. In February 2015, the OIE Regional Representation for the Americas distributed a questionnaire to determine the level of awareness and implementation of the Regional Strategy. This paper presents the results of the questionnaire. With a few exceptions, veterinary officials and stakeholders are only just becoming aware of the strategy and implementation is at an early stage. To promote the implementation of the Regional Strategy, it will be.necessary to continue building the capacity of the national Veterinary Services, strengthening public-private partnerships, modernising legislation and promoting veterinary involvement in animal welfare. Through the implementation of the Regional Strategy, the OIE will provide support to countries in establishing animal welfare standards, in line with government priorities and consumer concerns.


Assuntos
Bem-Estar do Animal/normas , Política Pública/legislação & jurisprudência , Matadouros/normas , América , Doenças dos Animais/prevenção & controle , Criação de Animais Domésticos/métodos , Criação de Animais Domésticos/normas , Bem-Estar do Animal/legislação & jurisprudência , Animais , Coleta de Dados , Guias como Assunto , Internacionalidade , Legislação Veterinária , Política Pública/tendências , Inquéritos e Questionários , Medicina Veterinária/normas
6.
Heredity (Edinb) ; 112(5): 543-51, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24496092

RESUMO

Tuberculosis (TB) caused by Mycobacterium bovis is a re-emerging disease of livestock that is of major economic importance worldwide, as well as being a zoonotic risk. There is significant heritability for host resistance to bovine TB (bTB) in dairy cattle. To identify resistance loci for bTB, we undertook a genome-wide association study in female Holstein-Friesian cattle with 592 cases and 559 age-matched controls from case herds. Cases and controls were categorised into distinct phenotypes: skin test and lesion positive vs skin test negative on multiple occasions, respectively. These animals were genotyped with the Illumina BovineHD 700K BeadChip. Genome-wide rapid association using linear and logistic mixed models and regression (GRAMMAR), regional heritability mapping (RHM) and haplotype-sharing analysis identified two novel resistance loci that attained chromosome-wise significance, protein tyrosine phosphatase receptor T (PTPRT; P=4.8 × 10(-7)) and myosin IIIB (MYO3B; P=5.4 × 10(-6)). We estimated that 21% of the phenotypic variance in TB resistance could be explained by all of the informative single-nucleotide polymorphisms, of which the region encompassing the PTPRT gene accounted for 6.2% of the variance and a further 3.6% was associated with a putative copy number variant in MYO3B. The results from this study add to our understanding of variation in host control of infection and suggest that genetic marker-based selection for resistance to bTB has the potential to make a significant contribution to bTB control.


Assuntos
Resistência à Doença/genética , Loci Gênicos/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/veterinária , Tuberculose Bovina/genética , Animais , Bovinos , Mapeamento Cromossômico , Cromossomos de Mamíferos/genética , Feminino , Frequência do Gene , Genótipo , Haplótipos , Interações Hospedeiro-Patógeno/genética , Modelos Lineares , Desequilíbrio de Ligação , Modelos Logísticos , Mycobacterium bovis/fisiologia , Fenótipo , Polimorfismo de Nucleotídeo Único , Tuberculose Bovina/microbiologia
7.
Ann Anat ; 245: 152000, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36183940

RESUMO

PURPOSE: The existence of the basivertebral nerve and meningeal branch of the spinal nerve has not been proven in dogs to date. The objectives of this study are to 1) determine whether dogs have a meningeal branch of the spinal nerve (MBSN) and a basivertebral nerve (BVN) and to (2) describe anatomical characteristics of these two nerves. Authors also put forward a discussion on the possible clinical relevance of these findings. MATERIAL AND METHODS: Dissections were performed on six embalmed dogs at the Veterinary Faculty of Barcelona with the use of stereomicroscopy and microsurgery equipment. RESULTS: The MBSN (grossly) and BVN (grossly and histologically) were identified in the cervical, thoracic, and lumbar region in all dog specimens. In addition, other small fibers (suspected nerves) entering the vertebral body through small foramina close to the end plates were identified. Histological examination of the tissues confirmed the presence of nerve fibers (myelinated and unmyelinated) in suspected BVN samples. Results of the present study indicated that dogs have BVNs. Also, suspected nerve fibers were identified among the epidural fat, running from the intervertebral foramina, that likely represent the MBSN. CONCLUSION: These findings open up the discussion on extrapolation of treatment options employed in human medicine for "low back pain", such as BVN ablation, which is discussed in this article. Further anatomic and clinical studies of the innervation for the vertebral body, periosteum, vasculature, dorsal longitudinal ligament and anulus fibrosus are necessary to elucidate possible anatomical variants and breed differences as well as potential clinical (e.g., therapeutic) relevance.


Assuntos
Dor Lombar , Nervos Espinhais , Cães , Humanos , Animais , Nervos Espinhais/cirurgia , Dor Lombar/cirurgia , Coluna Vertebral , Dissecação , Região Lombossacral
8.
Proc Biol Sci ; 277(1695): 2737-45, 2010 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-20519223

RESUMO

The prevalence of bovine tuberculosis (BTB) in the UK remains a significant economic burden and problem for the agri-food industry. Much effort has been directed towards improving diagnostics, finding vaccine candidates and assessing the usefulness of badger culling. The contribution that host genotype makes to disease outcome has, until recently, been overlooked; yet, it is biologically untenable that genetic variation does not play a role. In this review, we highlight the evidence, past and present, for a role of host genetics in determining susceptibility to BTB in livestock. We then address some of the major issues surrounding the design of future studies tasked with finding the exact causative genetic variation underpinning the TB susceptibility phenotype. Finally, we discuss some of the potential future benefits, and problems, that a knowledge of the genetic component to BTB resistance/susceptibility may bring to the agricultural industries and the wider scientific community.


Assuntos
Doenças dos Bovinos/genética , Predisposição Genética para Doença/genética , Tuberculose Bovina/genética , Animais , Bovinos/genética , Doenças dos Bovinos/epidemiologia , Doenças dos Bovinos/microbiologia , Variação Genética , Gado/genética , Mycobacterium bovis/patogenicidade , Especificidade da Espécie , Tuberculose Bovina/epidemiologia , Tuberculose Bovina/microbiologia , Tuberculose Bovina/prevenção & controle
9.
Neurobiol Stress ; 13: 100262, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33344715

RESUMO

Acute physical or psychological stress can elicit adaptive behaviors that allow an organism maintain homeostasis. However, intense and/or prolonged stressors often have the opposite effect, resulting in maladaptive behaviors and curbing goal-directed action; in the extreme, this may contribute to the development of psychiatric conditions like generalized anxiety disorder, major depressive disorder, or post-traumatic stress disorder. While treatment of these disorders generally focuses on reducing reactivity to potentially threatening stimuli, there are in fact impairments across multiple domains including valence, arousal, and cognition. Here, we use the genetically stress-susceptible 129S1 mouse strain to explore the effects of stress across multiple domains. We find that 129S1 mice exhibit a potentiated neuroendocrine response across many environments and paradigms, and that this is associated with reduced exploration, neophobia, decreased novelty- and reward-seeking, and spatial learning and memory impairments. Taken together, our results suggest that the 129S1 strain may provide a useful model for elucidating mechanisms underlying myriad aspects of stress-linked psychiatric disorders as well as potential treatments that may ameliorate symptoms.

10.
Osteoporos Int ; 20(6): 943-8, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18923884

RESUMO

SUMMARY: The extent to which fracture protection and safety varies with increasing time on teriparatide [rhPTH(1-34)] therapy is a clinically relevant unanswered question. In postmenopausal women with osteoporosis, increased duration of teriparatide versus placebo treatment was associated with a progressive decrease in the rates of nonvertebral fragility fractures and back pain. INTRODUCTION: The impact of duration of teriparatide [rhPTH(1-34)] therapy on patient outcomes is a relevant unanswered question. METHODS: Postmenopausal women with osteoporosis were randomized to once-daily subcutaneous injection with placebo (N = 544), teriparatide 20 microg (TPTD20; N = 541), or teriparatide 40 microg (TPTD40; N = 552) plus calcium and vitamin D supplementation. The time to first nonvertebral fragility fracture and new or worsening back pain following treatment initiation was analyzed using Cox partial likelihood regression treating time on therapy as a linear, time-dependent covariate. RESULTS: Compared with placebo, the relative hazard for nonvertebral fragility fractures decreased by 7.3% for each additional month of TPTD20 [hazard ratio = 0.927, 95% CI (0.876 to 0.982), p = 0.009] and by 7.6% for each additional month of TPTD40 [hazard ratio = 0.924, 95% CI (0.871 to 0.981), p = 0.009]. Clinical vertebral fractures appeared to increase over time in the placebo group and occurred primarily in the first time interval in the teriparatide treatment groups. Compared with placebo, the relative hazard of back pain was decreased by 8.3% for each additional month of TPTD20 [hazard ratio = 0.920, 95% CI (0.902 to 0.939), p < 0.001] and 8.7% for each additional month of TPTD40 [hazard ratio = 0.917, 95% CI (0.898 to 0.935), p < 0.001]. CONCLUSIONS: These findings suggest increased nonvertebral fracture protection, reduced back pain, and reduced occurrence of side effects with longer duration of teriparatide therapy.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Fraturas Ósseas/prevenção & controle , Osteoporose Pós-Menopausa/tratamento farmacológico , Teriparatida/administração & dosagem , Dor nas Costas/tratamento farmacológico , Dor nas Costas/prevenção & controle , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/efeitos adversos , Esquema de Medicação , Feminino , Fraturas Ósseas/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/diagnóstico por imagem , Radiografia , Fraturas da Coluna Vertebral/prevenção & controle , Teriparatida/efeitos adversos , Resultado do Tratamento
12.
J Cell Biol ; 32(3): 629-47, 1967 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-6034482

RESUMO

Morphological and metabolic observations have been made on the effects of endotoxin, deoxycholate, and digitonin (at less than 50 microg/ml) on polymorphonuclear leukocytes and mononuclear cells. The agents stimulate the respiration and glucose oxidation of these cells in a manner similar to that seen during phagocytosis. Electron microscopy revealed no morphological changes with the first two agents, but dramatic membrane changes were seen in the case of digitonin. Here tubular projections of characteristic size and shape formed on and split off the membrane. All the agents stimulated uptake of inulin, but efforts to demonstrate increased pinocytosis by electron microscopy have not so far succeeded, probably due to limitations in present experimental techniques.


Assuntos
Ácidos e Sais Biliares/farmacologia , Glicosídeos Digitálicos/farmacologia , Endotoxinas/farmacologia , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Tensoativos/farmacologia , Animais , Isótopos de Carbono , Membrana Celular/efeitos dos fármacos , Colesterol/farmacologia , Glucose/metabolismo , Cobaias , Inulina/metabolismo , Leucócitos/citologia , Microscopia Eletrônica , Consumo de Oxigênio/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Fosfolipídeos/análise , Isótopos de Fósforo , Pinocitose/efeitos dos fármacos
13.
BMC Bioinformatics ; 9: 386, 2008 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-18803844

RESUMO

BACKGROUND: Random community genomes (metagenomes) are now commonly used to study microbes in different environments. Over the past few years, the major challenge associated with metagenomics shifted from generating to analyzing sequences. High-throughput, low-cost next-generation sequencing has provided access to metagenomics to a wide range of researchers. RESULTS: A high-throughput pipeline has been constructed to provide high-performance computing to all researchers interested in using metagenomics. The pipeline produces automated functional assignments of sequences in the metagenome by comparing both protein and nucleotide databases. Phylogenetic and functional summaries of the metagenomes are generated, and tools for comparative metagenomics are incorporated into the standard views. User access is controlled to ensure data privacy, but the collaborative environment underpinning the service provides a framework for sharing datasets between multiple users. In the metagenomics RAST, all users retain full control of their data, and everything is available for download in a variety of formats. CONCLUSION: The open-source metagenomics RAST service provides a new paradigm for the annotation and analysis of metagenomes. With built-in support for multiple data sources and a back end that houses abstract data types, the metagenomics RAST is stable, extensible, and freely available to all researchers. This service has removed one of the primary bottlenecks in metagenome sequence analysis - the availability of high-performance computing for annotating the data. http://metagenomics.nmpdr.org.


Assuntos
Sistemas de Gerenciamento de Base de Dados , Bases de Dados Genéticas , Armazenamento e Recuperação da Informação/métodos , Internet , Filogenia , Proteoma/genética , Software , Algoritmos , Interface Usuário-Computador
14.
Anim Genet ; 39(5): 561-3, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18637877

RESUMO

The BoLA-DRB3 gene is a highly polymorphic major histocompatibility complex class II gene of cattle with over one hundred alleles reported. Most of the polymorphisms are located in exon 2, which encodes the peptide-binding cleft, and these sequence differences play a role in variability of immune responsiveness and disease resistance. However, the high degree of polymorphism in exon 2 leads to difficulty in accurately genotyping cattle, especially heterozygous animals. In this study, we have improved and simplified an earlier sequence-based typing method to easily and reliably genotype cattle for BoLA-DRB3. In contrast to the earlier method, which used a nested primer set to amplify exon 2 followed by sequencing with internal primers, the new method uses only internal primers for both amplification and sequencing, which results in high-quality sequence across the entire exon. The haplofinder software, which assigns alleles from the heterozygous sequence, now has a pre-processing step that uses a consensus of all known alleles and checks for errors in base calling, thus improving the ability to process large numbers of samples. In addition, advances in sequencing technology have reduced the requirement for manual editing and improved the clarity of heterozygous base calls, resulting in longer and clearer sequence reads. Taken together, this has resulted in a rapid and robust method for genotyping large numbers of heterozygous samples for BoLA-DRB3 polymorphisms. Over 400 Holstein-Charolais cattle have now been genotyped for BoLA-DRB3 using this approach.


Assuntos
Bovinos/genética , Antígenos de Histocompatibilidade Classe II/genética , Análise de Sequência de DNA/métodos , Animais , Genótipo , Heterozigoto
15.
J Small Anim Pract ; 49(12): 647-50, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18684140

RESUMO

Acquired canine myasthenia gravis is an autoimmune disease in which autoantibodies are directed against muscle postsynaptic nicotinic acetylcholine receptors. Three adult great dane littermates were evaluated over a four month time period for an acute onset of generalised neuromuscular signs. All three dogs had elevated serum acetylcholine receptor antibody titres, which were considered diagnostic for acquired myasthenia gravis. Identification of three littermates with acquired myasthenia gravis in a breed with a low relative risk of developing the disease suggests a familial and possibly a genetic predisposition to myasthenia gravis in this family of dogs.


Assuntos
Autoanticorpos/sangue , Doenças do Cão/epidemiologia , Miastenia Gravis/veterinária , Receptores Colinérgicos/imunologia , Animais , Cruzamento , Doenças do Cão/diagnóstico , Doenças do Cão/genética , Doenças do Cão/imunologia , Cães , Evolução Fatal , Feminino , Predisposição Genética para Doença , Masculino , Miastenia Gravis/epidemiologia , Miastenia Gravis/genética , Miastenia Gravis/imunologia , Linhagem
16.
Vet Immunol Immunopathol ; 119(3-4): 303-9, 2007 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-17629575

RESUMO

During infection, the acute phase response triggers the release of acute phase proteins (APP), alpha-(1) acid glycoprotein (AGP), serum amyloid A (SAA) and Pig-MAP into the circulation, accompanied by a decrease in plasma levels of transthyretin. We quantified the association between these APP in 26 apparently healthy pigs from two breeds, 13 Large White and 13 Meishan (16 male; 10 female). There was a significant correlation between plasma levels of haptoglobin and Pig-MAP (r=0.57; p<0.05), but no significant associations between any of the other APP tested. We also measured the relationship between PigMAP, transthyretin and SAA, and the proportions of peripheral blood mononuclear sub-sets, CD8(+) cells, CD4(+) cells, CD11R1(+) cells, MHC DQ(+) cells, and monocytes. There were correlations between both plasma levels of Pig-MAP and the proportion of monocytes (r=0.55; p<0.05) and plasma levels of transthyretin and the proportion of MHC DQ(+) cells (r=0.40; p<0.01). Breed and sex influenced plasma levels of Pig-MAP but not plasma levels of transthyretin. Overall, these results suggest closer links between the mechanisms that regulate the release haptoglobin, Pig-MAP and monocytes compared to those that regulate the release of AGP, SAA and transthyretin.


Assuntos
Proteínas de Fase Aguda/metabolismo , Haptoglobinas/metabolismo , Orosomucoide/metabolismo , Pré-Albumina/metabolismo , Proteína Amiloide A Sérica/metabolismo , Suínos/sangue , Proteínas de Fase Aguda/genética , Animais , Feminino , Masculino , Suínos/classificação , Suínos/imunologia
17.
Poult Sci ; 86(7): 1336-50, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17575180

RESUMO

The purpose of this study was 2-fold: 1) to develop a deterministic model that describes the development of immunocompetence and the kinetics of immunoresponsiveness to a pathogenic challenge in chicks and 2) to use this model to illustrate the importance of factors in experimental design, such as type of variable measured, measurement timing, and challenge age. Difficulties in evaluating immunological variables hinder attempts to improve animal health through selection on immunological variables. In young chicks, evaluating immunological variables is additionally complicated by immune system development and maternal immunity. The evaluation of immunocompetence and immunoresponsiveness and the definition of appropriate challenge and measurement strategies may be enabled through a mathematical model that captures the key components of the immune system and its development. Therefore, a model was developed that describes the development of immunocompetence as well as the kinetics of immunoresponsiveness to a pathogenic extracellular bacterial challenge in an individual chick from 0 to 56 d of age. The model consisted of 4 components describing immunocompetence (maternal and baseline immunity) and immunoresponsiveness (acute phase and antibody response). Individual component equations generally fit published data adequately. Four scenarios that represented combinations of challenge age and measurement timing were simulated. In each scenario, the immunoresponsiveness to a particular challenge was compared for 3 different levels of baseline immunity, representing 3 broiler genotypes. It was illustrated that experimental design (type of immunoresponsiveness measured, measurement timing, and challenge age) can have an important effect on the ranking of genotypes, groups, or individuals and on the reliability of extrapolations based on this ranking. It is concluded that this model is a potentially useful tool in the definition of appropriate challenge and measurement strategies when evaluating immunocompetence and immunoresponsiveness. Further, it may be used as a generator of hypotheses on global immunological relationships to be tested experimentally.


Assuntos
Envelhecimento/imunologia , Galinhas/crescimento & desenvolvimento , Galinhas/imunologia , Imunocompetência/imunologia , Modelos Imunológicos , Proteínas de Fase Aguda/metabolismo , Animais , Formação de Anticorpos , Galinhas/genética , Simulação por Computador , Seleção Genética
18.
Aust Vet J ; 95(8): 294-298, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28749028

RESUMO

CASE REPORT: We describe the MRI appearance and surgical outcome of a rare neuroendodermal cyst in the fourth ventricle of a German Shorthaired Pointer. The dog presented with uncoordinated gait and occasional falling that increased when she became excited. The MRI appearance is shown and the surgical treatment described. Recurrence occurred on two occasions and the dog was euthanased. CONCLUSION: Recurrence of these cysts is highly likely unless there is complete surgical resection.


Assuntos
Cistos/veterinária , Quarto Ventrículo , Imageamento por Ressonância Magnética/veterinária , Recidiva Local de Neoplasia/cirurgia , Animais , Cistos/cirurgia , Cães , Endoderma , Feminino
19.
J Hosp Infect ; 97(2): 133-139, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28602702

RESUMO

BACKGROUND: Staphylococcus aureus bacteraemia (SAB) is the second most common source of positive blood cultures, after Escherichia coli, reported within NHS Scotland. Laboratory surveillance has been mandatory in Scotland for SAB since 2001. AIM: To gain an understanding of the epidemiology of SAB cases and associated risk factors for healthcare and true community onset. Identification of these factors and the patient populations at greatest risk enables the development of focused improvement plans. METHODS: All NHS boards within NHS Scotland take part in the mandatory enhanced surveillance, with data collected by trained data collectors using nationally agreed definitions. FINDINGS: Between 1st October 2014 and 31st March 2016, 2256 episodes of SAB in adults were identified. The blood cultures were taken in 58 hospitals and across all 15 Scottish health boards. The data demonstrated that approximately one-third of all SAB cases are true community cases. Vascular access devices continue to be the most reported entry point (25.7%) in individuals who receive health care, whereas skin and soft tissue risk factors are present in all origins. A significant risk factor unique to community cases is illicit drug injection. CONCLUSION: Improvement plans for reduction of SAB should be targeted more widely than hospital care settings alone.


Assuntos
Bacteriemia/microbiologia , Bacteriemia/mortalidade , Infecção Hospitalar/microbiologia , Infecção Hospitalar/mortalidade , Infecções Estafilocócicas/mortalidade , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/epidemiologia , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Infecção Hospitalar/epidemiologia , Atestado de Óbito , Contaminação de Equipamentos , Feminino , Hospitais , Humanos , Modelos Logísticos , Masculino , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Pessoa de Meia-Idade , Pediatria , Fatores de Risco , Escócia/epidemiologia , Vigilância de Evento Sentinela , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus/isolamento & purificação , Medicina Estatal , Adulto Jovem
20.
J Hosp Infect ; 97(2): 127-132, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28645466

RESUMO

BACKGROUND: National enhanced surveillance of Staphylococcus aureus bacteraemia (SAB) commenced on 1st October 2014 to gain a more in-depth understanding of the epidemiology of SAB in Scotland. Children under 16 years of age were analysed separately from adults because previous studies had demonstrated epidemiological differences. AIM: To identify risk factors and patient populations at greatest risk to enable the development of focused improvement plans. METHODS: All National Health Service (NHS) boards within NHS Scotland take part in the mandatory enhanced surveillance, with data collected by trained data collectors using nationally agreed definitions. FINDINGS: Analysis of the first 18 months of data showed that hospital-acquired SAB was mostly associated with neonates with device risk factors, whereas community-associated SAB was found in older children who had few, if any, risk factors and most presented with a bone or joint infection. CONCLUSION: The enhanced SAB data highlighted the difference in risk factors and entry points for the acquisition of SAB within the paediatric population.


Assuntos
Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Infecções Estafilocócicas/epidemiologia , Adolescente , Distribuição por Idade , Bacteriemia/mortalidade , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Feminino , Hospitais , Humanos , Lactente , Modelos Logísticos , Masculino , Pediatria , Fatores de Risco , Escócia/epidemiologia , Vigilância de Evento Sentinela , Infecções Estafilocócicas/mortalidade , Staphylococcus aureus/isolamento & purificação , Medicina Estatal
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