RESUMO
BACKGROUND: Eradication of bovine tuberculosis (bTB) through the application of test-and-cull programs is a declared goal of developed countries in which the disease is still endemic. Here, longitudinal data from more than 1,700 cattle herds tested during a 12 year-period in the eradication program in the region of Madrid, Spain, were analyzed to quantify the within-herd transmission coefficient (ß) depending on the herd-type (beef/dairy/bullfighting). In addition, the probability to recover the officially bTB free (OTF) status in infected herds depending on the type of herd and the diagnostic strategy implemented was assessed using Cox proportional hazard models. RESULTS: Overall, dairy herds showed higher ß (median 4.7) than beef or bullfighting herds (2.3 and 2.2 respectively). Introduction of interferon-gamma (IFN-γ) as an ancillary test produced an apparent increase in the ß coefficient regardless of production type, likely due to an increase in diagnostic sensitivity. Time to recover OTF status was also significantly lower in dairy herds, and length of bTB episodes was significantly reduced when the IFN-γ was implemented to manage the outbreak. CONCLUSIONS: Our results suggest that bTB spreads more rapidly in dairy herds compared to other herd types, a likely cause being management and demographic-related factors. However, outbreaks in dairy herds can be controlled more rapidly than in typically extensive herd types. Finally, IFN-γ proved its usefulness to rapidly eradicate bTB at a herd-level.
Assuntos
Tuberculose Bovina/prevenção & controle , Animais , Bovinos , Indústria de Laticínios , Surtos de Doenças/veterinária , Espanha/epidemiologia , Fatores de Tempo , Tuberculose Bovina/epidemiologia , Tuberculose Bovina/transmissãoRESUMO
Metastasis is a sequential process that allows cells to move from the primary tumor and grow elsewhere. Because of their ability to cleave a variety of extracellular signaling and adhesion molecules, metalloproteases have been long considered key components of the metastatic program. However, the function of certain metalloproteases, such as ADAMTS1, is not clear and seems to depend on the cellular environment and/or the stage of tumor progression. To characterize the function of ADAMTS1, we performed two alternative proteomic approaches, difference gel electrophoresis and stable isotope labeling by amino acids in cell culture, to identify novel substrates of the metalloprotease. Both techniques showed that overexpression of ADAMTS1 leads to the release of semaphorin 3C from the extracellular matrix. Although semaphorins are well known regulators of axon guidance, accumulating evidence shows that they may also participate in tumor progression. Here, we show that the cleavage of semaphorin 3C induced by ADAMTS1 promotes the migration of breast cancer cells, indicating that the co-expression of these molecules in tumors may contribute to the metastatic program.
Assuntos
Proteínas ADAM/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/secundário , Movimento Celular/fisiologia , Semaforinas/metabolismo , Proteínas ADAM/genética , Proteína ADAMTS1 , Linhagem Celular Tumoral , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Feminino , Humanos , Metástase Neoplásica , Proteômica , Semaforinas/genética , Especificidade por Substrato , Transfecção , Veias Umbilicais/citologiaRESUMO
This study explores how the quality of leader-member exchange (LMX) is associated with employees' creativity via engagement, and the moderating role of a job characteristic related to knowledge (job complexity) in this relationship. A moderated mediation model was tested on a sample of 320 employees from emergent high-tech and knowledge-based small and medium enterprises (SMEs) in Spain. The results supported an indirect influence of LMX on individual creativity through engagement. Additionally, this study found that job complexity accentuated the impact of engagement on creativity. More importantly, the findings confirmed that the intensity of the LMX-engagement-creativity relationship was moderated by job complexity. That is, the relationship was stronger when job complexity was high. Taken together, this study improves the understanding of the factors that contribute to increased employee creativity, an important outcome for high-tech and knowledge-based SMEs.
Assuntos
Criatividade , Satisfação no Emprego , Bases de Conhecimento , Liderança , EspanhaRESUMO
BACKGROUND: There is evidence for a link between vitamin D deficiency and active tuberculosis (TB). In human beings, several trials have evaluated the role of vitamin D supplementation in TB treatment with conflicting results. However, the role of vitamin D supplementation in animal TB control has received less attention. The authors evaluated the beneï¬t of vitamin D supplementation for preventing mycobacterial infection or reducing TB lesions (TBL) in a controlled trial with goats naturally exposed to Mycobacterium caprae. METHODS: Two groups of goats, a vitamin D-supplemented group and a non-supplemented control group, were housed for 10 months in direct contact with M caprae-infected adult goats. Upon contact with the infected adult goats, all animals were TB-tested every two months. RESULTS: No experimental evidence of a protective effect of vitamin D supplementation based on M caprae culture prevalence, TBL prevalence, median TBL score or the proportion of single versus multiple organs presenting TBL was observed. CONCLUSION: The results indicate that, in the conditions used in this study, vitamin D supplementation in goats does not reduce TB infection risk nor the diffusion and severity of TBL. In addition, vitamin D-supplemented goats presented hyperphosphataemia and renal injury with calcifications suggestive of vitamin D intoxication.
Assuntos
Doenças das Cabras/prevenção & controle , Nefropatias/veterinária , Infecções por Mycobacterium/veterinária , Vitamina D/administração & dosagem , Vitamina D/efeitos adversos , Animais , Doenças das Cabras/induzido quimicamente , Doenças das Cabras/microbiologia , Cabras , Hiperfosfatemia/induzido quimicamente , Hiperfosfatemia/veterinária , Nefropatias/induzido quimicamente , Mycobacterium/classificação , Infecções por Mycobacterium/microbiologia , Infecções por Mycobacterium/prevenção & controle , Vitamina D/farmacologiaRESUMO
Caprine TB causes chronic disease with severe economic and health consequences. We assessed the effect of intramuscularly administered heat-inactivated Mycobacterium bovis (M. bovis) on 20 kid goats (10 vaccinated, 10 controls), naturally exposed to M. caprae through close contact with infected goats. At necropsy, visible TB-compatible lesions were recorded in all animals with the exception of 1 control and 2 vaccinated goats. The median of the total lesion score was 9 (IQR 3-13.5) and 5 (IQR 3-6.75) in control and vaccinated goats, respectively (median lesion reduction 44.4%, p = 0.224). The lung lesions of the vaccinated goats were restricted to the caudal lobes, while 6 controls had additional lung lobes affected (p = 0.01). The median lung lesion score reduction in vaccinated goats was 100%; however, this reduction was not significant (p = 0.124), possibly due to the low sample size. Regarding the abdomen, only one vaccinated goat presented visible lesions compared to three goats in the control group. The results provide further evidence of the potential of heat-inactivated M. bovis for controlling TB in different host species, including ruminants.
Assuntos
Doenças das Cabras/prevenção & controle , Mycobacterium bovis/imunologia , Vacinas contra a Tuberculose/uso terapêutico , Tuberculose/prevenção & controle , Vacinação/veterinária , Animais , Feminino , Doenças das Cabras/microbiologia , Cabras , Temperatura Alta , Injeções Intramusculares , Pulmão/microbiologia , Pulmão/patologia , Vacinas contra a Tuberculose/administração & dosagemRESUMO
The presence of H3K9me3 and heterochromatin protein 1 (HP1) are hallmarks of heterochromatin conserved in eukaryotes. The spreading and maintenance of H3K9me3 is effected by the functional interplay between the H3K9me3-specific histone methyltransferase Suv39h1 and HP1. This interplay is complex in mammals because the three HP1 isoforms, HP1α, ß, and γ, are thought to play a redundant role in Suv39h1-dependent deposition of H3K9me3 in pericentric heterochromatin (PCH). Here, we demonstrate that despite this redundancy, HP1α and, to a lesser extent, HP1γ have a closer functional link to Suv39h1, compared to HP1ß. HP1α and γ preferentially interact in vivo with Suv39h1, regulate its dynamics in heterochromatin, and increase Suv39h1 protein stability through an inhibition of MDM2-dependent Suv39h1-K87 polyubiquitination. The reverse is also observed, where Suv39h1 increases HP1α stability compared HP1ß and γ. The interplay between Suv39h1 and HP1 isoforms appears to be relevant under genotoxic stress. Specifically, loss of HP1α and γ isoforms inhibits the upregulation of Suv39h1 and H3K9me3 that is observed under stress conditions. Reciprocally, Suv39h1 deficiency abrogates stress-dependent upregulation of HP1α and γ, and enhances HP1ß levels. Our work defines a specific role for HP1 isoforms in regulating Suv39h1 function under stress via a feedback mechanism that likely regulates heterochromatin formation.
Assuntos
Proteínas Cromossômicas não Histona/metabolismo , Dano ao DNA , Retroalimentação Fisiológica , Metiltransferases/genética , Proteínas Repressoras/genética , Linhagem Celular , Montagem e Desmontagem da Cromatina , Homólogo 5 da Proteína Cromobox , Proteínas Cromossômicas não Histona/genética , Histonas/metabolismo , Humanos , Metiltransferases/metabolismo , Ligação Proteica , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Estabilidade Proteica , Proteínas Repressoras/metabolismo , UbiquitinaçãoRESUMO
Vaccination against tuberculosis (TB) is prohibited in cattle or other species subjected to specific TB eradication campaigns, due to the interference that it may cause with the official diagnostic tests. However, immunization with a heat-inactivated (HI) Mycobacterium bovis vaccine via the oral route has been suggested to overcome this issue. In this study, the main goal was to assess the interference of the HI vaccine by different routes of administration using a previous vaccination and re-vaccination (boosting) protocol. TB-free kid goats were divided into three groups: oral (n = 16), intramuscular (IM; n = 16), and control (n = 16). Results showed that there was a significant difference in the percentage of animals positive to the single intradermal test (SIT) and blood based interferon-gamma release assay (IGRA) caused by vaccination when performed in the IM group compared to the oral group (p < 0.001). Nevertheless, no positivity to the SIT or IGRA test was observed in orally vaccinated goats regardless of the different interpretation criteria applied. None of the groups presented positive antibody titers using an in-house ELISA and samples collected 2 months after the boost. These results suggest the potential usefulness of the HI vaccine by the oral route in goats to minimize the interference on diagnostic tests (skin and IGRA tests) and reducing the necessity of defined antigens to replace the traditional purified protein derivatives for diagnosis. Finally, the results pave the way to future efficacy studies in goats using different routes of HI vaccination.
RESUMO
HP1 is a structural component of heterochromatin. Mammalian HP1 isoforms HP1α, HP1ß, and HP1γ play different roles in genome stability, but their precise role in heterochromatin structure is unclear. Analysis of Hp1α-/-, Hp1ß-/-, and Hp1γ-/- MEFs show that HP1 proteins have both redundant and unique functions within pericentric heterochromatin (PCH) and also act globally throughout the genome. HP1α confines H4K20me3 and H3K27me3 to regions within PCH, while its absence results in a global hyper-compaction of chromatin associated with a specific pattern of mitotic defects. In contrast, HP1ß is functionally associated with Suv4-20h2 and H4K20me3, and its loss induces global chromatin decompaction and an abnormal enrichment of CTCF in PCH and other genomic regions. Our work provides insight into the roles of HP1 proteins in heterochromatin structure and genome stability.
Assuntos
Proteínas Cromossômicas não Histona/genética , Proteínas Cromossômicas não Histona/metabolismo , Sequência de Aminoácidos/genética , Animais , Cromatina/metabolismo , Homólogo 5 da Proteína Cromobox , Células HeLa , Humanos , Mamíferos/metabolismo , Ligação Proteica/genética , Ligação Proteica/imunologia , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
INTRODUCTION: It is generally believed that legislation is an essential resource in the prevention of discriminatory behaviour against older people. This study first examines the Spanish legislation for potential age discrimination and then uses the C-EVE-D questionnaire to ask professionals in social work and health care settings the extent to what certain ageist behaviours described in the questionnaire are observed in practice. METHODS: The field study was carried out with professionals in geriatrics and gerontology, who are members of Spanish Society for Geriatrics and Gerontology (SEGG). The EVE discrimination questionnaire consists of 28 items which investigate the existence of age discrimination in medical and social care contexts. RESULTS: A total of 174 people (63% women; mean age: 45.6 years) took part in the study, with a mean professional experience of 17.2 years. Doctors made up 59% of the sample, psychologists 19%, with the rest coming from other professions. The first 20 discrimination items of the EVE-D questionnaire were significantly positively reported by more than 60% of the sample. CONCLUSIONS: Although Spanish legislation, from the constitution down to the rules that govern social and health care settings, clearly prohibits any kind of discrimination with regard to age, our results show that Spanish professionals most closely involved in the care of older people perceive both direct and indirect age discrimination. Furthermore, evidence was found of prejudice in the treatment of older people as a phenomenon in day-to-day health and social services care, both when analysing medical cases and, to a greater extent, cases of a more general nature and/or relating to co-existence.
Assuntos
Etarismo , Atitude do Pessoal de Saúde , Geriatria , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Serviço Social , Inquéritos e QuestionáriosRESUMO
It has been suggested that infection with Corynebacterium pseudotuberculosis, the pathogen responsible for caseous lymphadenitis (CLA), might interfere with diagnostic testing for tuberculosis (TB), due to antigenic similarities between this particular type of bacterium and those expressed by mycobacteria. The aim of the present study was to investigate whether experimental infection with C. pseudotuberculosis in goats impacted on TB testing, using single and comparative intradermal tuberculin (SIT and SCIT respectively) tests and interferon (IFN)-γ assay. No positive reactors were detected among the CLA-affected goats using the SIT/SCIT tests or the interferon IFN-γ assay. A proportion of goats showed inconclusive results to the SIT test and reactions to Mycobacterium avium. There was no evidence that infection with C. pseudotuberculosis interferes with diagnostic testing for TB using standard interpretation of the SIT, SCIT and IFN-γ tests.
Assuntos
Infecções por Corynebacterium/veterinária , Corynebacterium pseudotuberculosis , Cabras , Teste Tuberculínico/veterinária , Tuberculose/veterinária , Animais , Infecções por Corynebacterium/complicações , Infecções por Corynebacterium/diagnóstico , Reações Cruzadas , Interferon gama , Sensibilidade e Especificidade , Tuberculose/complicações , Tuberculose/diagnósticoRESUMO
The immunogenicity and diagnostic interference caused by M. tuberculosis SO2, a prototype vaccine first time tested in goats was evaluated. Tuberculosis-free goats were distributed in four groups: [1], non-vaccinated; [2], subcutaneously (SC) BCG vaccinated; [3], intranasally (IN) SO2 vaccinated and [4], SC SO2 vaccinated. Intradermal tuberculin and IFN-γ tests using PPDs and alternative antigenic cocktails containing mainly ESAT-6 and CFP-10 (E/C) were applied at different times post-vaccination. Results showed a significant (p<0.05) increase in the number of reactors detected using both PPD-based intradermal and IFN-γ tests at different times in all the vaccinated groups. No intradermal reactivity was detected in the vaccinated goats using a cocktail containing E/C, Rv3615c and Rv3020c. A higher overall reactivity was observed in the group [4] in comparison with the other vaccinated groups. Results showed that antigens used to differentiate BCG vaccinated animals could be potentially used to differentiate SO2 vaccinated ones.
Assuntos
Doenças das Cabras/transmissão , Mycobacterium tuberculosis/imunologia , Vacinas contra a Tuberculose/imunologia , Tuberculose/veterinária , Animais , Feminino , Doenças das Cabras/microbiologia , Cabras , Espanha , Tuberculose/microbiologia , Tuberculose/transmissão , VacinaçãoRESUMO
The official technique for diagnosis of bovine tuberculosis (bTB) worldwide is the tuberculin skin test, based on the evaluation of the skin thickness increase after the intradermal inoculation of a purified protein derivative (PPD) in cattle. A number of studies performed on experimentally infected or sensitized cattle have suggested that the relative sensitivity of the cervical test (performed in the neck) may vary depending on the exact location in which the PPD is injected. However, quantitative evidence on the variation of the test accuracy associated to changes in the site of inoculation in naturally infected animals (the population in which performance of the test is most critical for disease eradication) is lacking. Here, the probability of obtaining a positive reaction (>2 or 4 millimeters and/or presence of local clinical signs) after multiple inoculations of bovine PPD in different cervical and scapular locations was assessed in animals from five bTB-infected herds (818 cattle receiving eight inoculations) using a hierarchical Bayesian logistic regression model and adjusting for the potential effect of age and sex. The effect of the inoculation site was also assessed qualitatively in animals from four officially tuberculosis free (OTF) herds (two inoculations in 210 animals and eight inoculations in 38 cattle). Although no differences in the qualitative outcome of the test were observed in cattle from OTF herds, a statistically important association between the test outcome and the inoculation site in animals from infected herds was observed, with higher probabilities of positive results when the test was performed in the neck anterior area. Our results suggest that test sensitivity may be maximized by considering the area of the neck in which the test is applied, although lack of effect of the inoculation site in the specificity of the test should be confirmed in a larger sample.
Assuntos
Pescoço/fisiologia , Dobras Cutâneas , Teste Tuberculínico/veterinária , Tuberculina/administração & dosagem , Tuberculose Bovina/diagnóstico , Animais , Teorema de Bayes , Bovinos , Feminino , Modelos Logísticos , Masculino , Mycobacterium bovis/imunologia , Prevalência , Sensibilidade e Especificidade , Espanha/epidemiologia , Tuberculose Bovina/epidemiologia , Tuberculose Bovina/microbiologiaRESUMO
Use of mathematical models to study the transmission dynamics of infectious diseases is becoming increasingly common in veterinary sciences. However, modeling chronic infectious diseases such as bovine tuberculosis (bTB) is particularly challenging due to the substantial uncertainty associated with the epidemiology of the disease. Here, the methodological approaches used to model bTB and published in the peer-reviewed literature in the last decades were reviewed with a focus on the impact that the models' assumptions may have had on their results, such as the assumption of density vs. frequency-dependent transmission, the existence of non-infectious and non-detectable stages, and the effect of extrinsic sources of infection (usually associated with wildlife reservoirs). Although all studies suggested a relatively low rate of within-herd transmission of bTB when test-and-cull programs are in place, differences in the estimated length of the infection stages, sensitivity and specificity of the tests used and probable type of transmission (density or frequency dependent) were observed. Additional improvements, such as exploring the usefulness of contact-networks instead of assuming homogeneous mixing of animals, may help to build better models that can help to design, evaluate and monitor control and eradication strategies against bTB.
Assuntos
Técnicas de Apoio para a Decisão , Modelos Biológicos , Modelos Teóricos , Tuberculose Bovina/transmissão , Animais , Bovinos , Tomada de Decisões , Prevalência , Sensibilidade e Especificidade , Tuberculose Bovina/epidemiologia , Medicina Veterinária/métodosRESUMO
Bovine tuberculosis (TB), mainly caused by Mycobacterium bovis, is a zoonotic disease with implications for Public Health and having an economic impact due to decreased production and limitations to the trade. Bovine TB is subjected to official eradication campaigns mainly based on a test and slaughter policy using diagnostic assays based on the cell-mediated immune response as the intradermal tuberculin test and the gamma-interferon (IFN-γ) assay. Moreover, several diagnostic assays based on the detection of specific antibodies (Abs) have been developed in the last few years with the aim of complementing the current diagnostic techniques in the near future. This review provides an overview of the current ante-mortem diagnostic tools for diagnosis of bovine TB regarding historical background, methodologies and sensitivity (Se) and specificity (Sp) obtained in previous studies under different epidemiological situations.
Assuntos
Anticorpos Antibacterianos/sangue , Diagnóstico , Mycobacterium bovis/imunologia , Testes Sorológicos/métodos , Teste Tuberculínico/métodos , Tuberculose Bovina/diagnóstico , Animais , Bovinos , Imunidade Celular , Técnicas In Vitro , Interferon gama/efeitos dos fármacos , Interferon gama/metabolismo , Sensibilidade e Especificidade , Tuberculina/farmacologia , Tuberculose Bovina/imunologia , Tuberculose Bovina/patologiaRESUMO
Goats can act as reservoirs for tuberculosis (TB) infection. The main etiological agents of TB in goats are Mycobacterium caprae and Mycobacterium bovis and they infect also a wide range of domestic and wild animals and humans. Control programmes based mainly on the application of single and comparative intradermal tuberculin (SIT and SCIT respectively) tests are being implemented in certain regions of Spain with a high density of caprine flocks as Castilla y León, including goats with epidemiological relationship with cattle. The aim of this study was to evaluate the performance of the intradermal tests in naturally TB-infected caprine flocks from this region. The study was performed using data from 17,450 goats in 54 different flocks that were classified as TB-infected in the control programmes executed in 2010 and 2011. Data from 1237 goats from 7 dairy flocks depopulated after the first intradermal testing were used to estimate the sensitivity (Se) using bacteriology as the gold-standard. Overall Se of the SIT test using the severe interpretation was 43.9% (CI 95%, 40.4-47.4) and decreased to 38.8% (CI 95%, 35.5-42.3) using the standard interpretation. Overall Se of the SCIT test ranged between 21.3% (CI 95%, 17.6-25.4) and 7% (CI 95%, 4.9-9.8) depending of the interpretation criteria. A significant weak positive correlation was found between age and skin fold thickness (Spearman's test p<0.05). Results from this study yielded, in general, low Se values probably due the systematic detection and slaughter of reactors as a consequence of the eradication programme in previous years or the presence of factors that may interfere in the diagnosis. Therefore, these results suggest the necessity of including ancillary diagnostic tools and/or strict interpretation criteria to maximize detection of positive animals in infected settings.
Assuntos
Doenças das Cabras/microbiologia , Mycobacterium/isolamento & purificação , Teste Tuberculínico/veterinária , Tuberculose/veterinária , Animais , Feminino , Doenças das Cabras/diagnóstico , Doenças das Cabras/epidemiologia , Cabras , Masculino , Sensibilidade e Especificidade , Espanha/epidemiologia , Estatísticas não Paramétricas , Teste Tuberculínico/normas , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Tuberculose/microbiologiaRESUMO
Diagnostic tests based on cell-mediated immunity are used in programmes for eradication of bovine tuberculosis (Mycobacterium bovis). Serological assays could be applied as ancillary methods to detect infected animals. Our objective was to evaluate two serological techniques: M. bovis Ab Test (IDEXX, USA) and Enferplex™ TB assay (Enfer, Ireland) in animals tested simultaneously with the single and comparative intradermal tests and the interferon-gamma assay. This work was performed at two stages. First, a preliminary panel of samples collected prior to intradermal tests from tuberculosis-free (n=60) and M. bovis-infected herds (n=78) was assayed, obtaining high specificity: 100% (M. bovis Ab Test) and 98.3% (Enferplex TB assay) but low sensitivity (detection of M. bovis infected animals): 23.9% (M. bovis Ab Test) and 32.6% (Enferplex TB assay). Subsequently, the use of serological techniques was further studied in two herds with M. bovis infection (n=77) using samples collected prior to, and 72 h and 15 days after PPD inoculation. The highest level of detection of infected animals for serology was achieved at 15 days post-intradermal tests taking advantage of the anamnestic effect: 70.4% and 85.2% in herd A, and 66.7% and 83.3% in herd B, using M. bovis Ab Test and Enferplex TB assay, respectively. Quantitative results (average values obtained with M. bovis Ab Test ELISA and degree of positivity obtained with Enferplex TB assay) were higher in animals showing lesions compatible with tuberculosis. No significant differences were observed in the number of confirmed infected animals detected with either serological technique.
Assuntos
Mycobacterium bovis/imunologia , Teste Tuberculínico/veterinária , Tuberculose Bovina/diagnóstico , Animais , Anticorpos Antibacterianos/sangue , Bovinos , Ensaio de Imunoadsorção Enzimática/veterinária , Feminino , Interferon gama , Testes Intradérmicos/veterinária , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Teste Tuberculínico/normas , Tuberculose Bovina/imunologia , Tuberculose Bovina/patologiaRESUMO
Expression of IGFBP2 (Insulin-like Growth Factor Binding Protein 2) has been positively correlated with glioma progression. Although the proteolysis of IGFBP2 has been widely recognized, with consequences as a major modulator of IGFII signaling, the relevance of this post-translational modification has not been well studied in tumors. Using an in vivo proteomic approach by Isotope-Coded Protein Label (ICPL), we identified IGFBP2 as a target of the extracellular protease ADAMTS1 (A Disintegrin And Metalloproteinase with ThromboSpondin motifs 1). Notably, the proteolytic pattern of IGFBP2 was also detected in human glioma culture cells and, more importantly, in all glioma samples evaluated. In addition, high expression of ADAMTS1 correlates with higher levels of cleaved IGFBP2 in glioblastoma multiforme cases. Using gene expression public databases, we confirmed that IGFBP2 is a poor prognosis marker for gliomas, and we also observed an important contribution of ADAMTS1.Finally, we showed the impact of ADAMTS1 on IGFII-mediated IGF1R phosphorylation and cellular migration. Our results support a functional interaction between IGFBP2 and ADAMTS1 and suggest the need to evaluate post-translational modifications of IGFBP2 in glioma, in order to approach new therapies.
Assuntos
Proteínas ADAM/genética , Proteínas ADAM/metabolismo , Neoplasias Encefálicas/genética , Glioma/genética , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Proteína ADAMTS1 , Linhagem Celular Tumoral , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Humanos , Fosforilação , Proteólise , Transdução de Sinais , TransfecçãoRESUMO
Progress in control of bovine tuberculosis (bTB) is often not uniform, usually due to the effect of one or more sometimes unknown epidemiological factors impairing the success of eradication programs. Use of spatial analysis can help to identify clusters of persistence of disease, leading to the identification of these factors thus allowing the implementation of targeted control measures, and may provide some insights of disease transmission, particularly when combined with molecular typing techniques. Here, the spatial dynamics of bTB in a high prevalence region of Spain were assessed during a three year period (2010-2012) using data from the eradication campaigns to detect clusters of positive bTB herds and of those infected with certain Mycobacterium bovis strains (characterized using spoligotyping and VNTR typing). In addition, the within-herd transmission coefficient (ß) was estimated in infected herds and its spatial distribution and association with other potential outbreak and herd variables was evaluated. Significant clustering of positive herds was identified in the three years of the study in the same location ("high risk area"). Three spoligotypes (SB0339, SB0121 and SB1142) accounted for >70% of the outbreaks detected in the three years. VNTR subtyping revealed the presence of few but highly prevalent strains within the high risk area, suggesting maintained transmission in the area. The spatial autocorrelation found in the distribution of the estimated within-herd transmission coefficients in herds located within distances <14 km and the results of the spatial regression analysis, support the hypothesis of shared local factors affecting disease transmission in farms located at a close proximity.
Assuntos
Mycobacterium bovis/isolamento & purificação , Tuberculose Bovina/diagnóstico , Tuberculose Bovina/epidemiologia , Criação de Animais Domésticos , Animais , Bovinos , Surtos de Doenças , Tipagem Molecular , Mycobacterium bovis/genética , Espanha/epidemiologiaRESUMO
Wildlife vaccination is increasingly being considered as an option for tuberculosis control. We combined data from laboratory trials and an ongoing field trial to assess the risk of an oral Mycobacterium bovis BCG vaccine and a prototype heat-inactivated Mycobacterium bovis preparation for Eurasian wild boar (Sus scrofa). We studied adverse reactions, BCG survival, BCG excretion, and bait uptake by nontarget species. No adverse reactions were observed after administration of BCG (n = 27) or inactivated M. bovis (n = 21). BCG was not found at necropsy (175 to 300 days postvaccination [n = 27]). No BCG excretion was detected in fecal samples (n = 162) or in urine or nasal, oral, or fecal swab samples at 258 days postvaccination (n = 29). In the field, we found no evidence of loss of BCG viability in baits collected after 36 h (temperature range, 11°C to 41°C). Camera trapping showed that wild boar (39%) and birds (56%) were the most frequent visitors to bait stations (selective feeders). Wild boar activity patterns were nocturnal, while diurnal activities were recorded for all bird species. We found large proportions of chewed capsules (29%) (likely ingestion of the vaccine) and lost baits (39%) (presumably consumed), and the proportion of chewed capsules showed a positive correlation with the presence of wild boar. Both results suggest proper bait consumption (68%). These results indicate that BCG vaccination in wild boar is safe and that, while bait consumption by other species is possible, this can be minimized by using selective cages and strict timing of bait deployment.
Assuntos
Vacina BCG/efeitos adversos , Vacina BCG/imunologia , Doenças dos Suínos/prevenção & controle , Tuberculose/veterinária , Administração Oral , Animais , Vacina BCG/administração & dosagem , Derrame de Bactérias , Aves , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Fezes/microbiologia , Boca/microbiologia , Cavidade Nasal/microbiologia , Sus scrofa , Suínos , Doenças dos Suínos/imunologia , Tuberculose/imunologia , Tuberculose/prevenção & controle , Urina/microbiologia , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/imunologia , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/imunologiaRESUMO
Mycobacterium bovis causes animal tuberculosis (TB) in cattle, humans, and other mammalian species, including pigs. The goal of this study was to experimentally assess the responses of pigs with and without a history of tonsillectomy to oral vaccination with heat-inactivated M. bovis and challenge with a virulent M. bovis field strain, to compare pig and wild boar responses using the same vaccination model as previously used in the Eurasian wild boar (Sus scrofa), to evaluate the use of several enzyme-linked immunosorbent assays (ELISAs) and lateral flow tests for in vivo TB diagnosis in pigs, and to verify if these tests are influenced by oral vaccination with inactivated M. bovis. At necropsy, the lesion and culture scores were 20% to 43% higher in the controls than those in the vaccinated pigs. Massive M. bovis growth from thoracic tissue samples was observed in 4 out of 9 controls but in none of the 10 vaccinated pigs. No effect of the presence or absence of tonsils was observed on these scores, suggesting that tonsils are not involved in the protective response to this vaccine in pigs. The serum antibody levels increased significantly only after challenge. At necropsy, the estimated sensitivities of the ELISAs and dual path platform (DPP) assays ranged from 89% to 94%. In the oral mucosa, no differences in gene expression were observed in the control group between the pigs with and without tonsils. In the vaccinated group, the mRNA levels for chemokine (C-C motif) receptor 7 (CCR7), interferon beta (IFN-ß), and methylmalonyl coenzyme A mutase (MUT) were higher in pigs with tonsils. Complement component 3 mRNA levels in peripheral blood mononuclear cells (PBMC) increased with vaccination and decreased after M. bovis challenge. This information is relevant for pig production in regions that are endemic for M. bovis and for TB vaccine research.