RESUMO
BACKGROUND: Measuring the size of free roaming dog populations quickly and accurately is critical in the implementation of numerous preventive health and population control interventions. However, few studies have investigated the relative performance of population size assessment tools when applied to dogs. The aim of this study was to compare the commonly used mark-resight methodology with distance sampling methods, which are less resource intensive, to estimate free-roaming dog abundance in Goa, India. Twenty-six working zones were surveyed along all roads twice by the same surveyor at the same time of day, following a vaccination campaign which included marking of vaccinated dogs with a coloured paint. The Chapman estimate was then used to evaluate the mark-resight abundance. Additionally, the number of dogs and perpendicular distance from the road for all dogs sighted was recorded. This was used to estimate dog density and abundance using distance sampling methods. The detection function was fitted based on goodness-of-fit and AIC. RESULTS: The Chapman abundance estimate for the entire study area was 5202 dogs (95%CI 4733.8-5671.0), and the distance sampling method abundance estimate was 5067 dogs (95%CI 4454.3-5764.2). For individual working zones, after taking other factors into account in a mixed effects model, the average distance sampling estimate was 35% higher (95%CI 20-53%) than the Chapman estimate. There was also evidence of a difference in estimates between surveyors of 21% (95%CI 7-37%) and between days (22% lower on day 2, 95%CI 8-38%) for individual working zones. CONCLUSION: Our study demonstrated that the distance sampling estimates were comparable overall to the Chapman method of abundance estimation of free roaming dogs across the entire study region but there was noticeable variation between the two methods when individual zones were compared. Consequently, distance sampling methods may be suitable to enumerate dogs over large areas in a more time efficient manner than the widely used mark-resight approach.
Assuntos
Sistemas de Identificação Animal/veterinária , Cães , Sistemas de Identificação Animal/métodos , Animais , Índia , Densidade Demográfica , Vigilância da População/métodos , Vacina Antirrábica/administração & dosagem , Vacinação/veterináriaRESUMO
The effective management of stray dogs is critically important in any rabies vaccination programme. In many rabies-endemic countries, stray dogs represent a significant proportion of both the free-roaming and total dog populations, and to ensure that rabies elimination programmes are successful, it is essential that this portion of the dog population (stray dogs) is vaccinated at high coverage. However, there are a number of challenges to managing and delivering rabies vaccinations to stray dogs. This paper will review the most pertinent issues relating to the problem of stray dogs and rabies elimination, focusing on the challenges relating to the estimation of population size, vaccination administration and vaccine coverage assessment in stray dog populations. The authors will highlight how these challenges can be overcome, notably by reviewing the census techniques that have been employed to assess stray dog populations, which then facilitate the planning and design of vaccination programmes. In addition, they discuss the range of vaccination strategies that are available and that have been used to vaccinate stray dogs and review how vaccination coverage can be assessed in this population. Finally, the benefits of population management in stray dogs through neutering programmes are reviewed. In short, this paper highlights the importance of ensuring that stray dogs, as well as owned dogs, are included in vaccination programmes and emphasises that many of the challenges related to protecting stray dogs from rabies can be overcome.
L'efficacité de la gestion des populations de chiens errants est un aspect essentiel de tout programme de vaccination contre la rage. Dans de nombreux pays où la rage est endémique, les chiens errants constituent un segment important des populations de chiens laissés en liberté et plus généralement de la population canine totale, de sorte que le succès des programmes d'élimination de la rage repose sur l'impératif d'assurer une forte couverture vaccinale au sein de cette partie de la population canine. Toutefois, s'agissant des chiens errants la gestion de la vaccination et l'administration des vaccins antirabiques présentent des difficultés particulières. Les auteurs font le point sur les principales questions posées par la problématique des chiens errants dans une perspective d'élimination de la rage, qui concernent notamment la difficulté d'évaluer la taille des populations concernées, d'administrer les vaccins dans ce cadre et d'évaluer la couverture vaccinale obtenue. Les auteurs soulignent les réponses qui peuvent être apportées à ces problèmes, en particulier en revoyant les techniques de recensement appliquées jusqu'à présent pour évaluer les populations de chiens errants, ce qui permettra ensuite de faciliter la planification et la conception des programmes de vaccination. En outre, ils examinent les différentes stratégies de vaccination mises en oeuvre en la matière et font le point sur les moyens d'évaluer la couverture vaccinale de ces populations. Enfin, ils analysent les avantages apportés par les programmes de stérilisation pour maîtriser les populations de chiens errants. En résumé, cet article met l'accent sur l'importance d'inclure les chiens errants au même titre que les chiens ayant un maître dans les programmes de vaccination et souligne que la plupart des difficultés liées à la protection des chiens errants contre la rage peuvent être résolues.
Uno de los aspectos capitales de todo programa de vacunación antirrábica es la gestión eficaz de las poblaciones de perros vagabundos. En muchos países con rabia endémica, estos perros representan un porcentaje sustancial tanto de la población canina total como de los perros en libertad. El éxito de todo programa de eliminación de la rabia pasa necesariamente por lograr una elevada cobertura de vacunación en este segmento de la población canina (los perros vagabundos). Sin embargo, la gestión y la vacunación antirrábica de los perros vagabundos presentan una serie de dificultades. Los autores pasan revista a los aspectos que más inciden en el problema de los perros vagabundos y la eliminación de la rabia, prestando especial atención a las dificultades que presentan la estimación del tamaño de la población, la administración de vacunas y el cálculo de la cobertura de vacunación de las poblaciones de perros vagabundos. Después explican la manera de superar estas dificultades, en particular describiendo las técnicas de censo empleadas para calcular el tamaño de las poblaciones, lo que a su vez facilita la concepción y planificación de programas de vacunación. Además, describen el arsenal existente de procedimientos de vacunación que se han utilizado para vacunar a los perros vagabundos y explican cómo estimar en estas poblaciones la cobertura de vacunación. Por último exponen los beneficios de gestionar las poblaciones de perros vagabundos con programas de esterilización. En resumidas cuentas, los autores recalcan aquí la importancia de que los programas de vacunación canina lleguen a los perros vagabundos, y no solo a los animales con dueño, e insisten en que muchos de los problemas que se plantean para proteger de la rabia a los perros vagabundos tienen solución.
Assuntos
Doenças do Cão/prevenção & controle , Propriedade , Vacina Antirrábica/imunologia , Raiva/veterinária , Animais , Participação da Comunidade , Erradicação de Doenças , Doenças do Cão/epidemiologia , Cães , Humanos , Índia/epidemiologia , Raiva/prevenção & controle , Vacina Antirrábica/administração & dosagem , Vacinação , ZoonosesRESUMO
Rabies is one of the oldest recorded pathogens, with the broadest distribution of any known viral zoonosis. Antarctica is believed to be free of all lyssaviruses, but no laboratory-based surveillance has taken place to support this supposition. Re-introduction of the disease is possible in Pacific Oceania, as evidenced by a historical outbreak in Guam and the translocation of rabid bats to Hawaii. Australia is the only inhabited continent with enzootic rabies, without the presence of rabies virus. Europe and North America have broken the cycle of dog-mediated rabies, with a few remaining focal points in Latin America and the Caribbean, but wildlife rabies predominates. The greatest burden resides in the 'Old World'. The elimination of human rabies mediated via dogs by 2030 in Africa, Asia and the Middle East will not be simple, rapid or inexpensive, but it may be achievable through the use of widely available tools and the application of lessons learned during the course of the 20th century.
La rage est l'une des plus anciennes maladies infectieuses enregistrées et la zoonose virale la plus largement représentée dans le monde. On présume que l'Antarctique est indemne de tout lyssavirus mais cette hypothèse n'est étayée par aucune surveillance basée sur des analyses de laboratoire. Il existe une menace de réintroduction de la maladie en Océanie, comme l'ont révélé le foyer historique survenu à Guam ainsi que l'arrivée de chauves-souris enragées à Hawaï. L'Australie est le seul continent habité où la rage ne sévit pas à l'état enzootique, le virus de la rage y étant absent. L'Europe et l'Amérique du Nord ont mis fin au cycle de la rage transmise par les chiens, dont il ne subsiste que quelques rares foyers de propagation en Amérique latine ; en revanche, la rage sylvatique reste prépondérante dans ces régions. Le fardeau le plus lourd est supporté par l'Ancien Monde. L'élimination de la rage humaine transmise par les chiens à l'horizon 2030 en Afrique, en Asie et au Moyen-Orient ne sera pas une tâche facile, rapide ni exempte de coûts mais elle peut réussir grâce aux outils disponibles partout dans le monde et aux enseignements tirés de l'expérience acquise tout au long du xxe siècle.
La rabia, causada por uno de los patógenos más antiguos de los que hay constancia, presenta la distribución más amplia de cuantas zoonosis víricas se conocen. Se piensa que la Antártida está libre de todo tipo de lisavirus, pero no ha habido labores de vigilancia en laboratorio que prueben tal suposición. Oceanía está bajo la amenaza de reintroducción de la enfermedad, como demuestran el histórico brote registrado en Guam o el desplazamiento de murciélagos rabiosos a Hawái. Australia es el único continente habitado en el que no hay rabia enzoótica, esto es, en que el virus rábico no está presente. Europa y América del Norte han interrumpido el ciclo de la rabia transmitida por perros, de la que aún quedan contados focos en América Latina y el Caribe, aunque sigue prevaleciendo la rabia de la fauna silvestre. La carga más importante recae en el «Viejo Mundo¼. La eliminación de la rabia humana transmitida por perros para 2030 en África, Asia y el Oriente Medio no será sencilla, rápida ni barata, pero es factible si se emplean herramientas que ya están extendidas y se aplican las lecciones que hemos aprendido a lo largo del siglo XX.
Assuntos
Saúde Global , Raiva/veterinária , Animais , Animais Domésticos , Animais Selvagens , Humanos , Raiva/epidemiologia , Raiva/prevenção & controle , ZoonosesRESUMO
Rabies is a major neglected zoonotic disease, despite the availability of highly sensitive diagnostic tests and efficacious human and animal vaccines. Perpetuation of rabies among multiple species of bats and wild carnivores, together with the presence of diverse lyssaviruses, remains a challenge for the prevention and control of this disease. However, most of the global burden may be reduced by mass vaccination of dogs, the major reservoir. Elimination of human rabies mediated by dogs may be feasible, based upon the elicitation of herd immunity, the application of sound health economic principles for appropriate disease management and technology transfer to those developing countries where rabies is hyper-endemic. Global canine rabies elimination has clear benefits for public health, veterinary medicine and conservation biology, so these sectors must collaborate using a transdisciplinary 'One Health' approach that allows the creation of long-term regional strategies for enhanced surveillance and practical intervention.
La rage est une maladie zoonotique majeure, qui demeure négligée malgré l'existence de tests de diagnostic hautement sensibles et de vaccins efficaces chez l'homme comme chez l'animal. La persistance de la rage chez de nombreuses espèces de carnivores sauvages et de chauves-souris et la diversité des espèces de Lyssavirus continuent de poser des difficultés en termes de prévention et de lutte contre la maladie. Néanmoins, le fardeau mondial de la rage peut être considérablement réduit en pratiquant la vaccination massive des chiens, ces derniers constituant le principal réservoir. L'élimination de la rage transmise par les chiens est un objectif atteignable si l'on s'appuie sur des concepts solides en matière d'immunité à l'échelle des troupeaux, d'économie de la santé et de transfert technologique, tout en apportant des bénéfices mutuels accrus pour la santé publique, la médecine vétérinaire et la biologie de la conservation grâce à la mise en oeuvre d'une approche régionale pour la surveillance, les interventions, la certification et la collaboration pluridisciplinaire dans un contexte Une seule santé.
La rabia es una importante enfermedad zoonótica desatendida, y ello pese a que existen pruebas de diagnóstico de gran sensibilidad y vacunas de contrastada eficacia en personas y animales. La perpetuación de la rabia en múltiples especies de carnívoros silvestres y murciélagos y la presencia de diversos lisavirus siguen dificultando el trabajo de prevención y control de la enfermedad. Con todo, cabe reducir buena parte de la carga mundial que impone la rabia mediante la vacunación masiva de perros, que son su principal reservorio. Si se aplican conceptos sólidos en materia de inmunidad de rebaño, economía de la salud y transferencia de tecnología, abordando las labores de vigilancia, intervención, certificación y colaboración multidisciplinar desde una lógica regional y desde los postulados de «Una sola salud¼, la eliminación de la rabia humana transmitida por perros puede ser un objetivo factible y muy beneficioso para la salud pública, la medicina veterinaria y la biología de la conservación.
Assuntos
Controle de Doenças Transmissíveis/métodos , Saúde Global , Raiva/prevenção & controle , Animais , Controle de Doenças Transmissíveis/organização & administração , Controle de Doenças Transmissíveis/normas , HumanosRESUMO
Free-roaming dogs (FRD) represent a large proportion of the canine population in India and are often implicated as a source of conflict with humans. However, objective data on the attitudes and perceptions of local communities toward FRD are lacking. This study collected baseline data from 1141 households in Goa, India, on FRD feeding practices and assessed people's attitudes toward FRD in urban and rural communities. Additionally, respondents identified problems caused by FRD and proposed potential solutions.The study reported that 37% of respondents fed FRD with dog owners and Hindus being the most likely to feed. The majority of respondents agreed FRD were a menace (57%), a nuisance (58%) and scary (60%). Most respondents also agreed FRD were a vulnerable population (59%), that belong in communities (66%) and have a right to live on the streets (53%). Barking was the most commonly reported problem associated with FRD and the preferred solution was to impound FRD in shelters. This study reveals the complex and often misunderstood relationship between local communities and FRD and highlights potential strategies to reduce human-dog conflict.
RESUMO
Sterilisation and rabies vaccination programs seek to manage free-roaming domestic dog (Canis familiaris) populations with the aim to reduce inter-species disease transmission and conflicts. As effective, permanent, remotely-administered options are not yet available for sterilisation, and oral vaccination is not yet commonly used; free-roaming dogs are typically captured for these interventions. There is a paucity of information describing how dog capture rates change over time within defined areas following repeated capture efforts. This data is needed to allow efficient dog capture programmes to be developed. Using spatial co-ordinates of dog capture, we characterise where dogs are more likely to be captured in six catch-sterilise-release campaigns, in Goa state, India. Combining capture numbers with population survey data collected in five sites, we document the increasing difficulty of catching entire (non-sterilised) dogs as sterilisation coverage increases and demonstrate how this leads to increased unit costs. Accounting for the extra resources required to capture dogs when sterilisation coverage is high will improve estimation of the resources required to manage free-roaming dog populations and assist in planning the most efficient intervention strategies.
RESUMO
Dog-mediated rabies kills tens of thousands of people each year in India, representing one third of the estimated global rabies burden. Whilst the World Health Organization (WHO), World Organization for Animal Health (OIE) and the Food and Agriculture Organization of the United Nations (FAO) have set a target for global dog-mediated human rabies elimination by 2030, examples of large-scale dog vaccination programs demonstrating elimination remain limited in Africa and Asia. We describe the development of a data-driven rabies elimination program from 2013 to 2019 in Goa State, India, culminating in human rabies elimination and a 92% reduction in monthly canine rabies cases. Smartphone technology enabled systematic spatial direction of remote teams to vaccinate over 95,000 dogs at 70% vaccination coverage, and rabies education teams to reach 150,000 children annually. An estimated 2249 disability-adjusted life years (DALYs) were averted over the program period at 526 USD per DALY, making the intervention 'very cost-effective' by WHO definitions. This One Health program demonstrates that human rabies elimination is achievable at the state level in India.
Assuntos
Doenças do Cão , Saúde Única , Raiva , Animais , Análise Custo-Benefício , Doenças do Cão/epidemiologia , Doenças do Cão/prevenção & controle , Cães , Humanos , Índia/epidemiologia , Raiva/epidemiologia , Raiva/prevenção & controle , Raiva/veterináriaRESUMO
Annual peaks in reproductive activity have been identified in multiple domestic dog populations. However, there is little evidence to describe how these peaks may be associated with environmental factors such as daylength, which plays a well-established role in breeding patterns of seasonally-reproductive species. Data were collected 2016-2020 during 7,743 and 4,681 neuter surgeries on adult female unowned free-roaming dogs in veterinary clinics in Goa and Tamil Nadu respectively. Temperature, precipitation, relative humidity, and daylength data were gathered for time periods preceding the neuter surgery that may have influenced the likelihood of pregnancy (potential influence periods). A multivariable generalised additive model was used to assess the relationship between these factors and pregnancy. The prevalence of pregnancy varied by month in both locations indicating seasonality of reproduction in these groups. The annual pattern was more distinct in Goa with a peak in pregnancies between September and December. In Goa, decreasing daylength was associated with a higher probability of pregnancy (p = 0.040). Decreasing temperature was associated with decreasing probability of pregnancy in the Nilgiris (p = 0.034). Bitches had a median of 6 foetuses, with no evidence of seasonal variation. Environmental factors were associated with patterns of pregnancy in free-roaming dogs, however statistically-significant factors varied by geographical location. Establishing local seasonal patterns of breeding in free-roaming dogs and assessing their relationship with environmental influences is recommended to facilitate effective and efficient population management strategies, which aim to reduce conflict between human and free-roaming dog populations.
Assuntos
Cães/fisiologia , Reprodução , Animais , Animais Selvagens/fisiologia , Feminino , Índia , Estações do AnoRESUMO
Despite successful eradication programmes in many regions, rabies remains responsible for approximately 60,000 human deaths annually, and no country in Africa is rabies-free. Dogs are the principal reservoir of the virus in Africa and the World Health Organisation recommends that at least 70% of the dog population be vaccinated in order to break the transmission cycle. Most attempts at mass rabies vaccinations in Africa have failed to vaccinate high numbers of dogs at a high coverage. Successful studies have often used a door-to-door (DTD) approach, which is logistically challenging and expensive compared to a static point (SP) approach. Mission Rabies has successfully implemented a combined SP and DTD method in cities in India and Malawi. This campaign used a combined methodology in rural Uganda, starting with a SP campaign, followed by a DTD campaign, and then subsequent transect surveys to assess vaccination coverage. This was facilitated by the use of a smartphone application which recorded all vaccinations and survey responses along with their Global Positioning System location. A total of 4172 dogs were vaccinated in 7 days, attaining an estimated 88.4% coverage. This campaign is of particular note as 95.9% of the vaccinations were performed at SPs. The human-to-dog ratio was 4.9 with a mean dogs per house of 1.2. Most dogs were owned (93.7%). This demonstrates that high-number, high-coverage vaccination is achievable in rural Uganda and provides data that may refine future campaign approaches.
Assuntos
Doenças do Cão/prevenção & controle , Vacinação em Massa/veterinária , Vacina Antirrábica/administração & dosagem , Animais , Cães , Feminino , Programas de Imunização , Masculino , Vacinação em Massa/métodos , UgandaRESUMO
Rabies has profound public health, social and economic impacts on developing countries, with an estimated 59,000 annual human rabies deaths globally. Mass dog vaccination is effective at eliminating the disease but remains challenging to achieve in India due to the high proportion of roaming dogs that cannot be readily handled for parenteral vaccination. Two methods for the vaccination of dogs that could not be handled for injection were compared in Goa, India; the oral bait handout (OBH) method, where teams of two travelled by scooter offering dogs an empty oral bait construct, and the catch-vaccinate-release (CVR) method, where teams of seven travel by supply vehicle and use nets to catch dogs for parenteral vaccination. Both groups parenterally vaccinated any dogs that could be held for vaccination. The OBH method was more efficient on human resources, accessing 35 dogs per person per day, compared to 9 dogs per person per day through CVR. OBH accessed 80% of sighted dogs, compared to 63% by CVR teams, with OBH accessing a significantly higher proportion of inaccessible dogs in all land types. All staff reported that they believed OBH would be more successful in accessing dogs for vaccination. Fixed operational team cost of CVR was four times higher than OBH, at 127 USD per day, compared to 34 USD per day. Mean per dog vaccination cost of CVR was 2.53 USD, whilst OBH was 2.29 USD. Extrapolation to a two week India national campaign estimated that 1.1 million staff would be required using CVR, but 293,000 staff would be needed for OBH. OBH was operationally feasible, economical and effective at accessing the free roaming dog population. This study provides evidence for the continued expansion of research into the use of OBH as a supplementary activity to parenteral mass dog vaccination activities in India.
RESUMO
Autism spectrum disorders (ASD) are highly heterogeneous developmental conditions characterized by deficits in social interaction, verbal and nonverbal communication, and obsessive/stereotyped patterns of behavior and repetitive movements. Social interaction impairments are the most characteristic deficits in ASD. There is also evidence of impoverished language and empathy, a profound inability to use standard nonverbal behaviors (eye contact, affective expression) to regulate social interactions with others, difficulties in showing empathy, failure to share enjoyment, interests and achievements with others, and a lack of social and emotional reciprocity. In developed countries, it is now reported that 1%-1.5% of children have ASD, and in the US 2015 CDC reports that approximately one in 45 children suffer from ASD. Despite the intense research focus on ASD in the last decade, the underlying etiology remains unknown. Genetic research involving twins and family studies strongly supports a significant contribution of environmental factors in addition to genetic factors in ASD etiology. A comprehensive literature search has implicated several environmental factors associated with the development of ASD. These include pesticides, phthalates, polychlorinated biphenyls, solvents, air pollutants, fragrances, glyphosate and heavy metals, especially aluminum used in vaccines as adjuvant. Importantly, the majority of these toxicants are some of the most common ingredients in cosmetics and herbicides to which almost all of us are regularly exposed to in the form of fragrances, face makeup, cologne, air fresheners, food flavors, detergents, insecticides and herbicides. In this review we describe various scientific data to show the role of environmental factors in ASD.
Assuntos
Transtorno do Espectro Autista/etiologia , Exposição Ambiental , Poluentes Ambientais/efeitos adversos , Substâncias Perigosas/efeitos adversos , Adolescente , Adulto , Transtorno do Espectro Autista/induzido quimicamente , Criança , Pré-Escolar , Feminino , Feto/efeitos dos fármacos , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-IdadeRESUMO
A genetic polymorphism in the vitronectin allele directs the production of two distinct forms of the 459 amino acid glycoprotein. A methionine present at position 381 favors production of the single-chain form of vitronectin, while threonine at this position increases the susceptibility of vitronectin to cleavage just beyond its heparin-binding domain at residue 379. This reaction gives rise to a disulfide-bonded, two-chain form of vitronectin. In order to investigate the functional significance of the vitronectin polymorphism, the baculovirus system has been used to express recombinant full-length vitronectin and a truncated form of the molecule that represents the 62-kDa fragment of two-chain vitronectin. Both forms of vitronectin bind and neutralize heparin anticoagulant activity. The proteins also bind PAI-1 and stabilize its active conformation. These experiments suggest that the C-terminal 80 amino acids do not confer a functional difference in the two allelic variants. Immunoassays and gel filtration experiments indicate that both full-length and truncated recombinant forms of vitronectin are multimeric. Together with other reports from this laboratory, these results provide information regarding the primary binding sites for two vitronectin ligands and further define regions that may be involved in multimerization of the protein.
Assuntos
Vitronectina/química , Animais , Linhagem Celular , Vetores Genéticos/genética , Heparina/metabolismo , Humanos , Substâncias Macromoleculares , Nucleopoliedrovírus/genética , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Conformação Proteica/efeitos dos fármacos , Estrutura Terciária de Proteína , Proteínas Recombinantes de Fusão/isolamento & purificação , Proteínas Recombinantes de Fusão/metabolismo , Deleção de Sequência , Spodoptera/citologia , Relação Estrutura-Atividade , Trombina/antagonistas & inibidores , Vitronectina/genética , Vitronectina/isolamento & purificação , Vitronectina/metabolismoAssuntos
Hematologia , Linfoma/tratamento farmacológico , Oncologia , Terapia Combinada , Alemanha , Humanos , São FranciscoRESUMO
Mammals can discriminate among a large number (> 10,000) of unique odorants. The most highly supported explanation for this ability is that olfactory neurons express a large number of seven transmembrane receptors that are not spatially organized at the level of the olfactory epithelium, but whose axonal projections form a distinct pattern within the olfactory bulb. The odor-induced signaling pathway in olfactory neurons includes a Gs-like protein (G(olf)) that activates a specific adenylyl cyclase (type III) isoform, resulting in elevations of cyclic AMP and subsequent activation of a cyclic nucleotide-gated channel. The channel also can be regulated by cyclic GMP. Recently, an olfactory neuron-specific guanylyl cyclase was discovered in rodents, and subsequently a large family of sensory neuronal guanylyl cyclases was identified in nematodes. These guanylyl cyclases are concentrated in the plasma membrane of the dendritic cilia and contain extracellular domains that retain many of the primary sequence characteristics of guanylyl cyclases known to be receptors for various peptides. Thus, the guanylyl cyclases appear to represent a second family of odorant/pheromone receptors.
Assuntos
Guanilato Ciclase/fisiologia , Receptores Odorantes/fisiologia , Animais , Humanos , Modelos Neurológicos , Condutos Olfatórios/fisiologia , Transdução de Sinais/fisiologia , Olfato/fisiologiaRESUMO
A primary heparin-binding site in vitronectin has been localized to a cluster of cationic residues near the C terminus of the protein. More recently, secondary binding sites have been proposed. In order to investigate whether the binding site originally identified on vitronectin functions as an exclusive and independent heparin-binding domain, solution binding methods have been used in combination with NMR and recombinant approaches to evaluate ligand binding to the primary site. Evaluation of the ionic strength dependence of heparin binding to vitronectin according to classical linkage theory indicates that a single ionic bond is prominent. It had been previously shown that chemical modification of vitronectin using an arginine-reactive probe results in a significant reduction in heparin binding (Gibson, A., Baburaj, K., Day, D. E., Verhamme, I. , Shore, J. D., and Peterson, C. B. (1997) J. Biol. Chem. 272, 5112-5121). The label has now been localized to arginine residues within the cyanogen bromide fragment-(341-380) that contains the primary heparin-binding site on vitronectin. One- and two-dimensional NMR on model peptides based on this primary heparin-binding site indicate that an arginine residue participates in the ionic interaction and that other nonionic interactions may be involved in forming a complex with heparin. A recombinant polypeptide corresponding to the C-terminal 129 amino acids of vitronectin exhibits heparin-binding affinity that is comparable to that of full-length vitronectin and is equally effective at neutralizing heparin anticoagulant activity. Results from this broad experimental approach argue that the behavior of the primary site is sufficient to account for the heparin binding activity of vitronectin and support an exposed orientation for the site in the structure of the native protein.