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1.
J Comp Pathol ; 181: 92-96, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33288158

RESUMO

Lesions caused by trombiculid mite larvae ('chiggers') in birds have been inadequately described. A juvenile red-legged partridge (Alectoris rufa) presented with multifocal, crater-like lesions of necrotizing dermatitis, which often contained multiple orange mites. Microscopically, there was a nodular necrotizing and pyogranulomatous dermatitis with occasional intralesional arthropods. Histologically, the mites were readily identified by the presence of stylostomes within the necrotic areas. Morphological and morphometrical studies on isolated mites identified them as Neoschoengastia (Hypogastia) simonovichi. This is the first report of N. simonovichi as an aetiological agent of severe trombiculosis in wild birds in Western Europe. Infestation with this parasite requires further study to understand its role in animal and human trombiculosis and its potential role as a vector of infectious, including zoonotic, agents.

2.
J Neurochem ; 2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33222205

RESUMO

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) exist in a variety of oligomeric forms, each with defined cellular and subcellular distributions. Although crystal structures of AChE and BChE have been available for many years, structures of the physiologically relevant ChE tetramer were only recently solved by cryo-electron microscopy (cryo-EM) single-particle analysis. Here, we briefly review how these structures contribute to our understanding of cholinesterase oligomerization, highlighting the advantages of using cryo-EM to resolve structures of protein assemblies that cannot be expressed recombinantly. We argue that the next frontier in cholinesterase structural biology is to image membrane-anchored ChE oligomers directly in their native environment-the cell.

3.
Animals (Basel) ; 10(11)2020 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-33114458

RESUMO

Four hundred and ninety-eight culled sheep received at the Ruminant Clinical Service of the Veterinary Faculty of Zaragoza, Spain, were examined in life and after humanitarian sacrifice in order to reach the final diagnosis of the cause of culling and to evaluate the presence of caseous lymphadenitis (CLA) lesions. One hundred and forty-seven of the 498 studied animals (29.52%) showed CLA compatible lesions that were subsequently confirmed by Corynebacterium pseudotuberculosis isolation. One hundred and seven of the 147 CLA affected animals presenting the visceral clinical form of the disease (72.79%), while only 32 animals were affected by the superficial form (21.77%). In addition, eight animals were found to be affected in both the visceral and the superficial presentations (5.44%). Eighty-four of the 147 CLA-affected animals (57.14%) did not show any concurrent disease, considering, in this case, CLA the main cause of culling (84/498: 16.87%). In the superficial presentation, the retropharyngeal lymph node, as a sole lesion, was the most frequently affected (13/32: 40.63%). Further, in the visceral form of the disease, 85.06% of the affected animals had the lesions located in the respiratory system (91/107: 85.06%). CLA was revealed as an important cause of culling in sheep production.

4.
J Virol ; 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33115880

RESUMO

Aluminum (Al)-based salts are widely used adjuvants in ruminants and other species strengthening the immune response elicited against vaccine antigen/s. However, they can lead to the formation of long-lasting granulomas composed of abundant activated macrophages. Small ruminant lentiviruses (SRLV) are widely distributed macrophage-tropic retroviruses that cause persistent infections in sheep and goats. Infected monocytes/macrophages and dendritic cells establish an inflammatory microenvironment that eventually leads to clinical manifestations. The aim of this work was to study the effect of Al-induced granulomas in the replication and pathogenesis of SRLV. Eleven adult, naturally SRLV-infected sheep showing clinical arthritis were distributed in Vaccine (n=6), Adjuvant-only (n=3) and Control (n=2) groups and inoculated with commercial Al-based vaccines, Al hydroxide adjuvant or phosphate buffered saline, respectively. In vitro studies demonstrated viral replication in Al-induced granulomas in 5 out of 10 sheep. Immunohistochemistry (IHC) evinced granular, intracytoplasmic SRLV presence in macrophages within granulomas. Viral sequences obtained from granulomas, blood monocytes and other tissues were highly similar in most animals, suggesting virus circulation among body compartments. However, notable differences between isolated strains in granulomas and other tissues in specific animals were also noted. Interestingly, the B2 subtype was the most commonly found SRLV genotype reaching a wider body distribution than previously described. Recombination events between genotypes B2 and A3 along gag region were identified in two sheep. Our results indicate that Al-hydroxide derived granulomas may represent an ideal compartment for SRLV replication, perhaps altering natural SRLV infection by providing a new, suitable target tissue.IMPORTANCE Granulomas are inflammation-derived structures elicited by foreign bodies or certain infections. Aluminum adjuvants included in vaccines induce granulomas in many species. In sheep, these are persistent and consist of activated macrophages. Small Ruminant Lentiviruses (SRLV), which are macrophage-tropic lentivirus, cause a chronic wasting disease affecting animal welfare and production. Here, we studied the occurrence of SRLV in post-vaccination granulomas retrieved from naturally infected ewes after vaccination or inoculation with aluminum only. SRLV infection was confirmed in granulomas by identification of viral proteins, genomic fragments and enzymatic activity. The infecting SRLV strain, previously found exclusively in carpal joints, reached the central nervous system, suggesting that occurrence of SRLV in post-vaccination granulomas may broaden tissue tropism. SRLV recombination was found in inoculated animals, a rare event in sheep lentiviruses. Potentially, virus-host interactions within granulomas may modify viral pathogenesis and lead to more widespread infection.

5.
Open Biol ; 10(9): 200186, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32931719

RESUMO

Mammalian gametes-the sperm and the egg-represent opposite extremes of cellular organization and scale. Studying the ultrastructure of gametes is crucial to understanding their interactions, and how to manipulate them in order to either encourage or prevent their union. Here, we survey the prominent electron microscopy (EM) techniques, with an emphasis on considerations for applying them to study mammalian gametes. We review how conventional EM has provided significant insight into gamete ultrastructure, but also how the harsh sample preparation methods required preclude understanding at a truly molecular level. We present recent advancements in cryo-electron tomography that provide an opportunity to image cells in a near-native state and at unprecedented levels of detail. New and emerging cellular EM techniques are poised to rekindle exploration of fundamental questions in mammalian reproduction, especially phenomena that involve complex membrane remodelling and protein reorganization. These methods will also allow novel lines of enquiry into problems of practical significance, such as investigating unexplained causes of human infertility and improving assisted reproductive technologies for biodiversity conservation.

6.
Transbound Emerg Dis ; 2020 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-32386079

RESUMO

Bovine viral diarrhoea virus (BVDV) is a pestivirus that affects both cattle and sheep, causing an array of clinical signs, which include abortions and malformations in the offspring. Manufacturing of modified live virus (MLV) vaccines often includes the use of bovine-derived products, which implies a risk of contamination with viable BVDV. Recently, the circulation of a specific strain of BVDV 2b among Spanish sheep flocks, associated with outbreaks of abortions and malformations, and whose origin was not determined, has been observed. On February 2018, a MLV orf vaccine was applied to a 1,600 highly prolific sheep flock in the Northeast of Spain that included 550 pregnant ewes. In May 2018, during the lambing season, an unusual high rate (72.7%) of abortions, stillbirths, congenital malformations and neurological signs in the offspring was observed. It was estimated that about 1,000 lambs were lost. Three 1- to 3-day-old affected lambs and a sealed vial of the applied vaccine were studied. Lambs showed variable degrees of central nervous system malformations and presence of pestiviral antigen in the brain. Molecular studies demonstrated the presence of exactly the same BVDV 2b in the tissues of the three lambs and in the orf vaccine, thus pointing to a pestivirus contamination in the applied vaccine as the cause of the outbreak. Interestingly, sequencing at the 5'-untranslated region-(UTR) of the contaminating virus showed a complete match with the virus described in the previously reported outbreaks in Spain, thus indicating that the same contaminated vaccine could have also played a role in those cases. This communication provides a clear example of the effects of the application of this contaminated product in a sheep flock. The information presented here can be of interest in putative future cases of suspected circulation of this or other BVDV strains in ruminants.

7.
Front Vet Sci ; 7: 182, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32426375

RESUMO

Small ruminant lentiviruses (SRLVs) are endemic in most areas of Europe, causing a chronic infection and a multisystemic disease affecting the udder, carpal joints, lungs, and central nervous system. Due to the lack of treatments and protective vaccination strategies, infection control is focused on the identification of infected animals through serological or molecular techniques. However, antigenic and genetic heterogeneity of SRLVs represent a clear drawback for diagnosis. Infected animals may present lower animal production parameters such as birth weight or milk production and quality, depending on productive systems considered and, likely, to the diagnostic method applied. In this study, four sheep flocks dedicated to dairy or meat production were evaluated using three different ELISA and two PCR strategies to classify animal population according to SRLV infection status. Productive parameters were recorded along one whole lactation or reproductive period and compared between positive and negative animals. SRLV was present in 19% of the total population, being unequally distributed in the different flocks. Less than half of the infected animals were detected by a single diagnostic method, highlighting the importance of combining different diagnostic techniques. Statistical analysis employing animal classification using all the diagnostic methods associated lambing size, lamb weight at birth, and daily weight gain with SRLV infection status in meat flocks. Milk production, somatic cell count, fat, and protein content in the milk were associated with SRLV infection in dairy flocks, to a greater extent in the flock showing higher seroprevalence. A multi-platform SRLV diagnostic strategy was useful for ensuring correct animal classification, thus validating downstream studies investigating production traits.

8.
J Inorg Biochem ; 204: 110871, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31901536

RESUMO

The use of vaccines containing aluminum (Al) adjuvants is widespread in ovine production. Al adjuvants induce an effective immune-response but lead to the formation of post-vaccination granulomas from which Al can disseminate. This work aims to study the accumulation of Al in the central nervous system of sheep subcutaneously inoculated with Al-hydroxide containing products. Lumbar spinal cord and parietal lobe from 21 animals inoculated with 19 doses of Vaccine (n = 7), Adjuvant-only (n = 7) or phosphate-buffered saline as Control (n = 7) were analyzed with transversely heated graphite furnace atomic absorption spectroscopy and lumogallion staining for Al analytical measurements and Al tisular localization respectively. In the lumbar spinal cord, Al median content was higher in both the Adjuvant-only and Vaccine group (p = .001) compared with the Control group. Animals of the Adjuvant-only group showed the higher individual measurements in the lumbar spinal cord (14.36 µg/g and 7.83 µg/g). In the parietal lobe, Al median content tended to be higher in the Adjuvant-only group compared with Control group (p = .074). Except for three replicates of the Adjuvant-only group, Al content was always below 1 µg/g. In the lumbar spinal cord, lumogallion-reactive Al deposits were more abundant in the gray matter than in the white matter in both Vaccine (p = .034) and Adjuvant-only groups (p = .017) and Al deposits were mostly associated with glial-like cells (p = .042). In the parietal lobe, few Al deposits, which were sometimes related to blood vessels, were found. In sheep, Al-hydroxide adjuvants inoculated in the subcutaneous tissue selectively accumulate in the lumbar spinal cord.

9.
Rev. colomb. cancerol ; 23(3): 92-98, jul.-set. 2019. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1042760

RESUMO

Resumen Objetivos: Los tumores del timo tienen incidencia global de 0,13 por 100.000 habitantes, pero representan un importante porcentaje de tumores del mediastino. Hay poca literatura basada en nuestra población, por esto, hacemos un aporte de nuestra experiencia en el Instituto Nacional de Cancerología (INC). Métodos: Se hizo un estudio tipo series de caso, revisando las historias clínicas de los pacientes con tumores del timo tratados en el INC entre 2006 y 2017. Resultados: Desde el 2006 al 2017 se encontraron 31 pacientes con tumores del timo tales como timoma, hiperplasia tímica, quistes tímicos y carcinomas tímicos, predominando en el género femenino y con una mediana de 62 años de edad. 2 pacientes presentaron miastenia gravis (MG). 27 fueron sometidos a timectomía por medio de esternotomía, videotoracoscopia, toracotomía, entre otros, obteniendo una supervivencia global mayor al 90% a 5 años de seguimiento. Los estadios de Masaoka I, II y III tienen mejor pronóstico que los tipos IV independientemente de la histología. Conclusiones: La timectomía es el tratamiento de primera línea en los casos resecables, incluso en los que existe compromiso de estructuras vecinas que permiten una resección quirúrgica completa. Los resultados presentados describen conductas y resultados similares a los encontrados en la literatura mundial.


Abstract Objectives: Thymic tumors have an overall incidence of 0.13 per 100,000 inhabitants, but they represent a significant percentage of mediastinal tumors. There is little literature based on our population, we make a contribution of our experience in the National Cancer Institute. Methods: We did a case series study, reviewing the clinical histories of patients with thymic tumors treated at the National Cancer Institute from 2006 to 2017. Results: From 2006 to 2017, 31 patients with thymic tumors such as thymoma, thymic hyperplasia, thymic cysts and thymic carcinomas were found, mainly in the female gender and with a median of 62 years of age. 2 patients presented Myasthenia Gravis (MG). 27 patients underwent thymectomy through sternotomy, video-thoracoscopy, thoracostomy among others, obtaining an overall survival greater than 90% at 5 years of follow-up. The stages of Masaoka I, II and III have a better prognosis than type IV regardless of the histological type. Conclusions: Thymectomy is the first-line treatment in resectable cases, even when there is a compromise of nearby structures that allow a complete surgical resection. Our results describe behaviors and results similar to those found in the world literature.


Assuntos
Humanos , Hiperplasia do Timo
10.
ACS Sens ; 4(6): 1654-1661, 2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31117363

RESUMO

Reliable and fast viral detection and quantification protocols are a requirement for the advance of basic research and clinical approaches with wild type or recombinant viruses. However, available cell-based assays are either time-consuming or require labeled viral particles, which may alter virus biology or pose safety issues in clinical applications. Since adenoviruses constitute a major healthcare burden but also, when engineered, widely used vectors in vaccination and gene and oncolytic therapies, herein we developed a genetically encoded switch-on fluorescent biosensor consisting of a cyclized Green fluorescent protein-cVisensor-with an adenoviral protease cleavable site as a switch. After initial sensor optimization (35% increase in performance), whole-cell biosensors were established-by stably expressing cVisensor in mammalian cells-and used for live-cell monitoring of adenovirus infection as the intracellular biosensor is specifically activated by the viral protease. A rapid flow cytometry-based bioassay using cVisensor cells was established 48 h postinfection, showing an estimated limit of detection of 105 infectious particles/mL, in-line with previously reported flow cytometry assays requiring labeled virus, and significantly faster than standard plaque-forming assays requiring up to 14 days. cVisensor was also successfully applied in the detection of HIV-1 protease activity, validating its wider potential for the detection of other viruses. Overall, this work presents a fast and easy method for detection and quantification of label-free infectious virus, allowing the establishment of new biosensing platforms for basic research in virology and biotechnological applications of recombinant virus biopharmaceuticals.


Assuntos
Adenoviridae/isolamento & purificação , Técnicas Biossensoriais/métodos , Corantes Fluorescentes/química , Proteínas de Fluorescência Verde/química , Infecções por Adenoviridae/diagnóstico , Corantes Fluorescentes/metabolismo , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Células HEK293 , Protease de HIV/análise , Protease de HIV/metabolismo , HIV-1/enzimologia , HIV-1/isolamento & purificação , Humanos , Inteínas , Limite de Detecção , Nostoc/química , Engenharia de Proteínas/métodos , Proteólise
11.
Ann Cardiothorac Surg ; 8(2): 233-240, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31032207

RESUMO

Background: Robotic assisted videothoracoscopic surgery (RVATS) adoption has increased worldwide from 3.4% in 2010 to 17.5% in 2015. However, in Latin America, the literature is limited to a report of a series of 10 patients who underwent RVATS lobectomy and one case report of an RVATS thymectomy from Brazil. Methods: This is a retrospective review of all RVATS performed in Bogotá Colombia since 2012. A single thoracic surgeon (RB) performed all the operations at three institutions: Clínica de Marly, Fundación Clínica Shaio and Instituto Nacional de Cancerología. Preoperative, intraoperative, postoperative and pathology report variables were included. Patients were analyzed in three groups: robotic RVATS pulmonary resections, RVATS mediastinal surgeries and other RVATS procedures. Descriptive statistics were used to report the median and interquartile range (IQR) of the continuous variables, and number and percentage were used to describe categorical variables. The association between total operative time and the year the surgery was analyzed using a linear regression model. Results: Forty-seven patients underwent RVATS pulmonary resections; 72.3% (n=34) of these patients underwent a RVATS lobectomy. The median total operative time was 220 (IQR: 200 to 250) minutes, 6.4% (n=3) had intraoperative complications, and the most frequent histologic diagnosis was adenocarcinoma (n=24, 51.1%). Of 18 patients who underwent RVATS mediastinal surgeries, 50.0% (n=9) had RVATS thymectomy, the median total operative time was 195.5 (IQR: 131 to 221) minutes and two patients (11.1%) had intraoperative complications. The linear regression model of the association between total operative time and the year the surgery showed a 10.3 minute reduction per year (P=0.006). Conclusions: This is the second series of RVATS published in Latin America and the first published in Colombia, with comparable perioperative results to other reports.

12.
J Mol Endocrinol ; 62(3): 117-128, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30689545

RESUMO

The crystal structures of the thyroid-stimulating hormone receptor (TSHR) leucine-rich repeat domain (amino acids 22-260; TSHR260) in complex with a stimulating human monoclonal autoantibody (M22TM) and in complex with a blocking human autoantibody (K1-70™) have been solved. However, attempts to purify and crystallise free TSHR260, that is not bound to an autoantibody, have been unsuccessful due to the poor stability of free TSHR260. We now describe a TSHR260 mutant that has been stabilised by the introduction of six mutations (H63C, R112P, D143P, D151E, V169R and I253R) to form TSHR260-JMG55TM, which is approximately 900 times more thermostable than wild-type TSHR260. These six mutations did not affect the binding of human TSHR monoclonal autoantibodies or patient serum TSHR autoantibodies to the TSHR260. Furthermore, the response of full-length TSHR to stimulation by TSH or human TSHR monoclonal autoantibodies was not affected by the six mutations. Thermostable TSHR260-JMG55TM has been purified and crystallised without ligand and the structure solved at 2.83 Å resolution. This is the first reported structure of a glycoprotein hormone receptor crystallised without ligand. The unbound TSHR260-JMG55TM structure and the M22 and K1-70 bound TSHR260 structures are remarkably similar except for small changes in side chain conformations. This suggests that neither the mutations nor the binding of M22TM or K1-70TM change the rigid leucine-rich repeat domain structure of TSHR260. The solved TSHR260-JMG55TM structure provides a rationale as to why the six mutations have a thermostabilising effect and provides helpful guidelines for thermostabilisation strategies of other soluble protein domains.


Assuntos
Cristalografia por Raios X/métodos , Leucina/química , Proteínas/metabolismo , Receptores da Tireotropina/sangue , Receptores da Tireotropina/química , Autoanticorpos/sangue , Humanos , Mutação/genética , Domínios Proteicos , Proteínas/química , Proteínas/genética , Receptores Acoplados a Proteínas-G/sangue , Receptores Acoplados a Proteínas-G/química , Receptores Acoplados a Proteínas-G/genética , Receptores da Tireotropina/genética
13.
Proc Natl Acad Sci U S A ; 115(52): 13270-13275, 2018 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-30538207

RESUMO

The quaternary structures of the cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), are essential for their localization and function. Of practical importance, BChE is a promising therapeutic candidate for intoxication by organophosphate nerve agents and insecticides, and for detoxification of addictive substances. Efficacy of the recombinant enzyme hinges on its having a long circulatory half-life; this, in turn, depends strongly on its ability to tetramerize. Here, we used cryoelectron microscopy (cryo-EM) to determine the structure of the highly glycosylated native BChE tetramer purified from human plasma at 5.7 Å. Our structure reveals that the BChE tetramer is organized as a staggered dimer of dimers. Tetramerization is mediated by assembly of the C-terminal tryptophan amphiphilic tetramerization (WAT) helices from each subunit as a superhelical assembly around a central lamellipodin-derived oligopeptide with a proline-rich attachment domain (PRAD) sequence that adopts a polyproline II helical conformation and runs antiparallel. The catalytic domains within a dimer are asymmetrically linked to the WAT/PRAD. In the resulting arrangement, the tetramerization domain is largely shielded by the catalytic domains, which may contribute to the stability of the human BChE (HuBChE) tetramer. Our cryo-EM structure reveals the basis for assembly of the native tetramers and has implications for the therapeutic applications of HuBChE. This mode of tetramerization is seen only in the cholinesterases but may provide a promising template for designing other proteins with improved circulatory residence times.


Assuntos
Acetilcolinesterase/química , Butirilcolinesterase/química , Microscopia Crioeletrônica/métodos , Conformação Proteica , Multimerização Proteica , Cristalografia por Raios X , Humanos
14.
Rev. colomb. gastroenterol ; 33(4): 448-453, oct.-dic. 2018. graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-985498

RESUMO

Resumen Introducción: los leiomiomas esofágicos son tumores benignos, que son resecados por enucleación esofágica cuando son mayores de 5 cm o en lesiones de cualquier tamaño que sean sintomáticos o sospechosos de malignidad. Tradicionalmente, se ha realizado la resección por técnica de enucleación abierta; sin embargo, la cirugía mínimamente invasiva ha surgido como una técnica con grandes ventajas y, en especial, la tecnología robótica parece ofrecer ventajas. Caso clínico: se reporta un caso de leiomioma esofágico del esófago medio con enucleación mediante el uso de una técnica toracoscópica asistida por robot. La esofagoscopia intraoperatoria y la transiluminación fueron complementos útiles para identificar el esófago y desarrollar un plano de disección extramucosa seguro, que junto con la asistencia robótica parecen minimizar los riesgos intraoperatorios, entre ellos, potencialmente la probabilidad de lesión mucosa, y mejoran el tiempo de recuperación postoperatoria.


Abstract Introduction: Esophageal leiomyomas are benign tumors which are resected by esophageal enucleation when they are symptomatic, suspected of malignancy, or larger than 5 cm. Traditional resection uses the open enucleation technique, but minimally invasive surgery has emerged as a technique that has great advantages, especially when combined with robotic technology. Case report: We report a case of leiomyoma of the middle esophagus with treated with enucleation using a robotic-assisted thoracoscopic technique. Intraoperative esophagoscopy and transillumination were useful for identifying the esophagus and developing a plan of safe extra mucosal dissection. Together with robotic assistance this seems to minimize intraoperative risks including that of mucosal injury while also improving postoperative recovery time.

15.
J Struct Biol ; 202(2): 150-160, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29289599

RESUMO

Cellular electron cryo-tomography enables the 3D visualization of cellular organization in the near-native state and at submolecular resolution. However, the contents of cellular tomograms are often complex, making it difficult to automatically isolate different in situ cellular components. In this paper, we propose a convolutional autoencoder-based unsupervised approach to provide a coarse grouping of 3D small subvolumes extracted from tomograms. We demonstrate that the autoencoder can be used for efficient and coarse characterization of features of macromolecular complexes and surfaces, such as membranes. In addition, the autoencoder can be used to detect non-cellular features related to sample preparation and data collection, such as carbon edges from the grid and tomogram boundaries. The autoencoder is also able to detect patterns that may indicate spatial interactions between cellular components. Furthermore, we demonstrate that our autoencoder can be used for weakly supervised semantic segmentation of cellular components, requiring a very small amount of manual annotation.


Assuntos
Microscopia Crioeletrônica/métodos , Processamento de Imagem Assistida por Computador/métodos , Substâncias Macromoleculares/química , Software , Algoritmos
16.
Ecol Evol ; 7(16): 6519-6526, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28861253

RESUMO

Water pollution due to human activities produces sedimentation, excessive nutrients, and toxic chemicals, and this, in turn, has an effect on the normal endocrine functioning of living beings. Overall, water pollution may affect some components of the fitness of organisms (e.g., developmental time and fertility). Some toxic compounds found in polluted waters are known as endocrine disruptors (ED), and among these are nonhalogenated phenolic chemicals such as bisphenol A and nonylphenol. To evaluate the effect of nonhalogenated phenolic chemicals on the endocrine system, we subjected two generations (F0 and F1) of Drosophila melanogaster to different concentrations of ED. Specifically, treatments involved wastewater, which had the highest level of ED (bisphenol A and nonylphenol) and treated wastewater from a constructed Heliconia psittacorum wetland with horizontal subsurface water flow (He); the treated wastewater was the treatment with the lowest level of ED. We evaluated the development time from egg to pupa and from pupa to adult as well as fertility. The results show that for individuals exposed to treated wastewater, the developmental time from egg to pupae was shorter in individuals of the F1 generation than in the F0 generation. Additionally, the time from pupae to adult was longer for flies growing in the H. psittacorum treated wastewater. Furthermore, fertility was lower in the F1 generation than in the F0 generation. Although different concentrations of bisphenol A and nonylphenol had no significant effect on the components of fitness of D. melanogaster (developmental time and fertility), there was a trend across generations, likely as a result of selection imposed on the flies. It is possible that the flies developed different strategies to avoid the effects of the various environmental stressors.

18.
Auto Immun Highlights ; 8(1): 2, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27921237

RESUMO

PURPOSE: The thyroid-stimulating hormone receptor (TSHR) is the target autoantigen for TSHR-stimulating autoantibodies in Graves' disease. The TSHR is composed of: a leucine-rich repeat domain (LRD), a hinge region or cleavage domain (CD) and a transmembrane domain (TMD). The binding arrangements between the TSHR LRD and the thyroid-stimulating autoantibody M22 or TSH have become available from the crystal structure of the TSHR LRD-M22 complex and a comparative model of the TSHR LRD in complex with TSH, respectively. However, the mechanism by which the TMD of the TSHR and the other glycoprotein hormone receptors (GPHRs) becomes activated is unknown. METHODS: We have generated comparative models of the structures of the inactive (TMD_In) and active (TMD_Ac) conformations of the TSHR, follicle-stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHR) TMDs. The structures of TMD_Ac and TMD_In were obtained using class A GPCR crystal structures for which fully active and inactive conformations were available. RESULTS: Most conserved motifs observed in GPCR TMDs are also observed in the amino acid sequences of GPHR TMDs. Furthermore, most GPCR TMD conserved helix distortions are observed in our models of the structures of GPHR TMDs. Analysis of these structures has allowed us to propose a mechanism for activation of GPHR TMDs. CONCLUSIONS: Insight into the mechanism of activation of the TSHR by both TSH and TSHR autoantibodies is likely to be useful in the development of new treatments for Graves' disease.

19.
J Mol Endocrinol ; 58(1): 25-41, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27875255

RESUMO

We have studied glycosylation patterns in glycoprotein hormones (GPHs) and glycoprotein hormone receptor (GPHR) extracellular domains (ECD) from different species to identify areas not glycosylated that could be involved in intermolecular or intramolecular interactions. Comparative models of the structure of the TSHR ECD in complex with TSH and in complex with TSHR autoantibodies (M22, stimulating and K1-70, blocking) were obtained based on the crystal structures of the FSH-FSHR ECD, M22-TSHR leucine-rich repeat domain (LRD) and K1-70-TSHR LRD complexes. The glycosylation sites of the GPHRs and GPHs from all species studied were mapped on the model of the human TSH TSHR ECD complex. The areas on the surfaces of GPHs that are known to interact with their receptors are not glycosylated and two areas free from glycosylation, not involved in currently known interactions, have been identified. The concave faces of GPHRs leucine-rich repeats 3-7 are free from glycosylation, consistent with known interactions with the hormones. In addition, four other non-glycosylated areas have been identified, two located on the receptors' convex surfaces, one in the long loop of the hinge regions and one at the C-terminus of the extracellular domains. Experimental evidence suggests that the non-glycosylated areas identified on the hormones and receptors are likely to be involved in forming intramolecular or intermolecular interactions.


Assuntos
Glicoproteínas/metabolismo , Hormônios Peptídicos/metabolismo , Receptores de Peptídeos/metabolismo , Sequência de Aminoácidos , Aminoácidos/metabolismo , Animais , Glicoproteínas/química , Glicosilação , Humanos , Modelos Moleculares , Hormônios Peptídicos/química , Ligação Proteica , Conformação Proteica , Domínios e Motivos de Interação entre Proteínas , Receptores de Peptídeos/química , Receptores da Tireotropina/química , Receptores da Tireotropina/metabolismo , Relação Estrutura-Atividade , Tireotropina/química , Tireotropina/metabolismo
20.
Rev. luna azul ; (41): 89-115, jul.-dic. 2015. ilus, graf, tab
Artigo em Espanhol | LILACS-Express | LILACS | ID: lil-783573

RESUMO

Objetivo: Presentar algunos hallazgos relacionados con el proceso de integración regional Bogotá-Cundinamarca en el periodo 2000-2010, en particular la dimensión ambiental, en las provincias de sabana occidente y sabana centro que hacen parte de esta región. Metodología: El estudio se basa en el análisis de los cambios presentados en el ambiente natural de los territorios objeto de estudio, durante el periodo de tiempo considerado (2000-2010), desde la perspectiva de los actores del mismo. En este caso, a través de ejercicios de participación en talleres realizados en los municipios objeto de estudio con dichos actores (representados en organizaciones sociales que tienen presencia allí) e incluyó recorridos en dichos territorios. Se pretende construir colectivamente información y conocimiento, planteando una línea del tiempo en la que los actores reconozcan momentos clave con referencia a dos grandes fenómenos que se presentaron: asentamientos humanos (urbanización) y entrada de empresas. Esta línea abarca la primera década del presente siglo. Resultados: La investigación intenta mostrar que dos elementos: asentamientos urbanos y entrada de empresas, son las dinámicas antrópicas que impactan los territorios, olvidando el elemento agua, como eje fundamental sobre el cual debería ordenarse el territorio. De ello se deriva que la misma comunidad reconoce que el ordenamiento del territorio nunca consultó sus intereses.


Objective: regional integration in the period 2000-2010, particularly the environmental dimension in the Western and Central Bogotá-Cundinamarca Savannah. Methodology: The study is based on the analysis of the changes shown in the natural environment of the territories under study during the period considered (2000-2010) from their actors' perception..In this case, through the participation exercises in workshops carried out in the municipalities under study with those actors (represented in social organizations present in the area), and included tours around those territories It is intended to collectively build information and knowledge presenting a timeline in which the actors recognize key moments with reference to two major events: Human Settlements (urbanization) and enterprise arrival. This line comprises the first decade of the current century. Results: The research attempts to show that two elements, urban settlements and enterprises arrival, are the anthropic dynamics that impact the territories forgetting the water element as the fundamental axis from which the territory should be planned. From this it is derived that the community recognizes that land use planning never consulted their interests.

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