RESUMO
Epithelial to mesenchymal transition (EMT) is a process whereby epithelial cells undergo transition to a mesenchymal phenotype and contribute directly to fibrotic disease. Recent studies support a role for EMT in cutaneous fibrotic diseases including scleroderma and hypertrophic scarring, although there is limited data on the cytokines and signalling mechanisms regulating cutaneous EMT. We investigated the ability of TGF-ß and TNF-α, both overexpressed in cutaneous scleroderma and central mediators of EMT in other epithelial cell types, to induce EMT in primary keratinocytes and studied the signalling mechanisms regulating this process. TGF-ß induced EMT in normal human epidermal keratinocytes (NHEK cells), and this process was enhanced by TNF-α. EMT was characterised by changes in morphology, proteome (down-regulation of E-cadherin and Zo-1 and up-regulation of vimentin and fibronectin), MMP secretion and COL1α1 mRNA expression. TGF-ß and TNF-α in combination activated SMAD and p38 signalling in NHEK cells. P38 inhibition with SB203580 partially attenuated EMT, whereas SMAD inhibition using SB431542 significantly inhibited EMT and also reversed established EMT. These data highlight the retained plasticity of adult keratinocytes and support further studies of EMT in clinically relevant in vivo models of cutaneous fibrosis and investigation of SMAD inhibition as a potential therapeutic intervention.
Assuntos
Transição Epitelial-Mesenquimal , Queratinócitos/citologia , Proteínas Smad/antagonistas & inibidores , Proteínas Smad/metabolismo , Benzamidas/química , Colágeno/metabolismo , Citocinas/metabolismo , Dioxóis/química , Regulação para Baixo , Células Epidérmicas , Fibronectinas/metabolismo , Fibrose/metabolismo , Humanos , Metaloproteinases da Matriz/metabolismo , Proteínas Recombinantes/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Vimentina/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Systemic sclerosis is an autoimmune connective tissue disorder, which can be progressive with multisystem involvement. Guidance on the management of complications is based on a limited data set and practice amongst clinicians can vary. The UK Scleroderma study group set up several working groups to agree some consensus pathways for the management of specific complications. Approximately nine out of ten patients with systemic sclerosis will have involvement of the gastrointestinal system and in this review article we explore the management of these complications in a symptom-based approach. The algorithms are a useful tool for clinicians, which we hope, will be a point of reference and highlight the need for further research in these areas.
Assuntos
Gastroenteropatias/terapia , Escleroderma Sistêmico/terapia , Dor Abdominal/etiologia , Dor Abdominal/terapia , Consenso , Constipação Intestinal/etiologia , Constipação Intestinal/terapia , Diarreia/etiologia , Diarreia/terapia , Transtornos da Motilidade Esofágica/etiologia , Transtornos da Motilidade Esofágica/terapia , Incontinência Fecal/etiologia , Incontinência Fecal/terapia , Refluxo Gastroesofágico/etiologia , Refluxo Gastroesofágico/terapia , Gastroenteropatias/etiologia , Humanos , Desnutrição/etiologia , Desnutrição/terapia , Guias de Prática Clínica como Assunto , Escleroderma Sistêmico/complicações , Reino UnidoRESUMO
INTRODUCTION: Pulmonary complications in systemic sclerosis (SSc) significantly increase morbidity and mortality. Our aim was to determine the factors limiting exercise capacity in SSc patients with and without interstitial lung disease (ILD), and to identify and quantify abnormalities during exercise that might assist in clinical assessment of this complication. METHODS: Fifteen patients with SSc and ILD (SSc-ILD) were compared with 10 patients with SSc without ILD and 9 age- and sex-matched normal volunteers. Subjects performed symptom-limited incremental treadmill exercise with online measurement of respiratory gas exchange, arterial blood gas sampling and measurement of neurohormones in venous blood. RESULTS: Patients with SSc-ILD had lower exercise capacity than SSc patients without ILD or normal subjects (peak oxygen consumption (PVÌO2 ) (17.1 [4.2] vs. 22.0 [4.7] and 23.0 [5.4] ml kg-1 min-1 , respectively, mean [SD], p < 0.01 ANOVA), but PVÌO2 did not correlate with static pulmonary function measurements. Ventilatory equivalent for CO2 (VÌE/VÌCO2 ; nadir) was higher in SSc-ILD patients than the other two groups (36.6 [8.0] vs. 29.9 [4.4] and 30.0 [2.5], p < 0.005) as were peak exercise dead-space tidal volume ratio (0.44 [0.06] vs. 0.26 [0.09] and 0.26 [0.05], p < 0.001) and peak exercise alveolar-arterial difference (28.9 [16.9] vs. 18.8 [14.0] and 11.5 [6.9] mmHg, p < 0.05). Atrial natriuretic peptide was elevated in both SSc patient groups. CONCLUSIONS: SSc-ILD results in lower exercise capacity than SSc without ILD, and abnormalities of gas exchange are seen. The possible use of cardiopulmonary exercise testing to identify disease and quantify impairment in SSc-ILD merits further study.
Assuntos
Hipertensão Pulmonar , Doenças Pulmonares Intersticiais , Escleroderma Sistêmico , Humanos , Pulmão , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/complicações , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico , Teste de Esforço/métodosRESUMO
Amphibian defensive skin secretions are known to contain a plethora of biologically-active peptides that are often structural and functional analogues of vertebrate neuropeptides. Here we report the structures of two invertebrate neuropeptide analogues, IPPQFMRF amide (IF-8 amide) and EGDEDEFLRF amide (EF-10 amide), from the defensive skin secretions of two different species of African hyperoliid frogs, Kassina maculata and Phylictimantis verrucosus, respectively. These represent the first canonical FMRF amide-related peptides (FaRPs) from a vertebrate source. The cDNA encoding IF-8 amide was cloned from a skin secretion library and found to contain a single copy of the peptide located at the C-terminus of a 58 amino acid residue open-reading frame. These data extend the potential targets of the defensive arsenal of amphibian tegumental secretions to parasitic/predatory invertebrates and the novel peptides described may represent the first vertebrate peptidic endectocides.
Assuntos
Anuros/imunologia , FMRFamida/imunologia , Pele/metabolismo , Sequência de Aminoácidos , Animais , Anuros/genética , Clonagem Molecular , DNA Complementar/genética , FMRFamida/química , FMRFamida/genética , FMRFamida/metabolismo , Dados de Sequência Molecular , Radioimunoensaio , Pele/imunologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
Inadequate information on the geographical distribution of biodiversity hampers decision-making for conservation. Major efforts are underway to fill knowledge gaps, but there are increasing concerns that publishing the locations of species is dangerous, particularly for species at risk of exploitation. While we recognize that well-informed control of location data for highly sensitive taxa is necessary to avoid risks, such as poaching or habitat disturbance by recreational visitors, we argue that ignoring the benefits of sharing biodiversity data could unnecessarily obstruct conservation efforts for species and locations with low risks of exploitation. We provide a decision tree protocol for scientists that systematically considers both the risks of exploitation and potential benefits of increased conservation activities. Our protocol helps scientists assess the impacts of publishing biodiversity data and aims to enhance conservation opportunities, promote community engagement and reduce duplication of survey efforts.
Assuntos
Biodiversidade , Árvores de Decisões , Disseminação de Informação , Animais , Comportamento Criminoso , Humanos , Editoração , RiscoRESUMO
Australian rangelands ecosystems cover 81% of the continent but are understudied and continental-scale research has been limited in part by a lack of precise data that are standardised between jurisdictions. We present a new dataset from AusPlots Rangelands that enables integrative rangelands analysis due to its geographic scope and standardised methodology. The method provides data on vegetation and soils, enabling comparison of a suite of metrics including fractional vegetation cover, basal area, and species richness, diversity, and composition. Cover estimates are robust and repeatable, allowing comparisons among environments and detection of modest change. The 442 field plots presented here span a rainfall gradient of 129-1437 mm Mean annual precipitation with varying seasonality. Vegetation measurements include vouchered vascular plant species, growth form, basal area, height, cover and substrate type from 1010 point intercepts as well as systematically recorded absences, which are useful for predictive modelling and validation of remote sensing applications. Leaf and soil samples are sampled for downstream chemical and genomic analysis. We overview the sampling of vegetation parameters and environments, applying the data to the question of how species abundance distributions (SADs) vary over climatic gradients, a key question for the influence of environmental change on ecosystem processes. We found linear relationships between SAD shape and rainfall within grassland and shrubland communities, indicating more uneven abundance in deserts and suggesting relative abundance may shift as a consequence of climate change, resulting in altered diversity and ecosystem function. The standardised data of AusPlots enables such analyses at large spatial scales, and the testing of predictions through time with longitudinal sampling. In future, the AusPlots field program will be directed towards improving coverage of space, under-represented environments, vegetation types and fauna and, increasingly, re-sampling of established plots. Providing up-to-date data access methods to enhance re-use is also a priority.
Assuntos
Mudança Climática , Ecossistema , Monitoramento Ambiental/normas , Pradaria , Chuva , Austrália , SoloRESUMO
Agricultural practices, including habitat alteration and application of agricultural chemicals, can impact wildlife resulting in their decline. Determining which of these practices are contributing to declines is essential if the declines are to be reversed. In this study, the health of two geographically separated sleepy lizard (Tiliqua rugosa) populations was compared between a rangeland environment and cropping environment using linear body size index (LBSI) and haematology. Animals in the cropping site were smaller, suggesting genetic differences as the result of geographical isolation. The animals in the cropping site had a lower LBSI and many were experiencing a regenerative anaemia. The anaemia was postulated to be the cause of the low LBSI. The anaemia appeared to be the result of haemolysis and was likely to be caused by exposure to agricultural chemicals applied in the cropping site but not the rangeland site. Elevated white blood cell counts in lizards in the rangeland site suggested that they were experiencing an inflammatory disease of possible ecological significance. Together, these results demonstrate the value of combining physical and haematological parameters when studying the impact of agricultural practices on wildlife. They also show that reptiles may be useful as sentinel species for livestock and humans.
RESUMO
We examined the impact of single-tree selective logging and fuel reduction burns on the abundance of hollow-nesting bird species at a regional scale in southeastem Queensland, Australia. Data were collected on species abundance and habitat structure of dry sclerophyll production forest at 36 sites with known logging and fire histories. Sixteen bird species were recorded with most being resident, territorial, obligate hollow nesters that used hollows that were either small (< 10 cm diameter) or very large (>18 cm diameter). Species densities were typically low, but combinations of two forest management and three habitat structural variables influenced the abundances of eight bird species in different and sometimes conflicting ways. The results suggest that habitat tree management for biodiversity in production forests cannot depend upon habitat structural characteristics alone. Management histories appear to have independent influence (on some bird species) that are distinguishable from their impacts on habitat structure per se. Rather than managing to maximize species abundances to maintain biodiversity, we may be better off managing to avoid extinctions of populations by identifying thresholds of acceptable fluctuations in populations of not only hollow-nesting birds but other forest dependent wildlife relative to scientifically valid forest management and habitat structural surrogates.