RESUMO
Symbiotic mutualisms are thought to be stabilized by correlations between the interacting genotypes which may be strengthened via vertical transmission and/or reduced genetic variability within each species. Vertical transmission, however, may weaken interactions over time as the endosymbionts would acquire mutations that could not be purged. Additionally, temporal variation in a conditional mutualism could create genetic variation and increased variation in the interaction outcome. In this study, we assessed genetic variation in both members of a symbiosis, the endosymbiotic fungal endophyte Epichloë canadensis and its grass host Canada wildrye (Elymus canadensis). Both species exhibited comparable levels of diversity, mostly within populations rather than between. There were significant differences between populations, although not in the same pattern for the two species, and the differences were not correlated with geographic distance for either species. Interindividual genetic distance matrices for the two species were significantly correlated, although all combinations of discriminant analysis of principle components (DAPC) defined multilocus genotype groups were found suggesting that strict genotype matching is not necessary. Variation in interaction outcome is common in grass/endophyte interactions, and our results suggest that the accumulation of mutations overtime combined with temporal variation in selection pressures increasing genetic variation in the symbiosis may be the cause.
Assuntos
Elymus , Epichloe , Endófitos/genética , Simbiose , Epichloe/genética , Poaceae/microbiologia , Elymus/genética , Elymus/microbiologiaRESUMO
Genetic diversity and divergence patterns of smallmouth bass Micropterus dolomieu spawning groups are analysed across its northern native range with mtDNA cytochrome b gene sequences and eight unlinked nuclear DNA microsatellite loci. Results reveal high levels of genetic variability and significant differences in allelic representation among populations (mtDNA: mean ± s.e., HD = 0·50 ± 0·06, mean ± s.e., θST = 0·41 ± 0·02 and microsatellites: mean ± s.e. HO = 0·46 ± 0·03, mean ± s.e. θST = 0·25 ± 0·01). The distributions of 28 variant mtDNA haplotypes, which differ by an average of 3·94 nucleotides (range = 1-8), denote divergent representation among geographic areas. Microsatellite data support nine primary population groups, whose high self-assignment probabilities likewise display marked divergence. Genetic patterns demonstrate: (1) high genetic diversity in both genomes, (2) significant divergence among populations, probably resulting from natal site homing and low lifetime migration, (3) support for three post-glacial refugia that variously contributed to the current northern populations, which remain evident today despite waterway connectivity and (4) a weak yet significant genetic isolation by geographic distance pattern, indicating that other processes affect the differences among populations, such as territoriality and site fidelity.
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Bass/genética , Variação Genética , Genoma , Repetições de Microssatélites , Alelos , Animais , DNA Mitocondrial/genética , Genética Populacional , HaplótiposRESUMO
We documented the effects of acidic atmospheric deposition and soil acidification on the canopy health, basal area increment, and regeneration of sugar maple (SM) trees across the Adirondack region of New York State, in the northeastern United States, where SM are plentiful but not well studied and where widespread depletion of soil calcium (Ca) has been documented. Sugar maple is a dominant canopy species in the Adirondack Mountain ecoregion, and it has a high demand for Ca. Trees in this region growing on soils with poor acid-base chemistry (low exchangeable Ca and % base saturation [BS]) that receive relatively high levels of atmospheric sulfur and nitrogen deposition exhibited a near absence of SM seedling regeneration and lower crown vigor compared with study plots with relatively high exchangeable Ca and BS and lower levels of acidic deposition. Basal area increment averaged over the 20th century was correlated (p < 0.1) with acid-base chemistry of the Oa, A, and upper B soil horizons. A lack of Adirondack SM regeneration, reduced canopy condition, and possibly decreased basal area growth over recent decades are associated with low concentrations of nutrient base cations in this region that has undergone soil Ca depletion from acidic deposition.
Assuntos
Acer/fisiologia , Ácidos/química , Ecossistema , Solo/química , Árvores/fisiologia , Atmosfera/química , Cálcio/análise , Geografia , New York , Folhas de Planta/fisiologia , Plântula/fisiologia , Poluentes do Solo/análise , Estatísticas não ParamétricasRESUMO
Whole-body morphometrics and 15 nuclear DNA microsatellite loci were analysed for 158 Perca flavescens collected during the spawning season from four spawning locations in central Lake Erie, two along the northern shore and two along the southern shore, to evaluate fine-scale variation (spanning 17-94 km). Results showed significant morphological and genetic differences among P. flavescens from the four locations. The magnitudes of differences were unrelated to geographic distance, demonstrating spatially heterogeneous levels of genetic divergence. These results linked morphometric and genetic variation, showing a discontinuity of scale between currently defined management units and population structure of P. flavescens in Lake Erie, and support that P. flavescens might exist as one or more metapopulations. Findings demonstrate the value of using complementary techniques for evaluating population structure.
Assuntos
Percas/genética , Animais , Conservação dos Recursos Naturais , Variação Genética , Geografia , Percas/anatomia & histologia , Percas/classificação , Dinâmica Populacional , Especificidade da EspécieRESUMO
Forest understory plant communities in the United States harbor most of the vegetation diversity of forests and are often sensitive to changes in climate and atmospheric deposition of nitrogen (N). As temperature increases from human-caused climate change and soils recover from long term atmospheric deposition of N and sulfur (S), it is unclear how these important ecosystem components will respond. We used the newly developed US-PROPS model - based on species response functions for over 1,500 species - to evaluate the potential impacts of atmospheric N deposition and climate change on species occurrence probability for a case study in the forested ecosystems of the Great Smoky Mountains National Park (GRSM), an iconic park in the southeastern United States. We evaluated six future scenarios from various combinations of two potential recoveries of soil pH (no change, +0.5 pH units) and three climate futures (no change, +1.5, +3.0 deg C). Species critical loads (CLs) of N deposition and projected responses for each scenario were determined. Critical loads were estimated to be low (< 2 kg N/ha/yr) to protect all species under current and expected future conditions across broad regions of GRSM and these CLs were exceeded at large spatial extents among scenarios. Northern hardwood, yellow pine, and chestnut oak forests were among the most N-sensitive vegetation map classes found within GRSM. Potential future air temperature conditions generally led to decreases in the maximum occurrence probability for species. Therefore, CLs were considered "unattainable" in these situations because the specified level of protection used for CL determination (i.e., maximum occurrence probability under ambient conditions) was not attainable. Although some species showed decreases in maximum occurrence probability with simulated increases in soil pH, most species were favored by increased pH. The importance of our study is rooted in the methodology described here for establishing regional CLs and for evaluating future conditions, which is transferable to other national parks in the U.S. and in Europe where the original PROPS model was developed.
RESUMO
Epichloë spp., fungal endophytes of cool season grasses, produce collars of mycelium (stromata) on host stems that Botanophila flies visit for egg laying. Flies transfer fungal gametes among stromata and thereby serve to cross-fertilize fungi. Hence, the interaction is analogous to insect pollination in angiosperms. While most Epichloë species are not interfertile, Epichloë typhina and Epichloë clarkii can hybridize. We investigated whether Botanophila flies play a role in the reproductive isolation of the two Epichloë species at a field site in southwestern Switzerland. We estimated the density of stromata and collected fly larvae and stromata occurring on plants. While most ascospores collected from both species indicated intraspecific mating, 9.3% of fungal fruiting bodies contained spores of hybrid origin. Two species of Botanophila larvae occurred on stromata and both preferred E. typhina. Yet, both fly species laid eggs on both fungal species. While preferences by Botanophila flies should influence reproductive isolation between the fungi, other mechanisms are likely more important. Our data, which show hybrid ascospores are produced, suggest postzygotic isolating mechanisms are an important means of reproductive isolation.
Assuntos
Dípteros/microbiologia , Epichloe/fisiologia , Isolamento Reprodutivo , Animais , Trânsito Gastrointestinal/fisiologia , Interações Hospedeiro-Parasita , Larva , Filogenia , Especificidade da Espécie , Esporos Fúngicos/fisiologia , Suíça , Fatores de TempoRESUMO
The OX-40 protein was selectively upregulated on encephalitogenic myelin basic protein (MBP)-specific T cells at the site of inflammation during the onset of experimental autoimmune encephalomyelitis (EAE). An OX-40 immunotoxin was used to target and eliminate MBP-specific T cells within the central nervous system without affecting peripheral T cells. When injected in vivo, the OX-40 immunotoxin bound exclusively to myelin-reactive T cells isolated from the CNS, which resulted in amelioration of EAE. Expression of the human OX-40 antigen was also found in peripheral blood of patients with acute graft-versus-host disease and the synovia of patients with rheumatoid arthritis during active disease. The unique expression of the OX-40 molecule may provide a novel therapeutic strategy for eliminating autoreactive CD4+T cells that does not require prior knowledge of the pathogenic autoantigen.
Assuntos
Artrite Reumatoide/sangue , Linfócitos T CD4-Positivos/patologia , Encefalomielite Autoimune Experimental/imunologia , Imunotoxinas/administração & dosagem , Proteína Básica da Mielina/imunologia , Receptores do Fator de Necrose Tumoral , Ricina/administração & dosagem , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/imunologia , Animais , Artrite Reumatoide/imunologia , Linfócitos T CD4-Positivos/imunologia , Separação Celular , Encefalomielite Autoimune Experimental/metabolismo , Encefalomielite Autoimune Experimental/patologia , Humanos , Ratos , Ratos Endogâmicos Lew , Receptores OX40 , Subpopulações de Linfócitos T/imunologia , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/sangueRESUMO
Acidic deposition contributes to a range of environmental impacts across forested landscapes, including acidification of soil and drainage water, toxic aluminum mobilization, depletion of available soil nutrient cations, and impacts to forest and aquatic species health and biodiversity. In response to decreasing levels of acidic deposition, soils and drainage waters in some regions of North America have become gradually less acidic. Thresholds of atmospheric deposition at which adverse ecological effects are manifested are called critical loads (CLs) and/or target loads (TLs). Target loads are developed based on approaches that account for spatial and temporal aspects of acidification and recovery. Exceedance represents the extent to which current or projected future levels of acidic deposition exceed the level expected to cause ecological harm. We report TLs of sulfur (S) and nitrogen (N) deposition and the potential for ecosystem recovery of watershed soils and streams in the Adirondack region of New York State, resources that have been less thoroughly investigated than lakes. Regional TLs were calculated by statistical extrapolation of hindcast and forecast simulations of 25 watersheds using the process-based model PnET-BGC coupled with empirical observations of stream hydrology and established sensitivity of sugar maple (Acer saccharum) to soil base saturation and brook trout (Salvelinus fontinalis) to stream acid neutralizing capacity (ANC). Historical impacts and the expected recovery timeline of regional soil and stream chemistry and fish community condition within the Adirondack Park were evaluated. Analysis suggests that many low-order Adirondack streams and associated watershed soils have low TLs (<40 meq/m2/yr of N + S deposition) to achieve specified benchmarks for recovery of soil base saturation or stream ANC. Acid-sensitive headwater and low-order streams and watershed soils in the region are expected to experience continued adverse effects from N and S deposition well into the future even under aggressive emissions reductions. Watershed soils and streams in the western Adirondack Park are particularly vulnerable to acidic deposition and currently in exceedance of TLs. The methods used for linking statistical and process-based models to consider chemical and biological response under varying flow conditions at the regional scale in this study can be applied to other areas of concern.
Assuntos
Chuva Ácida , Solo , Animais , Ecossistema , Monitoramento Ambiental , New York , Nitrogênio , América do Norte , Enxofre/análiseRESUMO
Purified rat peritoneal mast cells stimulated with the polycationic histamine-releasing agent compound 48/80 demonstrated a two- to four-fold increase in cellular levels of 1,2-diacylglycerol (DAG) within 1 min as detected by radioactive labeling and direct quantitation experiments. When 2-[1-14C]arachidonoyl-DAG was incubated in the presence of mast-cell homogenates, a rapid conversion to free arachidonate, and to a lesser extent, to monoacylglycerol, triglyceride, and phospholipid was observed. The release of arachidonate was proportional to the amount of broken-cell preparation added and the time of incubation, was prevented by preheating mast-cell preparations, and did not occur when 1-[1-14C]arachidonoyl-phosphatidylcholine was used as substrate, suggesting that the degradation was mediated by an enzyme with Dag-lipase activity. Although much work remains to be done to clarify the precise role of DAG in mast cells, DAG metabolism may be involved in secretion by generating substances which may faciliate membrane fusion and also in arachidonic acid-derived mediator formation by liberating esterified arachidonic acid from mast-cell lipids. Taken together, these studies indicate that the formation of DAG may play a central role in mast-cell function.
Assuntos
Ácidos Araquidônicos/biossíntese , Diglicerídeos/metabolismo , Glicerídeos/metabolismo , Mastócitos/metabolismo , Animais , Células Cultivadas , Lipídeos/biossíntese , Masculino , Mastócitos/efeitos dos fármacos , Ratos , p-Metoxi-N-metilfenetilamina/farmacologiaRESUMO
A recently introduced class of probabilistic (uncertainty-aware) solvers for ordinary differential equations (ODEs) applies Gaussian (Kalman) filtering to initial value problems. These methods model the true solution x and its first q derivatives a priori as a Gauss-Markov process X , which is then iteratively conditioned on information about x Ë . This article establishes worst-case local convergence rates of order q + 1 for a wide range of versions of this Gaussian ODE filter, as well as global convergence rates of order q in the case of q = 1 and an integrated Brownian motion prior, and analyses how inaccurate information on x Ë coming from approximate evaluations of f affects these rates. Moreover, we show that, in the globally convergent case, the posterior credible intervals are well calibrated in the sense that they globally contract at the same rate as the truncation error. We illustrate these theoretical results by numerical experiments which might indicate their generalizability to q ∈ { 2 , 3 , } .
RESUMO
Forest understory plant communities in the eastern United States are often diverse and are potentially sensitive to changes in climate and atmospheric inputs of nitrogen caused by air pollution. In recent years, empirical and processed-based mathematical models have been developed to investigate such changes in plant communities. In the study reported here, a robust set of understory vegetation response functions (expressed as version 2 of the Probability of Occurrence of Plant Species model for the United States [US-PROPS v2]) was developed based on observations of forest understory and grassland plant species presence/absence and associated abiotic characteristics derived from spatial datasets. Improvements to the US-PROPS model, relative to version 1, were mostly focused on inclusion of additional input data, development of custom species-level input datasets, and implementation of methods to address uncertainty. We investigated the application of US-PROPS v2 to evaluate the potential impacts of atmospheric nitrogen (N) and sulfur (S) deposition, and climate change on forest ecosystems at three forested sites located in New Hampshire, Virginia, and Tennessee in the eastern United States. Species-level N and S critical loads (CLs) were determined under ambient deposition at all three modeled sites. The lowest species-level CLs of N deposition at each site were between 2 and 11 kg N/ha/yr. Similarly, the lowest CLs of S deposition, based on the predicted soil pH response, were less than 2 kg S/ha/yr among the three sites. Critical load exceedance was found at all three model sites. The New Hampshire site included the largest percentage of species in exceedance. Simulated warming air temperature typically resulted in lower maximum occurrence probability, which contributed to lower CLs of N and S deposition. The US-PROPS v2 model, together with the PROPS-CLF model to derive CL functions, can be used to develop site-specific CLs for understory plants within broad regions of the United States. This study demonstrates that species-level CLs of N and S deposition are spatially variable according to the climate, light availability, and soil characteristics at a given location. Although the species niche models generally performed well in predicting occurrence probability, there remains uncertainty with respect to the accuracy of reported CLs. As such, the specific CLs reported here should be considered as preliminary estimates.
Assuntos
Poluição do Ar , Mudança Climática , Ecossistema , Florestas , Nitrogênio/análise , Tennessee , Estados Unidos , VirginiaRESUMO
INTRODUCTION: Vismodegib (Erivedge, Genentech) is a first-in-class inhibitor of the hedgehog (Hh) pathway, which is licensed for use in locally advanced basal cell carcinoma (BCC) and metastatic BCC. The National Institute for Health and Care Excellence withdrew recommendation for use of vismodegib secondary to a lack of data comparing vismodegib to standard supportive care. The purpose of this multicentre, international case series is to report outcomes of patients with locally advanced periocular BCC who have been treated with vismodegib. METHODS: The medical records of all patients treated with vismodegib were retrospectively reviewed across seven institutions in the United Kingdom, Australia, and New Zealand. RESULTS: Thirteen patients were identified. Seven (54%) patients were male. All BCCs were ill-defined, with seven (58%) having orbital involvement at presentation. Median treatment time was 7 months (range 2-36 months). Eleven out of 13 patients developed side effects, the most common being fatigue in six patients (46%). Median follow-up was 24 months (range 12-48 months). Complete response was found in 5/13 patients (38%) and a partial response in 8/13 patients (62%). Six patients had further surgery after vismodegib, with three classed as globe-sparing operations. Three patients developed recurrence (23%). Three patients (23%) ultimately underwent exenteration. DISCUSSION: This study demonstrates vismodegib to be a well-tolerated treatment which may, in some cases, facilitate globe-sparing surgery and hence avoid disfiguring operations such as exenteration. Uncertainty does remain regarding the long-term outcomes of patients treated with vismodegib.
Assuntos
Antineoplásicos , Carcinoma Basocelular , Neoplasias Cutâneas , Anilidas , Antineoplásicos/efeitos adversos , Austrália , Carcinoma Basocelular/tratamento farmacológico , Feminino , Proteínas Hedgehog/uso terapêutico , Humanos , Masculino , Recidiva Local de Neoplasia , Nova Zelândia , Piridinas , Estudos Retrospectivos , Neoplasias Cutâneas/tratamento farmacológico , Resultado do Tratamento , Reino UnidoRESUMO
Liver and lung metastases are the predominant cause of colorectal cancer (CRC)-related mortality. Recent research has indicated that CXCR3/chemokines interactions that orchestrate haematopoetic cell movement are implicated in the metastatic process of malignant tumours, including that of CRC cells to lymph nodes. To date, however, the contribution of CXCR3 to liver and lung metastasis in CRC has not been addressed. To determine whether CXCR3 receptors regulate malignancy-related properties of CRC cells, we have used CXCR3-expressing CRC cell lines of human (HT29 cells) and murine (C26 cells) origins that enable the development of liver and lung metastases when injected into immunodeficient and immunocompetent mice, respectively, and assessed the effect of CXCR3 blockade using AMG487, a small molecular weight antagonist. In vitro, activation of CXCR3 on human and mouse CRC cells by its cognate ligands induced migratory and growth responses, both activities being abrogated by AMG487. In vivo, systemic CXCR3 antagonism by preventive or curative treatments with AMG487 markedly inhibited the implantation and the growth of human and mouse CRC cells within lung without affecting that in the liver. In addition, we measured increased levels of CXCR3 and ligands expression within lung nodules compared with liver tumours. Altogether, our findings indicate that activation of CXCR3 receptors by its cognate ligands facilitates the implantation and the progression of CRC cells within lung tissues and that inhibition of this axis decreases pulmonary metastasis of CRC in two murine tumour models.
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Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Receptores CXCR3/antagonistas & inibidores , Animais , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Movimento Celular , Neoplasias do Colo/tratamento farmacológico , Humanos , Ligantes , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Camundongos , Transplante de Neoplasias , Especificidade de Órgãos , Receptores CXCR3/metabolismo , Taxa de SobrevidaRESUMO
Changes in climate and atmospheric nitrogen (N) deposition caused pronounced changes in soil conditions and habitat suitability for many plant species over the latter half of the previous century. Such changes are expected to continue in the future with anticipated further changing air temperature and precipitation that will likely influence the effects of N deposition. To investigate the potential long-term impacts of atmospheric N deposition on hardwood forest ecosystems in the eastern United States in the context of climate change, application of the coupled biogeochemical and vegetation community model VSD+PROPS was explored at three sites in New Hampshire, Virginia, and Tennessee. This represents the first application of VSD+PROPS to forest ecosystems in the United States. Climate change and elevated (above mid-19th century) N deposition were simulated to be important factors for determining habitat suitability. Although simulation results suggested that the suitability of these forests to support the continued presence of their characteristic understory plant species might decline by the year 2100, low data availability for building vegetation response models with PROPS resulted in uncertain results at the extremes of simulated N deposition. Future PROPS model development in the United States should focus on inclusion of additional foundational data or alternate candidate predictor variables to reduce these uncertainties.
Assuntos
Poluição do Ar/análise , Mudança Climática , Árvores/crescimento & desenvolvimento , Ecossistema , Florestas , Modelos Teóricos , Nitrogênio/análise , Nitrogênio/metabolismo , Solo/química , Tennessee , Estados Unidos , VirginiaRESUMO
Ecological effects of atmospheric nitrogen (N) and sulfur (S) deposition on two hardwood forest sites in the eastern United States were simulated in the context of a changing climate using the dynamic coupled biogeochemical/ecological model chain ForSAFE-Veg. The sites are a mixed oak forest in Shenandoah National Park, Virginia (Piney River) and a mixed oak-sugar maple forest in Great Smoky Mountains National Park, Tennessee (Cosby Creek). The sites have received relatively high levels of both S and N deposition and the climate has warmed over the past half century or longer. The model was used to evaluate the composition of the understory plant communities, the alignment between plant species niche preferences and ambient conditions, and estimate changes in relative species abundances as reflected by plant cover under various scenarios of future atmospheric N and S deposition and climate change. The main driver of ecological effects was soil solution N concentration. Results of this research suggested that future climate change might compromise the capacity for the forests to sustain habitat suitability. However, vegetation results should be considered preliminary until further model validation can be performed. With expected future climate change, preliminary estimates suggest that sustained future N deposition above 7.4 and 5.0â¯kgâ¯N/ha/yr is expected to decrease contemporary habitat suitability for indicator plant species located at Piney River and Cosby Creek, respectively.
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Poluentes Atmosféricos/análise , Monitoramento Ambiental , Florestas , Nitrogênio/análise , Árvores/efeitos dos fármacos , Acer/efeitos dos fármacos , Poluentes Atmosféricos/toxicidade , Mudança Climática , Ecologia , Ecossistema , Nitrogênio/toxicidade , Parques Recreativos , Plantas/efeitos dos fármacos , Solo , Enxofre , Tennessee , VirginiaRESUMO
To investigate the impact that physiological variation in serum cortisol has on IgE-mediated events, 10 atopic subjects underwent cutaneous antigen challenge with measurement of the early phase wheal (EPW) at 20 min and the late phase reaction (LPR) at 6 h. All subjects were challenged during control conditions between 8:00 and 9:00 a.m. Repeat challenges were performed in five subjects at 6:00 p.m. and in eight subjects after ingestion of metyrapone, a specific inhibitor of cortisol synthesis. Compared with control values, mean serum cortisol was suppressed in the evening and after metyrapone (P less than 0.05 all time points). No effect was seen on the EPW, but mean LPR diameters at three antigen dilutions were significantly increased by cortisol suppression (P less than 0.05). Replacement doses of hydrocortisone given in the evening and with metyrapone abrogated these increases. Blinded analysis of LPR biopsies from cortisol-suppressed subjects revealed increases in leukocytoclasis (P less than or equal to 0.0001), interstitial leukocytes (P less than or equal to 0.01), and eosinophils (P less than or equal to 0.04). These results indicate that physiological levels of serum cortisol can regulate IgE-dependent cutaneous inflammation by affecting the expression of cellular events at late phase sites.
Assuntos
Hidrocortisona/fisiologia , Hipersensibilidade/imunologia , Imunoglobulina E/imunologia , Ritmo Circadiano , Humanos , Hipersensibilidade/patologia , Metirapona/farmacologia , Pele/imunologia , Pele/patologia , Testes Cutâneos , Fatores de TempoRESUMO
In this study ethanol and certain other short-chain aryl (benzyl and phenethyl) and aliphatic (methyl, propyl, butyl, and amyl) alcohols produced up to 10-fold increases in cyclic AMP (cAMP) concentrations in purified human peripheral blood lymphocytes. Ethanol concentrations as low as 80 mg/dl produced significant elevations in lymphocyte cAMP. Significant but less marked augmentation of cAMP in response to alcohols was observed in human platelets, human granulocytes, and rabbit alveolar macrophages. The mechanism of the alcohol-induced cAMP accumulation is probably secondary to membrane perturbation and consequent activation of adenylate cyclase, because ethanol directly stimulated this enzyme in lymphocyte membrane preparations but had no effect on lymphocyte phosphodiesterase activity. Lysosomal enzyme release, by phagocytosing human leukocytes, and aminoisobutyric acid transport in mitogen-stimulated human lymphocytes were shown to be inhibited by ethanol and other alcohols at concentrations which also elevate cAMP. In general, the magnitude of the inhibition of these inflammatory processes correlated with the ability of the alcohol to elevate cAMP concentrations. Lectin-and anti-thymocyte globulin-induced lymphocyte mitogenesis was inhibited or unaffected depending upon both the concentration and type of mitogenic stimulus and the concentration and type of alcohol utilized. Inflammatory mediator release from rat mast cells also was inhibited by ethanol and certain other alcohols, but whole cell cAMP was not increased. Ethanol may alter these inflammatory responses and other biologic processes at least in part by modulating cellular levels of cAMP.
Assuntos
Álcoois/farmacologia , AMP Cíclico/sangue , Etanol/farmacologia , Linfócitos/metabolismo , Adenilil Ciclases/sangue , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Membrana Celular/enzimologia , Epinefrina/farmacologia , Granulócitos/efeitos dos fármacos , Granulócitos/metabolismo , Humanos , Imunidade , Inflamação , Cinética , Linfócitos/efeitos dos fármacos , Microssomos/enzimologia , Prostaglandinas E/farmacologia , Relação Estrutura-Atividade , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Teofilina/farmacologiaRESUMO
BACKGROUND: Adults with recalcitrant mechanical low back pain of more than six weeks duration can encounter unacceptable waiting periods for specialised care. AIM: To evaluate the effectiveness of rapid treatment by means of group sessions. METHODS: We instituted a rapidly accessed patient education programme in physiotherapy for low back pain. Pain and disability were assessed before and after the programme. The programme included four sessions of group instruction for self-actuated physiotherapy There were six to 10 patients per group. RESULTS: In eight months, 160 patients were admitted to the programme. The average waiting time was 16 business days for the first appointment. Seventy-three per cent of the patients who attended some portion of the programme completed all sessions. At least 30% of the incompletions were ascribable to rapid improvement. Of patients completing the programme, 80% reported significant resolution of the pain and improvement in function. Twenty per cent reported no significant response, but no patients worsened during participation. Of the 20% with no subjective improvement, 50% were pursuing medico-legal claims. In comparison, 9% of those reporting a successful response were pursuing litigation. CONCLUSIONS: Group instruction in physiotherapy for low back pain is safe, generally successful, and highly acceptable to patients.
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Processos Grupais , Dor Lombar/reabilitação , Educação de Pacientes como Assunto/métodos , Modalidades de Fisioterapia , Avaliação de Programas e Projetos de Saúde , Resultado do Tratamento , Doença Aguda , Adulto , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Satisfação do Paciente , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
Stream-dwelling species in the U.S. southern Appalachian Mountains region are particularly vulnerable to climate change and acidification. The objectives of this study were to quantify the spatial extent of contemporary suitable habitat for acid- and thermally sensitive aquatic species and to forecast future habitat loss resulting from expected temperature increases on national forest lands in the southern Appalachian Mountain region. The goal of this study was to help watershed managers identify and assess stream reaches that are potentially vulnerable to warming, acidification, or both. To our knowledge, these results represent the first regional assessment of aquatic habitat suitability with respect to the combined effects of stream water temperature and acid-base status in the United States. Statistical models were developed to predict July mean daily maximum water temperatures and air-water temperature relations to determine potential changes in future stream water temperatures. The length of stream considered suitable habitat for acid- and thermally sensitive species, based on temperature and acid neutralizing capacity thresholds of 20°C and 50 µeq/L, was variable throughout the national forests considered. Stream length displaying temperature above 20°C was generally more than five times greater than the length predicted to have acid neutralizing capacity below 50 µeq/L. It was uncommon for these two stressors to occur within the same stream segment. Results suggested that species' distributional shifts to colder, higher elevation habitats under a warming climate can be constrained by acidification of headwater streams. The approach used in this study can be applied to evaluate climate change impacts to stream water resources in other regions.
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Ecossistema , Peixes/fisiologia , Animais , Região dos Apalaches , Mudança Climática , Concentração de Íons de Hidrogênio , Modelos Lineares , Modelos Biológicos , Rios , Temperatura , IncertezaRESUMO
The binding of two 5-substituted-1,3,4-thiadiazole-2-thione inhibitors to the matrix metalloproteinase stromelysin (MMP-3) have been characterized by protein crystallography. Both inhibitors coordinate to the catalytic zinc cation via an exocyclic sulfur and lay in an unusual position across the unprimed (P1-P3) side of the proteinase active site. Nitrogen atoms in the thiadiazole moiety make specific hydrogen bond interactions with enzyme structural elements that are conserved across all enzymes in the matrix metalloproteinase class. Strong hydrophobic interactions between the inhibitors and the side chain of tyrosine-155 appear to be responsible for the very high selectivity of these inhibitors for stromelysin. In these enzyme/inhibitor complexes, the S1' enzyme subsite is unoccupied. A conformational rearrangement of the catalytic domain occurs that reveals an inherent flexibility of the substrate binding region leading to speculation about a possible mechanism for modulation of stromelysin activity and selectivity.