RESUMO
Naturally subdivided populations such as those occupying high-altitude habitat patches of the 'alpine archipelago' can provide significant insight into past biogeographical change and serve as useful models for predicting future responses to anthropogenic climate change. Among New Zealand's alpine taxa, phylogenetic studies support two major radiations: the first correlating with geological forces (Pliocene uplift) and the second with climatic processes (Pleistocene glaciations). The rock wren (Xenicus gilviventris) is a threatened alpine passerine belonging to the endemic New Zealand wren family (Acanthisittidae). Rock wren constitute a widespread, naturally fragmented population, occurring in patches of suitable habitat over c. 900 m in altitude throughout the length of the South Island, New Zealand. We investigated the relative role of historical geological versus climatic processes in shaping the genetic structure of rock wren (N = 134) throughout their range. Using microsatellites combined with nuclear and mtDNA sequence data, we identify a deep north-south divergence in rock wren (3.7 ± 0.5% at cytochrome b) consistent with the glacial refugia hypothesis whereby populations were restricted in isolated refugia during the Pleistocene c. 2 Ma. This is the first study of an alpine vertebrate to test and provide strong evidence for the glacial refugia hypothesis as an explanation for the low endemicity central zone known as the biotic 'gap' in the South Island of New Zealand.
Assuntos
Mudança Climática , Evolução Molecular , Genética Populacional , Refúgio de Vida Selvagem , Aves Canoras/genética , Animais , Teorema de Bayes , DNA Mitocondrial/genética , Ecossistema , Fluxo Gênico , Genótipo , Funções Verossimilhança , Repetições de Microssatélites , Modelos Genéticos , Nova Zelândia , Filogenia , Filogeografia , Análise de Sequência de DNARESUMO
Background: Shoulder arthroplasty is becoming increasingly common. With evolving implant designs, multiple humeral stem options exist for the surgeon to choose from. New stemless and short-stem systems are modular, remove less native bone stock, and better adapt to patient anatomy. It has been suggested that shorter stem implants may be protective against periprosthetic fracture; however, this has not been mechanistically evaluated. Therefore, this study aimed to biomechanically test synthetic humeri with long-stem, short-stem, and stemless arthroplasty components in a torsional manner to evaluate their response to loading and characterize failure. Methods: Twenty-four synthetic humeri were implanted with long stem, short stem, or stemless uncemented prosthesis, 8 in each group. Humeri were mounted in a custom testing jig with a morse taper interfacing with a mechanical testing system. After a 20N axial force, specimens were torsionally loaded to failure at 15 degrees/sec, with 50 Hz collection. Torque vs. rotation curves were generated for each specimen, and stiffness, yield, ultimate strength, and failure load were measured. ANOVA and post hoc pairwise comparisons were used to assess effect of stem type on mechanical test variable. The association of the stem type with fracture type was analyzed by a Fisher's Exact test. Statistical significance was set at P < .05. Results: During torsional loading, long-stem implants were significantly stiffer than short or stemless implants. The angle of implant yielding was similar across stem designs; however, stemless implants had a lower yield torque. This correlated with a decreased yield energy in stemless compared to short stems as well. Maximum torque and failure torque was also significantly higher in short-stem and long-stem implants compared to stemless. Discussion: Periprosthetic fractures in shoulder arthroplasty are a concern in low-energy trauma, and stem design likely plays a significant role in early implant-bone failure. Our results suggest stemless implants under torsional load fail at lower stress and are less stiff than stemmed implants. The failure mechanism of stemless implants through metaphyseal cancellous bone emphasizes the effect bone quality has on implant fixation. There is likely a balance of torsional stability to survive physiologic loads while minimizing diaphyseal stress and risk of diaphyseal periprosthetic fracture. This combined with revision and fixation options represent decisions the surgeon is faced with when performing shoulder arthroplasty.
RESUMO
We have developed an atomic magnetometer based on the rubidium isotope 87Rb and a microfabricated silicon/glass vapor cell for the purpose of qualifying the instrument for space flight during a ride-along opportunity on a sounding rocket. The instrument consists of two scalar magnetic field sensors mounted at 45° angle to avoid measurement dead zones, and the electronics consist of a low-voltage power supply, an analog interface, and a digital controller. The instrument was launched into the Earth's northern cusp from Andøya, Norway on December 8, 2018 on the low-flying rocket of the dual-rocket Twin Rockets to Investigate Cusp Electrodynamics 2 mission. The magnetometer was operated without interruption during the science phase of the mission, and the acquired data were compared favorably with those from the science magnetometer and the model of the International Geophysical Reference Field to within an approximate fixed offset of about 550 nT. Residuals with respect to these data sources are plausibly attributed to offsets resulting from rocket contamination fields and electronic phase shifts. These offsets can be readily mitigated and/or calibrated for a future flight experiment so that the demonstration of this absolute-measuring magnetometer was entirely successful from the perspective of increasing the technological readiness for space flight.
RESUMO
OBJECTIVES: To evaluate the relationship between timing of definitive fixation, injury severity, and the development of systemic complications in severely injured patients with pelvic ring injuries. DESIGN: Retrospective review. SETTINGS: Level 1 trauma center. PATIENTS: One hundred eighteen severely injured [Injury Severity Score (ISS) ≥ 16] adult patients with pelvic ring injuries undergoing definitive fixation, excluding patients treated with external fixation for hemodynamic instability. INTERVENTION: Early fixation (≤36 hours) in 37 patients and delayed fixation (>36 hours) in 81 patients. MAIN OUTCOME MEASUREMENTS: Systemic complications (acute respiratory distress syndrome, pulmonary embolism, deep venous thrombosis, sepsis, multi-organ failure, and death). RESULTS: The delayed fixation group had a higher ISS and had more patients with chest injuries. There was no detectable difference in the number of patients with systemic complications between early versus delayed fixation groups [8 (22%) vs. 29 (35%), P = 0.1]. The only difference detected in specific complications was a higher incidence of pneumonia with delayed fixation [16 (20%) vs. 0 (0%), P = 0.004] with 11 of the 16 cases being associated with chest injury. Univariate analysis showed an association between complication and time to fixation, ISS, Glasgow Coma Scale, pH, base excess, and injuries to the head, chest, and abdomen. On multivariate analysis, only ISS remained significantly associated with the development of complications [Odds ratio 2.6 per 10 point increase, 95% confidence interval (CI), 1.4-4.4]. CONCLUSIONS: These data suggest that the severity of injury is most highly associated with systemic complications after definitive fixation of pelvic ring injuries. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Assuntos
Fixação de Fratura , Centros de Traumatologia , Adulto , Humanos , Escala de Gravidade do Ferimento , Duração da Cirurgia , Estudos RetrospectivosRESUMO
A conditional time-averaged gradient (COTAG) system has been developed to provide direct long-term (weekly to monthly) average flux gradient measurements for a range of trace gases, between land and atmosphere. Over daily periods, atmospheric conditions can range from high stability, where the vertical gradients of ambient concentration are enhanced due to very small diffusivity, to highly unstable conditions, in which concentration gradients are small due to the intense turbulent activity of the surface layer. The large vertical gradients generated by high stability would bias the estimate of the actual flux: to avoid this, the COTAG system samples conditionally, within a carefully refined range of stability. A comparison with a continuous flux gradient system suggested that the removal of stable conditions from the sampling period does not substantially modify the evaluation of the long-term fluxes.
Assuntos
Monitoramento Ambiental/economia , Monitoramento Ambiental/métodos , Compostos de Amônio Quaternário/análise , Dióxido de Enxofre/análise , Modelos TeóricosRESUMO
The use of ultrasound to enhance the regeneration of zeolite 13X for efficient utilization of thermal energy was investigated as a substitute to conventional heating methods. The effects of ultrasonic power and frequency on the desorption of water from zeolite 13X were analyzed to optimize the desorption efficiency. To determine and justify the effectiveness of incorporating ultrasound from an energy-savings point of view, an approach of constant overall input power of 20 or 25 W was adopted. To measure the extent of the effectiveness of using ultrasound, the ultrasonic-power-to-total power ratios of 0.2, 0.25, 0.4 and 0.5 were investigated and the results compared with those of no-ultrasound (heat only) at the same total power. To analyze the effect of ultrasonic frequency, identical experiments were performed at three nominal ultrasonic frequencies of ~28, 40 and 80 kHz. The experimental results showed that using ultrasound enhances the regeneration of zeolite 13X at all the aforementioned power ratios and frequencies without increasing the total input power. With regard to energy consumption, the highest energy-savings power ratio (0.25) resulted in a 24% reduction in required input energy and with an increase in ultrasonic power, i.e. an increase in acoustic-to-total power ratio, the effectiveness of applying ultrasound decreased drastically. At a power ratio of 0.2, the time required for regeneration was reduced by 23.8% compared to the heat-only process under the same experimental conditions. In terms of ultrasonic frequency, lower frequencies resulted in higher efficiency and energy savings, and it was concluded that the effect of ultrasonic radiation becomes more significant at lower ultrasonic frequencies. The observed inverse proportionality between the frequency and ultrasound-assisted desorption enhancement suggests that acoustic dissipation is not a significant mechanism to enhance mass transfer, but rather other mechanisms must be considered.
RESUMO
Myb transcription factors are crucial to the control of proliferation and differentiation in a number of cell types but their mechanism of action is unclear. Regulation of Myb proteins by phosphorylation and intermolecular cooperation has recently been demonstrated, together with a new role for the proteins, in the control of apoptosis.
Assuntos
Proteínas de Ciclo Celular , Proteínas de Ligação a DNA/fisiologia , Proteínas Proto-Oncogênicas/fisiologia , Transativadores/fisiologia , Fatores de Transcrição/fisiologia , Animais , Morte Celular , Diferenciação Celular , Sobrevivência Celular , Proteínas de Ligação a DNA/genética , Humanos , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-myb , Transativadores/genética , Fatores de Transcrição/genéticaRESUMO
The purpose of this research was to investigate the potential causes of low oxygen levels in the bottom water of the Oyster Grounds region of the shallow southern North Sea, an area which provides suitable conditions for low oxygen levels to develop. At the end of the summer stratified period, relevant biogeochemical processes were investigated using a combination of sedimentary and water column rate measurements. Phytoplankton nitrate and ammonium uptake was measured throughout the water column using (15)N labelled isotopes and showed ammonium uptake dominated in the upper and bottom mixed layer with a maximum 294.4 micromol N m(-3)h(-1). In the deep chlorophyll maximum at the thermocline, primary production was dominated by nitrate uptake, with an average of 35.0 micromol N m(-3)h(-1), relative to ammonium uptake, with an average of 24.6 micromol N m(-3)h(-1). This high relative nitrate uptake will in part result in exportable new production to the isolated bottom mixed layer and sediments, as opposed to regenerated ammonium driven uptake. This biomass export was indicated by significant benthic oxygen consumption rates in the stratified region (782-1275 micromol O(2)m(-2)h(-1)micromol N m(-3)h(-1)) long after the end of the spring bloom. The sediments were also an active net source of nitrate, ammonium, phosphate and silicate into the bottom mixed layer of 4.4, 8.4, 2.3 and 68.8 micromol m(-2)h(-1), respectively. The export of new production within the thermocline to the bottom mixed layer and the consequent sediment oxygen consumption in the isolated bottom mixed layer in the Oyster Grounds are expected to have contributed to the low bottom water oxygen concentrations of 2.07 mg l(-1) (64.7 micromol l(-1)) measured. The long stratified period associated with this low oxygen is predicted to occur more regularly in the future and continued monitoring of this ecologically important region is therefore essential if the causes of these potentially damaging low oxygen levels are to be fully understood.
Assuntos
Ecossistema , Monitoramento Ambiental , Ostreidae/metabolismo , Oxigênio/análise , Oxigênio/metabolismo , Animais , Biomassa , Sedimentos Geológicos , Hipóxia , Nitratos/metabolismo , Isótopos de Nitrogênio , Mar do Norte , Fotossíntese , Fitoplâncton/metabolismo , Compostos de Amônio Quaternário/metabolismo , Estações do AnoRESUMO
Occupational fatigue in anaesthetists is recognised as a patient safety risk. Better understanding of the issues surrounding their fatigue is needed. This study aimed to ascertain the sources and effects of occupational fatigue amongst anaesthetists in Australia and New Zealand. An anonymous online survey was sent to 979 anaesthetists. The response rate was 38.0%. Most participants reported regularly working over 40 hours per week; men reported five more hours per week than women. Stated contributors to fatigue included long work hours, mental strain at work, and personal and family demands. Fatigue-related behaviour was reported more by men (OR [odds ratio]=2.6) and less by respondents reporting eight or more hours of sleep before work (OR=0.6). Reporting at least one instance of less than five hours off between shifts was predictive of falling asleep while administering an anaesthetic (OR=1.6). More data are required to support practices and policies that promote more time off between work periods and increased time for sleep to reduce risk of fatigue.
Assuntos
Anestesistas , Fadiga/epidemiologia , Doenças Profissionais/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Admissão e Escalonamento de Pessoal , Sono , Inquéritos e QuestionáriosRESUMO
During T-cell activation, c-Myb is induced upon interleukin 2 (IL-2) stimulation and is required for correct proliferation of cells. In this paper, we provide evidence that IL-2-mediated induction of the c-myb gene occurs via the phosphoinositide 3-kinase (PI3K) signaling pathway, that protein kinase B (PKB) is the principal transducer of this signal, and that activation of the c-myb promoter can be abolished by deletion of conserved E2F and NF-kappaB binding sites. We show that Myb is required to protect activated peripheral T cells from bcl-2-independent apoptosis and that overexpression of oncogenic v-Myb is antiapoptotic. Overexpression of a Myb dominant-negative transgene abrogates PKB-mediated protection from apoptosis. Taken together, these results suggest that induction of c-myb transcription is an important downstream event for PKB-mediated protection of T cells from programmed cell death.
Assuntos
Apoptose , Proteínas de Ciclo Celular , Proteínas de Ligação a DNA , Interleucina-2/metabolismo , Proteínas Serina-Treonina Quinases , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas/metabolismo , Transdução de Sinais , Ativação Transcricional , Células 3T3 , Animais , Sítios de Ligação , Fatores de Transcrição E2F , Humanos , Interleucina-2/farmacologia , Ativação Linfocitária , Camundongos , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas c-akt , Proteínas Proto-Oncogênicas c-myb/metabolismo , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
This paper summarises the results of the EU funded MEAD project, an interdisciplinary study of the effects of atmospheric nitrogen deposition on the Kattegat Sea between Denmark and Sweden. The study considers emissions of reactive nitrogen gases, their transport, transformations, deposition and effects on algal growth together with management options to reduce these effects. We conclude that atmospheric deposition is an important source of fixed nitrogen to the region particularly in summer, when nitrogen is the limiting nutrient for phytoplankton growth, and contributes to the overall eutrophication pressures in this region. However, we also conclude that it is unlikely that atmospheric deposition can, on its own, induce algal blooms in this region. A reduction of atmospheric nitrogen loads to this region will require strategies to reduce emissions of ammonia from local agriculture and Europe wide reductions in nitrous oxide emissions.
Assuntos
Poluentes Atmosféricos , Eucariotos/crescimento & desenvolvimento , Eutrofização , Nitrogênio , Agricultura , Amônia , Disponibilidade Biológica , Biomassa , Dinamarca , Monitoramento Ambiental/métodos , Poluição Ambiental/prevenção & controle , Modelos Teóricos , Óxido Nitroso , Oceanos e Mares , Fitoplâncton/crescimento & desenvolvimento , Estações do Ano , SuéciaRESUMO
Inventories of fallout (210)Pb and (137)Cs have been measured in moorland and woodland soils around the Edinburgh urban area, using a high purity germanium detector. The (210)Pb inventories in moorland soils were relatively uniform, with a mean value of 2520+/-270Bqm(-2). The mean (137)Cs inventory in moorland soils varied greatly from 1310 to 2100Bqm(-2), with a mean value of 1580+/-310Bqm(-2). The variability was ascribed mainly to the non-uniform distribution of fallout Chernobyl (137)Cs. The mean (210)Pb and (137)Cs inventories in woodland canopy soils were found to be 3630+/-380Bqm(-2) and 2510+/-510Bqm(-2), respectively. At sites for which both moorland and woodland data were available, the mean inventories provided fairly similar average enhancements of (47+/-7)% and (46+/-18)% of (210)Pb and (137)Cs under woodland canopy soils relative to open grassland soils, respectively. The enhancement factors are broadly in line with other independent findings in literature. Enhancement of both (210)Pb and (137)Cs in woodland soils relative to moorland soils is, in part, due to deposition by impaction during air turbulence, wash-off, gravitational settling and deposition during leaf senescence. Results of this study suggest that these processes affect both (210)Pb and (137)Cs carrier aerosols in a similar way.
Assuntos
Radioisótopos de Césio/análise , Radioisótopos de Chumbo/análise , Poluentes Radioativos do Solo/análise , EscóciaRESUMO
Hematopoietic tumors in both humans and mice frequently up-regulate expression of the c-myb gene, but it is unclear whether this is a cause or a consequence of the leukemic state. Recent results placing super-activation of the c-Myb protein at the bottom of a kinase-activated signal transduction pathway indicate that it may be a downstream effector of transformation induced by other oncogenes. The relationship between c-Myb and the serine-threonine kinase pim-1, its immediate activator, is discussed, together with the possibility that c-Myb, like pim-1, may be able to synergize with c-Myc to induce tumors.
Assuntos
Neoplasias/genética , Oncogenes/fisiologia , Animais , Transformação Celular Neoplásica/genética , Humanos , Neoplasias Experimentais/genéticaRESUMO
In hematopoiesis, self-renewal, proliferation, differentiation and apoptosis represent opposing decisions made by stem cells and progenitor cells, which when dysregulated can result in leukaemia. Here, we have investigated the function of Myb proteins in regulating these key cellular decisions, using the cell line FDCP-mix A4 as a model of early hematopoiesis. High concentrations of IL-3 in these cells favour self-renewal over differentiation and apoptosis. However when endogenous Myb activity was inhibited with an inducible dominant interfering protein, self-renewal was replaced by apoptosis and differentiation. Differentiation was to granulocytes and monocyte/macrophages and was closely associated with a G1-S phase block in the cell cycle. As for normal hematopoiesis, cytokine-induced terminal differentiation of FDCP-mix cells is associated with concomitant proliferation prior to its completion. However, when Myb activity was inhibited during this process, proliferation and survival were both reduced, resulting in a much lower yield of mature cells. These results indicate multiple cellular roles of Myb proteins during normal hematopoiesis.
Assuntos
Hematopoese/fisiologia , Modelos Biológicos , Proteínas Proto-Oncogênicas c-myb/fisiologia , Animais , Apoptose/genética , Células da Medula Óssea/citologia , Ciclo Celular , Diferenciação Celular , Divisão Celular/genética , Linhagem Celular , Sobrevivência Celular/genética , Vetores Genéticos/biossíntese , Vetores Genéticos/fisiologia , Inibidores do Crescimento/fisiologia , Hematopoese/genética , Camundongos , Proteínas Proto-Oncogênicas c-myb/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-myb/biossíntese , Proteínas Proto-Oncogênicas c-myb/genética , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/fisiologia , TransfecçãoRESUMO
The v-Myb oncogene causes late onset T cell lymphomas when expressed in the T cell lineage of transgenic mice. In order to define the cellular mutations cooperating with s-Myb to cause lymphomas, we have infected v-Myb transgenic mice with Moloney murine leukemia virus (M-MuLV). Tumor formation is significantly accelerated from a mean age of onset of 60 weeks in uninfected vMyb transgenics to 13 weeks in infected vMyb transgenics. We studied the loci into which the M-MuLV had inserted, and found that in 73% of animals, either the c-myc or the N-myc genes had been disrupted and deregulated. Therefore, v-myb and c-myb can cooperate to induce T cell lymphomas.
Assuntos
Genes myc/genética , Linfoma de Células T/genética , Mutagênese Insercional , Oncogenes/genética , Proteínas Oncogênicas de Retroviridae/genética , Linfócitos T/patologia , Timoma/genética , Idade de Início , Animais , Citometria de Fluxo , Expressão Gênica , Vírus da Leucemia Murina/fisiologia , Linfoma de Células T/patologia , Linfoma de Células T/virologia , Camundongos , Camundongos Endogâmicos CBA , Camundongos Transgênicos , Proteínas Oncogênicas v-myb , Reação em Cadeia da Polimerase , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Linfócitos T/metabolismo , Linfócitos T/virologia , Timoma/patologia , Timoma/virologia , Neoplasias do Timo/genética , Neoplasias do Timo/patologia , Neoplasias do Timo/virologiaRESUMO
v-Myb, the transforming protein of avian myeloblastosis virus, causes acute myeloid leukemia in chickens. Similarly, truncation and rearrangement of the c-myb proto-oncogene to yield a v-Myb-like protein leads to myeloid and B cell lymphomas in chickens and mice, and may be a factor in a number of human cancers. To study the effects of deregulation of v-Myb on T cell development, we have generated lines of transgenic mice in which the v-Myb oncoprotein is expressed in a T-cell-specific fashion. Analysis of T cell development in the v-Myb transgenic mice shows that ectopic expression of v-Myb affects the ratio of helper to cytotoxic T cells, by increasing the number of CD4+ helper cells, and inhibits thymic involution, such that mature animals have elevated numbers of thymocytes and circulating mature T cells. In a significant proportion of older animals, high grade T cell lymphomas develop, demonstrating that v-Myb is oncogenic in T cells.
Assuntos
Linfócitos T CD4-Positivos/citologia , Linfócitos T CD8-Positivos/citologia , Linfoma não Hodgkin/genética , Linfoma de Células T/genética , Proteínas Oncogênicas de Retroviridae/metabolismo , Animais , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Linfoma não Hodgkin/patologia , Linfoma de Células T/patologia , Camundongos , Camundongos Nus , Transplante de Neoplasias , Proteínas Oncogênicas v-myb , Proto-Oncogene MasRESUMO
Activation of the sympathoadrenal system (SAS, comprising the sympathetic nervous system and the adrenal medulla) in response to stressful stimuli is an important defense mechanism as well as a contributor to several cardiovascular diseases. There is variability in the SAS response to stress, although the extent to which this is genetically regulated is unclear. Some rodent models, including the hereditary hypertriglyceridemic (hHTg) rat, are hyperresponsive to stress. We investigated whether quantitative trait loci (QTLs) that affect sympathoadrenal response to stress could be identified. Second filial generation rats (n = 189) derived from a cross of the hHTg rat and the Brown Norway rat had plasma norepinephrine (NE) and epinephrine (Epi) levels, indices of activation of the sympathoneural and adrenal medulla components, respectively, measured in the resting state and in response to an immobilization stress. Responses were assessed early (20 min) and late (120 min) after the application of the stress. A genome scan was conducted using 153 microsatellite markers. Two QTLs (maximum peak LOD scores of 4.17 and 3.52, respectively) influencing both the early and late plasma NE response to stress were found on chromosome 10. Together, the QTLs accounted for approximately 20% of the total variation in both the early and late NE responses in the F(2) rats. Interestingly, the QTLs had no effect on plasma Epi response to stress. These findings provide evidence for a genetic determination of the response of a specific component of the SAS response to stress. Genetically determined variation in sympathetic nervous system response to stress may contribute to cardiovascular diseases.
Assuntos
Sistema Nervoso Simpático/patologia , Animais , Pressão Sanguínea , Catecolaminas/metabolismo , Mapeamento Cromossômico , Biologia Computacional , Cruzamentos Genéticos , Epinefrina/sangue , Feminino , Ligação Genética , Marcadores Genéticos , Variação Genética , Genótipo , Escore Lod , Masculino , Repetições de Microssatélites , Norepinefrina/sangue , Fenótipo , Locos de Características Quantitativas , Ratos , Ratos Endogâmicos BN , Especificidade da Espécie , Estresse Fisiológico , Fatores de TempoRESUMO
The effects of drug on phospholipid composition of cell surface membranes are not well understood at this time. The effects of membrane-active drugs and membrane depolarization on the phospholipid composition were determined in murine LM fibroblasts. Receptor-aggregating drugs such as concanavalin A and cytoskeleton-disrupting agents such as colchicine, vinblastine, and cytochalasin B decreased phosphatidylserine content of the plasma membrane from 5.4 +/- 1.5% to as low as 1.4 +/- 0.2%. In addition, concanavalin A and colchicine increased the phosphatidylglycerol content from 6.9 +/- 1.6% to 13.1 +/- 0.7% and 10.6 +/-1.7%, respectively, while vinblastine and cytochalasin B had no effect. Pentobarbital decreased the content of phosphatidylinositol+ phosphatidylserine and of phosphatidylglycerol almost 2-fold. Propranolol, ethanol, and depolarization with 120 mM KCl had small or ne effects on plasma membrane phospholipid composition. None of the above drugs or treatments significantly altered the asymmetric distribution of phosphatidylethanolamine across the LM cell plasma membrane under the conditions tested. In addition, energy inhibitors that deplete the proton-motive force of the cell (NaN3 and KCN) and inhibitors of ATP synthesis such as NaAsO4 did not affect the asymmetric distribution of phosphatidylethanolamine. It is concluded that the mechanism of action of membrane-active drugs such as concanavalin A, vinblastine, colchicine and pentobarbital may involve alterations in plasma membrane composition. It also appears that microfilaments, microtubules, beta-adrenergic receptors, membrane fluidity, and membrane potential are not critical for the regulation of the asymmetric distribution of membrane phosphatidylethanolamine.
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Membrana Celular/metabolismo , Lipídeos de Membrana/metabolismo , Fosfolipídeos/metabolismo , Animais , Membrana Celular/efeitos dos fármacos , Colchicina/farmacologia , Concanavalina A/farmacologia , Citocalasina B/farmacologia , Etanol/farmacologia , Fibroblastos/metabolismo , Células L/metabolismo , Camundongos , Pentobarbital/farmacologia , Propranolol/farmacologia , Vimblastina/farmacologiaRESUMO
We have determined the DNA sequence (46 kilobases) of the short unique region, the short repeat, and part of the long repeat of human cytomegalovirus strain AD169. Analysis of the sequence has revealed at least 38 possible regions that may code for protein. Many of these open reading frames show homology to each other, and five groups of homologous reading frames are identified. Half of the predicted translation products appear to be membrane proteins, and fall into two distinct classes; those that have potential signal and anchor sequences, and those that have seven potential membrane-spanning regions and appear to be integral membrane proteins. A number of the former class contain sites for N-linked glycosylation and may therefore be glycoproteins. None of the 38 open reading frames shows homology to other known herpesvirus proteins.
Assuntos
Citomegalovirus/genética , DNA Viral/genética , Sequências Repetitivas de Ácido Nucleico , Sequência de Aminoácidos , Composição de Bases , Sequência de Bases , Humanos , Biossíntese de Proteínas , Software , Proteínas ViraisRESUMO
1 The effects of chemical irritants on the membrane potential and input resistance of the giant amoeba, Chaos carolinense, have been investigated. The membrane potential and input resistance were -111.5 mV and 8.6 M pi respectively. 2 In the resting state the cell membrane of Chaos carolinense was found to be impermeable to Na+ but permeable to K+. The distribution of K+ across the cell membrane conformed to a Donnan equilibrium with the resting membrane potential being the K+ equilibrium potential. 3 The chemical irritants dibenzoxazepine and its 2-chloro- and 3-chloro-analogues and o-chlorobenzylidene malononitrile produced a fall in input resistance but no change in membrane potential. It is suggested that these effects are caused by an increase in K+ permeability. 4 The potencies of a series of chemical irritants with respect to dibenzoxazepine were measured on the giant amoeba. These potencies did not reflect those found in mammalian preparations.