RESUMO
Among other approaches, differential equations are used for a deterministic quantitative description of time-dependent biological processes. For intracellular systems, such as signaling pathways, most existing models are based on ordinary differential equations. These models describe temporal processes, while they neglect spatial aspects. We present a model for the SMAD signaling pathway, which gives a temporal and spatial description on the basis of reaction diffusion equations to answer the question whether cell geometry plays a role in signaling. In this article we simulate the ordinary differential equations as well as partial differential equations of parabolic type with suile numerical methods, the latter on different cell geometries. In addition to manual construction of idealized cells, we also construct meshes from microscopy images of real cells. The main focus of the paper is to compare the results of the model without and with spatial aspects to answer the addressed question. The results show that diffusion in the model can lead to significant intracellular gradients of signaling molecules and changes the level of response to the signal transduced by the signaling pathway. In particular, the extent of these observations depends on the geometry of the cell.
Assuntos
Modelos Biológicos , Transdução de Sinais/fisiologia , Proteínas Smad/fisiologia , Simulação por Computador , Hepatócitos/fisiologia , CinéticaRESUMO
In the frigid desert of the Antarctic dry valleys there are no visible life forms on the surface of the soil or rocks. Yet in certain rock types a narrow subsurface zone has a favorable microclimate and is colonized by microorganisms. Dominant are lichens of unusual organization. They survive not by physiological adaptation to lower temperatures, but by changing their mode of growth, being able to grow between the crystals of porous rocks. Their activity results in mobilization of iron compounds and in rock weatherning with a characteristic pattern of exfoliation. This simple ecosystem lacks both higher consumers and predators.
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In the Antarctic cold desert (Ross Desert), the survival of the cryptoendolithic microorganisms that colonize the near-surface layer of porous sandstone rocks depends on a precarious equilibrium of biological and geological factors. An unfavorable shift of this equilibrium results in death, and this may be followed by formation of trace fossils that preserve the characteristic iron-leaching pattern caused by microbial activity. Similar microbial trace fossil may exist in the geological record. If life ever arose on early Mars, similar processes may have occurred there and left recognizable traces.
Assuntos
Clima Frio , Clima Desértico , Microbiologia Ambiental , Fósseis , Tempo (Meteorologia) , Regiões Antárticas , Exobiologia , Fenômenos Geológicos , Geologia , Ferro , Marte , QuartzoRESUMO
Endolithic unicellular blue-green algae occur under the surface of orthoquartzite rocks in the dry valleys of southern Victoria Land, Antarctica. This report of primary producers in the Antarctic desert ecosystem suggests that, in future efforts to detect life in extraterrestrial (for example, martian) environments, scientists should consider the possible existence of endolithic life forms.
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Calcium oxalate crystals occur in the marine green algae Penicillus, Rhipocephalus, and Udotea, known as producers of sedimentary aragonite needles. In contrast to the externally deposited aragonite crystals which are generally < 15 micrometers long, the oxalate crystals are larger (up to 150 micrometers) and are located in the vacuolar system of the plant. No calcium oxalate was found in the related but noncalcifying genera Avrainvillea and Cladocephalus.
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Fas ligand (FasL) is a type II transmembrane protein belonging to the tumor necrosis factor family. Its binding to the cognate Fas receptor triggers the apoptosis that plays a pivotal role in the maintenance of immune system homeostasis. The cell death-inducing property of FasL has been associated with its extracellular domain, which can be cleaved off by metalloprotease activity to produce soluble FasL. The fate of the remaining membrane-anchored N-terminal part of the FasL molecule has not been determined. Here we show that post-translational processing of overexpressed and endogenous FasL in T-cells by the disintegrin and metalloprotease ADAM10 generates a 17-kDa N-terminal fragment, which lacks the receptor-binding extracellular domain. This FasL remnant is membrane anchored and further processed by SPPL2a, a member of the signal peptide peptidase-like family of intramembrane-cleaving proteases. SPPL2a cleavage liberates a smaller and highly unstable fragment mainly containing the intracellular FasL domain (FasL ICD). We show that this fragment translocates to the nucleus and is capable of inhibiting gene transcription. With ADAM10 and SPPL2a we have identified two proteases implicated in FasL processing and release of the FasL ICD, which has been shown to be important for retrograde FasL signaling.
Assuntos
Proteínas ADAM/metabolismo , Ácido Aspártico Endopeptidases/metabolismo , Proteína Ligante Fas/metabolismo , Linfócitos T/metabolismo , Linhagem Celular Tumoral , Células Cultivadas , Proteína Ligante Fas/química , Humanos , Microscopia Confocal , Estrutura Terciária de Proteína , RNA Interferente PequenoRESUMO
Antarctic permafrost soils have not received as much geocryological and biological study as has been devoted to the ice sheet, though the permafrost is more stable and older and inhabited by more microbes. This makes these soils potentially more informative and a more significant microbial repository than ice sheets. Due to the stability of the subsurface physicochemical regime, Antarctic permafrost is not an extreme environment but a balanced natural one. Up to 10(4) viable cells/g, whose age presumably corresponds to the longevity of the permanently frozen state of the sediments, have been isolated from Antarctic permafrost. Along with the microbes, metabolic by-products are preserved. This presumed natural cryopreservation makes it possible to observe what may be the oldest microbial communities on Earth. Here, we describe the Antarctic permafrost habitat and biodiversity and provide a model for martian ecosystems.
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Biodiversidade , Exobiologia , Microbiologia do Solo , Regiões Antárticas , Gelo , ÁguaRESUMO
INTRODUCTION: Implantable cardioverter defibrillators (ICDs) are effective at reducing mortality in patients at high risk for sudden cardiac death (SCD) but can cause psychological distress and reduce quality of life (QOL). The full benefits of ICDs can only be achieved when the patient's QOL and psychological status are maintained. We examined psychological status and QOL post ICD implantation; the relationship of psychological status to QOL; the relationship of time since implantation to psychological status and QOL; and the relationship of time since ICD implantation and age of patient to these variables. METHODS AND RESULTS: A cross-sectional self-administered assessment of QOL, depression, anxiety, demographic characteristics and cardiovascular health history of patients (n = 48) who had received ICDs within the past 10 years at an urban hospital. Patients who had ICDs for longer experienced worse depression and QOL. Patients who were younger had worse depression, anxiety, and QOL. The combination of anxiety, depression, age, and time since ICD implant significantly predicted overall QOL and the psychosocial and physical dimensions of QOL explaining 55.5, 54, and 34.9% of the variance, respectively. CONCLUSION: Younger ICD patients are at highest risk for psychological distress and poor QOL. Longitudinal research would facilitate determination of the trajectory of changes in psychological status and QOL over the duration of the ICD experience.
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Ansiedade/epidemiologia , Desfibriladores Implantáveis/psicologia , Desfibriladores Implantáveis/estatística & dados numéricos , Depressão/epidemiologia , Qualidade de Vida , Medição de Risco/métodos , Perfil de Impacto da Doença , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade/psicologia , Comorbidade , Depressão/psicologia , Humanos , Incidência , Maryland/epidemiologia , Pessoa de Meia-Idade , Psicologia/estatística & dados numéricos , Fatores de RiscoRESUMO
Dried monolayers of Chroococcidiopsis sp. 029, a desiccation-tolerant, endolithic cyanobacterium, were exposed to a simulated martian-surface UV and visible light flux, which may also approximate to the worst-case scenario for the Archean Earth. After 5 min, there was a 99% loss of cell viability, and there were no survivors after 30 min. However, this survival was approximately 10 times higher than that previously reported for Bacillus subtilis. We show that under 1 mm of rock, Chroococcidiopsis sp. could survive (and potentially grow) under the high martian UV flux if water and nutrient requirements for growth were met. In isolated cells, phycobilisomes and esterases remained intact hours after viability was lost. Esterase activity was reduced by 99% after a 1-h exposure, while 99% loss of autofluorescence required a 4-h exposure. However, cell morphology was not changed, and DNA was still detectable by 4',6-diamidino-2-phenylindole staining after an 8-h exposure (equivalent to approximately 1 day on Mars at the equator). Under 1 mm of simulant martian soil or gneiss, the effect of UV radiation could not be detected on esterase activity or autofluorescence after 4 h. These results show that under the intense martian UV flux the morphological signatures of life can persist even after viability, enzymatic activity, and pigmentation have been destroyed. Finally, the global dispersal of viable, isolated cells of even this desiccation-tolerant, ionizing-radiation-resistant microorganism on Mars is unlikely as they are killed quickly by unattenuated UV radiation when in a desiccated state. These findings have implications for the survival of diverse microbial contaminants dispersed during the course of human exploratory class missions on the surface of Mars.
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Cianobactérias/crescimento & desenvolvimento , Cianobactérias/efeitos da radiação , Marte , Raios Ultravioleta , Cianobactérias/enzimologia , FósseisRESUMO
Social support and pet ownership, a nonhuman form of social support, have both been associated with increased coronary artery disease survival. The independent effects of pet ownership, social support, disease severity, and other psychosocial factors on 1-year survival after acute myocardial infarction are examined prospectively. The Cardiac Arrhythmia Suppression Trial provided physiologic data on a group of post-myocardial infarction patients with asymptomatic ventricular arrhythmias. An ancillary study provided psychosocial data, including pet ownership, social support, recent life events, future life events, anxiety, depression, coronary prone behavior, and expression of anger. Subjects (n = 424) were randomly selected from patients attending participating Cardiac Arrhythmia Suppression Trial sites and completed baseline psychosocial questionnaires. One year survival data were obtained from 369 patients (87%), of whom 112 (30.4%) owned pets and 20 (5.4%) died. Logistic regression indicates that high social support (p < 0.068) and owning a pet (p = 0.085) tend to predict survival independent of physiologic severity and demographic and other psychosocial factors. Dog owners (n = 87, 1 died) are significantly less likely to die within 1 year than those who did not own dogs (n = 282, 19 died; p < 0.05); amount of social support is also an independent predictor of survival (p = 0.065). Both pet ownership and social support are significant predictors of survival, independent of the effects of the other psychosocial factors and physiologic status. These data confirm and extend previous findings relating pet ownership and social support to survival among patients with coronary artery disease.
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Animais Domésticos/psicologia , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/psicologia , Apoio Social , Adulto , Animais , Gatos , Ensaios Clínicos como Assunto , Cães , Feminino , Nível de Saúde , Humanos , Masculino , Estudos ProspectivosRESUMO
Patient adherence to therapy is essential to assess treatment efficacy, particularly in clinical trials. Active treatment usually is expected to benefit patients. The healthy adherer effect, the association or greater adherence to all health-promoting behaviors, including medication and overall concern for health, explains the improved survival of more adherent patients in both active and placebo medication groups of several clinical trials. The Cardiac Arrhythmia Suppression Trial (CAST), a placebo-controlled double-blind clinical trial of post-myocardial infarction (MI) patients with asymptomatic ventricular arrhythmias, in which active medication (encainide or flecainide) led to increased mortality, provided an opportunity to examine the relationship of adherence to survival from a different perspective. We consider whether adherence to active treatment was related to arrhythmic mortality and whether a healthy adherer effect might counteract the effect of treatment on mortality among patients taking active medication. Adherence (average pill count) at the first follow-up visit did not differ in the active treatment (92.2%, standard deviation (SD) = 11.97, n = 574) and placebo (90.8%, SD = 13.66, n = 579) groups. In a Cox proportional hazard regression model, medication adherence predicted arrhythmic mortality among the active (P < 0.0062) but not the placebo medication group. The effect of adherence on arrhythmic mortality was significant beyond the effects of ejection fraction, race, spouse, smoking status, diuretic medication, and history of MI. A 10% increase in adherence led to more than a threefold increase of risk of arrhythmic death. The design of the CAST, which included a titration phase, may have tended to select relatively adherent patients since only those whose arrhythmias were suppressed with active medication were randomized into the trial. The data do not support a strong healthy adherer effect in the CAST. There was no evidence in this study that a healthy adherer effect counterbalanced the effect of the active medication.
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Arritmias Cardíacas/mortalidade , Comportamentos Relacionados com a Saúde , Cooperação do Paciente , Antiarrítmicos/efeitos adversos , Arritmias Cardíacas/tratamento farmacológico , Encainida/efeitos adversos , Feminino , Flecainida/efeitos adversos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
A subgroup of growth hormone (GH)-secreting pituitary tumors carries somatic mutations within the gene coding for the alpha subunit of the stimulatory heterotrimeric guanosine 5'-triphosphate-binding protein, Gs alpha. These so-called gsp mutations result in constitutively activated Gs alpha and the signal transduction cascade downstream of it, with eventual markedly and continuously elevated cyclic adenosine monophosphate levels as a result of constitutive adenylyl cyclase activity. It is this elevation of intracellular cyclic adenosine monophosphate that is thought to be the cause of excessive GH secretion and somatotroph proliferation. We examined the clinical and biochemical characteristics of acromegalics harboring gsp-positive and gsp-negative pituitary tumors. Of 19 tumors studied, 8 (42%) were gsp positive. There was a slight tendency for basal GH levels in serum to be lower and to be further reduced by an oral glucose tolerance test in gsp-positive patients. However, there was no difference between the two groups in terms of clinical features, tumor size, mitotic activity (as assessed by cytosolic deoxyribonucleic acid polymerase and KI-67 staining), and in vitro GH response to GH releasing factor. We conclude that there is, in general, little difference in the clinical and biochemical characteristics between gsp-positive and gsp-negative human pituitary GH-secreting tumors.
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Acromegalia/genética , Adenoma/genética , Proteínas de Ligação ao GTP/genética , Neoplasias Hipofisárias/genética , Acromegalia/enzimologia , Adenoma/enzimologia , Adenoma/patologia , Adenoma/cirurgia , Adenilil Ciclases/fisiologia , Adulto , AMP Cíclico/fisiologia , DNA de Neoplasias/genética , Feminino , Regulação Neoplásica da Expressão Gênica/fisiologia , Teste de Tolerância a Glucose , Humanos , Masculino , Pessoa de Meia-Idade , Mitose/fisiologia , Mutação , Hipófise/patologia , Neoplasias Hipofisárias/enzimologia , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/cirurgia , Reação em Cadeia da Polimerase , Transdução de Sinais/genética , Transdução de Sinais/fisiologiaRESUMO
A method for controlling relative humidity based on temperature differentials, rather than on salt solutions, is described. This method has the following advantages: (1) it does not exhibit the anomalous CO2 solution effects that we have found to occur with salt solutions; (2) humidity is continuously adjustable without sample removal; (3) circulation of the atmosphere results in short equilibration times.
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Umidade , Técnicas Microbiológicas , Temperatura , Microbiologia da Água , Água/química , Atmosfera , Dióxido de Carbono/análise , Dióxido de Carbono/química , Gases , Fotossíntese , Cloreto de Sódio/química , SoluçõesRESUMO
There has been extensive research on the factors associated with patient satisfaction with communication during medical encounters, however, little attention has been paid to satisfaction among subgroups of patients, including the elderly. It is inappropriate to assume that all patients have the same physician-patient relationship needs, and thus, they will all be satisfied with the same communication approaches during medical visits. In this study, we examine the interactional correlates of older patient satisfaction with an initial visit with a general internist. A multidisciplinary team composed of social scientists and physicians used the Multi-dimensional Interaction Analysis system to code audiotapes. Patients and physicians completed post-visit satisfaction questionnaires. Older patient satisfaction was positively correlated with the following variables: physician questioning and supportiveness on patient-raised topics; patient information-giving on patient-raised topics; the length of the visit; the physician's use of questions worded in the negative; shared laughter between the physician and the patient; and physician satisfaction. These findings suggest that older patients prefer encounters in which: (1) there is physician supportiveness and shared laughter; (2) they are questioned about and given an opportunity to provide information on their own agenda items; and (3) physicians provide some structure for the first meeting through their use of questions worded in the negative. The authors caution that although this sample of older patients appears to be satisfied with a communication style usually considered characteristic of the traditional model of the physician-patient relationship (i.e. a warm interpersonal style and physician-generated structure for the visit), older patients in other settings and future cohorts of elderly patients may prefer other communication approaches. It is also suggested that aspects of communication which provide satisfaction to patients in first visits may be different than aspects of communication associated with patient satisfaction in follow-up visits.
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Idoso/psicologia , Comunicação , Satisfação do Paciente , Relações Médico-Paciente , Médicos/psicologia , Adulto , Assistência ao Convalescente/psicologia , Atitude do Pessoal de Saúde , Estudos de Avaliação como Assunto , Feminino , Necessidades e Demandas de Serviços de Saúde , Humanos , Medicina Interna , Masculino , Pessoa de Meia-Idade , Modelos Psicológicos , Equipe de Assistência ao Paciente , Educação de Pacientes como Assunto , Participação do Paciente , Apoio Social , Inquéritos e Questionários , Gravação em Fita , Fatores de TempoRESUMO
To test the hypothesis that less concordance exists between older patients and their physicians than between younger patients and their physicians, we examined agreements between physicians and patients on the major goals and topics discussed during an outpatient medical encounter. Using coded audiotapes of the medical visit, patient postvisit interviews, and physician questionnaires, concordance was found to be significantly greater for younger patients and their physicians than for older patients and their physician on the major goals and major medical topics discussed during the primary care interview. This paper explores possible explanations for these findings.
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Relações Médico-Paciente , Fatores Etários , Humanos , Entrevistas como Assunto , Cidade de Nova Iorque , Atenção Primária à Saúde , Inquéritos e Questionários , Gravação em FitaRESUMO
Continued interest in the possibility of evidence for life in the ALH84001 Martian meteorite has focused on the magnetite crystals. This review is structured around three related questions: is the magnetite in ALH84001 of biological or non-biological origin, or a mixture of both? does magnetite on Earth provide insight to the plausibility of biogenic magnetite on Mars? could magnetotaxis have developed on Mars? There are credible arguments for both the biological and non-biological origin of the magnetite in ALH84001, and we suggest that more studies of ALH84001, extensive laboratory simulations of non-biological magnetite formation, as well as further studies of magnetotactic bacteria on Earth will be required to further address this question. Magnetite grains produced by bacteria could provide one of the few inorganic traces of past bacterial life on Mars that could be recovered from surface soils and sediments. If there was biogenic magnetite on Mars in sufficient abundance to leave fossil remains in the volcanic rocks of ALH84001, then it is likely that better-preserved magnetite will be found in sedimentary deposits on Mars. Deposits in ancient lakebeds could contain well-preserved chains of magnetite clearly indicating a biogenic origin.
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Bactérias/isolamento & purificação , Planeta Terra , Ferro , Magnetismo , Marte , Óxidos , Bactérias/classificação , Bactérias/efeitos da radiação , Movimento Celular/efeitos da radiação , Óxido Ferroso-Férrico , ÁguaRESUMO
The Atacama along the Pacific Coast of Chile and Peru is one of the driest and possibly oldest deserts in the world. It represents an extreme habitat for life on Earth and is an analog for life in dry conditions on Mars. We report on four years (September 1994-October 1998) of climate and moisture data from the extreme arid region of the Atacama. Our data are focused on understanding moisture sources and their role in creating suitable environments for photosynthetic microorganisms in the desert surface. The average air temperature was 16.5 degrees C and 16.6 degrees C in 1995 and 1996, respectively. The maximum air temperature recorded was 37.9 degrees C, and the minimum was -5.7 degrees C. Annual average sunlight was 336 and 335 W m(-2) in 1995 and 1996, respectively. Winds averaged a few meters per second, with strong föhn winds coming from the west exceeding 12 m s(-1). During our 4 years of observation there was only one significant rain event of 2.3 mm, which occurred near midnight local time. We suggest that this event was a rainout of a heavy fog. It is of interest that the strong El Niño of 1997-1998 brought heavy rainfall to the deserts of Peru, but did not bring significant rain to the central Atacama in Chile. Dew occurred at our station frequently following high nighttime relative humidity, but is not a significant source of moisture in the soil or under stones. Groundwater also does not contribute to surface moisture. Only the one rain event of 2.3 mm resulted in liquid water in the soil and beneath stones for a total of only 65-85 h over 4 years. The paucity of liquid water under stones is consistent with the apparent absence of hypolithic (under-stone) cyanobacteria, the only known primary producers in such extreme deserts.
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Clima Desértico , Marte , Chile , Umidade , Conceitos Meteorológicos , Modelos Biológicos , Peru , Estações do Ano , TemperaturaRESUMO
The 52 children in the study were recruited from two fifth grade classes in Baltimore city. The blood pressures and heart rates were recorded both at rest and while they read aloud in a classroom setting. A computerized monitoring system was used to measure blood pressures. Rapid and highly significant increases in blood pressure and heart rate were observed when the children read aloud. A total of 84 measurements of 312 systolic and diastolic readings were not within the 95th percentile of normal pressure for the child's age and sex. The data indicate that a routine school task, that is, reading aloud, may have significant effects on the cardiovascular system. These findings are discussed in terms of previously unexamined links between certain childhood school experiences and potential problems with adult hypertension.
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Pressão Sanguínea , Frequência Cardíaca , Leitura , População Negra , Criança , Feminino , Humanos , Hipertensão/etiologia , Masculino , Maryland , Descanso , Fatores Sexuais , População BrancaRESUMO
The objective of the study was to determine whether coitus during menstruation in perimenopausal women is associated with increased menstrual flow defined as either heavier flow, more days of flow, or both. Initial interviews for the Stanford Menopause Study were conducted locally with 160 perimenopausal women. Six weeks later, additional data were gathered from 121 women. At a third interview, 6-10 weeks later at Stanford University, 56 of 57 subjects (mean age 48.8 +/- 3.9 SD) provided data on menstrual flow and coital behavior. At both the first and third interview, more than half of the women reported a pattern of increased menstrual flow. At the third interview, 83% of those reporting increased menstrual flow also reported a behavioral pattern of coitus during menses. Only 10% with diminished flow acknowledged such a pattern. Women who abstained from sex during menses were not less regular in coital activity at other times nor did the data reveal them to be less orgasmic than women who did not abstain. Our data reveal an association between coitus during menstruation and longer and/or heavier menstrual flow. The etiology of such increased flow is usually believed to be hormonal, but coitus during menstruation may be another important variable.