RESUMO
Many species have multi-stage life cycles in which the youngest stages (e.g., larvae) are small, dispersive, and abundant, whereas later stages are sessile or sedentary. Quantifying survival throughout such early stages is critical for understanding dispersal, population dynamics, and life history evolution. However, dispersive stages can be very difficult to sample in situ, and estimates of survival through the entire duration of these stages are typically poor. Here we describe how demographic information from juveniles and adults can be used to estimate survival throughout a dispersive larval stage that was not sampled directly. Using field measurements of demography, we show that detailed information on post-settlement growth, survival, and reproduction can be used to estimate average larval survivorship under the assumption that a typical individual replaces itself over its lifetime. Applying this approach to a common coral reef fish (bicolor damselfish, Stegastes partitus), we estimated average larval survivorship to be 0.108% (95% CI 0.025-0.484). We next compared this demography-based estimate to an expected value derived from published estimates of larval mortality rates. Our estimate of larval survivorship for bicolor damselfish was approximately two orders of magnitude greater than what would be expected if larval mortality of this species followed the average, size-dependent pattern of mortality inferred from a published sample of marine fishes. Our results highlight the importance of understanding mortality during the earliest phases of larval life, which are typically not sampled, as well as the need to understand the details of how larval mortality scales with body size.
Assuntos
Recifes de Corais , Peixes/crescimento & desenvolvimento , Distribuição Animal , Animais , Evolução Biológica , Tamanho Corporal , Conservação dos Recursos Naturais , Peixes/fisiologia , Larva/crescimento & desenvolvimento , Larva/fisiologia , Estágios do Ciclo de Vida , Densidade Demográfica , Dinâmica Populacional , ReproduçãoRESUMO
BACKGROUND: Phase III trials of the anti-insulin-like growth factor type 1 receptor (IGF-IR) antibody figitumumab (F) in unselected non-small-cell lung cancer (NSCLC) patients were recently discontinued owing to futility. Here, we investigated a role of free IGF-1 (fIGF-1) as a potential predictive biomarker of clinical benefit from F treatment. MATERIALS AND METHOD: Pre-treatment circulating levels of fIGF-1 were tested in 110 advanced NSCLC patients enrolled in a phase II study of paclitaxel and carboplatin given alone (PC) or in combination with F at doses of 10 or 20 mg kg(-1) (PCF10, PCF20). RESULTS: Cox proportional hazards model interactions were between 2.5 and 3.5 for fIGF-1 criteria in the 0.5-0.9 ng ml(-1) range. Patients above each criterion had a substantial improvement in progression-free survival on PCF20 related to PC alone. Free IGF-1 correlated inversely with IGF binding protein 1 (IGFBP-1, ρ=-0.295, P=0.005), and the pre-treatment ratio of insulin to IGFBP-1 was also predictive of F clinical benefit. In addition, fIGF-1 levels correlated with tumour vimentin expression (ρ=0.594, P=0.021) and inversely with E-cadherin (ρ=-0.389, P=0.152), suggesting a role for fIGF-1 in tumour de-differentiation. CONCLUSION: Free IGF-1 may contribute to the identification of a subset of NSCLC patients who benefit from F therapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Fator de Crescimento Insulin-Like I/metabolismo , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/administração & dosagem , Biomarcadores Tumorais/sangue , Caderinas/sangue , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Ensaios Clínicos Fase II como Assunto , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Humanos , Imunoglobulinas Intravenosas , Insulina/sangue , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Many field measurements of viability and sexual selection on body size indicate that large size is favoured. However, life-history theory predicts that body size may be optimized and that patterns of selection may often be stabilizing rather than directional. One reason for this discrepancy may be that field estimates of selection tend to focus on limited components of fitness and may not fully measure life-history trade-offs. We use an 8-year, demographic field study to examine both sexual selection and lifetime selection on body size of a coral reef fish (the bicolour damselfish, Stegastes partitus). Selection via reproductive success of adults was very strong (standardized selection differential=1.04). However, this effect was balanced by trade-offs between large adult size and reduced cumulative survival during the juvenile phase. When we measured lifetime fitness (net reproductive rate), selection was strongly stabilizing and only weakly directional, consistent with predictions from life-history theory.
Assuntos
Preferência de Acasalamento Animal , Perciformes/genética , Seleção Genética , Fatores Etários , Animais , Tamanho Corporal , Recifes de Corais , Feminino , Longevidade , Masculino , Perciformes/anatomia & histologia , Perciformes/crescimento & desenvolvimento , ReproduçãoRESUMO
Although body size can affect individual fitness, ontogenetic and spatial variation in the ecology of an organism may determine the relative advantages of size and growth. During an 8-year field study in the Bahamas, we examined selective mortality on size and growth throughout the entire reef-associated life phase of a common coral-reef fish, Stegastes partitus (the bicolour damselfish). On average, faster-growing juveniles experienced greater mortality, though as adults, larger individuals had higher survival. Comparing patterns of selection observed at four separate populations revealed that greater population density was associated with stronger selection for larger adult size. Large adults may be favoured because they are superior competitors and less susceptible to gape-limited predators. Laboratory experiments suggested that selective mortality of fast-growing juveniles was likely because of risk-prone foraging behaviour. These patterns suggest that variation in ecological interactions may lead to complex patterns of lifetime selection on body size.
Assuntos
Tamanho Corporal/fisiologia , Ecossistema , Longevidade/fisiologia , Perciformes/crescimento & desenvolvimento , Animais , Comportamento AnimalRESUMO
Substrates located within the defended territories of Hawaiian damselfish for 1 year were subjected to intermediate grazing intensity and, as a result, showed greater diversity of algae than substrates either protected within fish-exclusion cages or exposed to intense fish grazing outside territories. Thus, this damselfish enhances local diversity on reefs through "intermediate-disturbance" effects, and is a keystone species that decreases rather than increases overall predation intensity relative to areas where it is absent.
RESUMO
Diving observations off Santa Barbara, California, indicate that Pacific electric rays (Torpedo californica) enter inshore reefs at night and actively prey on fish with the aid of powerful electric discharges.
RESUMO
Vascular smooth muscle cells (VSMCs) at capacitance arteries of hypertensive individuals and animals undergo marked age- and blood pressure-dependent polyploidization and hypertrophy. We show here that VSMCs at capacitance arteries of rat models of hypertension display high levels of Akt1/PKB protein and activity. Gene transfer of Akt1 to VSMCs isolated from a normotensive rat strain was sufficient to abrogate the activity of the mitotic spindle cell-cycle checkpoint, promoting polyploidization and hypertrophy. Furthermore, the hypertrophic agent angiotensin II induced VSMC polyploidization in an Akt1-dependent manner. These results demonstrate that Akt1 regulates ploidy levels in VSMCs and contributes to vascular smooth muscle polyploidization and hypertrophy during hypertension.
Assuntos
Hipertensão/genética , Músculo Liso Vascular/patologia , Poliploidia , Proteínas Serina-Treonina Quinases/biossíntese , Proteínas Proto-Oncogênicas , Angiotensina II/farmacologia , Animais , Aorta/patologia , Hipertensão/patologia , Hipertrofia , Artérias Mesentéricas/patologia , Músculo Liso Vascular/citologia , Mutagênicos/farmacologia , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas c-akt , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Ratos Zucker , Proteínas Recombinantes/biossíntese , Regulação para CimaRESUMO
Primary human fibroblasts arrest growth in response to the inhibition of mitosis by mitotic spindle-depolymerizing drugs. We show that the mechanism of mitotic arrest is transient and implicates a decrease in the expression of cdc2/cdc28 kinase subunit Homo sapiens 1 (CKsHs1) and a delay in the metabolism of cyclin B. Primary human fibroblasts infected with a retroviral vector that drives the expression of a mutant p53 protein failed to downregulate CKsHs1 expression, degraded cyclin B despite the absence of chromosomal segregation, and underwent DNA endoreduplication. In addition, ectopic expression of CKsHs1 interfered with the control of cyclin B metabolism by the mitotic spindle cell cycle checkpoint and resulted in a higher tendency to undergo DNA endoreduplication. These results demonstrate that an altered regulation of CKsHs1 and cyclin B in cells that carry mutant p53 undermines the mitotic spindle cell cycle checkpoint and facilitates the development of aneuploidy. These data may contribute to the understanding of the origin of heteroploidy in mutant p53 cells.
Assuntos
Proteínas de Transporte/genética , Proteínas de Ciclo Celular , Ciclina B/metabolismo , Mitose/fisiologia , Proteínas Quinases , Fuso Acromático/fisiologia , Proteína Quinase CDC2/fisiologia , Quinases relacionadas a CDC2 e CDC28 , Proteína Quinase CDC28 de Saccharomyces cerevisiae/fisiologia , Ciclo Celular/fisiologia , Quinases Ciclina-Dependentes , Replicação do DNA/genética , Fibroblastos , Citometria de Fluxo , Regulação da Expressão Gênica/genética , Genes Virais/genética , Humanos , Papillomaviridae/genética , Ploidias , RNA Mensageiro/metabolismo , Transfecção/genética , Proteína Supressora de Tumor p53/genéticaRESUMO
Transforming mutants of the p53 tumor suppressor gene can positively regulate transcription from several promoters that do not contain known p53 binding sites. Here, we report the identification of a novel p53 binding site in the human immunodeficiency virus long terminal repeat that specifically mediates mutant p53 transactivation. This DNA element was bound by endogenous Jurkat p53 when these cells were stimulated by tumor necrosis factor. Mutation of this sequence inhibited p53 transactivation and tumor necrosis factor inducibility of the human immunodeficiency virus type 1 long terminal repeat. In addition, this DNA element was found to be sufficient to confer mutant p53 responsiveness on a heterologous minimal promoter. It has been hypothesized that transforming mutants of p53 represent a proliferative conformational stage that can be adopted by the native protein under stimulation by growth factors. The data presented suggest that proliferative and antiproliferative p53 conformations recognize different DNA binding sites in order to mediate distinct biological functions. Thus, transforming mutants of p53 that fold into the proliferative conformation would favor proliferative over antiproliferative functions.
Assuntos
HIV-1/genética , Sequências Repetitivas de Ácido Nucleico/efeitos dos fármacos , Ativação Transcricional , Fator de Necrose Tumoral alfa/farmacologia , Proteína Supressora de Tumor p53/genética , Sequência de Bases , Sítios de Ligação/genética , HIV-1/metabolismo , Humanos , Dados de Sequência Molecular , Mutação , Sequências Repetitivas de Ácido Nucleico/genética , Linfócitos T/metabolismo , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/metabolismoRESUMO
An assay for beta-alanine transaminase activity in extracts of Drosophila melanogaster has been developed. By use of this assay, the levels of beta-alanine transaminase activity in several strains of flies has been examined as a function of developmental age. The black mutation shows elevated levels of activity compared to wild type, while suppressor of black strains show decreased levels compared to wild type.
Assuntos
4-Aminobutirato Transaminase/metabolismo , Drosophila melanogaster/genética , Pigmentação/genética , Animais , Drosophila melanogaster/enzimologia , Drosophila melanogaster/crescimento & desenvolvimento , Glutamato Desidrogenase/metabolismo , Cinética , beta-Alanina/metabolismoRESUMO
BACKGROUND: Calcineurin may play a pivotal role in the signaling of cardiac hypertrophy; since this hypothesis was first put forward, controversial reports have been published using various experimental models. This study was designed to compare the physiological left ventricular hypertrophy (LVH) induced by voluntary exercise with LVH induced by aortic constriction and to determine whether calcineurin participates in the signaling of exercise-induced LVH. METHODS AND RESULTS: Wistar rats were assigned to 1 of the following 5 groups: 10 weeks of voluntary exercise (EX), a sedentary regimen, a 1-week (AC1) or 4-week (AC4) ascending aortic constriction period, or a sham operation. EX rats ran 2.4+/-0.7 km/day voluntarily in specially manufactured cages; this was associated with an increase of LV diastolic dimension and stroke volume. Myocardial calcineurin activity markedly increased in EX rats (46.4+/-8.3 versus 18.4+/-0.5 pmol. min(-1). mg(-1) in sedentary rats; P<0.001) and in AC1 rats (44.9+/-6.7 versus 22.1+/-3.7 pmol. min(-1). mg(-1) in sham-operated rats; P<0.001), but not in AC4 rats (29.0+/-3.4 pmol. min(-1). mg(-1)). Treatment with cyclosporin A completely inhibited the development of LVH in EX rats, but it only partially attenuated the development of LVH in AC4 rats. CONCLUSIONS: Calcineurin was activated in exercise-induced physiological LVH and in the developing phase of LVH (AC1), but not in decompensated pressure-overload hypertrophy (AC4). Cyclosporin therapy for the prevention of LVH may be harmful because it does not block the development of pathological hypertrophy but rather that of favorable adaptive hypertrophy.
Assuntos
Calcineurina/fisiologia , Hipertrofia Ventricular Esquerda/metabolismo , Condicionamento Físico Animal/fisiologia , Animais , Hipertrofia Ventricular Esquerda/fisiopatologia , Ratos , Transdução de SinaisRESUMO
An O2-consuming side reaction of D-ribulose 1,5-bisphosphate carboxylase causes photorespiration in plants. This reaction may be an inevitable consequence of the enzyme's inability to protect its ene-diolate reaction intermediate from O2, a notion that is supported by the failure of persistent efforts to eliminate selectively its oxygenase activity by genetic manipulation. We have examined two a1dolases with similar ene-diolate intermediates, L-rhamnulose 1-phosphate aldolase and L-fuculose 1-phosphate aldolase. The former enzyme has an oxygenase activity, while the latter does not, suggesting that the reaction with O2 is not inevitable.
Assuntos
Aldeído Liases/metabolismo , Frutose-Bifosfato Aldolase/metabolismo , Oxigênio/metabolismo , Respiração Celular , Escherichia coli/enzimologia , Peróxido de Hidrogênio/metabolismo , Metais/metabolismo , Modelos BiológicosRESUMO
A precise coordination of multiple cell cycle events is required to ensure proper mitosis. Chromosome cohesion must be maintained until all chromosomes are attached to opposite poles of the mitotic spindle and aligned at the metaphase plate. At the onset of anaphase, the activity of separins contributes to the release of cohesins from chromosomes, allowing for the segregation of bivalents to opposite spindle poles. Separin activity is blocked by binding to a class of proteins known as securins, whose turnover at the metaphase-to-anaphase transition is triggered by the Anaphase Promoting Complex or cyclosome. The mitotic spindle cell cycle checkpoint coordinates the timing of these events and acts as input mechanism for DNA damage/stress pathways. Failure of this precise network leads to genomic instability and/or cell death.
Assuntos
Cromátides/fisiologia , Mitose/fisiologia , Proteína da Polipose Adenomatosa do Colo , Anáfase/fisiologia , Animais , Ciclo Celular , Cromátides/genética , Proteínas do Citoesqueleto/metabolismo , Humanos , Mitose/genética , Fuso Acromático/fisiologiaRESUMO
Mutations in the p53 tumor suppressor gene locus predispose human cells to chromosomal instability. This is due in part to interference of mutant p53 proteins with the activity of the mitotic spindle and postmitotic cell cycle checkpoints. Recent data demonstrates that wild type p53 is required for postmitotic checkpoint activity, but plays no role at the mitotic spindle checkpoint. Likewise, structural dominant p53 mutants demonstrate gain-of-function properties at the mitotic spindle checkpoint and dominant negative properties at the postmitotic checkpoint. At mitosis, mutant p53 proteins interfere with the control of the metaphase-to-anaphase progression by up-regulating the expression of CKs1, a protein that mediates activatory phosphorylation of the anaphase promoting complex (APC) by Cdc2. Cells that carry mutant p53 proteins overexpress CKs1 and are unable to sustain APC inactivation and mitotic arrest. Thus, mutant p53 gain-of-function at mitosis constitutes a key component to the origin of chromosomal instability in mutant p53 cells.
Assuntos
Mitose/fisiologia , Transdução de Sinais/fisiologia , Fuso Acromático/fisiologia , Proteína Supressora de Tumor p53/metabolismo , Animais , Ciclo Celular , Humanos , Mutagênese , Proteína Supressora de Tumor p53/genéticaRESUMO
The prevalence of heart failure increases as individuals age. The causes of heart failure in the older adult are essentially the same as in the general adult population. However, clinical presentation is altered in older adults because symptoms and physical findings may not be those classically described and taught. This article addresses the pathophysiology and clinical presentation, diagnostic evaluation, and therapy of heart failure in the older adult.
Assuntos
Insuficiência Cardíaca/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Fármacos Cardiovasculares/efeitos adversos , Fármacos Cardiovasculares/uso terapêutico , Enfermagem em Saúde Comunitária , Insuficiência Cardíaca/enfermagem , Insuficiência Cardíaca/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Hemodinâmica/fisiologia , Humanos , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Função Ventricular Esquerda/efeitos dos fármacos , Função Ventricular Esquerda/fisiologiaRESUMO
Patients with chronic heart failure are known not only for exceptionally high mortality rates, but also for having the highest reported hospital readmission rates for all patient groups. Analysis of preliminary descriptive data from 24 patients currently enrolled in an experimental study to examine the effects of a nursing model upon reducing readmission rates and improving quality of life are reported in this paper. Results indicate that heart failure patients experience significant mood disruption that appears to be greater than that reported by other cardiac patients; mood disruption is also related to reported quality of life. Reported exercise tolerance was unrelated to ejection fraction; this finding underscores the importance of psychosocial interventions in improving the quality of life and care outcomes for patients with heart failure.
Assuntos
Atividades Cotidianas/psicologia , Depressão/psicologia , Insuficiência Cardíaca/psicologia , Qualidade de Vida , Papel do Doente , Depressão/enfermagem , Depressão/reabilitação , Feminino , Seguimentos , Insuficiência Cardíaca/enfermagem , Insuficiência Cardíaca/reabilitação , Humanos , Masculino , Pessoa de Meia-Idade , Enfermeiros Clínicos , Educação de Pacientes como Assunto/métodos , Readmissão do Paciente , Projetos Piloto , Autocuidado/métodos , Resultado do TratamentoRESUMO
Rufous hummingbirds periodically establish and defend territories along their summer southward migration route. Using artificial perches attached to spring or electronic balances in the field, we were able to measure daily weight changes in undistributed, individually marked birds. The territory size (number of flowers) of individual birds varied from day to day. Four of five intensively studied birds adjusted their territories to that size which was associated with the fastest sustained rate of weight gain attained at any stable territory size. The one exception was explicable on the basis of its unusually high weight. These results are consistent with the assumption of optimization theory that animals are capable of assessing when their behavior (e.g., territory size) is suboptimal and then making adjustments toward an optimum. The results also suggest, although not conclusively, that these birds are selected to maximize their rate of weight gain on each stopover prior to resuming migration.
RESUMO
Cytosolic group IV phospholipase A2 (cPLA2) plays a role in liberating arachidonic acid from the sn-2 position of mammalian cellular phospholipids. The enzyme consists of a catalytic domain joined to an N-terminal calcium-dependent, membrane binding domain (C2 domain). The interfacial binding properties of the full-length, nonphosphorylated enzyme and its C2 domain to phospholipid vesicles were studied as a function of vesicle phospholipid composition and calcium concentration. The binding of cPLA2 to phosphatidylcholine vesicles is mostly governed by its C2 domain; binding is relatively weak, and calcium enhances binding and interfacial catalysis by about 10-fold. Catalytically productive interfacial binding was measured by monitoring the increase in the rate of cPLA2-catalyzed hydrolysis of a fluorimetric substrate present in vesicles as a function of bulk vesicle concentration. Enzyme-vesicle binding was also measured by fluorescence as was enzyme-calcium binding. Compared to zwitterionic vesicles, cPLA2 binding to anionic phosphatidylmethanol vesicles is of higher affinity and calcium-independent, although calcium is required for the binding of the C2 domain to these anionic vesicles. cPLA2 is fully catalytically active on phosphatidylmethanol vesicles in the absence of calcium. Phosphatidylserine is not a good replacement for phosphatidylmethanol for inducing high-affinity, calcium-independent binding of cPLA2. These results reveal two modes of catalytically productive interfacial binding of cPLA2: calcium-dependent anchoring via the C2 domain and a calcium-independent component involving a phosphatidylmethanol recognition element in the catalytic domain. They also show that membrane binding of cPLA2 is not, in general, predicted by the interfacial binding properties of its C2 domain.
Assuntos
Cálcio/metabolismo , Citosol/enzimologia , Fosfolipases A/metabolismo , Sequência de Aminoácidos , Sítios de Ligação , Catálise , Fosfolipases A2 do Grupo VI , Cinética , Lipossomos/metabolismo , Dados de Sequência Molecular , Ácidos Fosfatídicos/metabolismo , Fosfatidilcolinas/metabolismo , Fosfatidilserinas/metabolismo , Fosfolipases A/química , Fosfolipases A2 , Fosfolipídeos/metabolismo , Estrutura Terciária de ProteínaRESUMO
The basis for tight binding of bee venom phospholipase A2 (bvPLA2) to anionic versus zwitterionic phospholipid interfaces is explored by charge reversal mutagenesis of basic residues (lysines/arginines to glutamates) on the putative membrane binding surface. Single-site mutants and, surprisingly, multisite mutants (2-5 of the 6 basic residues mutated) are fully functional on anionic vesicles. Mutants bind tightly to anionic vesicles, and active-site substrate and Ca2+ binding are not impaired. Multisite mutants undergo intervesicle exchange slightly faster than wild type, especially in the presence of salt. It is estimated that electrostatic contribution to interfacial binding is modest, perhaps 2-3 kcal/mol of the estimated 15 kcal/mol. Elution properties of bvPLA2 from HPLC columns containing solid phases of tightly packed monolayers of phosphocholine amphiphiles suggest that ionic effects provide a modest portion of the interfacial binding energy and that this contribution decreases as the number of cationic residues mutated is increased. These results are consistent with the observation that Gila monster venom PLA2 (Pa2), which is homologous to bvPLA2, has high activity on anionic vesicles despite the fact that it has only a single basic residue on its putative interfacial recognition face. Results with bvPLA2 mutants show that manoalogue and 12-epi-scalaradial inactivate bvPLA2 by modification of K94. Also, deletion of the large beta-loop (residues 99-118) is without consequence for interfacial binding and catalysis of bvPLA2. All together, the preferential binding of bvPLA2 to anionic vesicles versus phosphatidylcholine vesicles is mainly due to factors other than electrostatics. Therefore hydrogen-bonding and hydrophobic interactions must provide a major portion of the interfacial binding energy, and this is consistent with recent spectroscopic studies.