RESUMO
BACKGROUND: While children of parents with criminal behavior (CB) are at increased risk for CB, we have limited knowledge about the causes of this cross-generational transmission. METHOD: We examined intergenerational continuity in CB in the Swedish population ascertained from the national conviction registers in three family types: intact (n = 21 11 074), 'not-lived-with' (n = 16 53 15 where biological parents never lived with their offspring) and 'step' (n = 1 24 800 offspring) which reflected, respectively, the effects of genes + rearing, genes only and rearing only. We also examined three criminal conviction subtypes: violent CB (VCB), property CB (PCB) and white-collar CB (WCCB). RESULTS: Combined across mothers and fathers, the hazard ratio (HR) for CB in offspring given parental CB was 1.95 in intact, 1.56 in 'not-lived-with' and 1.28 in stepfamilies. In all three family types, all forms of CB in parents (VCB, PCB and WCCB) significantly predicted risk for all forms of CB in offspring. However, VCB in offspring was most strongly predicted by VCB in parents in intact, not-lived-with and stepfamilies. In intact families only, some specific parent-offspring transmission was also seen for WCCB. CONCLUSIONS: Both genetic and environmental factors contribute substantially to parent-offspring resemblance for CB. With respect to criminal subtypes, much of parent-offspring transmission appears to be non-specific. However, specific genetic and environmental risk factors for VCB are transmitted across generations. A limitation of these analyses is that CB was assessed only via official criminal convictions.
Assuntos
Comportamento Criminoso , Interação Gene-Ambiente , Relação entre Gerações , Pais , Sistema de Registros , Meio Social , Adolescente , Adulto , Criança , Feminino , Humanos , Armazenamento e Recuperação da Informação , Masculino , Modelos de Riscos Proporcionais , SuéciaRESUMO
BACKGROUND: We sought to clarify the etiological contribution of genetic and environmental factors to total criminal behavior (CB) measured as criminal convictions in men and women, and to violent (VCB), white-collar (WCCB) and property criminal behavior (PCB) in men only. METHOD: In 21 603 twin pairs from the Swedish Twin Registry, we obtained information on all criminal convictions from 1973 to 2011 from the Swedish Crime Register. Twin modeling was performed using the OpenMx package. RESULTS: For all criminal convictions, heritability was estimated at around 45% in both sexes, with the shared environment accounting for 18% of the variance in liability in females and 27% in males. The correlation of these risk factors across sexes was estimated at +0.63. In men, the magnitudes of genetic and environmental influence were similar in the three criminal conviction subtypes. However, for violent and white-collar convictions, nearly half and one-third of the genetic effects were respectively unique to that criminal subtype. About half of the familial environmental effects were unique to property convictions. CONCLUSIONS: The familial aggregation of officially recorded CB is substantial and results from both genetic and familial environmental factors. These factors are moderately correlated across the sexes suggesting that some genetic and environmental influences on criminal convictions are unique to men and to women. Violent criminal behavior and property crime are substantially influenced respectively by genetic and shared environmental risk factors unique to that criminal subtype.
Assuntos
Crime/classificação , Comportamento Criminoso , Gêmeos/genética , Gêmeos/psicologia , Adulto , Meio Ambiente , Feminino , Interação Gene-Ambiente , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Sistema de Registros , Fatores de Risco , SuéciaRESUMO
Acute acetaminophen (ACT) ingestion has been reported to reduce thermal strain during cycling in the heat. In this study, nine active participants ingested 20 mg of ACT per kg of total body mass (ACT) or a placebo (PLA), 60 min prior to cycling at a fixed rate of metabolic heat production (ACT: 8.3 ± 0.3 W/kg; PLA: 8.5 ± 0.5 W/kg), which was equivalent to 55 ± 6% VO2max , for 60 min at 34.5 ± 0.1 °C, 52 ± 1% relative humidity. Resting rectal temperature (Tre ; ACT: 36.70 ± 0.17 °C; PLA: 36.80 ± 0.16 °C, P = 0.24), esophageal temperature (Tes ; ACT: 36.54 ± 0.22 °C; PLA: 36.61 ± 0.17 °C, P = 0.50) and mean skin temperature (Tsk ; ACT: 34.00 ± 0.14 °C; PLA: 33.96 ± 0.20 °C, P = 0.70) were all similar among conditions. At end-exercise, no differences in ΔTre (ACT: 1.12 ± 0.15 °C; PLA: 1.11 ± 0.21 °C, P = 0.92), ΔTes (ACT: 0.90 ± 0.28 °C; PLA: 0.88 ± 0.23 °C, P = 0.84), ΔTsk (ACT: 0.80 ± 0.39 °C; PLA: 0.70 ± 0.46 °C, P = 0.63), mean local sweat rate (ACT: 1.02 ± 0.15 mg/cm(2) /min; PLA: 1.02 ± 0.13 mg/cm(2) /min, P = 0.98) and whole-body sweat loss (ACT: 663 ± 83 g; PLA: 663 ± 77 g, P = 0.995) were evident. Furthermore, ratings of perceived exertion and thermal sensation and thermal comfort were not different between ACT and PLA conditions. In conclusion, ACT ingested 60 min prior to moderate intensity exercise in hot-humid conditions does not alter physiologic thermoregulatory control nor perceived strain.
Assuntos
Acetaminofen/farmacologia , Antipiréticos/farmacologia , Temperatura Corporal/efeitos dos fármacos , Exercício Físico/fisiologia , Transtornos de Estresse por Calor/prevenção & controle , Temperatura Alta/efeitos adversos , Umidade/efeitos adversos , Acetaminofen/uso terapêutico , Adulto , Antipiréticos/uso terapêutico , Ciclismo/fisiologia , Regulação da Temperatura Corporal/efeitos dos fármacos , Regulação da Temperatura Corporal/fisiologia , Método Duplo-Cego , Esquema de Medicação , Feminino , Transtornos de Estresse por Calor/etiologia , Humanos , Masculino , Esforço Físico/efeitos dos fármacos , Esforço Físico/fisiologia , Sudorese/efeitos dos fármacos , Resultado do TratamentoRESUMO
The X-ray mammogram remains the cornerstone of most public health programmes aimed at the early diagnosis of breast cancer. Its virtues of safety, reliability and cheapness maintain its established position, and Western social and cultural traditions of ambivalence to pain push any questions concerning the painfulness of the procedure into the background. As part of a larger UK/USA-based empirical study, we undertook a qualitative analysis of women's accounts of pain experienced in mammograms and their reaction to it, comparing their accounts with professional views and advice to patients as reflected in interviews, patient leaflets and practice guidelines. We found considerable variability of experience and reaction to pain among patients, and indications of similar variability in professionals' views and practice, contrasting with a uniformly reassuring message in formal institutional advice. We suggest that in practice professional work-arounds and patients' felt obligation to tolerate pain bridge this gap, but that action to tackle the problems of dropout and the emotional and operational costs of the current system is nonetheless needed. The need is for concerned groups to combine to establish a serious and sustained programme of amelioration and innovative technological development to assure more compassionate patient care and operational efficiency.
Assuntos
Neoplasias da Mama/psicologia , Mamografia/psicologia , Dor/psicologia , Atitude do Pessoal de Saúde , Atitude Frente a Saúde , Neoplasias da Mama/diagnóstico por imagem , Detecção Precoce de Câncer/psicologia , Empatia , Feminino , Humanos , Dor/prevenção & controle , Educação de Pacientes como Assunto/métodos , Assistência Centrada no Paciente/normas , Relações Profissional-Paciente , Terminologia como AssuntoRESUMO
UNLABELLED: BACKGROUND. Violent criminal behaviour (VCB) runs strongly in families partly because of shared environmental factors. Can we clarify the environmental processes that contribute to similarity of risk for VCB in siblings? METHOD: We assessed VCB from the Swedish National Crime Register for the years 1973-2011 in siblings born 1950-1991. We examined by conditional logistic and Cox proportional hazard regression, respectively, whether resemblance for VCB in sibling pairs was influenced by their age difference and whether VCB was more strongly 'transmitted' from olderâyounger versus youngerâolder siblings. RESULTS: In our best-fit logistic model, for each year of age difference in full sibling pairs, the risk for VCB in the sibling of a case versus control proband declined by 2.6% [95% confidence interval (CI) 2.2-3.0]. In our best-fit Cox model, the hazard rate for VCB in a sibling when the affected proband was older versus younger was 1.4, 2.1 and 2.9 respectively for a 1-, 5- and 10-year difference in siblings. CONCLUSIONS: Controlling for genetic effects by examining only full siblings, sibling resemblance for risk for VCB was significantly greater in pairs closer versus more distant in age. Older siblings more strongly transmitted risk for VCB to their younger siblings than vice versa. These results strongly support the importance of familial-environmental influences on VCB and provide some insight into the possible mechanisms at work.
Assuntos
Meio Ambiente , Sistema de Registros/estatística & dados numéricos , Irmãos , Violência/estatística & dados numéricos , Adulto , Fatores Etários , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Risco , Suécia/epidemiologiaRESUMO
BACKGROUND: To clarify the role of genetic and environmental factors in criminal behavior (CB), we examined all CB and violent and non-violent subtypes (VCB and NVCB, respectively) in a Swedish national sample of adoptees and their relatives. METHOD: CB was defined by a conviction in the Swedish Crime Register with standard definitions for VCB and NVCB subtypes. We examined adoptees born 1950-1991 (n = 18 070) and their biological (n = 79 206) and adoptive (n = 47 311) relatives. RESULTS: The risk for all CB was significantly elevated in the adopted-away offspring of biological parents of which at least one had CB [odds ratio (OR) 1.5, 95% confidence interval (CI) 1.4-1.6] and in the biological full and half-siblings of CB adoptees (OR 1.4, 95% CI 1.2-1.6 and OR 1.3, 95% CI 1.2-1.3, respectively). A genetic risk index (including biological parental/sibling history of CB and alcohol abuse) and an environmental risk index (including adoptive parental and sibling CB and a history of adoptive parental divorce, death, and medical illness) both strongly predicted probability of CB. These genetic and environmental risk indices acted additively on adoptee risk for CB. Moderate specificity was seen in the transmission of genetic risk for VCB and NVCB between biological parents and siblings and adoptees. CONCLUSIONS: CB is etiologically complex and influenced by a range of genetic risk factors including a specific liability to CB and a vulnerability to broader externalizing behaviors, and by features of the adoptive environment including parental CB, divorce and death. Genetic risk factors for VCB and NVCB may be at least partially distinct.
Assuntos
Adoção , Criminosos/estatística & dados numéricos , Interação Gene-Ambiente , Pais , Sistema de Registros/estatística & dados numéricos , Violência/estatística & dados numéricos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Risco , Suécia/epidemiologiaRESUMO
Interpretation of the latent meaning of manifest content is the core of the traditional approach to psychoanalytic treatment. The main purpose of such interpretation is to enhance the patient's self-knowledge, in particular his or her awareness of unconscious wishes and their embeddedness in inner conflicts. An assumption of classical psychoanalysis is that veridical interpretations-as Freud put it, interpretations that tally with what is real in the patient-will be especially effective therapeutically. These basic assumptions have been called into question, as reflected in such concepts as "narrative truth" and the overriding importance of the patient's "assured conviction" regarding interpretations. Also called into question is the therapeutic value of "deep" interpretations intended to uncover repressed impulses. To an important extent, these have been replaced by interpretations of defensive processes just below the surface of consciousness, and interpretations that make connections among different experiences, both of which are intended to help the patient understand how his or her mind works. There is also an increased emphasis on nonsemantic aspects of interpretation, as well as some degree of skepticism toward the therapeutic value of interpretation itself, along with an increased emphasis on the implicit interpretive aspects of the therapeutic relationship. Finally, representative research is presented on the relation between transference interpretation and therapeutic outcome.
Assuntos
Psicanálise , Terapia Psicanalítica , Masculino , Feminino , Humanos , Teoria Psicanalítica , Interpretação PsicanalíticaRESUMO
We compared insertion rates of single-use polyvinyl chloride laryngeal mask airways (LMAs) vs single-use silicone LMAs in 72 anaesthetised patients. Both airways were produced by Flexicare Medical. Laryngeal mask airway insertion was successful on the first attempt in 68/72 (94%) polyvinyl chloride LMAs vs 64/72 (89%) silicone LMAs (p = 0.39). Overall insertion rates were 72/72 (100%) for the polyvinyl chloride LMAs and 71/72 (99%) for the silicone LMAs (p = 1.0). Mean (SD) insertion times were similar for polyvinyl chloride and silicone LMAs: 24.3 (5.1)s vs 24.8 (7.8)s (p = 0.64). Laryngeal mask airway position, as assessed using a fibrescope, was not different (p = 0.077). The median (IQR [range]) leak pressure was 16 (12-20 [6-30]) cmH(2) O for the polyvinyl LMA and 18 (13-22 [6-30]) cmH(2) O or the silicone LMA (p = 0.037). In conclusion, we did not find any important differences between polyvinyl chloride and silicone laryngeal mask airways.
Assuntos
Equipamentos Descartáveis , Máscaras Laríngeas , Cloreto de Polivinila , Silicones , Adulto , Estudos Cross-Over , Desenho de Equipamento , Feminino , Humanos , MasculinoRESUMO
INTRODUCTION: Screening to assess likelihood of preclinical dilated cardiomyopathy (PC-DCM) prior to advanced diagnostic tests in Doberman Pinschers (DP) is desirable. OBJECTIVE: To investigate the combined value of physical examination (PE), N-terminal pro B-type natriuretic peptide (NTproBNP) and cardiac troponin I (cTnI) for identifying PC-DCM in DP. ANIMALS, MATERIALS AND METHODS: All dogs underwent: PE, echocardiogram, 3-min ECG and cardiac biomarker measurement. Asymptomatic DP (414) were classified based on 3-min ECG and echocardiogram as: No-DCM/MMVD or myxomatous mitral valve disease (MMVD), PC-DCM based on echocardiogram (PC-DCM-Echo), PC-DCM based on arrhythmias with a normal echocardiogram (PC-DCM-ECG), equivocal DCM (EQ-DCM), and MMVD. Receiver operator characteristic curves and prediction models were derived. RESULTS: Heart murmurs and arrhythmias were rare and gallop sounds were absent in No-DCM/MMVD DP. Dogs ≥ four years old and males had higher probabilities of PC-DCM-Echo. Prediction models incorporating PE variables with NTproBNP had an area under the curve (AUC) of 0.940 for distinguishing between PC-DCM-Echo and all other groups, which was similar to the AUC for NTproBNP (0.939) or cTnI (0.932) alone. Discrimination between No-DCM/MMVD and all other groups was similar for NTproBNP (0.781) and cTnI (0.742) as individual tests, however, models combining PE variables and NTproBNP increased the AUC to 0.812. An NTproBNP cut-off of ≥548 pmol/L, was 100% sensitive and 77.3% specific for detecting PC-DCM-Echo. CONCLUSIONS: Both NTproBNP and cTnI had good utility as sole tests to discriminate PC-DCM-Echo DP from all others. Models differentiating No-DCM/MMVD DP from all other DP were improved by using PE and NTproBNP together.
Assuntos
Cardiomiopatia Dilatada , Doenças do Cão , Animais , Biomarcadores , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/veterinária , Doenças do Cão/diagnóstico , Cães , Masculino , Exame Físico , Troponina IRESUMO
BACKGROUND: Saddle pulmonary embolism represents a large clot and a risk for sudden hemodynamic collapse. However, the clinical presentation and outcomes vary widely. On the basis of the findings of right heart dysfunction on echocardiograms, computed tomography angiography, or cardiac enzyme elevation, some argue for the use of thrombolytics or catheter thrombectomy even for hemodynamically stable patients. OBJECTIVE: To investigate the outcomes and management of patients with saddle pulmonary embolism, including radiographic appearance (estimate of clot burden) and echocardiographic features. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: This study is a retrospective evaluation of all patients with computed tomography angiography positive for pulmonary embolism from June 1, 2004, to February 28, 2009. Two radiologists selected those with saddle pulmonary embolism and evaluated the clot burden score. The clinical information, echocardiography, treatments, and outcomes of these patients were extracted via chart review. Saddle pulmonary embolism was found in 37 of 680 patients (5.4%, 95% confidence interval 4% to 7%) with documented pulmonary embolism on computed tomography angiography. For patients with saddle pulmonary embolism, the median age was 60 yrs and 41% were males. Major comorbidities were neurologic (24%), recent surgery (24%), and malignancy (22%). Transient hypotension occurred in 14% and persistent shock in 8%. One patient required mechanical ventilation. Echocardiography was performed in 27 patients (73%). Right ventricle enlargement and dysfunction were found in 78% and elevated pulmonary artery systolic pressure in 67%. Computed tomography angiography demonstrated a high median pulmonary artery clot burden score of 31 points. The median right ventricle to left ventricle diameter ratio was 1.39. Inferior vena cava filters were placed in 46%. Unfractionated heparin was administered in 33 (87%) and thrombolytics in four (11%). The median hospital length of stay was 9 days. Two of 37 saddle pulmonary embolism patients (5.4%) died in the hospital (95% confidence interval 0.7% to 18%). CONCLUSIONS: Most patients with saddle pulmonary embolism found on computed tomography angiography responded to the standard management for pulmonary embolism with unfractionated heparin. Although ominous in appearance, most patients with saddle pulmonary embolism are hemodynamically stable and do not require thrombolytic therapy or other interventions.
Assuntos
Fibrinolíticos/uso terapêutico , Heparina/uso terapêutico , Avaliação de Processos e Resultados em Cuidados de Saúde , Embolia Pulmonar/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Ecocardiografia , Feminino , Ventrículos do Coração , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/classificação , Embolia Pulmonar/diagnóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Disfunção Ventricular DireitaRESUMO
The nucleus, like other smaller organelles in the cell, is dynamic and can move about in the cytoplasm. In some cells, nuclear movements are concerned with mitosis or meiosis; in others, they are concerned with orienting nuclear divisions; and in still others, they deal with distributing nuclei through the cytoplasm. Recent interest in nuclear positioning has shown that nuclear movements are often mediated by the interactions of dynein and other proteins at the plus ends of astral microtubules with the cell cortex. How the microtubule minus ends interact with the nucleus also affects nuclear movements.
Assuntos
Movimento Celular/fisiologia , Núcleo Celular/metabolismo , Células Eucarióticas/metabolismo , Microtúbulos/metabolismo , Proteínas Motores Moleculares/fisiologia , Animais , Núcleo Celular/ultraestrutura , Polaridade Celular/fisiologia , Centrossomo/metabolismo , Centrossomo/ultraestrutura , Células Eucarióticas/ultraestrutura , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/ultraestrutura , Humanos , Microtúbulos/ultraestruturaAssuntos
Ortodontia/história , Sociedades Odontológicas/história , Informação de Saúde ao Consumidor , Conselho Diretor/história , Conselho Diretor/organização & administração , Regulamentação Governamental , História do Século XXI , Humanos , Relações Interprofissionais , Cultura Organizacional , Inovação Organizacional , Objetivos Organizacionais , Ortodontia/legislação & jurisprudência , Ortodontia/organização & administração , Sociedades Odontológicas/organização & administração , Estados UnidosRESUMO
INTRODUCTION: Menthol topical application and mouth rinsing are ergogenic in hot environments, improving performance and perception, with differing effects on body temperature regulation. Consequently, athletes and federations are beginning to explore the possible benefits to elite sport performance for the Tokyo 2021 Olympics, which will take place in hot (~ 31 °C), humid (70% RH) conditions. There is no clear consensus on safe and effective menthol use for athletes, practitioners, or researchers. The present study addressed this shortfall by producing expert-led consensus recommendations. METHOD: Fourteen contributors were recruited following ethical approval. A three-step modified Delphi method was used for voting on 96 statements generated following literature consultation; 192 statements total (96/96 topical application/mouth rinsing). Round 1 contributors voted to "agree" or "disagree" with statements; 80% agreement was required to accept statements. In round 2, contributors voted to "support" or "change" their round 1 unaccepted statements, with knowledge of the extant voting from round 1. Round 3 contributors met to discuss voting against key remaining statements. RESULTS: Forty-seven statements reached consensus in round 1 (30/17 topical application/rinsing); 14 proved redundant. Six statements reached consensus in round 2 (2/4 topical application/rinsing); 116 statements proved redundant. Nine further statements were agreed in round 3 (6/3 topical application/rinsing) with caveats. DISCUSSION: Consensus was reached on 62 statements in total (38/24 topical application/rinsing), enabling the development of guidance on safe menthol administration, with a view to enhancing performance and perception in the heat without impairing body temperature regulation.
Assuntos
Administração Tópica , Desempenho Atlético/fisiologia , Mentol/administração & dosagem , Antissépticos Bucais , Substâncias para Melhoria do Desempenho , Técnica Delphi , Humanos , TóquioRESUMO
SUMMARY: We recruited a population-based sample of 58 males and 74 females aged 20-79 from a primary care medical practice to provide normative and descriptive data for high-resolution peripheral quantitative computed tomography (pQCT) parameters. Important effects of ageing and contrasts in the effects of sex on the micro-architecture and strength of upper and lower limb bones were revealed. INTRODUCTION: The advent of high-resolution pQCT scanners has permitted non-invasive assessment of structural data on cortical and trabecular bone. METHODS: We investigated age-related changes in pQCT and finite element (FE) modelling parameters at the distal radius and distal tibia in a population-based cross-sectional study of 58 males and 74 females aged 20-79 years. Linear regression models including quadratic terms for age were used for inference. RESULTS: Age-related changes and sex differences were generally similar for pQCT parameters at the radius and tibia. At each site, mean values for bone density, cortical thickness and trabecular micro-architecture (number, separation and thickness) were lower (trabecular separation higher) in women than men. Changes with age were most apparent for bone density and cortical thickness, which declined with age, in contrast to trabecular micro-architecture parameters which were not significantly associated with age (p > 0.05) in either sex. Cortical bone density and thickness declined faster in women than men after age 50 and trabecular bone density was consistently lower in women. FE-analysis predicted failure load decreased with age and percentage of load carried by trabecular bone increased (p < 0.05). CONCLUSIONS: These data show contrasts in the effects of sex on the micro-architecture and strength of upper and lower limb bones with ageing. The faster decline in cortical bone thickness and density in women than men after age 50 and consistently lower trabecular bone density in women have implications for the excess risks of wrist and hip fractures in women.
Assuntos
Envelhecimento/fisiologia , Rádio (Anatomia)/fisiologia , Tíbia/fisiologia , Absorciometria de Fóton/métodos , Adulto , Idoso , Envelhecimento/patologia , Métodos Epidemiológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rádio (Anatomia)/anatomia & histologia , Rádio (Anatomia)/diagnóstico por imagem , Valores de Referência , Caracteres Sexuais , Tíbia/anatomia & histologia , Tíbia/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto JovemRESUMO
Nuclear migration encompasses three areas: separation of daughter nuclei during mitosis, congress of parental nuclei before they fuse during fertilization, and positioning of nuclei in interphase cells. This review deals primarily with interphase nuclear migration, which is crucial for events as disparate as vertebrate embryonic development and growth of fungal mycelia. Mutants of Aspergillus nidulans, Neurospora crassa and Saccharomyces cerevisiae have been particularly informative, and a detailed molecular analysis of this process is now well under way.
RESUMO
During the past 20 years, biologists have become used to finding that proteins first identified in simple, genetically manipulable eukaryotic organisms are conserved in higher eukaryotes. This article draws attention to the similarity between NUDF protein, which is required for nuclear migration in the filamentous fungus Aspergillus nidulans, and a mammalian homologue, LIS1, whose malfunction causes lissencephaly, a neuronal migration disease. The authors suggest that there might be an underlying similarity of mechanism between nuclear migration in the fungus and neuronal migration in the brain.
Assuntos
Núcleo Celular/fisiologia , Proteínas Fúngicas/metabolismo , Proteínas Associadas aos Microtúbulos , Proteínas/metabolismo , Animais , Movimento Celular , Neurônios/fisiologiaRESUMO
In order to develop a method for obtaining mitotic synchrony in aspergillus nidulans, we have characterized previously isolated heat-sensitive nim mutations that block the nuclear division cycle in interphase at restrictive temperature. After 3.5 h at restrictive temperature the mitotic index of a strain carrying one of these mutations, nimA5, was 0, but when this strain was subsequently shifted from restrictive to permissive temperature the mitotic index increased rapidly, reaching a maximum of 78 percent after 7.5 min. When this strain was examined electron-microscopically, mitotic spindles were absent at restrictive temperature. From these data we conclude that at restrictive temperature nimA5 blocks the nuclear division cycle at a point immediately preceding the initiation of chromosomal condensation and mitotic microtubule assembly, and upon shifting to permissive control over the initiation of microtubule assembly and chromosomal condensation in vivo through a simple temperature shift and, consequently, nimA5 should be a powerful tool for studying these processes. Electron-microscopic examination of spindles of material synchronized in this manner reveals that spindle formation, although very rapid, is gradual in the sense that spindle microtubule numbers increase as spindle formation proceeds.
Assuntos
Aspergillus nidulans/genética , Mitose , Mutação , Interfase , PrófaseRESUMO
We used immunofluorescent microscopy to characterize microtubule (MT) architecture in wild-type and mutant protoplasts of Aspergillus nidulans at interphase and at mitosis. Because the visualization of MTs by immunofluorescence is technically difficult in intact hyphae of A. nidulans, we developed a method for removing the cell wall under conditions that do not perturb cell physiology, as evidenced by the fact that the resulting protoplasts undergo nuclear division at a normal rate and that cell cycle mutant phenotypes are expressed at restrictive temperature. Interphase cells exhibited an extensive network of cytoplasmic MTs. During mitosis the cytoplasmic MTs mostly disappeared and an intranuclear mitotic spindle appeared. We have previously shown that the benA 33 beta-tubulin mutation causes hyperstabilization of the mitotic spindle, and we have presented additional indirect evidence that suggested that the tubA1 and tubA4 alpha-tubulin mutations destabilize spindle MTs. In this paper, we show that the benA33 mutation increases the stability of cytoplasmic MTs as well as spindle MTs and that the tubA1 and tubA4 mutations destabilize both spindle and cytoplasmic MTs.
Assuntos
Aspergillus nidulans/citologia , Microtúbulos/ultraestrutura , Mutação , Tubulina (Proteína)/genética , Aspergillus nidulans/ultraestrutura , Núcleo Celular/ultraestrutura , Imunofluorescência , Cinética , Microscopia Eletrônica , Mitose , Protoplastos/ultraestruturaRESUMO
The nudF gene of the filamentous fungus Aspergillus nidulans acts in the cytoplasmic dynein/dynactin pathway and is required for distribution of nuclei. NUDF protein, the product of the nudF gene, displays 42% sequence identity with the human protein LIS1 required for neuronal migration. Haploinsufficiency of the LIS1 gene causes a malformation of the human brain known as lissencephaly. We screened for multicopy suppressors of a mutation in the nudF gene. The product of the nudE gene isolated in the screen, NUDE, is a homologue of the nuclear distribution protein RO11 of Neurospora crassa. The highly conserved NH(2)-terminal coiled-coil domain of the NUDE protein suffices for protein function when overexpressed. A similar coiled-coil domain is present in several putative human proteins and in the mitotic phosphoprotein 43 (MP43) of X. laevis. NUDF protein interacts with the Aspergillus NUDE coiled-coil in a yeast two-hybrid system, while human LIS1 interacts with the human homologue of the NUDE/RO11 coiled-coil and also the Xenopus MP43 coiled-coil. In addition, NUDF coprecipitates with an epitope-tagged NUDE. The fact that NUDF and LIS1 interact with the same protein domain strengthens the notion that these two proteins are functionally related.
Assuntos
Aspergillus nidulans , Proteínas Fúngicas/metabolismo , Estrutura Terciária de Proteína , 1-Alquil-2-acetilglicerofosfocolina Esterase , Sequência de Aminoácidos , Animais , Sítios de Ligação , Clonagem Molecular , Sequência Conservada , Evolução Molecular , Proteínas Fúngicas/genética , Humanos , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Dados de Sequência Molecular , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Ligação Proteica , Homologia de Sequência de Aminoácidos , Supressão Genética , Técnicas do Sistema de Duplo-HíbridoRESUMO
The Aspergillus nidulans bimA gene is required for mitosis. Loss of function mutations in bimA cause cells to arrest growth with condensed chromatin and a short, metaphaselike mitotic spindle. bimA is a member of a gene family defined by a repeated motif called the Tetratrico Peptide Repeat (TPR), which is found in genes from bacteria, yeast and insects. Several yeast TPR genes are also required for mitosis, including Saccharomyces cerevisiae CDC27 and Schizosaccharomyces pombe nuc2+, which appear to be functional homologs of bimA. We have developed antisera specific to the bimA protein (BIMA) and have characterized BIMA by western blot and immunocytochemical analyses. BIMA is heterogeneous in apparent molecular weight, consisting of a major 90-kD species and at least two minor species of approximately 105 kD. The results of BIMA localization by immunofluorescence microscopy depend on the level of BIMA expression. Overexpression of BIMA, which had no deleterious affect on growth or mitosis, resulted in localization of BIMA on or throughout most nuclei. Nuclear staining was granular, and overlapped but was not completely coincident with DNA staining by DAPI. In contrast, when expressed at normal levels, BIMA colocalized with the spindle pole body (SPB). BIMA localized to the SPB in a cell cycle independent manner. These results show that BIMA is either associated with or is a component of the SPB, and they suggest that BIMA functions at the spindle poles to promote the onset of anaphase.