RESUMO
Time-restricted eating (TRE) has gained popularity in recent years as a weight loss option. Although many studies have explored the effectiveness of fasting, few have investigated the successful implementation of this method. Therefore, the purpose of this study is to examine the successful and failed experiences of overweight adults who have implemented TRE for weight loss, in order to identify strategies for maintaining a favorable weight over time. The study utilized semi-structured interviews and followed Constructivist Grounded Theory to collect and analyze data. Data saturation was achieved through purposive and theoretical sampling of 30 overweight adults. The research confirms four stages in the process of weight loss using a TRE strategy, namely, preparation, adaptation, challenge, and maintenance. The findings revealed that the successful implementation of TRE and its maintenance over time require viewing TRE as a lifestyle rather than a tool for short-term weight loss, the development of specific action plans to overcome obstacles, and a positive attitude and self-belief as important sources of support. Based on the study's results, a guide has been provided for those who wish to use TRE as a dietary control method.
Assuntos
Obesidade , Sobrepeso , Adulto , Humanos , Sobrepeso/terapia , Estilo de Vida , Jejum , Redução de PesoRESUMO
Measures of phylogenetic diversity are basic tools in many studies of systematic biology. Faith's PD (sum of branch lengths of a phylogenetic tree connecting all focal species) is the most widely used phylogenetic measure. Like species richness, Faith's PD based on sampling data is highly dependent on sample size and sample completeness. The sample-size- and sample-coverage-based integration of rarefaction and extrapolation of Faith's PD was recently developed to make fair comparison across multiple assemblages. However, species abundances are not considered in Faith's PD. Based on the framework of Hill numbers, Faith's PD was generalized to a class of phylogenetic diversity measures that incorporates species abundances. In this article, we develop both theoretical formulae and analytic estimators for seamless rarefaction and extrapolation for this class of abundance-sensitive phylogenetic measures, which includes simple transformations of phylogenetic entropy and of quadratic entropy. This work generalizes the previous rarefaction/extrapolation model of Faith's PD to incorporate species abundance, and also extends the previous rarefaction/extrapolation model of Hill numbers to include phylogenetic differences among species. Thus a unified approach to assessing and comparing species/taxonomic diversity and phylogenetic diversity can be established. A bootstrap method is suggested for constructing confidence intervals around the phylogenetic diversity, facilitating the comparison of multiple assemblages. Our formulation and estimators can be extended to incidence data collected from multiple sampling units. We also illustrate the formulae and estimators using bacterial sequence data from the human distal esophagus and phyllostomid bat data from three habitats.
Assuntos
Classificação/métodos , Modelos Biológicos , Filogenia , Animais , Bactérias/classificação , Bactérias/genética , Biodiversidade , Quirópteros/classificação , Interpretação Estatística de Dados , Ecossistema , Esôfago/microbiologia , Genes Bacterianos/genética , Humanos , MicrobiotaRESUMO
OBJECTIVES: This study correlated immunohistochemical studies with fluorodeoxyglucose (FDG) uptake on positron emission tomography-computed tomography (PET-CT) and identified prognostic factors for radiotherapy (RT)-based treatment outcomes in patients with squamous cell carcinoma of the oropharynx and hypopharynx. METHODS: Genomic data from pre-treatment biopsy specimens (Glut1, CAIX, VEGF, HIF-1α, EGFR, Ki-67, Bcl-2, CLAUDIN-4, YAP-1, c-Met and p16) of 76 patients were analysed using tissue microarrays. FDG uptake was evaluated using the maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG). RESULTS: The overexpression of Glut1 positively associated with increased values of the SUVmax, MTV and TLG, whereas VEGF and HIF-1α expression with the MTV and TLG, respectively. A VEGF immunoreactive score (IRS) >2 (P = 0.001, hazard ratio [HR] = 3.94) and an MTV defined by an SUV of 2.5 (MTV2.5) >14.5 mL (P = 0.004, HR = 3.31) were prognostic factors for low cause-specific survival, whereas a VEGF IRS >2 (P = 0.02, HR = 2.83) for low primary relapse-free survival. CONCLUSION: The overexpression of Glut1, VEGF and HIF-1α associated with increased FDG uptake. For patients with pharyngeal cancer requiring RT, the treatment outcome can be stratified by VEGF and MTV2.5.
Assuntos
Biomarcadores Tumorais/análise , Fluordesoxiglucose F18/farmacocinética , Imuno-Histoquímica/métodos , Estadiamento de Neoplasias , Neoplasias Faríngeas/diagnóstico por imagem , Neoplasias Faríngeas/radioterapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Adulto , Idoso , Biópsia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Faríngeas/metabolismo , Compostos Radiofarmacêuticos/farmacocinética , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Based on a sample of individuals, we focus on inferring the vector of species relative abundance of an entire assemblage and propose a novel estimator of the complete species-rank abundance distribution (RAD). Nearly all previous estimators of the RAD use the conventional "plug-in" estimator Pi (sample relative abundance) of the true relative abundance pi of species i. Because most biodiversity samples are incomplete, the plug-in estimators are applied only to the subset of species that are detected in the sample. Using the concept of sample coverage and its generalization, we propose a new statistical framework to estimate the complete RAD by separately adjusting the sample relative abundances for the set of species detected in the sample and estimating the relative abundances for the set of species undetected in the sample but inferred to be present in the assemblage. We first show that P, is a positively biased estimator of pi for species detected in the sample, and that the degree of bias increases with increasing relative rarity of each species. We next derive a method to adjust the sample relative abundance to reduce the positive bias inherent in j. The adjustment method provides a nonparametric resolution to the longstanding challenge of characterizing the relationship between the true relative abundance in the entire assemblage and the observed relative abundance in a sample. Finally, we propose a method to estimate the true relative abundances of the undetected species based on a lower bound of the number of undetected species. We then combine the adjusted RAD for the detected species and the estimated RAD for the undetected species to obtain the complete RAD estimator. Simulation results show that the proposed RAD curve can unveil the true RAD and is more accurate than the empirical RAD. We also extend our method to incidence data. Our formulas and estimators are illustrated using empirical data sets from surveys of forest spiders (for abundance data) and soil ciliates (for incidence data). The proposed RAD estimator is also applicable to estimating various diversity measures and should be widely useful to analyses of biodiversity and community structure.
Assuntos
Simulação por Computador , Modelos Biológicos , Animais , Modelos Estatísticos , Densidade Demográfica , Viés de SeleçãoRESUMO
Cirrhosis patients have immunologic insufficiency and a high seroprevalence of human herpesvirus type 8 (HHV-8). Nearly all hepatocellular carcinoma (HCC) patients are cirrhotic and have immunoabnormalities. This study aimed to assess the HHV-8 seroprevalence and hemograms in HCC patients. Blood samples from 95 HCC patients, 95 age-, sex-, and Child-Pugh class-matched cirrhotics, and 95 age- and sex-matched healthy controls were analyzed for anti-HHV-8 antibodies, HHV-8 DNA, and lymphocyte, monocyte, and platelet counts. HCC patients had lower lymphocyte and platelet counts and a higher monocyte count than the healthy controls (each p < 0.0001). HCC patients, and particularly those with a severe Child-Pugh class, had higher platelet counts than the corresponding cirrhosis patients (p = 0.003 and 0.002, respectively). HHV-8 seropositivity and antibody titers in HCC patients were comparable with values in cirrhosis patients and were much higher than in controls (both p < 0.0001). HCC patients, but not cirrhosis patients, had a higher prevalence of high anti-HHV-8 antibody titers (≥ 1:160) than healthy controls (p = 0.003). HCC patients with lymphopenia or thrombocytopenia had lower HHV-8 seropositivity than those without lymphopenia and thrombocytopenia (p = 0.04 and 0.01, respectively). One each of HCC and cirrhosis patients were positive for HHV-8 DNA. HCC patients seemed to suffer from less severe or shorter duration of portal hypertension compared with Child-Pugh class-matched cirrhosis patients. HCC patients had a high HHV-8 seroprevalence, which seemed to be inversely associated with lymphopenia and thrombocytopenia.
Assuntos
Carcinoma Hepatocelular/complicações , Infecções por Herpesviridae/epidemiologia , Herpesvirus Humano 8/imunologia , Adulto , Idoso , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos SoroepidemiológicosRESUMO
STUDY QUESTION: What human tissues and cell types express the X-linked reproductive homeobox (RHOX) gene cluster? SUMMARY ANSWER: The RHOX homeobox genes and proteins are selectively expressed in germ cells in both the ovary and testis. WHAT IS KNOWN ALREADY: The RHOX homeobox transcription factors are encoded by an X-linked gene cluster whose members are selectively expressed in the male and female reproductive tract of mice and rats. The Rhox genes have undergone strong selection pressure to rapidly evolve, making it uncertain whether they maintain their reproductive tissue-centric expression pattern in humans, an issue we address in this report. STUDY DESIGN, SIZE, DURATION: We examined the expression of all members of the human RHOX gene cluster in 11 fetal and 8 adult tissues. The focus of our analysis was on fetal testes, where we evaluated 16 different samples from 8 to 20 weeks gestation. We also analyzed fixed sections from fetal testes, adult testes and adult ovaries to determine the cell type-specific expression pattern of the proteins encoded by RHOX genes. PARTICIPANTS/MATERIALS, SETTING, METHODS: We used quantitative reverse transcription-polymerase chain reaction analysis to assay human RHOX gene expression. We generated antisera against RHOX proteins and used them for western blotting, immunohistochemical and immunofluorescence analyses of RHOXF1 and RHOXF2/2B protein expression. MAIN RESULTS AND THE ROLE OF CHANCE: We found that the RHOXF1 and RHOXF2/2B genes are highly expressed in the testis and exhibit low or undetectable expression in most other organs. Using RHOXF1- and RHOXF2/2B-specific antiserum, we found that both RHOXF1 and RHOXF2/2B are primarily expressed in germ cells in the adult testis. Early stage germ cells (spermatogonia and early spermatocytes) express RHOXF2/2B, while later stage germ cells (pachytene spermatocytes and round spermatids) express RHOXF1. Both RHOXF1 and RHOXF2/2B are expressed in prespermatogonia in human fetal testes. Consistent with this, RHOXF1 and RHOXF2/2B mRNA expression increases in the second trimester during fetal testes development when gonocytes differentiate into prespermatogonia. In the human adult ovary, we found that RHOXF1 and RHOXF2/2B are primarily expressed in oocytes. LIMITATIONS, REASONS FOR CAUTION: While the average level of expression of RHOX genes was low or undetectable in all 19 human tissues other than testes, it is still possible that RHOX genes are highly expressed in a small subset of cells in some of these non-testicular tissues. As a case in point, we found that RHOX proteins are highly expressed in oocytes within the human ovary, despite low levels of RHOX mRNA in the whole ovary. WIDER IMPLICATIONS OF THE FINDINGS: The cell type-specific and developmentally regulated expression pattern of the RHOX transcription factors suggests that they perform regulatory functions during human fetal germ cell development, spermatogenesis and oogenesis. Our results also raise the possibility that modulation of RHOX gene levels could correct some cases of human infertility and that their encoded proteins are candidate targets for contraceptive drug design.
Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Homeodomínio/genética , Oócitos/metabolismo , Espermatozoides/metabolismo , Adulto , Sequência de Aminoácidos , Western Blotting , Feminino , Proteínas de Homeodomínio/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Família Multigênica , Placenta/metabolismo , Gravidez , Primeiro Trimestre da Gravidez , Segundo Trimestre da Gravidez , Testículo/metabolismoRESUMO
There have been intense debates about the decomposition of regional diversity (gamma) into its within-community component (alpha) and between-community component (beta). Although a recent Ecology Forum achieved consensus in the use of "numbers equivalents" (Hill numbers) as the proper choice of diversity measure, three related major issues were still left unresolved. (1) What is the precise meaning of the "independence" or "statistical independence" of alpha diversity and beta diversity? (2) Which partitioning (additive vs. multiplicative) should be used for a given application? (3) What is the proper formula for alpha diversity, as there are two formulas in the literature? This paper proposes a possible resolution to each of these issues. For the first issue, we clarify the definitions of "independence" and "statistical independence" from two perspectives so that confusion about this issue can be cleared up. We also discuss the causes of dependence, so that the dependence relationship between any two diversity components in both partitioning schemes can be rigorously justified by theory and also intuitively understood by simulation. For the second issue, both multiplicative and additive beta diversities based on Hill numbers are useful measures and quantify different aspects of communities. However, neither can be directly applied to compare relative compositional similarity or differentiation across multiple regions with different numbers of communities because multiplicative beta diversity depends on the number of communities, and additive beta diversity additionally depends on alpha (equivalently, on gamma). Such dependences should be removed. We propose transformations to remove these dependences, and we show that the transformed multiplicative beta and additive beta both lead to the same classes of measures, which are always in a range of [0, 1] and thus can be used to compare relative similarity or differentiation among communities across multiple regions. These similarity measures include multiple-community generalizations of the Sørenson, Jaccard, Horn, and Morisita-Horn measures. For the third issue, we present some observations including a finding about which alpha formula produces independent alpha and beta components. These may help to resolve the choice of a proper formula for alpha diversity. Some related issues are also briefly discussed.
Assuntos
Biodiversidade , Modelos Biológicos , Animais , Modelos Estatísticos , Dinâmica PopulacionalRESUMO
BACKGROUND: Aneurysms located at non-branching sites, protruding from the dorsal wall of the supraclinoid internal carotid artery (ICA) with rapid configurational changes, were retrospectively reviewed in effort to identify and characterize these high-risk aneurysms. METHODS: A total of 447 patients with 491 intracranial aneurysms were treated from March 2005 to August 2008, and of these, eight patients had ICA dorsal wall aneurysms. Four of them suffered subarachnoid hemorrhage (SAH), and all had aneurysms undergoing rapid configuration changes during the treatment course. Digital subtraction cerebral angiography (DSA) performed soon after the SAH events. Data analyzed were patient age, sex, Hunt and Kosnik grade, time interval from first DSA to second DSA, aneurysm treatment, and modified Rankin scale score after treatment for 3 months. Success or failure of therapeutic management was examined among the patients. RESULTS: Digital subtraction cerebral angiography showed only lesions with small bulges in the dorsal walls of the ICAs. However, the patients underwent DSA again for re-bleeding or for post-treatment follow-up, confirming the SAH source. ICA dorsal wall aneurysms with rapid growth and configurational changes were found on subsequent DSA studies. CONCLUSIONS: Among the four patients, ICA dorsal wall aneurysms underwent rapid growth with configurational change from a blister type to a saccular type despite different management. ICA trapping including the lesion segment can be considered as the first treatment option if the balloon occlusion test (BOT) is successful. If a BOT is not tolerated by the patient, extracranial-intracranial bypass revascularization surgery with endovascular ICA occlusion is another treatment option.
Assuntos
Dissecação da Artéria Carótida Interna/diagnóstico , Dissecação da Artéria Carótida Interna/cirurgia , Aneurisma Intracraniano/diagnóstico , Aneurisma Intracraniano/cirurgia , Procedimentos Neurocirúrgicos/métodos , Procedimentos Cirúrgicos Vasculares/métodos , Idoso , Dissecação da Artéria Carótida Interna/patologia , Progressão da Doença , Feminino , Humanos , Aneurisma Intracraniano/patologia , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/instrumentação , Estudos Retrospectivos , Procedimentos Cirúrgicos Vasculares/instrumentaçãoRESUMO
The objective of this study was to determine the prevalence of high-risk sexual behaviours and sexually transmitted infections (STIs) and associated risk factors in Taiwanese high school students. Students in grades 10 and 11 (mean age: 15.9 +/- 0.9; range: 13-20 years) at two schools were recruited. An anonymous online real-time computer-assisted self-interviewing questionnaire was designed to assess demographic factors and sexual behaviours. Urine specimens were tested for genital chlamydial and gonococcal infections. The same survey and screening was conducted one year later on the same group of students. Overall, 670 individual students (993 visits) were enrolled with 323 students in both surveys. Twenty-seven percent had had sexual intercourse, and more than three quarters (79%) of them had engaged in high-risk sexual behaviours. Having friends using drugs increased the odds of practicing high-risk sexual behaviours (odds ratio [OR] 1.99, 95% CI: 1.13 to 3.50). Among 182 sexually active students, 8.8% had chlamydial (female: 12.5%; male: 5.3%) and 1.1% had gonococcal infections. Having sex with someone met on the Internet was the most significant risk factor for acquiring chlamydia (OR 8.14, 95% CI: 2.82 to 23.51). In conclusion, this adolescent population reported high prevalence of high-risk sexual behaviours and had a high prevalence of chlamydia supportive of a potential epidemic of STIs and HIV.
Assuntos
Comportamento do Adolescente , Infecções por Chlamydia/epidemiologia , Chlamydia trachomatis/isolamento & purificação , Assunção de Riscos , Comportamento Sexual/estatística & dados numéricos , Adolescente , Infecções por Chlamydia/psicologia , Chlamydia trachomatis/classificação , Preservativos/estatística & dados numéricos , Feminino , Gonorreia/epidemiologia , Gonorreia/psicologia , Inquéritos Epidemiológicos , Humanos , Masculino , Prevalência , Sorotipagem , Estudantes , Taiwan/epidemiologia , Adulto JovemRESUMO
Traumatic vertebral artery (VA) injury has been neglected and mistaken to be innocuous. Herein, we present a rare case with a as subarachnoid hemorrhage (SAH) following blunt suboccipital trauma. Initially, it was mistaken as a saccular aneurysm and was just coincident with traumatic SAH. Surgical clipping was performed by our senior neurosurgeon and looked secure. But massive bleeding occurred before complete closure of the dura wound. Opening the wound again, blood gushed out from the junction of the aneurysm and the parent artery. Because preoperative angiography evaluation had revealed good collateral flow from the contralateral VA, the involved segment of VA was trapped. The patient recovered well with uneventful course. Blunt suboccipital trauma may result in traumatic VA injury which may cause catastrophic complications if neglected. The incidence, risk factors, the pathophysiology of traumatic VA aneurysm, and the treatments are reviewed.
Assuntos
Aneurisma/diagnóstico por imagem , Angiografia Cerebral , Traumatismos Craniocerebrais/diagnóstico por imagem , Hemorragia Subaracnoídea Traumática/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Artéria Vertebral/lesões , Ferimentos não Penetrantes/diagnóstico por imagem , Aneurisma/cirurgia , Traumatismos Craniocerebrais/cirurgia , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva , Reoperação , Hemorragia Subaracnoídea Traumática/cirurgia , Artéria Vertebral/diagnóstico por imagem , Artéria Vertebral/cirurgia , Ferimentos não Penetrantes/cirurgiaRESUMO
Onconase (ONC), an antitumor ribonuclease from oocytes of a frog Rana pipiens, capable of inducing apoptosis in many cell lines is synergistic with several other anticancer drugs. Since cytotoxic effects of numerous drugs are modulated by reactive oxygen intermediates (ROI), we have studied effects of ONC on the intracellular level of oxidants in several normal cell types as well as tumor cell lines. It is demonstrated for the first time that ONC substantially decreases the content of ROI in all cell lines studied. This effect depends on the ribonucleolytic activity of the enzyme and is due to both, decreased rate of ROI generation and accelerated rate of their degradation. Onconase decreases the mitochondrial transmembrane potential and consequently, generation of ATP. Simultaneously the enzyme decreases the expression of an antiapoptotic protein Bcl-2, and upregulates the proapoptotic Bax protein. These finding are consistent with the enzyme propensity to induce apoptosis. The observed antioxidant activity of ONC may be an important element of its cytotoxicity towards cancer cells. The enzyme seems to exert its biological activities by interfering with the redox system of cellular regulation.
Assuntos
Antineoplásicos/farmacologia , Ribonucleases/fisiologia , Animais , Antineoplásicos/química , Apoptose , Linhagem Celular Tumoral , Humanos , Células Jurkat , Oxidantes/metabolismo , Oxirredução , Estresse Oxidativo , Rana pipiens , Espécies Reativas de Oxigênio , Ribonucleases/metabolismo , Superóxido Dismutase/metabolismoRESUMO
Epidemiological studies have shown that the regular consumption of red wine may in part account for the apparent compatibility of a high fat diet with a low incidence of coronary atherosclerosis. This phenomenon, commonly referred to as the French paradox, may be associated with red wine constituents that exhibit tumor-preventive properties as well as inhibit reactions that increase the risk of coronary heart disease. Here we show that resveratrol, a polyphenol in red wine, induces nitric oxide synthase, the enzyme responsible for the biosynthesis of NO, in cultured pulmonary artery endothelial cells, suggesting that resveratrol could afford cardioprotection by affecting the expression of nitric oxide synthase. We also show that resveratrol inhibits the proliferation of pulmonary artery endothelial cells, which, based on flow cytometric analysis, correlates with the suppression of cell progression through S and G2 phases of the cell cycle. Western blot analysis and immunocytochemical protein detection combined with multiparameter flow cytometry further demonstrate that the perturbed progression through S and G2 phases is accompanied by an increase in the expression of tumor suppressor gene protein p53 and elevation of the level of cyclin-dependent kinase inhibitor p21(WAF1/CIP1). All of the observed effects of resveratrol, including induction of apoptosis at its higher concentration, are also compatible with its putative chemopreventive and/or antitumor activity.
Assuntos
Anticarcinógenos/farmacologia , Endotélio Vascular/efeitos dos fármacos , Estilbenos/farmacologia , Animais , Bovinos , Divisão Celular/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p21 , Ciclinas/efeitos dos fármacos , Ciclinas/metabolismo , Endotélio Vascular/citologia , Fase G2/efeitos dos fármacos , Óxido Nítrico Sintase/efeitos dos fármacos , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo III , Artéria Pulmonar/citologia , Artéria Pulmonar/efeitos dos fármacos , Resveratrol , Fase S/efeitos dos fármacos , Proteína Supressora de Tumor p53/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismoRESUMO
Fenretinide (4-HPR) is a synthetic retinoid that displays a broad range of biological effects and has also demonstrated clinical efficacy as a chemopreventative agent. One cellular activity of 4-HPR is its ability to induce apoptosis. This effect has been proposed to relate to changes in intracellular reactive oxygen species. We show herein that a 1-h treatment of HL-60 cells with 4-HPR led to a dose-dependent increase in hydroperoxides. Pretreatment of cells with the antioxidant vitamin C abolished apoptosis, measured as the appearance of the sub-G1 peak, in 4-HPR-treated cells. The retinoid also elicited a 3.6-fold increase in caspase 3 activity; however, this increase was not affected by vitamin C treatment. Analysis of caspase 3 protein expression by Western blot analysis revealed that 4-HPR resulted in a significant increase in the appearance of the active p17 subunit without effecting a concomitant change in p32 procaspase 3 levels. Studies on de novo synthesis and stability of caspase 3 by pulse-chase and immunoprecipitation methods show that 4-HPR-treated samples had decreased incorporation of radioactive amino acid precursors into newly synthesized procaspase 3 but, during the chase (for up to 9 h), had more labeled caspase 3 remaining when compared with controls. These studies suggest that 4-HPR may effect changes in caspase 3 activity by modulating changes in zymogen stability by a mechanism distinct from the retinoid-elicited increase in reactive oxygen species.
Assuntos
Anticarcinógenos/farmacologia , Caspases/metabolismo , Inibidores Enzimáticos/farmacologia , Fenretinida/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Acetilcisteína/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Ácido Ascórbico/farmacologia , Caspase 3 , Caspases/biossíntese , Relação Dose-Resposta a Droga , Interações Medicamentosas , Ativadores de Enzimas/farmacologia , Precursores Enzimáticos/metabolismo , Estabilidade Enzimática/efeitos dos fármacos , Células HL-60/efeitos dos fármacos , Células HL-60/enzimologia , Humanos , Peróxido de Hidrogênio/metabolismo , Testes de PrecipitinaRESUMO
The repertoire of IgG antibody responses to infection and vaccination varies depending on the characteristics of the immunogen and the ability of the host to mount a protective immune response. Chronic hepatitis B virus (HBV) infections are marked by persistent infection and immune tolerance to vaccination. This disease offers a unique opportunity to discover key repertoire signatures during infection and in response to vaccination. Complementarity determining region 3 of an antibody heavy chain (CDR-H3) has a major impact on the antigenic specificity of an antibody. We used next-generation sequencing to characterize the CDR-H3 sequences in paired siblings of 4 families in which only one member of each pair had chronic HBV infection. Blood samples were obtained before and 2 weeks after HBV vaccination. The analysis revealed a huge network of sequence-related CDR-H3 clones found almost exclusively among carriers. In contrast, vaccination induced significant increases of CDR-H3 cluster diversities among siblings without hepatitis B. Several vaccination-associated clone clusters were identified. Similar findings of vaccination-associated clone networks were observed in healthy adults receiving HBV boosters. These strategies can be used to identify signatures of other infectious diseases and accelerate discoveries of antibody sequences with important biomedical implications.
Assuntos
Anticorpos Anti-Hepatite B/imunologia , Vacinas contra Hepatite B/administração & dosagem , Hepatite B Crônica/imunologia , Imunoglobulina G/imunologia , Feminino , Anticorpos Anti-Hepatite B/sangue , Hepatite B Crônica/sangue , Hepatite B Crônica/prevenção & controle , Humanos , Imunoglobulina G/sangue , MasculinoRESUMO
This investigation describes the isolation and characterization of oligosaccharides of the basement membrane glycoprotein, laminin. Pronase-released glycopeptides of isolated laminin, from a mouse Engelbreth-Holm-Swarm tumor, were fractionated using a combination of gel permeation chromatography and Con A-Sepharose affinity chromatography. The glycopeptides were analyzed for sugar linkage patterns by methylation analysis. Glycopeptides and hydrazine-released oligosaccharides were further analyzed using endo-beta-galactosidase, endo-beta-N-acetylglucosaminidase H and specific exoglycosidases in conjunction with calibrated gel permeation chromatography. Based on these experiments, murine tumor laminin was shown to contain asparagine-linked oligosaccharides with the following structures: bi-, tri- and tetraantennary complex-type oligosaccharides; polylactosaminyl side chains containing Gal(beta 1----4)GlcNAc(beta 1----3) repeating units attached to the trimannose core portion of the bi-, tri- and tetraantennary complex-type oligosaccharides; unusual complex-type oligosaccharides terminated at the nonreducing end with sialic acid, alpha-galactose, beta-galactose and beta-N-acetylglucosamine; alpha-galactosyl residues linked to N-acetyllactosamine sequences; high-mannose-type oligosaccharides. These results, in conjunction with analytical data, indicate that most of the carbohydrate of this laminin is N-linked to asparagine and that there are about 43 such N-linked oligosaccharides per laminin molecule.
Assuntos
Asparagina , Laminina/análise , Oligossacarídeos/análise , Animais , Membrana Basal/análise , Configuração de Carboidratos , Cromatografia de Afinidade , Cromatografia em Gel , Galactose/análise , Glucosamina/análise , Glicopeptídeos/análise , Camundongos , Peso Molecular , Neoplasias Experimentais/análiseRESUMO
Akt is a serine/threonine kinase that has been shown to play a central role in promoting cell survival and opposing apoptosis. We evaluated the effect of hypoxia on Akt in rat pheochromocytoma (PC12) cells. PC12 cells were exposed to varying levels of hypoxia, including 21%, 15%, 10%, 5%, and 1% O(2). Hypoxia dramatically increased phosphorylation of Akt (Ser(473)). This effect peaked after 6 h exposure to hypoxia, but persisted strongly for up to 24 h. Phosphorylation of Akt was paralleled with a progressive increase in phosphorylation of glycogen synthase kinase-3 (GSK-3), one of its downstream substrates. The effect of hypoxia on phosphorylation of Akt was completely blocked by pretreatment of the cells with wortmannin (100 nM), indicating that this effect is mediated by phosphatidylinositol 3-kinase (P13K). In contrast, whereas hypoxia also strongly induced phosphorylation of the transcription factors CREB and EPAS1, these effects persisted in the presence of wortmannin. Thus, hypoxia regulates both P13K-dependent and P13K-independent signaling pathways. Furthermore, activation of the P13K and Akt signaling pathways may be one mechanism by which cells adapt and survive under conditions of hypoxia.
Assuntos
Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Hipóxia Celular/fisiologia , Fosfotransferases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Androstadienos/metabolismo , Androstadienos/farmacologia , Animais , Quinase 3 da Glicogênio Sintase , Quinases da Glicogênio Sintase , Células PC12 , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Isoformas de Proteínas , Proteínas Proto-Oncogênicas c-akt , Ratos , Transdução de Sinais/fisiologia , Especificidade por Substrato , Fatores de Transcrição/efeitos dos fármacos , Fatores de Transcrição/metabolismo , WortmaninaRESUMO
Shannon entropy H and related measures are increasingly used in molecular ecology and population genetics because (1) unlike measures based on heterozygosity or allele number, these measures weigh alleles in proportion to their population fraction, thus capturing a previously-ignored aspect of allele frequency distributions that may be important in many applications; (2) these measures connect directly to the rich predictive mathematics of information theory; (3) Shannon entropy is completely additive and has an explicitly hierarchical nature; and (4) Shannon entropy-based differentiation measures obey strong monotonicity properties that heterozygosity-based measures lack. We derive simple new expressions for the expected values of the Shannon entropy of the equilibrium allele distribution at a neutral locus in a single isolated population under two models of mutation: the infinite allele model and the stepwise mutation model. Surprisingly, this complex stochastic system for each model has an entropy expressable as a simple combination of well-known mathematical functions. Moreover, entropy- and heterozygosity-based measures for each model are linked by simple relationships that are shown by simulations to be approximately valid even far from equilibrium. We also identify a bridge between the two models of mutation. We apply our approach to subdivided populations which follow the finite island model, obtaining the Shannon entropy of the equilibrium allele distributions of the subpopulations and of the total population. We also derive the expected mutual information and normalized mutual information ("Shannon differentiation") between subpopulations at equilibrium, and identify the model parameters that determine them. We apply our measures to data from the common starling (Sturnus vulgaris) in Australia. Our measures provide a test for neutrality that is robust to violations of equilibrium assumptions, as verified on real world data from starlings.
Assuntos
Proteínas Aviárias/genética , Estorninhos/genética , Alelos , Animais , Entropia , Análise de Elementos Finitos , Heterozigoto , Processos EstocásticosRESUMO
Blood samples were collected from 101 untreated pulmonary tuberculosis (TB) patients and 101 age- and sex-matched healthy control subjects. TB patients had lower lymphocyte and a higher monocyte counts than control subjects (p <0.0001 for both). The seropositive rate of human herpesvirus (HHV) type 8 antibody was higher in patients (30/101) than in control subjects (15/101) (p = 0.01). Antibody titres in patients also exceeded those in control subjects (p 0.006). Lymphocyte and monocyte counts between seronegative and seropositive subjects were not different. Four patients were positive for HHV-8 DNA. The study revealed a significantly higher HHV-8 seroprevalence in untreated pulmonary TB patients than in general population.
Assuntos
Coinfecção , Infecções por Herpesviridae/epidemiologia , Herpesvirus Humano 8 , Tuberculose Pulmonar/epidemiologia , Adulto , Idoso , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Estudos de Casos e Controles , Feminino , Infecções por Herpesviridae/imunologia , Herpesvirus Humano 8/classificação , Herpesvirus Humano 8/genética , Herpesvirus Humano 8/imunologia , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Prevalência , Sarcoma de Kaposi/epidemiologia , Sarcoma de Kaposi/imunologia , Estudos Soroepidemiológicos , Taiwan/epidemiologia , Tuberculose Pulmonar/imunologiaRESUMO
Nursing students have particularly experienced stressful lives during nursing education. This cross-sectional study aimed to investigate depressive symptoms and related factors in junior college nursing students. A total of 625 nursing students from a junior college in Taiwan were assessed by Pittsburgh Sleep Quality Index, Adolescent Depression Inventory, Situational Anxiety Scale and the Taiwanese-Chinese version of Stress in Nursing Students Scale. The results showed that (1) the prevalence of depressive symptoms among junior college nursing students was 32.6%; (2) depressive symptoms are significantly related to grade point average, interest in nursing, interest in their clinical placement, career planning after graduation, overeating as a stress-relief strategy, sleep problems, stress, and anxiety; and (3) anxiety, sleep quality, and stress are three major variables that can significantly predict depressive symptoms. Psychological factors may influence young nursing students' willingness to seek assistance from teachers. These factors should be considered when designing strategies to promote their emotional health and well-being. Nursing educators can plan appropriate strategies tailored to junior college nursing students' problems and needs, which thereby may facilitate learning experience and prevent depressive symptoms.
Assuntos
Depressão/epidemiologia , Bacharelado em Enfermagem/estatística & dados numéricos , Estudantes de Enfermagem/estatística & dados numéricos , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Taiwan/epidemiologia , Adulto JovemRESUMO
Recent studies on the Chinese herbal medicine PC SPES showed biological activities against prostate cancer in vitro, in vivo and in patients with advanced stages of the disease. In investigating its mode of action, we have isolated a few of the active compounds. Among them, baicalin was the most abundant (about 6%) in the ethanol extract of PC SPES, as determined by HPLC. Baicalin is known to be converted in vivo to baicalein by the cleavage of the glycoside moiety. Therefore, it is useful to compare their activities in vitro. The effects of baicalin and baicalein were studied in androgen-positive and -negative human prostate cancer lines LNCaP and JCA-1, respectively. Inhibition of cell growth by 50% (ED(50)) in LNCaP cells was seen at concentrations of 60.8 +/- 3.2 and 29.8 +/- 2.2 microM baicalin and baicalein, respectively. More potent growth inhibitory effects were observed in androgen-negative JCA-1 cells, for which the ED(50) values for baicalin and baicalein were 46.8 +/- 0.7 and 17.7 +/- 3.4, respectively. Thus, it appears that cell growth inhibition by these flavonoids is independent of androgen receptor status. Both agents (1) caused an apparent accumulation of cells in G(1) at the ED(50) concentration, (2) induced apoptosis at higher concentrations, and (3) decreased expression of the androgen receptor in LNCaP cells.