RESUMO
DM intake (DMI) for individual pens of cattle is recorded daily or averaged across each week by most commercial feedlots as an index of performance. Numerous factors impact DMI by feedlot cattle. Some are available at the start of the feedlot period (initial BW, sex), and others become available early in the feeding period (daily DMI during adaptation) or more continuously (daily DMI from the previous week). To evaluate the relative impact of these factors on daily DMI during individual weeks within the feedlot period, we employed a dataset compiled from 2009 to 2014 from one commercial feedlot, including 4 132 pens (485 458 cattle), which were split into two fractions: 80% were used to calculate DMI regressions on these factors to develop a prediction equation for mean DMI for each week of the feeding period, and 20% were reserved to test the adequacy of these prediction equations. Correlations were used to determine the relationship between all available variables with observed DMI. These variables were then included in the generalized least squares regression models. A veracity test of the model was performed against the reserved data. Daily DMI from previous week was the factor most highly correlated with daily DMI (P < 0.10) during from week 6 to week 31, accounting for approximately 70% of the variation, followed by mean daily DMI during adaptation period (weeks 1-4), including in the prediction model from weeks 5 to 12. Initial shrunk BW (ISBW) was the third most correlated factor, which was included in prediction equations from week 5 to week 20. Sex entered the prediction model only after week 8. Daily DMI for each test week within the feeding period was predicted closely (r2 = 0.98) by these four factors (RMSE = 0.155 kg). In conclusion, the mean daily DMI during each week of the finishing period for a pen of cattle could be predicted closely based on mean daily DMI intake during the previous week plus other variables available early in a feedlot period (daily DMI during adaptation period, ISBW and sex).
Assuntos
Ração Animal , Dieta , Bovinos , Animais , Dieta/veterinária , Ração Animal/análiseRESUMO
The discovery that overexpressing one or a few critical transcription factors can switch cell state suggests that gene regulatory networks are relatively simple. In contrast, genome-wide association studies (GWAS) point to complex phenotypes being determined by hundreds of loci that rarely encode transcription factors and which individually have small effects. Here, we use computer simulations and a simple fitting-free polymer model of chromosomes to show that spatial correlations arising from 3D genome organisation naturally lead to stochastic and bursty transcription as well as complex small-world regulatory networks (where the transcriptional activity of each genomic region subtly affects almost all others). These effects require factors to be present at sub-saturating levels; increasing levels dramatically simplifies networks as more transcription units are pressed into use. Consequently, results from GWAS can be reconciled with those involving overexpression. We apply this pan-genomic model to predict patterns of transcriptional activity in whole human chromosomes, and, as an example, the effects of the deletion causing the diGeorge syndrome.
Assuntos
Redes Reguladoras de Genes , Genoma Humano , Modelos Genéticos , Fatores de Transcrição/metabolismo , Cromatina/química , Cromatina/metabolismo , Cromossomos Humanos/química , Cromossomos Humanos/metabolismo , Estudo de Associação Genômica Ampla , Humanos , Polímeros/química , Polímeros/metabolismo , Locos de Características Quantitativas , Transcrição GênicaRESUMO
The application of gold nanoparticle-peptide conjugates as theranostic agents for colorectal cancer shows much promise. This study aimed at determining the neurotoxic impact of 14 nm gold nanoparticles (AuNPs) functionalized with colorectal cancer-targeting peptides (namely p.C, p.L or p.14) in a rat model. Brain tissue samples, obtained from Wistar rats that received a single injection of citrate-capped AuNPs, polyethylene glycol-coated (PEG) AuNPs, p.C-PEG-AuNPs, p.L-PEG-AuNPs or p.14-PEG-AuNPs, and sacrificed after 2- and 12-weeks, respectively, were analysed. Inflammation marker (tumour necrosis factor-α, interleukin-6, interleukin-1ß), oxidative stress (superoxide dismutase, catalase, glutathione peroxidase) and apoptotic biomarker (cytochrome c, caspase-3) levels were measured. Gold nanoparticle-treated groups sacrificed after 2-weeks did not exhibit any significant inflammatory, oxidative stress or apoptotic effects in brain tissue compared to the untreated control group. In brain tissue from rats that were exposed to citrate-capped AuNPs for 12-weeks, tumour necrosis factor-α and interleukin-6 levels were significantly increased compared to the untreated control. Exposure to PEG-AuNP, p.C-PEG-AuNP, p.L-PEG-AuNP and p.14-PEG-AuNP did not elicit significant toxic effects compared to the control after 12-weeks, as evidenced by the absence of inflammatory, oxidative stress and apoptotic effects in brain tissue. We thus report on the safety of PEG-coated AuNP-peptide conjugates for potential application in the diagnosis of colorectal cancer; however, exposure to citrate-capped AuNPs could induce delayed neuro-inflammation, and as such, warrants further investigation.
Assuntos
Neoplasias Colorretais/tratamento farmacológico , Ouro/toxicidade , Ouro/uso terapêutico , Nanopartículas Metálicas/toxicidade , Nanopartículas Metálicas/uso terapêutico , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/fisiopatologia , Animais , Masculino , Terapia de Alvo Molecular/efeitos adversos , Ratos , Ratos WistarRESUMO
PURPOSE: Brain tumors are the most common solid tumor in children. The prevalence of survivors from these cancers has been increasing, presenting endocrine sequelae in more than 40% of the cases. Our aim was to characterize the endocrinopathies diagnosed in this population, exploring the outcomes of growth hormone treatment. METHODS: We have performed a retrospective analysis of the survivors that were followed-up through a close protocol at our endocrine late-effects clinic. RESULTS: 242 survivors, followed during 6.4 (0-23.4) years, were considered. The median age at tumor diagnosis was 6.7 (0-18) years and pilocytic astrocytoma was the most frequent neoplasm (33.5%). The prevalence of endocrinopathies was of 71.5%, with growth hormone deficiency being the most frequent (52.9%). An indirect correlation between the age at the beginning of somatropin and growth velocity in the first year of treatment was observed. Those treated with craniospinal radiotherapy presented a smaller final upper/lower segments ratio comparing with those that only received cranial radiotherapy. However, their final height was not compromised when compared to their family height target. We found pubertal delay in 12%; accelerated/precocious puberty in 13.2%; central and primary hypogonadism in 21.9% and 3.3%, respectively; primary and central hypothyroidism in 23.6% and 14.5%, respectively; thyroid nodules in 7.4%; ACTH deficiency in 10.3% and diabetes insipidus in 12%. CONCLUSION: This study reveals a higher prevalence of endocrinopathies in brain tumors survivors and explores the influence of craniospinal irradiation in the adult body proportions. It reinforces the importance of routine follow-up among survivors.
Assuntos
Neoplasias Encefálicas , Sobreviventes de Câncer/estatística & dados numéricos , Doenças do Sistema Endócrino , Transtornos do Crescimento , Hormônio do Crescimento , Radioterapia , Adolescente , Fatores Etários , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Criança , Diabetes Insípido/diagnóstico , Diabetes Insípido/etiologia , Doenças do Sistema Endócrino/diagnóstico , Doenças do Sistema Endócrino/epidemiologia , Doenças do Sistema Endócrino/etiologia , Feminino , Seguimentos , Transtornos do Crescimento/epidemiologia , Transtornos do Crescimento/etiologia , Transtornos do Crescimento/metabolismo , Transtornos do Crescimento/terapia , Hormônio do Crescimento/análise , Hormônio do Crescimento/deficiência , Hormônio do Crescimento/uso terapêutico , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Hipotireoidismo/diagnóstico , Hipotireoidismo/epidemiologia , Hipotireoidismo/etiologia , Masculino , Portugal/epidemiologia , Prevalência , Puberdade Tardia/diagnóstico , Puberdade Tardia/epidemiologia , Puberdade Tardia/etiologia , Radioterapia/efeitos adversos , Radioterapia/métodos , Radioterapia/estatística & dados numéricosRESUMO
PURPOSE: Lipid nanoparticles (SLN and NLC) were functionalized with the RVG29 peptide in order to target the brain and increase the neuronal uptake through the nicotinic acetylcholine receptors. These nanosystems were loaded with quercetin to take advantage of its neuroprotective properties mainly for Alzheimer's disease. METHODS: The functionalization of nanoparticles with RVG29 peptide was confirmed by NMR and FTIR. Their morphology was assessed by transmission electron microscopy and nanoparticles size, polydispersity and zeta potential were determined by dynamic light scattering. The in vitro validation tests were conducted in hCMEC/D3 cells, a human blood-brain barrier model and thioflavin T binding assay was conducted to assess the process of amyloid-beta peptide fibrillation typical of Alzheimer's disease. RESULTS: RVG29-nanoparticles displayed spherical morphology and size below 250 nm, which is compatible with brain applications. Zeta potential values were between -20 and -25 mV. Quercetin entrapment efficiency was generally higher than 80% and NLC nanoparticles were able to encapsulate up to 90%. The LDH assay showed that there is no cytotoxicity in hCMEC/D3 cell line and RVG29-nanoparticles clearly increased in 1.5-fold the permeability across the in vitro model of blood-brain barrier after 4 h of incubation compared with non-functionalized nanoparticles. Finally, this nanosystem was capable of inhibiting amyloid-beta aggregation in thioflavin T binding assay, suggesting its great potential for neuroprotection. CONCLUSIONS: RVG29-nanoparticles that simultaneously target the blood-brain barrier and induce neurons protection against amyloid-beta fibrillation proved to be an efficient way of quercetin delivery and a promising strategy for future approaches in Alzheimer's disease. Graphical Abstract.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Antígenos Virais/metabolismo , Encéfalo/metabolismo , Lipídeos/química , Fármacos Neuroprotetores/metabolismo , Fragmentos de Peptídeos/metabolismo , Quercetina/metabolismo , Proteínas do Envelope Viral/metabolismo , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Antígenos Virais/química , Barreira Hematoencefálica/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Permeabilidade Capilar , Linhagem Celular , Composição de Medicamentos , Humanos , Lipossomos , Nanopartículas , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/química , Fragmentos de Peptídeos/química , Agregados Proteicos , Agregação Patológica de Proteínas , Quercetina/administração & dosagem , Quercetina/química , Receptores Nicotínicos/metabolismo , Distribuição Tecidual , Proteínas do Envelope Viral/químicaRESUMO
The energy content of finishing diets offered to feedlot cattle may vary across countries. We assumed that the lower is the energy content of the finishing diet, the shorter can be the adaptation period to high-concentrate diets without negatively impacting rumen health while still improving feedlot performance. This study was designed to determine the effects of adaptation periods of 6, 9, 14 and 21 days on feedlot performance, feeding behaviour, blood gas profile, carcass characteristics and rumen morphometrics of Nellore cattle. The experiment was designed as a completely randomised block, replicated 6 times, in which 96 20-month-old yearling Nellore bulls (391.1 ± 30.9 kg) were fed in 24 pens (4 animals/pen) according to the adaptation period adopted: 6, 9, 14 or 21 days. The adaptation diets contained 70%, 75% and 80.5% concentrate, and the finishing diet contained 86% concentrate. After adaptation, one animal per pen was slaughtered (n = 24) for rumen morphometric evaluations and the remaining 72 animals were harvested after 88 days on feed. Orthogonal contrasts were used to assess linear, quadratic and cubic relationships between days of adaptation and the dependent variable. Overall, as days of adaptation increased, final BW (P = 0.06), average daily gain (ADG) (P = 0.07), hot carcass weight (P = 0.04) and gain to feed ratio (G : F) (P = 0.07) were affected quadratically, in which yearling bulls adapted by 14 days presented greater final BW, ADG, hot carcass weight and improved G : F. No significant (P > 0.10) days of adaptation effect was observed for any of feeding behaviour variables. As days of adaptation increased, the absorptive surface area of the rumen was affected cubically, where yearling bulls adapted by 14 days presented greater absorptive surface area (P = 0.03). Thus, Nellore yearling bulls should be adapted by 14 days because it led to improved feedlot performance and greater development of rumen epithelium without increasing rumenitis scores.
Assuntos
Ração Animal , Bovinos/fisiologia , Rúmen , Adaptação Fisiológica , Ração Animal/análise , Animais , Dieta/veterinária , Comportamento Alimentar , MasculinoRESUMO
Quercetin was encapsulated in lipid nanoparticles (SLN and NLC) to take advantage of its neuroprotective properties in Alzheimer's disease. The nanoparticles were functionalized with transferrin to facilitate the passage across the blood-brain barrier through the transferrin receptors overexpressed in brain endothelial cells. NMR and FTIR confirmed the functionalization of the nanoparticles with transferrin. TEM results showed all nanoparticles presented spherical morphology. Nanoparticles exhibited size around 200 nm and zeta potential values higher than -30 mV. Quercetin entrapment efficiency was around 80-90%. LDH cytotoxicity assays in hCMEC/D3 cell line demonstrated that even for the highest concentration (30 µM) nanoparticles did not reveal cytotoxicity after 4 h of incubation. Permeability studies across hCMEC/D3 cell monolayers showed NLC permeate more the blood-brain barrier, while amyloid-beta studies demonstrated NLC-transferrin have the capacity to inhibit fibril formation. Nanoparticles seem to be suitable for brain applications, mainly for Alzheimer's disease due to inhibition of amyloid-beta aggregation.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Quercetina/administração & dosagem , Peptídeos beta-Amiloides , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Linhagem Celular , Sobrevivência Celular , Portadores de Fármacos/química , Células Endoteliais/metabolismo , Humanos , Lipídeos/química , Tamanho da Partícula , Quercetina/metabolismo , Transferrina/químicaRESUMO
Drug therapy for Chagas disease remains a major challenge as potential candidate drugs have failed clinical trials. Currently available drugs have limited efficacy and induce serious side effects. Thus, the discovery of new drugs is urgently needed in the fight against Chagas' disease. Here, we synthesized and evaluated the biological effect of pyrazole-imidazoline (1a-i) and pyrazole-tetrahydropyrimidine (2a-i) derivatives against relevant clinical forms of Trypanosoma cruzi. The structure-activity relationship (SAR), drug-target search, physicochemical and ADMET properties of the major active compounds in vitro were also assessed in silico. Pyrazole derivatives showed no toxicity in Vero cells and also no cardiotoxicity. Phenotypic screening revealed two dichlorinated pyrazole-imidazoline derivatives (1c and 1d) with trypanocidal activity higher than that of benznidazole (Bz) against trypomastigotes; these were also the most potent compounds against intracellular amastigotes. Replacement of imidazoline with tetrahydropyrimidine in the pyrazole compounds completely abolished the trypanocidal activity of series 2(a-i) derivatives. The physicochemical and ADMET properties of the compounds predicted good permeability, good oral bioavailability, no toxicity and mutagenicity of 1c and 1d. Pyrazole nucleus had high frequency hits for cruzipain in drug-target search and structure activity relationship (SAR) analysis of pyrazole-imidazoline derivatives revealed enhanced activity when chlorine atom was inserted in meta-positions of the benzene ring. Additionally, we found evidence that both compounds (1c and 1d) have the potential to interact non-covalently with the active site of cruzipain and also inhibit the cysteine proteinase activity of T. cruzi. Collectively, the data presented here reveal pyrazole derivatives with promise for further optimization in the therapy of Chagas disease.
Assuntos
Doença de Chagas/tratamento farmacológico , Imidazolinas/farmacologia , Pirazóis/farmacologia , Pirimidinas/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Células Cultivadas , Chlorocebus aethiops , Relação Dose-Resposta a Droga , Humanos , Imidazolinas/química , Estrutura Molecular , Testes de Sensibilidade Parasitária , Pirazóis/química , Pirimidinas/química , Relação Estrutura-Atividade , Tripanossomicidas/síntese química , Tripanossomicidas/química , Células VeroRESUMO
Special attention has emerged towards biomass smoke-induced chronic obstructive pulmonary disease (COPD), providing new knowledge for prevention and therapeutic approach of non-smoker COPD patients. However, the understanding of biomass smoke COPD is still limited and somewhat controversial. The aim of the present study was to compare COPD exclusively caused by tobacco smoking with COPD exclusively caused by environmental or occupational exposures. For this cross-sectional study, COPD patients were recruited from outpatient clinics and formed two groups: non-smoker COPD group (n=16) with exposure to biomass smoke who did not smoke cigarette and tobacco smoker COPD group (n=15) with people who did not report biomass smoke exposure. Subjects underwent pulmonary function tests, thoracic high-resolution computed tomography, 6-min walk test, and sputum induction. The non-smoker COPD group had biomass smoke exposure of 133.3±86 hour-years. The tobacco COPD group smoked 48.5±27.4 pack-years. Women were 62.5 and 66.7%, respectively, of non-smokers and smokers. The non-smoker COPD group showed higher prevalence of dyspnea, lower arterial oxygen tension (PaO2), and lower arterial oxygen saturation (SaO2%) with similar spirometry results, lung volumes, and diffusion capacity. Regarding inflammatory biomarkers, differences were detected in sputum number of lymphomononuclear cells and in sputum concentrations of interleukin (IL)-6 and IL-8 with higher values in the smoker group. Emphysema was more prevalent in the tobacco smoker group, which also showed higher relative bronchial wall thickness and lower lung density by quantitative analysis. Biomass smoke induced more hypoxemia compared to tobacco in COPD patients with similar severity.
Assuntos
Biomassa , Hipóxia/diagnóstico por imagem , Nicotiana/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Fumaça/efeitos adversos , Idoso , Estudos Transversais , Exposição Ambiental , Feminino , Humanos , Hipóxia/etiologia , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/etiologia , Testes de Função Respiratória , Espirometria , Escarro/química , Tomografia Computadorizada por Raios XRESUMO
Glioblastoma multiforme is the most lethal type of brain tumor and the established therapy only extends patients survival to approximately one year. Its first-line treatment is based on of chemotherapy with the alkylating agent temozolomide (TMZ). As many other chemotherapeutic drugs, TMZ presents several limitations as high toxicity and low bioavailability. The delivery of TMZ using poly(lactic-co-glycolic acid) nanoparticles is proposed in this work. Stable nanoparticles functionalized with a OX26 type monoclonal antibody for transferrin receptor were developed, targeting the glioblastoma tumor cells, since these cells are known for overexpressing this receptor. The release profile of TMZ from the nanoparticles was studied mimicking physiological conditions, and targeted cellular internalization was also investigated. Two glioblastoma cell lines - U215 and U87 - were used to evaluate the in vitro cytotoxicity of the drug, showing that the prepared nanocarriers enhance the anticancer activity of TMZ. The functionalization with the monoclonal antibody for transferrin receptor proved to be advantageous in enhancing the cellular internalization in glioblastoma cells.
Assuntos
Anticorpos Monoclonais/metabolismo , Antineoplásicos Alquilantes/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Dacarbazina/análogos & derivados , Portadores de Fármacos , Glioblastoma/tratamento farmacológico , Ácido Láctico/química , Nanopartículas , Ácido Poliglicólico/química , Receptores da Transferrina/metabolismo , Anticorpos Monoclonais/química , Antineoplásicos Alquilantes/química , Antineoplásicos Alquilantes/metabolismo , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Dacarbazina/química , Dacarbazina/metabolismo , Dacarbazina/farmacologia , Relação Dose-Resposta a Droga , Composição de Medicamentos , Liberação Controlada de Fármacos , Glioblastoma/imunologia , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Cinética , Nanotecnologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Receptores da Transferrina/imunologia , Tecnologia Farmacêutica/métodos , TemozolomidaRESUMO
The functionalization of alumina nanoparticles of specific morphology with antimicrobial peptides (AMP) can be a promising strategy for modeling medical devices and packaging materials for cosmetics, medicines or food, since the contamination by pathogens could be reduced. In this paper, we show the synthesis of a fibrous-like alumina nanobiostructure, as well as its functionalization with the peptide EAAA-BP100, an analog of the antimicrobial peptide BP100. The antibacterial activity of the obtained material against some bacterial strains is also investigated. The covalent binding of the peptide to the nanoparticles was promoted by a reaction between the carboxyl group of the glutamate side chain (E1) of the peptide and the amino groups of the alumina nanoparticles, previously modified by reaction with 3-aminopropyltrietoxysilane (APTES). The functionalized nanoparticles were characterized by zeta potential measurements, Fourier transform infrared spectroscopy, and other physicochemical techniques. Although the obtained alumina nanobiostructure shows a relatively low degree of substitution with EAAA-BP100, antibacterial activities against Escherichia coli and Salmonella typhimurium strains are appreciably higher than the activities of the free peptide. The obtained results can affect the design of new hybrid nanobiomaterials based on nanoparticles functionalized with AMP.
Assuntos
Óxido de Alumínio/química , Nanoestruturas/química , Oligopeptídeos/química , Oligopeptídeos/síntese química , Sequência de Aminoácidos , Antibacterianos/química , Antibacterianos/farmacologia , Fluoresceínas/química , Testes de Sensibilidade Microbiana , Nanoestruturas/ultraestrutura , Oligopeptídeos/farmacologia , Propilaminas/química , Silanos/química , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , Temperatura , Difração de Raios XRESUMO
The limited efficacy of benznidazole (Bz) indicated by failures of current Phase II clinical trials emphasizes the urgent need to identify new drugs with improved safety and efficacy for treatment of Chagas disease (CD). Herein, we analyzed the efficacy of a series of 2-hydroxy-3-phenylsulfanylmethyl-[1,4]-naphthoquinones against different Trypanosoma cruzi discrete type units (DTUs) of relevant clinical forms of CD. Cytotoxic and trypanocidal effect of naphthoquinone derivatives were assessed in mammalian cells, trypomastigotes and intracellular amastigotes using, luminescent assays (CellTiter-Glo and T. cruzi Dm28c-luciferase) and/or counting with a light microscope. Reactive oxygen species (ROS) production and intracellular targets of promising compounds were assessed with 2',7'-dichlorodihydrofluorescein diacetate (H2DCFDA) probe and ultrastructural analysis, respectively. ADMET properties were analyzed by in silico modeling. Most of the compounds showed low cytotoxic effect. Only two compounds (Compounds 2 and 11) had IC50 values lower than Bz, showing higher susceptibility of bloodstream trypomastigotes. Compound 2 exhibited greater efficacy against trypomastigotes from different T. cruzi DTUs, even better than Bz against Brazil and CL strains. Ultrastructural analysis revealed changes in intracellular compartments, suggesting autophagy as one possible mechanism of action. Oxidative stress, induced by Compound 2, resulted in elevated level of ROS, leading to parasite death. Compound 2 was also effective against intracellular amastigotes, showing high selectivity index. ADMET analysis predicted good oral bioavailability, reduced drug metabolism and no carcinogenic potential for Compound 2. The data highlight Compound 2 as a hit compound and stimulate further structural and pharmacological optimization to potentiate its trypanocidal activity and selectivity.
Assuntos
Naftoquinonas/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Linhagem Celular , Chlorocebus aethiops , Relação Dose-Resposta a Droga , Macaca mulatta , Estrutura Molecular , Naftoquinonas/síntese química , Naftoquinonas/química , Testes de Sensibilidade Parasitária , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade , Tripanossomicidas/síntese química , Tripanossomicidas/química , Trypanosoma cruzi/metabolismo , Células VeroRESUMO
We study the compression and extension dynamics of a DNA-like polymer interacting with non-DNA binding and DNA-binding proteins, by means of computer simulations. The geometry we consider is inspired by recent experiments probing the compressional elasticity of the bacterial nucleoid (DNA plus associated proteins), where DNA is confined into a cylindrical container and subjected to the action of a "piston"-a spherical bead to which an external force is applied. We quantify the effect of steric interactions (excluded volume) on the force-extension curves as the polymer is compressed. We find that non-DNA-binding proteins, even at low densities, exert an osmotic force which can be a lot larger than the entropic force exerted by the compressed DNA. The trends we observe are qualitatively robust with respect to changes in protein sizes and are similar for neutral and charged proteins (and DNA). We also quantify the dynamics of DNA expansion following removal of the "piston": while the expansion is well fitted by power laws, the apparent exponent depends on protein concentration and protein-DNA interaction in a significant way. We further highlight an interesting kinetic process which we observe during the expansion of DNA interacting with DNA-binding proteins when the interaction strength is intermediate: the proteins bind while the DNA is packaged by the compression force, but they "pop-off" one-by-one as the force is removed, leading to a slow unzipping kinetics. Finally, we quantify the importance of supercoiling, which is an important feature of bacterial DNA in vivo.
Assuntos
Cromossomos Bacterianos/química , DNA Bacteriano/química , Proteínas de Ligação a DNA/química , Elasticidade , Entropia , Simulação de Dinâmica Molecular , CinéticaRESUMO
OBJECTIVE: Quality of life (QOL), sexual satisfaction (SS) and physical performance have been assessed in the management of numerous chronic diseases. METHODS: In this study, the following tests and surveys were applied: (i) QOL questionnaire [Cystic Fibrosis Questionnaire (CFQ)]; (ii) SS questionnaire (SSQ) [female sexual quotient (FSQ) and male sexual quotient (MSQ)]; (iii) 6-minute walk test (6MWT). Spearman's correlation was used for comparison between the data; the Mann-Whitney test was applied to analyze the difference between genders. A total of 52 adult patients with CF were included in this study. RESULTS: There was a positive correlation between CFQ domains and SSQ questions. The CFQ showed a positive correlation with peripheral oxygen saturation of hemoglobin (SpO2) and the distance walked in the 6MWT, and a negative correlation with the Borg scale. The SSQ showed positive correlation with the distance walked and a negative correlation with the Borg scale. For some markers evaluated in the 6MWT, there was sometimes association with the evaluated domains and questions. Male patients showed better scores in the emotional CFQ domain, better performance in SSQ and physical performance. CONCLUSIONS: There was a correlation between CFQ, SSQ and 6MWT in CF. Finally; we believe that QOL surveys should assess the domain "sexuality" as well as physical performance tests.
Assuntos
Fibrose Cística/fisiopatologia , Orgasmo , Qualidade de Vida , Teste de Caminhada , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , AutorrelatoRESUMO
The objective of this study was to examine the relationship of DMI fluctuation, feedlot performance, feeding behavior, rumen morphometrics, and carcass characteristics in Nellore cattle classified by residual feed intake (RFI). One experiment was conducted in 2 consecutive years using individual pens (1.0 × 7.0 m) at the São Paulo State University feedlot, Dracena campus, Brazil. The experiment in year 1 started in June of 2012 with forty-eight 20-mo-old Nellore yearling bulls with an initial BW of 358.2 ± 19.4 kg. The experiment in year 2 started in January of 2013 with sixty 20-mo-old Nellore yearling bulls with an initial BW of 402.5 ± 33.0 kg. Experiments in years 1 and 2 lasted 94 and 84 d, respectively. All yearling bulls were categorized as high RFI (>0.5 SD above the mean, = 25), medium RFI (±0.5 SD from the mean, = 56), and low RFI (<0.5 SD below the mean, = 27). Visual appraisal to collect behavior data was made on d 40 (finishing period) of both years. Yearling bulls were harvested when average across treatment groups achieved a fat thickness of 4 mm at the 12th rib. Low-RFI yearling bulls had lower daily DMI, expressed either in kilograms ( < 0.01) or as percentage of BW ( < 0.01), and improved G:F ( < 0.01) when compared to high-RFI animals. No differences were observed ( > 0.10) for ADG, final BW, or HCW among RFI groups. Also, low-RFI yearling bulls had thinner final 12th rib ( < 0.01) and biceps femoris (P8) fat thickness ( < 0.01). Low-RFI yearling bulls were slower to consume ( = 0.03) and ruminate ( < 0.01) 1 kg of either DM or NDF. No significant ( > 0.10) RFI effect was observed for any ruminal morphometrics variables evaluated, with the exception of papillae area, in which low-RFI Nellore yearling bulls tended to have smaller ( = 0.07) papillae area than medium-RFI animals. In general, low-RFI Nellore yearling bulls consumed more particles larger than 19 and 8 mm and had a similar performance when compared to both medium- and high-RFI bulls; however, carcass fat composition was negatively impacted.
Assuntos
Ração Animal/análise , Composição Corporal/fisiologia , Bovinos/fisiologia , Comportamento Alimentar/fisiologia , Abrigo para Animais , Rúmen/anatomia & histologia , Fenômenos Fisiológicos da Nutrição Animal , Animais , Brasil , Bovinos/anatomia & histologia , Dieta/veterinária , MasculinoRESUMO
In this paper we show a very simple route for the incorporation of catalytically active niobium species on the surface of carbon materials, such as graphene oxide, carbon nanotubes and activated carbon. Some existing methods of incorporating a transition metal on a support have involved co-precipitation or wet impregnation, to obtain the corresponding oxides. These methods, however, cause reduction in the specific area of the support and can also form large metal oxide particles with loss of metal exposure. Therefore, here we present a novel way to add catalytically active species on the surfaces of different types of carbon through the formation of interaction complexes between the metal precursor and the functional groups of the carbon matrix. Because of the excellent catalytic properties exhibited by the niobium species we choose the NH4[NbO(C2O4)2(H2O)2]·2H2O salt as the model precursor. The characterization by XPS reveals the presence of the niobium species indicated by the displacement of the peaks between 206-212 eV related to the oxalate species according to the spectrum from pure niobium oxalate. Images obtained by TEM and SEM show the typical morphologies of carbonaceous materials without the niobium oxide formation signal, which indicates the presence of niobium complexes as isolated sites on the carbon surfaces. This new class of materials exhibited excellent properties as catalysts for pollutant oxidation. The presence of Nb promotes the catalytic activation of H2O2 generating hydroxyl radicals in situ, which allows their use in the organic compound oxidation processes. Tests for DBT oxidation indicate that Nb significantly improves the removal of such pollutants in biphasic reactions with removal around 90% under the tested conditions. Theoretical calculations showed that the most favorable adsorption model is an ionic complex presenting a ΔG = -108.7 kcal mol(-1) for the whole adsorption process.
RESUMO
In the present study, we describe the testis morphology and spermatogenesis of the sugarcane borer, one of the most destructive pests of sugarcane, using light, transmission, and scanning electron microscopies. Diatraea saccharalis (F.) larvae have paired, kidney-shaped testes that are limited externally and divided into four follicles by tunica cells. The adults have two fused whitish and spherical testes that are divided into eight follicles and are composed of spermatogonia, spermatocyte, spermatid, and sperm bundles. The spermatogonia and spermatocyte cysts are located at the apical extremity of the follicle, while the spermatid cysts and sperm bundles are located at the basal extremity of the follicle. Inside of the cysts, which are formed by the somatic cells, the germ line cells develop synchronously and are interconnected by cytoplasmic bridges. Each cyst contains only apyrene or eupyrene, and none of the cysts contain both of the cells. The inner part of the apyrene cyst consists of an electron-dense cap as opposed to a nucleus. The eupyrene sperm contains a nucleus, acrosome, and reticular and lacinate appendages. Both of the sperm types have a "9 + 9 + 2" axoneme and two mitochondrial derivatives at the tail region. The spermatogenesis process and spermatozoa morphology are similar to that of other Lepidoptera.
Assuntos
Lepidópteros/fisiologia , Espermátides/citologia , Espermatogênese , Testículo/fisiologia , Animais , Masculino , SaccharumRESUMO
Investigaram-se estratégias utilizadas por pais para transmitir valores aos filhos. Assistir a um filmeinfantil e simular sua recontação à criança foi o procedimento usado para introduzir nessa temáticadez pais/mães, com filho de 6 a 9 anos. Eles participaram de entrevista semiestruturada cujas respostasforam analisadas qualitativamente, revelando diferentes estratégias intencionais para transmitirvalores: instruir ativamente o filho; aproveitar notória motivação da criança e lhe agregar valor; eensinar pela experiência (ou privação dela) proporcionada ao filho. A recontação revelou-se umprocedimento adequado de pesquisa, pois os entrevistados realçaram ou minimizaram trechos doenredo para transmitir valores aos filhos ou comentaram que assim o fariam. Destaca-se o potencial dese explorar a temática sob o foco dos estudos intergeracionais(AU)
Assuntos
Humanos , Masculino , Feminino , Criança , Adulto , Valores Sociais , Relações Pai-FilhoRESUMO
The objectives of the present study were to investigate the influence of yearling weight on the occurrence of early pregnancy and to determine differences between precocious and non-precocious heifers in terms of pre- and postnatal calf mortality, calf weight and height, mature cow weight, and stayability of the cow in the herd. Data from 26 977 females of a Nelore herd that participated in the breeding season between 1986 and 2004 were analyzed. The influence of yearling weight on sexual precocity and differences between precocious and non-precocious heifers in pre- and postnatal calf mortality and stayability were analyzed using the GENMOD procedure of the SAS program. Differences in the growth traits between precocious and non-precocious animals were estimated by contrast analysis. Three groups were analyzed for postnatal mortality: first calving of the heifers, calves born from the third calving and all offspring of the cow. In order to have a standardized calving to conception period for all females (precocious and non-precocious), calves born from the second calving were not included in the analysis. This was necessary because the first calving to conception period (days open) of precocious heifers was longer than for non-precocious due to farm reproductive management. No differences in postnatal mortality rates, from the third calving, were observed between the two groups of heifers studied. Analysis of all offspring of the dams showed a 9% higher probability of death of calves born to precocious heifers compared with calves born to non-precocious heifers. With respect to stayability, precocious heifers presented 33% greater odds to remain in the herd until 5 and 6 years of age and 28% greater odds to remain in the herd until 7 years when compared with non-precocious heifers. Precocious heifers weaned calves (205 days) significantly heavier than non-precocious ones, 1.410 and 0.797 kg considering the weaning weights of all offspring and of the third calving, respectively. With respect to sexual precocity, the results suggest that the probability of heifers to become pregnant at 16 months of age increases with increasing weight. However, heifers weighing more than 240 kg present practically the same pregnancy probability. Nevertheless, exposure of heifers during the early breeding season is recommended for beef cattle herds raised in tropical regions in view of the numerous benefits demonstrated here.
Assuntos
Peso Corporal , Bovinos/fisiologia , Longevidade , Reprodução , Maturidade Sexual , Animais , Brasil , Cruzamento , Bovinos/crescimento & desenvolvimento , Feminino , Gravidez , Estações do Ano , Aumento de PesoRESUMO
This work aims to characterize levels and phase distribution of polycyclic aromatic hydrocarbons (PAHs) in indoor air of preschool environment and to assess the impact of outdoor PAH emissions to indoor environment. Gaseous and particulate (PM1 and PM(2.5)) PAHs (16 USEPA priority pollutants, plus dibenzo[a,l]pyrene, and benzo[j]fluoranthene) were concurrently sampled indoors and outdoors in one urban preschool located in north of Portugal for 35 days. The total concentration of 18 PAHs (ΣPAHs) in indoor air ranged from 19.5 to 82.0 ng/m(3) ; gaseous compounds (range of 14.1-66.1 ng/m(3)) accounted for 85% ΣPAHs. Particulate PAHs (range 0.7-15.9 ng/m(3)) were predominantly associated with PM1 (76% particulate ΣPAHs) with 5-ring PAHs being the most abundant. Mean indoor/outdoor ratios (I/O) of individual PAHs indicated that outdoor emissions significantly contributed to PAH indoors; emissions from motor vehicles and fuel burning were the major sources.