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We report density functional theory calculations for single layer MoS2 in its 2H, semiconducting and 1T metallic phases in order to understand the relative stability of these two phases and transition between them in the presence of adsorbed lithium atoms and under compressive strain. We have determined the diffusion barriers between the two phases and demonstrate how the presence of Li adatoms or strain can significantly reduce these barriers. We show that the 2H and 1T structures have the same energy under 15% biaxial, compressive strain. This is the same strain value posited by Lin et al (2014 Nat. Nanotechnology 9 391-396) for their intermediate α phase. Calculations of the 1T and 2H permittivity and electron energy loss spectrum are also performed and characterized.
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A pair of coupled gold nanorods excited by a beam of free electrons acts as a transmitting Hertzian antenna in the optical part of the spectrum. Significantly enhanced resonant emission is observed from the antenna when the electron beam is injected around the junction between the rods, where the local density of electromagnetic states is elevated.
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1. Two studies were conducted to investigate the effect of feeding different concentration and forms of zinc (Zn) on the performance and tibia Zn status of broiler chicks. 2. In Experiment 1, chicks fed on the control or the diet supplemented with 12?mg of Zn as sulphate had lower feed intake, weight gain and tibia Zn content than other treatment groups. Chicks given 12 and 24 mg of organic Zn in starter and grower phases, respectively, had the same performance and tibia Zn content as those fed 40 mg of Zn as sulphate and the same performance but higher tibia Zn content than those given 12 mg of Zn as organic over the 42 d. 3. In Experiment 2, chicks given 24 mg organic Zn had greater weight gain than chicks fed on the other treatment diets in the starter period. Chicks fed on the control diet had lower tibia Zn content than chicks fed other treatment diets. Chicks given 80 mg Zn as sulphate had higher tibia Zn content than chicks fed the other treatment diets except those given 40 mg of Zn as sulphate. 4. The results from these trials indicate that feeding lower concentration of Zn as organic form may better promote the growth performance of broiler chicks.
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Ração Animal/análise , Galinhas/crescimento & desenvolvimento , Galinhas/metabolismo , Dieta/veterinária , Tíbia/química , Zinco/administração & dosagem , Fenômenos Fisiológicos da Nutrição Animal , Animais , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Kentucky , Masculino , Distribuição Aleatória , Aumento de Peso , Zinco/análise , Zinco/metabolismoRESUMO
First principles calculations have been used to predict the optical properties for a range of intermetallic compounds for which little or no experimental optical data are currently available. Density functional theory combined with the random phase approximation is used to calculate the dielectric functions for these compounds. The aim of this work is to investigate how the band edge and plasma frequency vary with composition in order to identify materials with promising plasmonic properties. Towards this end the intermetallic compounds chosen are composed of elements which on their own have reasonable optical properties for plasmonic applications. The position of the band edge relative to the plasma frequency is most favourable in the simple binary compounds formed from the alkali plus noble metals NaAu, KAu and KAg. In particular, for KAu the band edge and plasma frequency occur at almost the same frequency, and hence the imaginary part of the dielectric function is practically zero for frequencies below the plasma frequency. In addition, the plasma frequency in this compound is at relatively low frequency, promising a material with strong plasmon response in the infrared.
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A study was conducted to investigate the effects of feeding inorganic or organic Zn and Cu on the performance and tissue mineral content of chicks. A corn-soybean meal diet without Cu and Zn supplementation, containing 31 mg of Zn/kg of diet and 6.6 mg of Cu/kg of diet, was used as a basal diet. Organic Zn (a chelated Zn proteinate) and organic Cu (a chelated Cu proteinate) were used as organic sources for comparison with inorganic reagent-grade sulfates. Supplements provided 20 mg/kg of Zn and 8 mg/kg of Cu. A 3x3 factorial arrangement of treatments consisting of feeding the basal diet with 3 supplements (none, sulfate, or organic) of Cu and of Zn was used. Ten groups of 6 one-day-old male broilers were assigned to each of 9 dietary treatments. Tap water and feed were supplied on an ad libitum basis during the 3-wk trial. The Zn and Cu content in the mucosa of the duodenum of the chick was determined. Dietary supplementation of Zn increased (P<0.01) weight gain, feed intake, and G:F of chicks. The G:F for chicks fed both inorganic sources of Zn and Cu was lower (P<0.01) than that for chicks fed only the inorganic source of Zn. Dietary inclusion of Zn increased (P<0.01) tibia and plasma Zn content. The tibia Zn content for chicks fed organic Zn was higher (P<0.01) than that for chicks fed inorganic Zn. Liver Cu content was decreased (P<0.05) by dietary inclusion of Zn. The Zn and Cu contents in the mucosa of chicks fed the organic source were higher (P<0.01) than those of chicks fed the control diet. The feed conversion data suggest that the antagonism between Zn and Cu occurred when the inorganic forms, but not organic forms, of these 2 minerals were included in a chick diet.
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Fenômenos Fisiológicos da Nutrição Animal/fisiologia , Quelantes/farmacologia , Galinhas/metabolismo , Cobre/metabolismo , Zinco/metabolismo , Animais , Peso Corporal/fisiologia , Cobre/sangue , Duodeno/química , Ingestão de Alimentos/fisiologia , Absorção Intestinal/fisiologia , Fígado/química , Masculino , Distribuição Aleatória , Tíbia/química , Zinco/sangueRESUMO
Two experiments were conducted to examine the effects of alpha-galactosidase supplementation and acidification of diets on nutrient digestibility and growth performance of broiler chicks. In experiment 1, dietary treatments consisted of feeding a low-energy basal diet (2.74 Mcal of ME/kg) alone, the basal diet supplemented with 1,724 units of alpha-galactosidase per kg, the basal diet supplemented with 2% citric acid, or the basal diet supplemented with both. alpha-Galactosidase significantly increased feed intake, weight gain, AME(n) of the diets, and retention of CP and neutral detergent fiber (NDF) (P < 0.05). Citric acid significantly increased the retention of DM, CP, and NDF, but decreased feed intake and weight gain. The greatest values for DM and NDF retention and for AME(n) were obtained with the combination of alpha-galactosidase plus citric acid. In experiment 2, chicks were fed diets with 2 levels of energy (2.74 or 3.11 Mcal/kg), 2 levels of citric acid (0 or 1.5%), and 2 levels of alpha-galactosidase (0 or 1,724 units/kg) in a 2 x 2 x 2 factorial arrangement of treatments. alpha-Galactosidase significantly increased the reducing sugar concentration in the crop content, whereas citric acid decreased the pH and increased the reducing sugar concentration in the crop content. Citric acid decreased the gain to feed ratio in the absence but not in the presence of alpha-galactosidase. The data from these studies indicate that acidification of diet improves the efficacy of alpha-galactosidase.
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Ração Animal/análise , Galinhas/crescimento & desenvolvimento , Ácido Cítrico/farmacologia , Dieta/veterinária , Digestão/efeitos dos fármacos , alfa-Galactosidase/farmacologia , Fenômenos Fisiológicos da Nutrição Animal , Animais , Digestão/fisiologia , Metabolismo Energético , Concentração de Íons de Hidrogênio , MasculinoRESUMO
We perform density functional theory (DFT) calculations on molecular junctions consisting of a single molecule between two Au(111) electrodes. The molecules consist of an alkane or aryl bridge connecting acceptor, donor or thiol endgroups in various combinations. The molecular geometries are optimized and wavefunctions and eigenstates of the junction calculated using the DFT method, and then the electron transport properties for the junction are calculated within the non-equilibrium Green's function (NEGF) formalism. The current-voltage or i(V) characteristics for the various molecules are then compared. Rectification is observed for these molecules, particularly for the donor-bridge-acceptor case where the bridge is an alkane, with rectification being in the same direction as the original findings of Aviram and Ratner (1974 Chem. Phys. Lett. 29 277-83), at least for relatively large negative and positive applied bias. However, at smaller bias rectification is in the opposite direction and is attributed to the lowest unoccupied orbital associated with the acceptor group.
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Two studies were conducted to evaluate the effect of dietary Ca levels (low, 1% and high, 3%) on ileal endogenous amino acid losses (IEAAL) and standardized ileal amino acid digestibility (SIAAD) in broilers (BR) and laying hens (LH) fed nitrogen-free diets (NFD) and distiller's dried grain with solubles (DDGS)-based diets. A total of 384 male Cobb 500 BR and 288 LH were used in a completely randomized design (CRD) with 16 (BR) or 12 (LH) replicate cages with 6 birds/replicate. IEAAL and apparent ileal digestibility (AID) of AA were analyzed using the GLM procedure of SAS appropriate for a CRD while SIAAD values were analyzed using the GLM procedure of SAS appropriate for a 2 × 2 factorial arrangement of treatments. For BR, IEAAL and N losses (mg/kg of dry matter intake, DMI) were higher (P < 0.05) when NFD with high Ca level was fed (total AA was 39%, N was 35% higher). For most of the AA, AID was higher (P < 0.05) in BR fed DDGS-based diet with high Ca level. High dietary Ca resulted in higher (P < 0.05) SIAAD for all the AA except for Arg, Lys, Met, Cys, and Tyr. For LH, AID of AA was higher (P < 0.05) for the DDGS diet with high Ca level in 13 of the 18 AA evaluated. There was interaction (P < 0.05) between diet Ca level and correction method on LH SIAAD values for Thr, Asp, Gly, and Ser. The SIAAD values for 8 AA were higher (P < 0.05) in birds on high Ca DDGS diet. Correction with low Ca NFD resulted in higher (P < 0.05) SIAAD values for all the AA. Result from this study showed that high Ca increased total IEAAL in BR by 39% but decreased same by 27% in LH. Finally, SIAAD values were increased in BR fed high Ca DDGS-based diet while SIAAD value in LH was lower when correction was done using values from high Ca-NFD fed birds.
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Aminoácidos/metabolismo , Cálcio da Dieta/metabolismo , Digestão , Íleo/fisiologia , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Animais , Cálcio da Dieta/administração & dosagem , Galinhas , Dieta/veterinária , Digestão/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , MasculinoRESUMO
For accurate estimation of nutrient digestibility, an ideal drying and sampling method is required to preserve the quality of the digesta. A standard corn-soybean meal (corn-SBM) broiler starter diet was fed from d 0 to 10 before birds were placed on the experimental diets until d 21. One hundred and sixty-eight male Cobb 500 broiler chicks were used to evaluate the effect of two drying methods (freeze-dryer vs. forced air-oven) and two drying temperatures (40 vs. 55°C) (Exp 1), while ninety-six chicks were used to evaluate the effect of flushing and squeezing as well as marker types (titanium vs. chromium) on apparent ileal DM, N, Ca, P, and AA digestibility (Exp 2). There were seven (Exp 1) or eight (Exp 2) replicate cages per treatment with 6 birds/cage. Digesta from the distal two thirds of the ileum was obtained from birds following euthanasia on d 21 by squeezing (Exp 1) and squeezing or flushing (Exp 2). Samples collected were stored in the freezer at -20°C until they were either freeze-dried (FD) or oven-dried (OD) at 40 or 55°C. There were no interactions between the drying methods and drying temperatures (Exp 1) on apparent ileal DM, N, and AA digestibility. Met had the highest (92.3%) while Cys had the lowest (73.8%) digestibility value. In Exp 2, no interaction between sampling methods and marker types was observed. The effect of sampling methods was not significant except for Arg and Met where squeezing resulted in higher (P < 0.05) digestibility values. Furthermore, apparent ileal His, Ile, Cys, Ser, and Tyr digestibility tended to be higher (P < 0.1) in squeezed digesta compared to the flushed digesta. Results from these studies showed that OD ileal digesta at 40 or 55°C had no negative effect on apparent ileal AA digestibility. Likewise, marker type did not influence apparent ileal AA digestibility values.
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Ração Animal/análise , Galinhas/fisiologia , Digestão , Manipulação de Alimentos/métodos , Aminoácidos/fisiologia , Fenômenos Fisiológicos da Nutrição Animal , Animais , Dieta/veterinária , Hordeum/química , Íleo/fisiologia , Masculino , Distribuição Aleatória , Glycine max/química , Zea mays/químicaRESUMO
1. The purpose of this study was to investigate the effects of Bioplex Zn (a chelated zinc proteinate) and phytase supplementation in a maize-soybean meal diet on the performance and tissue zinc (Zn) content of broiler chicks. Treatment structure consisted of a 2 x 6 factorial arrangement with two inclusions of phytase (0 or 500 PU/kg) and 6 of Bioplex Zn providing 0, 2, 4, 8, 16 and 32 mg Zn/kg diet. A total of 864 chicks were randomly assigned to each of 12 dietary treatments with 6 replicate cages of 12 chicks. 2. Dietary inclusion of phytase increased feed intake, weight gain, plasma Zn content, tibia Zn content, tibia and ash weight. 3. Dietary supplementation of Bioplex Zn linearly increased feed intake, weight gain, gain to feed ratio, plasma Zn concentration, liver Zn concentration, tibia Zn content, tibia and ash weight. 4. An interactive effect of phytase and Bioplex Zn on feed intake, weight gain, tibia Zn concentration and tibia ash weight was found. 5. One slope, straight broken-line analysis of weight gain regressed on the supplemental Zn level provided as Bioplex Zn indicated that 12 mg/kg supplemental Zn without phytase and 7.4 mg/kg supplemental Zn with phytase were required for the optimal weight gain of chicks.
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6-Fitase/farmacologia , Ração Animal/análise , Galinhas/crescimento & desenvolvimento , Glycine max , Zea mays , Zinco/análise , Zinco/farmacologia , Fenômenos Fisiológicos da Nutrição Animal , Animais , Galinhas/metabolismo , Dieta/veterinária , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Masculino , Aumento de Peso , Zinco/metabolismoRESUMO
In this work, we implement approximate Bayesian computational methods to improve the design of a wound-healing assay used to quantify cell-cell interactions. This is important as cell-cell interactions, such as adhesion and repulsion, have been shown to play a role in cell migration. Initially, we demonstrate with a model of an unrealistic experiment that we are able to identify model parameters that describe agent motility and adhesion, given we choose appropriate summary statistics for our model data. Following this, we replace our model of an unrealistic experiment with a model representative of a practically realisable experiment. We demonstrate that, given the current (and commonly used) experimental set-up, our model parameters cannot be accurately identified using approximate Bayesian computation methods. We compare new experimental designs through simulation, and show more accurate identification of model parameters is possible by expanding the size of the domain upon which the experiment is performed, as opposed to increasing the number of experimental replicates. The results presented in this work, therefore, describe time and cost-saving alterations for a commonly performed experiment for identifying cell motility parameters. Moreover, this work will be of interest to those concerned with performing experiments that allow for the accurate identification of parameters governing cell migratory processes, especially cell migratory processes in which cell-cell adhesion or repulsion are known to play a significant role.
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The effect of dietary electrolyte balance (DEB), energy source (ES), and length of feeding of nitrogen-free diet (NFD) on ileal endogenous amino acid (EAA) loss in mg/kg dry matter intake (DMI) was evaluated in broiler chickens. In Experiment 1, 720 chickens consisting of 15 replicate cages with 6 chickens/replicate were used. Treatments were arranged in a 2 × 2 × 2 factorial and consisted of 4 NFD with 2 levels (low or high) of DEB and 2 ES [corn starch (CS) or dextrose (DX)], and 2 sampling time-points (diets were fed for either 72 h (d 16 to 19) or 120 h (d 16 to 21). Experiment 2 used 360 chickens in a 2 × 2 factorial arrangement of treatments with 2 levels (low or high) of DEB and 2 ES (CS or DX). Diets were fed for 72 h (d 18 to 21). All birds had access to feed and water on an ad libitum basis. Data were analyzed using the GLM procedure of SAS appropriate for a completely randomized design for a factorial arrangement of treatments. For Experiment 1, there were interactions (P < 0.05) between the 3 main factors for nitrogen and all the AA except Trp. Broilers that were fed DX-based NFD with high DEB for 72 h had the highest (P < 0.05) EAA losses. In Experiment 2, there was no interaction between DEB and ES except for His and Lys. When ileal EAA losses from birds fed the low DEB, CS-based NFD were used to standardize apparent ileal digestibility values from a previous study, there was no effect of length of feeding on standardized ileal AA digestibility values. In conclusion, DX-based NFD with high DEB increased endogenous AA loses. Despite differences in ileal EAA losses from CS-based NFD, standardized ileal AA digestibility values were not influenced by the length of feeding of NFD. Based on the results from these studies, NFD could be fed for 72 h without influencing SIAAD values.
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Aminoácidos/fisiologia , Galinhas/fisiologia , Íleo/fisiologia , Nitrogênio/metabolismo , Equilíbrio Hidroeletrolítico , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Animais , Dieta/veterinária , Íleo/efeitos dos fármacos , Distribuição Aleatória , Fatores de Tempo , Equilíbrio Hidroeletrolítico/efeitos dos fármacosRESUMO
We present the results of a restriction site survey of variation at five loci in Drosophila athabasca, complimenting a previous study of the period locus. There is considerably greater differentiation between the three semispecies of D. athabasca at the period locus and two other X-linked genes (no-on-transient-A and E74A) than at three autosomal genes (Xdh, Adh and RC98). Using a modification of the HKA test, which uses fixed differences between the semispecies and a test based on differences in Fst among loci, we show that the greater differentiation of the X-linked loci compared with the autosomal loci is inconsistent with a neutral model of molecular evolution. We explore several evolutionary scenarios by computer simulation, including differential migration of X and autosomal genes, very low levels of migration among the semispecies, selective-sweeps, and background selection, and conclude that X-linked selective sweeps in at least two of the semispecies are the best explanation for the data. This evidence that natural selection acted on the X-chromosome suggests that another X-linked trait, mating song differences among the semispecies, may have been the target of selection.
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Álcool Desidrogenase/genética , Proteínas de Ligação a DNA/genética , Proteínas de Drosophila , Drosophila/genética , Genes de Insetos , Proteínas Nucleares/genética , Seleção Genética , Fatores de Transcrição , Cromossomo X , Xantina Desidrogenase/genética , Animais , Sequência de Bases , DNA , Feminino , Variação Genética , Masculino , Dados de Sequência Molecular , Mapeamento por RestriçãoRESUMO
Density functional calculations of the adsorption of ethynylbenzene on the Au(111) surface show that, after cleavage of the C-H bond, the terminal carbon makes a strong covalent bond to the surface. The bond energy is shown to be about 70 kcal.mol(-1) with the fcc hollow site being most stable and the molecule oriented perpendicular to the surface. Adsorption without elimination of hydrogen is also possible via a hydrogen 1,2 shift to form a vinylidene surface-bound species, or opening of the C-C triple bond and adsorption through the two carbon atoms in a flat conformation. The reaction energy for formation of the surface-bound vinylidene is estimated to be 5 kcal.mol(-1) exothermic relative to the isolated ethynylbenzene and gold substrate.
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Expression of genes encoding prodrug-activating enzymes can increase the susceptibility of tumor cells to prodrugs, and may ultimately achieve a better therapeutic index than conventional chemotherapy. CB1954 is a weak, monofunctional alkylating agent which can be activated by Escherichia coli nitroreductase to a potent dysfunctional alkylating agent which crosslinks DNA. We have inserted the nitroreductase gene into an LNCX-based retroviral vector, to allow efficient gene transfer and expression in colorectal (LS174T) and pancreatic (SUIT2, BxPC3, and AsPC1) cancer cell lines. A clone of LS174T cells expressing nitroreductase showed > 50-fold increased sensitivity to CB1954, and nitroreductase-expressing clones of pancreatic tumor lines were up to approximately 500-fold (SUIT2) more sensitive than parental cells. Concentrations of CB1954 minimally toxic to nontransduced cells achieved 100% cell death in a 50:50 mix of parental cells with SUIT2 cells expressing nitroreductase; and marked "bystander" cell killing was seen with just 10% of cells expressing nitroreductase. Significant bystander cell killing was dependent on a high cell density. In conjunction with regional delivery of vectors and tumor selectivity of cell entry and/or gene expression, nitroreductase and CB1954 may be an attractive combination for prodrug-activating enzyme gene therapy of colorectal and pancreatic cancer.
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Antineoplásicos/uso terapêutico , Aziridinas/uso terapêutico , Neoplasias Colorretais/terapia , Terapia Genética , Nitrorredutases/genética , Neoplasias Pancreáticas/terapia , Pró-Fármacos/uso terapêutico , Antineoplásicos/farmacologia , Aziridinas/farmacologia , Relação Dose-Resposta a Droga , Escherichia coli/genética , Vetores Genéticos , Humanos , Pró-Fármacos/farmacologia , Retroviridae , Células Tumorais CultivadasRESUMO
The level of expression of normal cellular prion protein, PrP(c) (cellular prion protein), controls both the rate and the route of neuroinvasive infection, from peripheral entry portal to the CNS. Paradoxically, an overview of the distribution of PrP(c) within tissues outside the CNS is lacking. We have used novel antibodies that recognise cellular prion protein in glutaraldehyde-fixed tissue (in order to optimise immunohistochemical labelling of this conformationally labile protein), in combination with in situ hybridisation, to examine the expression of PrP(c) in peripheral tissues of the adult mouse. We found that although prion protein is expressed in many tissues, it is expressed at high levels only in discrete subpopulations of cells. Prominent amongst these are elements of the "hardwired neuroimmune network" that integrate the body's immune defence and neuroendocrine systems under CNS control. These prion protein-expressing elements include small diameter afferent nerves in the skin and the lamina propria of the aerodigestive tract, sympathetic ganglia and nerves, antigen presenting and processing cells (both follicular and non-follicular dendritic cells) and sub-populations of lymphocytes particularly in skin, gut- and bronchus-associated lymphoid tissues. Prion protein is also expressed in the parasympathetic and enteric nervous systems, in the dispersed neuroendocrine system, and in peripheral nervous system axons and their associated Schwann cells. This selective expression of cellular prion protein provides a variety of alternative routes for the propagation and transport of prion infection entering from peripheral sites, either naturally (via the aerodigestive tract or abraded skin) or experimentally (by intraperitoneal injection) to the brain. Key regulatory cells that express prion protein, and in particular enteroendocrine cells in the mucosal wall of the gut, and dendritic cells that convey pathogens from epithelial layers to secondary lymphoid organs, may be particularly important in the transmission of infection in the periphery.
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Proteínas PrPC/análise , Animais , Western Blotting , Sistema Digestório/química , Sistema Imunitário/química , Imuno-Histoquímica , Hibridização In Situ , Camundongos , Sistema Nervoso/química , Proteínas PrPC/genética , Proteínas PrPC/imunologia , RNA Mensageiro/análise , Sistema Respiratório/química , Distribuição Tecidual , Sistema Urogenital/químicaRESUMO
Expression of the normal cellular form of prion protein is both necessary and rate-limiting in the spread of prion disease, yet its cellular expression in vivo is poorly understood. To optimise immunohistochemical labelling of this protein in mouse brain, we have developed novel antibodies that recognise cellular prion protein in glutaraldehyde-fixed tissue. Expression was found to be predominantly neuronal, and to differ between different classes of neurone. Thus, neurones immunoreactive for GABA expressed very high levels of normal prion protein; most projection neurones expressed much lower levels, particularly on their axons in the major fibre tracts, and some neurones (e.g. those positive for dopamine) displayed no detectable prion protein. In marked contrast, all neurones, even those that were immunonegative, expressed high levels of message for prion protein, shown by non-radioactive in situ hybridisation. Glia expressed very low levels of message, and undetectable levels of prion protein. We conclude that the steady-state level of prion protein, which differs so markedly between different neuronal types, is primarily controlled post-transcriptionally, possibly by differences in protein trafficking or degradation. These marked differences in the way different neurones produce and/or degrade their normal cellular prion protein may influence the selective spread and neurotoxic targeting of prion diseases within the CNS.
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Sistema Nervoso Central/citologia , Sistema Nervoso Central/metabolismo , Neurônios/metabolismo , Proteínas PrPC/biossíntese , RNA Mensageiro/biossíntese , Animais , Especificidade de Anticorpos , Sistema Nervoso Central/química , Digoxigenina , Dopamina/análise , Dopamina/biossíntese , Immunoblotting , Imuno-Histoquímica , Hibridização In Situ , Camundongos , Camundongos Endogâmicos , Camundongos Knockout , Neuroglia/citologia , Neuroglia/metabolismo , Neurônios/citologia , Proteínas PrPC/análise , Proteínas PrPC/genética , Processamento Pós-Transcricional do RNA , RNA Mensageiro/análise , Distribuição Tecidual , Ácido gama-Aminobutírico/análise , Ácido gama-Aminobutírico/biossínteseRESUMO
Accell particle-mediated gene delivery technology was employed for the intracellular delivery of antigen-encoding expression vectors in epidermal tissues in laboratory animals. Delivery of plasmid DNA-coated gold microparticles using the Accell gene delivery system resulted in de novo antigen expression in epidermal cells that stimulated the induction of antigen-specific humoral and cytotoxic cellular immune responses. Optimal DNA delivery conditions favoring maximal humoral responses required the delivery of 5 x 10(7) micron-sized gold particles containing 300 plasmid copies per particle (80 ng of vector total) into a 4-cm2 area of abdominal skin. Comparison of immune responses between animals that received intramuscular injections of relatively large quantities of vector DNA (100 micrograms) and those that received intracellular deliveries of submicrogram quantities of the same DNA to the epidermis demonstrated that the latter approach was considerably more effective at eliciting strong humoral responses. In addition, cytotoxic cellular immune responses were elicited to HIV-1 gp120 following epidermal delivery of HIV-1 gp160 or gp120 expression constructs. A qualitative shift from predominantly cytotoxic cellular to predominantly humoral immune responses with continued immunization indicated the potential for optimizing delivery conditions to favor specifically one type of response over the other.
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Vacinas contra a AIDS/administração & dosagem , DNA Viral/administração & dosagem , DNA Viral/imunologia , HIV-1/imunologia , Sequência de Aminoácidos , Animais , Citotoxicidade Imunológica , DNA Viral/genética , Produtos do Gene env/genética , Produtos do Gene env/imunologia , Vetores Genéticos , Anticorpos Anti-HIV/biossíntese , Proteína gp120 do Envelope de HIV/genética , Proteína gp120 do Envelope de HIV/imunologia , Proteína gp160 do Envelope de HIV , Infecções por HIV/prevenção & controle , HIV-1/genética , Humanos , Imunização , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/imunologia , Precursores de Proteínas/genética , Precursores de Proteínas/imunologia , Pele/imunologia , Linfócitos T Citotóxicos/imunologiaRESUMO
AIM: To review the physiology of colonic motility and sensation in healthy humans and the pathophysiological changes associated with constipation and diarrhoea. SOURCE: Medline Search from 1965 using the index terms: human, colonic motility, sensation, pharmacology, neurohormonal control, gastrointestinal transit, constipation, diarrhoea and combinations of these. RESULTS: In health, the ascending and transverse regions of colon function as reservoirs to accommodate ileal chyme and the descending colon acts as a conduit; the neuromuscular functions and transmitters control colonic motility and sensation and play pivotal roles in disorders associated with constipation and/or diarrhoea. Disorders of proximal colonic transit contribute to symptoms in idiopathic constipation, diarrhoea-predominant irritable bowel syndrome and carcinoid diarrhoea. Colonic function in patients presenting with constipation is best assessed clinically by colonic transit time using radiopaque markers ingested orally. Measurements of colonic contractility are less useful clinically but they can help identify motor abnormalities including colonic inertia; in some patients with irritable bowel syndrome, abdominal pain, urgency and diarrhoea are temporally associated with high amplitude contractions, which originate in the proximal colon and traverse the distal conduit at very high propagation velocities. Visceral hypersensitivity contributes to the urgency and tenesmus in irritable bowel syndrome and inflammatory bowel disease. Colonic motility and sensation can be reduced by anticholinergic agents, somatostatin analogues and 5HT3 antagonists. CONCLUSION: Physiological and pharmacological studies of the human colon have provided new insights into the pathophysiology of colonic disorders, and offer possibilities of novel therapeutic approaches for constipation or diarrhoea associated with colonic motor or sensory dysfunction.
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Colo/fisiologia , Doenças do Colo/fisiopatologia , Constipação Intestinal/fisiopatologia , Diarreia/fisiopatologia , Motilidade Gastrointestinal/fisiologia , Doenças do Colo/diagnóstico , Humanos , Junção Neuromuscular/fisiologiaRESUMO
A case of scrotal and penile extramammary Paget's disease (EMPD) and concurrent prostate adenocarcinoma in a 59-year-old patient is presented. Immunohistochemically, the tumor cells of both the EMPD and prostate stained positively for prostate-specific antigen. Six previously reported cases of EMPD associated with prostate adenocarcinoma are reviewed, along with a discussion of current theories of the pathogenesis of EMPD.