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1.
Chemistry ; 28(57): e202201856, 2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-35924459

RESUMO

The synthesis of heterobimetallic AuI /RuII complexes of the general formula syn- and anti-[{AuCl}(L1∩L2){Ru(bpy)2 }][PF6 ]2 is reported. The ditopic bridging ligand L1∩L2 refers to a P,N hybrid ligand composed of phosphine and bipyridine substructures, which was obtained via a post-functionalization strategy based on Diels-Alder reaction between a phosphole and a maleimide moiety. It was found that the stereochemistry at the phosphorus atom of the resulting 7-phosphanorbornene backbone can be controlled by executing the metal coordination and the cycloaddition reaction in a different order. All precursors, as well as the mono- and multimetallic complexes, were isolated and fully characterized by various spectroscopic methods such as NMR, IR, and UV-vis spectroscopy as well as cyclic voltammetry. Photophysical measurements show efficient phosphorescence for the investigated monometallic complex anti-[(L1∩L2){Ru(bpy)2 }][PF6 ]2 and the bimetallic analogue syn-[{AuCl}(L1∩L2){Ru(bpy)2 }][PF6 ]2 , thus indicating a small influence of the {AuCl} fragment on the photoluminescence properties. The heterobimetallic AuI /RuII complexes syn- and anti-[{AuCl}(L1∩L2){Ru(bpy)2 }][PF6 ]2 are both active catalysts in the P-arylation of aryldiazonium salts promoted by visible light with H-phosphonate affording arylphosphonates in yields of up to 91 %. Both dinuclear complexes outperform their monometallic counterparts.

2.
Chemistry ; 27(61): 15066-15073, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34459528

RESUMO

Novel multistimuli-responsive phosphine ligands comprising a redox-active [3]dioxaphosphaferrocenophane backbone and a P-bound imidazolin-2-ylidenamino entity that allows switching by protonation are reported. Investigation of the corresponding metal complexes and their redox behaviour are reported and show the sensitivity of the system towards protonation and metal coordination. The experimental findings are supported by DFT calculations. Protonation and oxidation events are applied in Rh-catalysed hydrosilylations and demonstrate a remarkable influence on reactivity and/or selectivity.

3.
Phys Rev Lett ; 120(20): 201101, 2018 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-29864326

RESUMO

Spectral lines are among the most powerful signatures for dark matter (DM) annihilation searches in very-high-energy γ rays. The central region of the Milky Way halo is one of the most promising targets given its large amount of DM and proximity to Earth. We report on a search for a monoenergetic spectral line from self-annihilations of DM particles in the energy range from 300 GeV to 70 TeV using a two-dimensional maximum likelihood method taking advantage of both the spectral and spatial features of the signal versus background. The analysis makes use of Galactic center observations accumulated over ten years (2004-2014) with the H.E.S.S. array of ground-based Cherenkov telescopes. No significant γ-ray excess above the background is found. We derive upper limits on the annihilation cross section ⟨σv⟩ for monoenergetic DM lines at the level of 4×10^{-28} cm^{3} s^{-1} at 1 TeV, assuming an Einasto DM profile for the Milky Way halo. For a DM mass of 1 TeV, they improve over the previous ones by a factor of 6. The present constraints are the strongest obtained so far for DM particles in the mass range 300 GeV-70 TeV. Ground-based γ-ray observations have reached sufficient sensitivity to explore relevant velocity-averaged cross sections for DM annihilation into two γ-ray photons at the level expected from the thermal relic density for TeV DM particles.

4.
Phys Rev Lett ; 117(15): 151302, 2016 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-27768338

RESUMO

A search for dark matter linelike signals iss performed in the vicinity of the Galactic Center by the H.E.S.S. experiment on observational data taken in 2014. An unbinned likelihood analysis iss developed to improve the sensitivity to linelike signals. The upgraded analysis along with newer data extend the energy coverage of the previous measurement down to 100 GeV. The 18 h of data collected with the H.E.S.S. array allow one to rule out at 95% C.L. the presence of a 130 GeV line (at l=-1.5°, b=0° and for a dark matter profile centered at this location) previously reported in Fermi-LAT data. This new analysis overlaps significantly in energy with previous Fermi-LAT and H.E.S.S. RESULTS: No significant excess associated with dark matter annihilations was found in the energy range of 100 GeV to 2 TeV and upper limits on the gamma-ray flux and the velocity weighted annihilation cross section are derived adopting an Einasto dark matter halo profile. Expected limits for present and future large statistics H.E.S.S. observations are also given.

5.
Phys Rev Lett ; 117(11): 111301, 2016 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-27661677

RESUMO

The inner region of the Milky Way halo harbors a large amount of dark matter (DM). Given its proximity, it is one of the most promising targets to look for DM. We report on a search for the annihilations of DM particles using γ-ray observations towards the inner 300 pc of the Milky Way, with the H.E.S.S. array of ground-based Cherenkov telescopes. The analysis is based on a 2D maximum likelihood method using Galactic Center (GC) data accumulated by H.E.S.S. over the last 10 years (2004-2014), and does not show any significant γ-ray signal above background. Assuming Einasto and Navarro-Frenk-White DM density profiles at the GC, we derive upper limits on the annihilation cross section ⟨σv⟩. These constraints are the strongest obtained so far in the TeV DM mass range and improve upon previous limits by a factor 5. For the Einasto profile, the constraints reach ⟨σv⟩ values of 6×10^{-26} cm^{3} s^{-1} in the W^{+}W^{-} channel for a DM particle mass of 1.5 TeV, and 2×10^{-26} cm^{3} s^{-1} in the τ^{+}τ^{-} channel for a 1 TeV mass. For the first time, ground-based γ-ray observations have reached sufficient sensitivity to probe ⟨σv⟩ values expected from the thermal relic density for TeV DM particles.

6.
Phys Rev Lett ; 114(8): 081301, 2015 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-25768750

RESUMO

An annihilation signal of dark matter is searched for from the central region of the Milky Way. Data acquired in dedicated on-off observations of the Galactic center region with H.E.S.S. are analyzed for this purpose. No significant signal is found in a total of ∼9 h of on-off observations. Upper limits on the velocity averaged cross section, ⟨σv⟩, for the annihilation of dark matter particles with masses in the range of ∼300 GeV to ∼10 TeV are derived. In contrast to previous constraints derived from observations of the Galactic center region, the constraints that are derived here apply also under the assumption of a central core of constant dark matter density around the center of the Galaxy. Values of ⟨σv⟩ that are larger than 3×10^{-24} cm^{3}/s are excluded for dark matter particles with masses between ∼1 and ∼4 TeV at 95% C.L. if the radius of the central dark matter density core does not exceed 500 pc. This is the strongest constraint that is derived on ⟨σv⟩ for annihilating TeV mass dark matter without the assumption of a centrally cusped dark matter density distribution in the search region.

7.
Int J Cardiol ; 323: 47-53, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-32889020

RESUMO

BACKGROUND: Coarctation of the Aorta (CoA) is associated with increased aortic stiffness and diastolic left ventricular dysfunction. The mechanisms involved and impact of age remain unclear. It was the aim of this study to characterize arterial and cardiac function, their correlation, and the effect of age in children and adults with repaired CoA. METHODS: Multimodal cardiovascular assessment from the ascending aorta to microcirculation and endothelial function was performed prospectively. Statistical analyses included multivariable linear regression and correlation of vascular parameters with age and diastolic function. RESULTS: Fifty-seven patients with well-repaired CoA and 77 healthy controls were included (age 8-59). There was no significant difference in age, gender, body surface area and BMI between the groups. Ascending aortic distensibility was decreased while common carotid intima media thickness, central augmentation index corrected to a heart rate of 75/min [Aix75], peripheral Aix75 and aging index were increased in the CoA group. Interestingly, in a subgroup analysis of CoA patients with tricuspid vs. bicuspid aortic valves (BAV), only the latter had increased Aix75. Carotid-femoral pulse wave velocity [cfPWV], reactive hyperemia index and microcirculation were not significantly different between CoA and control patients. Diastolic function was impaired in the CoA group relative to controls. Both diastolic function and age correlated moderate-strongly with arterial parameters. CONCLUSIONS: Patients with well repaired CoA have increased proximal arterial stiffness which correlates with diastolic function and age. Increased Aix75 may be attributed to a high prevalence of associated BAV. Neither cfPWV nor peripheral endothelial or microcirculatory function are impaired.


Assuntos
Coartação Aórtica , Rigidez Vascular , Adolescente , Adulto , Coartação Aórtica/diagnóstico por imagem , Coartação Aórtica/cirurgia , Espessura Intima-Media Carotídea , Criança , Humanos , Microcirculação , Pessoa de Meia-Idade , Análise de Onda de Pulso , Função Ventricular , Adulto Jovem
8.
Ann Thorac Surg ; 111(4): 1380-1386, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32619613

RESUMO

BACKGROUND: After surgical repair of aortic coarctation (CoA) there is a risk for restenosis (reCoA), particularly in the first year of life. This study aimed to identify reCoA risk factors by analyzing postoperative predischarge echocardiograms. METHODS: This was a retrospective analysis of echocardiograms of children born operated on for CoA in Sweden in 2011 to 2017. RESULTS: A total of 253 children were included. Median age at surgery was 10 days; median follow-up was 4.6 years. Risk for restenosis occurred in 34 patients (13%; 74% by 6 months and 91% by 12 months). We generated 2 reCoA risk models applying aortic dimensions and the respective Z-scores combined with surgical and demographic factors. We defined reCoA risk categories as low (≤10%), moderate (11% to 29%), moderate to high (30% to 49%), or high (≥50%). Patients with either isthmus of 3.3 mm or less (1- and 5-year event-free survival of 38% and 32%, respectively) or isthmus Z-score of -2.8 or less with a weight at surgery of less than 4.4 kg (1- and 5-year event free survival of 21% and 16%, respectively) were at highest risk for reCoA. Conversely, patients at low risk had isthmus greater than 3.7 mm and distal aortic arch greater than 3.5mm (1- and 5-year event free survival of 97% and 97%, respectively), and isthmus and proximal aortic arch Z-score greater than -2.8 or operative weight greater than 4.4 kg with an isthmus Z-score of -2.8 or less (1- and 5-year event-free survival of 97% and 97%, respectively). CONCLUSIONS: Risk for reCoA can be predicted based on postoperative predischarge echocardiographic variables combined with surgical and demographic factors. We suggest tailoring follow-up intervals individually according to the predicted reCoA risk.


Assuntos
Angioplastia com Balão/métodos , Aorta Torácica/diagnóstico por imagem , Coartação Aórtica/cirurgia , Ecocardiografia/métodos , Complicações Pós-Operatórias/epidemiologia , Aorta Torácica/cirurgia , Coartação Aórtica/diagnóstico , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Recidiva , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Suécia/epidemiologia , Fatores de Tempo
9.
Science ; 234(4780): 1081-6, 1986 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-3775377

RESUMO

The concentrations of enzyme sites in cells are usually higher than the concentrations of cognate intermediary metabolites. Therefore metabolic pathways or substantial segments of pathways may proceed by the direct transfer of metabolites from one enzyme site to the next by means of enzyme-enzyme complex formation. This mechanism of metabolite transfer differs from that usually assumed where dissociation and random diffusion of metabolite through the aqueous environment is responsible for the transfer to the next enzyme site. Since the direct transfer mechanism does not involve the aqueous environment, the energetics of metabolite interconversion can differ from expectations based on aqueous solution data. Evidence is summarized suggesting that metabolite is transformed and transferred with equal facility everywhere in the direct transfer pathway.


Assuntos
Complexos Multienzimáticos/metabolismo , Enzimas/metabolismo , Cinética , Metabolismo , Complexos Multienzimáticos/biossíntese , NAD/metabolismo
10.
Nat Biotechnol ; 14(7): 845-51, 1996 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9631008

RESUMO

Human immunoglobulin transgenic mice provide a method of obtaining human monoclonal antibodies (Mabs) using conventional hybridoma technology. We describe a novel strain of human immunoglobulin transgenic mice and the use of this strain to generate multiple high-avidity human sequence IgG kappa Mabs directed against a human antigen. The light chain transgene is derived in part from a yeast artificial chromosome clone that includes nearly half of the germline human V kappa region. In addition, the heavy-chain transgene encodes both human mu and human gamma 1 constant regions, the latter of which is expressed via intratransgene class switching. We have used these animals to isolate human IgG kappa Mabs that are specific for the human T-cell marker CD4, have high binding avidities, and are immunosuppressive in vitro. The human Mab-secreting hybridomas display properties similar to those of wild-type mice including stability, growth, and secretion levels. Mabs with four distinct specificities were derived from a single transgenic mouse, consistent with an extensive diversity in the primary repertoire encoded by the transgenes.


Assuntos
Anticorpos Monoclonais/biossíntese , Afinidade de Anticorpos , Imunoglobulina G/imunologia , Cadeias kappa de Imunoglobulina/imunologia , Animais , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/imunologia , Antígenos CD4/imunologia , Ensaio de Imunoadsorção Enzimática , Humanos , Hibridomas , Teste de Cultura Mista de Linfócitos , Camundongos , Camundongos Transgênicos , Linfócitos T/imunologia
11.
Chem Commun (Camb) ; 54(1): 26-29, 2017 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-29226923

RESUMO

For the first time, free base and N-methylated porphyrins have been utilized as bifunctional organocatalysts in Michael additions and it was found that distortion of the macrocycle is a vital prerequisite for their catalytic activity. Conformational design has been used to tailor the properties of nonplanar porphyrins with regards to availability of the N-H units for hydrogen bonding (distortion-dependent hydrogen bonding) and the basicity of the heterocyclic groups. NMR spectroscopic- and catalyst screening studies provided insight into the likely mode of catalyst action. This unprecedented use of free base and N-substituted porphyrins as organocatalysts opens a new functional role for porphyrins.

12.
Cancer Res ; 52(11): 3056-62, 1992 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-1375534

RESUMO

In vivo efficacy testing of monoclonal antibody-based drugs specific for human leukemias is hampered by the paucity of suitable animal models, due in part to the inability of many anti-human monoclonal antibodies to cross-react with antigens expressed in animal tissues or cells. Moreover, human leukemic cells have proven difficult to establish in immunosuppressed mice except as solid tumors. We report here the establishment of a murine model for human leukemia displaying features of human disease, such as growth of malignant cells and localization of such cells to lymphoid compartments, and the effective depletion of leukemic cells from these mice by an immunoconjugate. Human T-leukemia cells (CEM) injected into cyclophosphamide-pretreated NIH-III mice engrafted in all mice (n = 41), with CEM cells detected in the bone marrow, spleen, and blood 4 weeks after injection. There was no evidence of solid tumors. Treatment of CEM-engrafted mice with 4A2-RTA30, an immunoconjugate of an anti-CD7 monoclonal antibody and ricin A chain (RTA30), resulted in a 100- to 200-fold overall depletion of CEM cells from the spleen and the bone marrow (P less than 0.02). This depletion was specific and toxin-dependent, as a control immunoconjugate had no demonstrable effect (P greater than 0.5). Depletion of CEM cells was also observed after treatment with unconjugated anti-CD7 mAb, but this effect was not significantly different from controls (P greater than 0.1). Therefore, significant depletion of CEM cells required the presence of the ricin A chain moiety. Further investigations revealed that CEM cells recovered from NIH-III mice expressed less CD7 antigen, but remained sensitive to subsequent in vitro exposure to 4A2-RTA30. In conclusion, we have established a model for studying the efficacy of immunoconjugates and have successfully depleted human T-leukemic cells from lymphoid tissues in immunodeficient mice by treatment with an anti-CD7-RTA30 immunoconjugate.


Assuntos
Antígenos CD/imunologia , Antígenos de Diferenciação de Linfócitos T/imunologia , Imunotoxinas/uso terapêutico , Leucemia-Linfoma de Células T do Adulto/terapia , Ricina/uso terapêutico , Animais , Anticorpos Monoclonais/uso terapêutico , Antígenos CD/análise , Antígenos CD7 , Linhagem Celular , Ciclofosfamida/farmacologia , Esquema de Medicação , Avaliação Pré-Clínica de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Antígenos de Histocompatibilidade/análise , Humanos , Terapia de Imunossupressão , Imunotoxinas/toxicidade , Antígenos Comuns de Leucócito , Masculino , Glicoproteínas de Membrana/análise , Camundongos , Camundongos Endogâmicos , Transplante de Neoplasias/métodos , Ricina/toxicidade , Transplante Heterólogo
13.
Eur Heart J Cardiovasc Imaging ; 17(2): 225-30, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26072912

RESUMO

AIMS: Aortic stiffness and diastolic function are abnormal in adults with bicuspid aortic valves (BAVs). The goal of this study was to determine the relationship between aortic stiffness and left ventricular (LV) diastolic impairment in children with well-functioning BAV and no associated congenital heart disease. METHODS AND RESULTS: This is a retrospective review of echocardiograms in children with isolated BAV (group BAV; N = 50) and healthy frequency-matched controls (group Control; N = 50). We analysed LV systolic and diastolic function, proximal and distal ascending aortic stiffness index (SI), distensibility, and strain. Age range was 0.2-20 (median 11) years. There was no significant difference in blood pressure, normalized LV size and systolic function between the groups. Several parameters of LV diastolic function were lower in group BAV compared with group Control (e.g. septal E': BAV 12 ± 2.3 cm/s; Control 13.5 ± 1.8 cm/s, P < 0.001). All parameters of proximal and distal ascending aortic elasticity were abnormal in group BAV vs. Control (SI proximal ascending aorta: BAV 4.2 ± 1.6; Control 3.0 ± 0.9, P < 0.001). There was no significant correlation between parameters of aortic elasticity and diastolic function. In a subgroup analysis of children with fusion of the right-non vs. right-left coronary cusps, there was no significant difference for any of the parameters analysed. CONCLUSION: Even children with well-functioning isolated BAV have abnormalities in aortic elasticity and diastolic function when compared with the Control group. However, a relationship between the two could not be established.


Assuntos
Valva Aórtica/anormalidades , Diástole , Doenças das Valvas Cardíacas/diagnóstico por imagem , Doenças das Valvas Cardíacas/fisiopatologia , Rigidez Vascular , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia , Adolescente , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/fisiopatologia , Doença da Válvula Aórtica Bicúspide , Estudos de Casos e Controles , Criança , Pré-Escolar , Ecocardiografia , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Adulto Jovem
14.
Math Biosci ; 269: 104-16, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26367184

RESUMO

In computational cardiovascular models, parameters are one of major sources of uncertainty, which make the models unreliable and less predictive. In order to achieve predictive models that allow the investigation of the cardiovascular diseases, sensitivity analysis (SA) can be used to quantify and reduce the uncertainty in outputs (pressure and flow) caused by input (electrical and structural) model parameters. In the current study, three variance based global sensitivity analysis (GSA) methods; Sobol, FAST and a sparse grid stochastic collocation technique based on the Smolyak algorithm were applied on a lumped parameter model of carotid bifurcation. Sensitivity analysis was carried out to identify and rank most sensitive parameters as well as to fix less sensitive parameters at their nominal values (factor fixing). In this context, network location and temporal dependent sensitivities were also discussed to identify optimal measurement locations in carotid bifurcation and optimal temporal regions for each parameter in the pressure and flow waves, respectively. Results show that, for both pressure and flow, flow resistance (R), diameter (d) and length of the vessel (l) are sensitive within right common carotid (RCC), right internal carotid (RIC) and right external carotid (REC) arteries, while compliance of the vessels (C) and blood inertia (L) are sensitive only at RCC. Moreover, Young's modulus (E) and wall thickness (h) exhibit less sensitivities on pressure and flow at all locations of carotid bifurcation. Results of network location and temporal variabilities revealed that most of sensitivity was found in common time regions i.e. early systole, peak systole and end systole.


Assuntos
Artérias Carótidas/anatomia & histologia , Artérias Carótidas/fisiologia , Modelos Cardiovasculares , Algoritmos , Simulação por Computador , Hemorreologia , Humanos , Conceitos Matemáticos , Fluxo Sanguíneo Regional , Incerteza
15.
J Exp Psychol Hum Percept Perform ; 41(6): 1734-47, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26280259

RESUMO

The vista paradox is the illusion in which an object seen through a window appears to shrink in apparent size (and appears farther away) as the observer approaches the window. Paradoxically, the distal object appears smaller as its visual angle increases. We investigated the effect in four experiments varying object size, distance, point of fixation, and texture of the frame and of the object. In the first experiment, we tried to confirm the illusion and to test the robustness of the phenomenon. In the second experiment, we manipulated where subjects fixated (on the frame or on the object) as well as the texture of the object and the frame. Fixation was essential for the illusion: fixating the frame led to an apparent shrinking of the object, whereas fixation on the object did not. Texture of the frame intensified the apparent shrinking of the object. In a third experiment, we separated the point of fixation from the frame in a between-subjects design. Finally, in Experiment 4, we showed that the paradox does not require a frame, but it requires a fixation on a location different from the object. That is, the window or frame is dispensable for the vista paradox, but fixation is critical.


Assuntos
Percepção de Distância/fisiologia , Percepção de Forma/fisiologia , Percepção de Movimento/fisiologia , Ilusões Ópticas/fisiologia , Percepção de Tamanho/fisiologia , Adulto , Feminino , Fixação Ocular , Humanos , Masculino , Adulto Jovem
16.
Biochimie ; 63(2): 131-41, 1981 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-7225460

RESUMO

A variety of species of GPDH undergo acylation at two of the four active cystein sites per mole of tetrameric enzyme. This reaction requires tightly bound NAD+, a situation restricted to two of the four NAD sites per tetramer. S leads to N acyl transfer from cysteins to lysine in the diacyl enzyme yields an inactive enzyme. The thiol ester bond of acyl enzyme is activated by NAD+ and NADH for the group transfer and reduction reactions, respectively. In furyl acryloyl-GPDH this activation is accompanied by large acyl-spectral shifts, a "blue shift" with NADH and a "red shift" with NAD+. The group transfer reaction as well as spectral shifts show biphasic kinetics. The amplitude of the fast phase of NAD+-induced spectral change in apo-enzyme is equal to that of the fast phase in phosphorolysis (or arsenolysis) at low [NAD+]. The kinetic pattern of spectral shifts by NAD+ and NADH are complementary; the amplitude of the fast phase in one is equal to that of the slow phase in the other. It has been proposed that the acyl enzyme exists in two conformational states. The relative proportion of these states varies with the extent of covalent (acyl group) or non-covalent (NAD+ or NADH) ligation in a manner consistent with the allosteric model of Monod, Wyman and Changeux. These conclusions apply equally to the true substrate acyl enzyme. With 1,3-diphosphoglycerate, a tetra-acylated enzyme is obtained. Two of these four acyl groups react very much faster than the remaining two. A comparison of their specific rates with the steady state turnover numbers indicates that only the less reactive two acyl groups govern the turnover number of the enzyme.


Assuntos
Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Sítios de Ligação , Cinética , NAD , Conformação Proteica
17.
Cell Stress Chaperones ; 8(2): 144-52, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-14627200

RESUMO

A complementary deoxyribonucleic acid (cDNA) and the corresponding gene segment encoding a member of the 70-kDa heat shock protein (Hsp70) family have been cloned and sequenced from Locusta migratoria, the African migratory locust. These animals are noted for their thermotolerance, which can exceed temperatures of 50 degrees C. Conceptually translated, the sequence shows a 654-residue protein with theoretical molecular weight of 71.4 kDa, which more closely resembles the mammalian Hsp70 (84-85% similarity) than Hsp70 from other insects, with approximately 75% similarity to the sequence from the fruit fly. Comparisons of cDNA and genomic sequences show that the gene contains 2 introns, a 245-bp intron located in the 5' untranslated region and a 91-bp intron in the coding region. Transcript abundance, as estimated by Northern blot analysis and reverse transcription-polymerase chain reaction, shows that heat shock treatment (45 degrees C for 3 hours) does not elevate hsp70 messenger ribonucleic acid levels in fat bodies or in neural tissues. Immunological assays of Hsp70 show that the protein is constitutively expressed, with a modest, approximately 2-fold induction after a 3-hour heat shock in fat body preparations. Although this sequence could be an hsc70 rather than an hsp70, it was the only cDNA isolated from heat-shocked tissue. Whatever the formal designation, such modest induction and constitutive expression may be ideally suited as an adaptation to the locust's chronic exposure to heat shock temperatures and the consequent demand for chaperone proteins.


Assuntos
Gafanhotos/genética , Proteínas de Choque Térmico HSP70/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Feminino , Gafanhotos/metabolismo , Proteínas de Choque Térmico HSP70/imunologia , Proteínas de Choque Térmico HSP70/metabolismo , Temperatura Alta , Íntrons , Dados de Sequência Molecular , RNA Mensageiro/metabolismo , Análise de Sequência de DNA
18.
Chemistry ; 6(5): 849-57, 2000 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-10826607

RESUMO

The anti dimer of cyclobutadiene (anti-tricyclo[4.2.0.0(2.5)]octa-3,7-diene, TOD) is subjected to ionization by gamma-irradiation in Freon matrices, pulse radiolysis in hydrocarbon matrices, and photoinduced electron transfer in solution. The resulting species are probed by optical and ESR spectroscopy (solid phase) as well as by CIDNP spectroscopy (solution). Thereby it is found that ionization of anti-TOD invariably leads to spontaneous decay to two products, that is bicyclo[4.2.0]octa-2,4,7-triene (BOT) and 1,4-dihydropentalene (1,4-DHP), whose relative yield strongly depends on the conditions of the experiment. Exploration of the C8H8*+ potential energy surface by the B3LYP/6-31G* density functional method leads to a mechanistic hypothesis for the observed rearrangements which involves a bifurcation between a pathway leading to the simple valence isomer, BOT*+, and another one leading to an unprecedented other valence isomer, the anti form of the bicyclo[3.3.0]octa-2,6-diene-4,8-diyl radical cation (anti-BOD*+). The latter product undergoes a very facile H-shift to yield the radical cation of 1,3a-dihydropentalene (1,3a-DHP*+) which ultimately rearrranges by a further H-shift to the observed product, 1,4-DHP*+.

19.
Chemistry ; 6(5): 858-68, 2000 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-10826608

RESUMO

The syn dimer of cyclobutadiene (tricyclo[4.2.0.0(2.5)]octa-3,7-diene, TOD) is subjected to ionization under different conditions and the resulting species are probed by optical and ESR spectroscopy. By means of quantum chemical modelling of the potential energy surfaces and the optical spectra, it is possible to assign the different products that arise spontaneously after ionization or after subsequent warming or illumination of the samples. Based on these findings, we propose a mechanistic scheme which involves a partitioning of the incipient radical cation of TOD between two electronic states. These two states engage in (near) activation-less decay to the more stable valence isomers, cyclooctatetraene (COT*+) and a bis-cyclobutenylium radical cation BCB*+. The latter product undergoes further rearrangement, first to tetracyclo[4.2.0.0(2,4).0(3,5]oct-7-ene (TCO*+) and eventually to bicyclo[4.2.0]octa-2,4,7-triene (BOT*+) which can also be generated photochemically from BCB*+ or TCO*+. The surprising departure of syn-TOD*+ from the least-motion reaction path leading to BOT*+ can be traced to strong vibronic interactions (second-order Jahn-Teller effects) which prevail in both possible ground states of syn-TOD*+. Such effects seem to be more important in determining the intramolecular reactivity of radical cations than orbital or state symmetry rules.

20.
Am J Hypertens ; 9(8): 719-25, 1996 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8862216

RESUMO

The Medication Event Monitoring System (MEMS), an electronic monitor which records the date and time of bottle cap openings, and pill counts were used to assess patterns of adherence for the primary antihypertensive drug in the African American Study of Kidney Disease and Hypertension Pilot Study (AASK). Blacks with hypertension and moderately reduced renal function were randomized to one of two levels of blood pressure control and to one of three antihypertensive drug regimens: primary therapy with a calcium channel blocker, an angiotension converting enzyme inhibitor, or a beta-blocker. Of the 94 participants in AASK, 91 had MEMS recordings and pill counts for 313 regularly scheduled monthly follow-up visits. The average length of follow-up was 4.6 months. An acceptable level of adherence by pill count was achieved if 80% to 100% of the prescribed pills were not returned to the clinic. Adherence by MEMS to a once-a-day drug dosing schedule was acceptable if 80% of the time intervals between MEMS openings were within 24 +/- 6 h. Acceptable adherence by pill count was observed at 68% of the follow-up visits; MEMS indicated nonadherence at 47% of those visits. Blood pressure was within goal in 50% of the participants who were adherent by both pill count and MEMS throughout their follow-up visits, and only 14% of the participants who were identified nonadherent by one or both methods. These findings suggest that electronic monitoring is a useful adjunct to pill counts in assessing adherence to antihypertensive drugs. Feedback of electronically collected information on dosing intervals to participants and staff may enhance adherence.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Nefropatias/tratamento farmacológico , Cooperação do Paciente , Adolescente , Adulto , Negro ou Afro-Americano , Idoso , Anti-Hipertensivos/administração & dosagem , Pressão Sanguínea/fisiologia , Feminino , Seguimentos , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estados Unidos
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