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1.
Space Sci Rev ; 217(1): 24, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33612866

RESUMO

Mastcam-Z is a multispectral, stereoscopic imaging investigation on the Mars 2020 mission's Perseverance rover. Mastcam-Z consists of a pair of focusable, 4:1 zoomable cameras that provide broadband red/green/blue and narrowband 400-1000 nm color imaging with fields of view from 25.6° × 19.2° (26 mm focal length at 283 µrad/pixel) to 6.2° × 4.6° (110 mm focal length at 67.4 µrad/pixel). The cameras can resolve (≥ 5 pixels) ∼0.7 mm features at 2 m and ∼3.3 cm features at 100 m distance. Mastcam-Z shares significant heritage with the Mastcam instruments on the Mars Science Laboratory Curiosity rover. Each Mastcam-Z camera consists of zoom, focus, and filter wheel mechanisms and a 1648 × 1214 pixel charge-coupled device detector and electronics. The two Mastcam-Z cameras are mounted with a 24.4 cm stereo baseline and 2.3° total toe-in on a camera plate ∼2 m above the surface on the rover's Remote Sensing Mast, which provides azimuth and elevation actuation. A separate digital electronics assembly inside the rover provides power, data processing and storage, and the interface to the rover computer. Primary and secondary Mastcam-Z calibration targets mounted on the rover top deck enable tactical reflectance calibration. Mastcam-Z multispectral, stereo, and panoramic images will be used to provide detailed morphology, topography, and geologic context along the rover's traverse; constrain mineralogic, photometric, and physical properties of surface materials; monitor and characterize atmospheric and astronomical phenomena; and document the rover's sample extraction and caching locations. Mastcam-Z images will also provide key engineering information to support sample selection and other rover driving and tool/instrument operations decisions.

2.
Space Sci Rev ; 217(2): 29, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33678912

RESUMO

The NASA Perseverance rover Mast Camera Zoom (Mastcam-Z) system is a pair of zoomable, focusable, multi-spectral, and color charge-coupled device (CCD) cameras mounted on top of a 1.7 m Remote Sensing Mast, along with associated electronics and two calibration targets. The cameras contain identical optical assemblies that can range in focal length from 26 mm ( 25.5 ∘ × 19.1 ∘ FOV ) to 110 mm ( 6.2 ∘ × 4.2 ∘ FOV ) and will acquire data at pixel scales of 148-540 µm at a range of 2 m and 7.4-27 cm at 1 km. The cameras are mounted on the rover's mast with a stereo baseline of 24.3 ± 0.1  cm and a toe-in angle of 1.17 ± 0.03 ∘ (per camera). Each camera uses a Kodak KAI-2020 CCD with 1600 × 1200 active pixels and an 8 position filter wheel that contains an IR-cutoff filter for color imaging through the detectors' Bayer-pattern filters, a neutral density (ND) solar filter for imaging the sun, and 6 narrow-band geology filters (16 total filters). An associated Digital Electronics Assembly provides command data interfaces to the rover, 11-to-8 bit companding, and JPEG compression capabilities. Herein, we describe pre-flight calibration of the Mastcam-Z instrument and characterize its radiometric and geometric behavior. Between April 26 t h and May 9 t h , 2019, ∼45,000 images were acquired during stand-alone calibration at Malin Space Science Systems (MSSS) in San Diego, CA. Additional data were acquired during Assembly Test and Launch Operations (ATLO) at the Jet Propulsion Laboratory and Kennedy Space Center. Results of the radiometric calibration validate a 5% absolute radiometric accuracy when using camera state parameters investigated during testing. When observing using camera state parameters not interrogated during calibration (e.g., non-canonical zoom positions), we conservatively estimate the absolute uncertainty to be < 10 % . Image quality, measured via the amplitude of the Modulation Transfer Function (MTF) at Nyquist sampling (0.35 line pairs per pixel), shows MTF Nyquist = 0.26 - 0.50 across all zoom, focus, and filter positions, exceeding the > 0.2 design requirement. We discuss lessons learned from calibration and suggest tactical strategies that will optimize the quality of science data acquired during operation at Mars. While most results matched expectations, some surprises were discovered, such as a strong wavelength and temperature dependence on the radiometric coefficients and a scene-dependent dynamic component to the zero-exposure bias frames. Calibration results and derived accuracies were validated using a Geoboard target consisting of well-characterized geologic samples. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11214-021-00795-x.

3.
Science ; 170(3954): 183-5, 1970 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-5456612

RESUMO

Lesions induced by aspirin in the small intestine of the rat were visualized after 4 hours by the intravenous administration of a 5 percent solution of pontamine sky blue, 6 BX dye. Dose-response curves in fasted and fed rats indicated that the fed rat was about eight times more susceptible to aspirin-induced intestinal damage than was the fasted rat, while the fasted rat was about 13 times more susceptible to aspirin-induced gastric damage than was the fed rat.


Assuntos
Aspirina , Enteropatias/induzido quimicamente , Intestino Delgado/efeitos dos fármacos , Animais , Compostos Azo , Privação de Alimentos , Íleo , Mucosa Intestinal/patologia , Jejuno , Masculino , Naftalenos , Necrose , Ratos , Ácidos Sulfônicos
4.
Environ Entomol ; 37(2): 615-23, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18419936

RESUMO

Popcorn was evaluated in a series of experiments conducted over four growing seasons for its potential as a refuge for European corn borer, Ostrinia nubilalis (Hübner). Objectives of these studies were to determine whether more larvae were produced in popcorn than in field corn and to determine how popcorn influenced female oviposition and larval distribution in neighboring field corn. Two varieties of popcorn (M140, 105d and M3374Y, 118d), one mixture of popcorn (50% 105d and 50% 118d), and field corn (DK580, 108d) were evaluated. Number of egg masses, eggs per egg mass, and larvae were significantly higher in popcorn compared with field corn. Moth oviposition and larval distribution were evaluated using 105d popcorn embedded in several cornfields across Iowa. The row of field corn adjacent to popcorn had significantly more larvae compared with background field corn. In larger field experiments, O. nubilalis larval survival after overwintering was significantly different, with 2.2-18.7 times more O. nubilalis larvae surviving in popcorn than field corn. The potential use of popcorn as an O. nubilalis refuge for genetically engineered corn is considered.


Assuntos
Mariposas/fisiologia , Controle Biológico de Vetores/métodos , Zea mays/parasitologia , Agricultura , Animais , Zea mays/classificação , Zea mays/genética
5.
ACS Appl Mater Interfaces ; 9(44): 38706-38715, 2017 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-29022714

RESUMO

Organic solar cells (OSCs) are a complex assembly of disparate materials, each with a precise function within the device. Typically, the electrodes are flat, and the device is fabricated through a layering approach of the interfacial layers and photoactive materials. This work explores the integration of high surface area transparent electrodes to investigate the possible role(s) a three-dimensional electrode could take within an OSC, with a BHJ composed of a donor-acceptor combination with a high degree of electron and hole mobility mismatch. Nanotree indium tin oxide (ITO) electrodes were prepared via glancing angle deposition, structures that were previously demonstrated to be single-crystalline. A thin layer of zinc oxide was deposited on the ITO nanotrees via atomic layer deposition, followed by a self-assembled monolayer of C60-based molecules that was bound to the zinc oxide surface through a carboxylic acid group. Infiltration of these functionalized ITO nanotrees with the photoactive layer, the bulk heterojunction comprising PC71BM and a high hole mobility low band gap polymer (PDPPTT-T-TT), led to families of devices that were analyzed for the effect of nanotree height. When the height was varied from 0 to 50, 75, 100, and 120 nm, statistically significant differences in device performance were noted with the maximum device efficiencies observed with a nanotree height of 75 nm. From analysis of these results, it was found that the intrinsic mobility mismatch between the donor and acceptor phases could be compensated for when the electron collection length was reduced relative to the hole collection length, resulting in more balanced charge extraction and reduced recombination, leading to improved efficiencies. However, as the ITO nanotrees increased in height and branching, the decrease in electron collection length was offset by an increase in hole collection length and potential deleterious electric field redistribution effects, resulting in decreased efficiency.

6.
Bone Marrow Transplant ; 37(9): 851-6, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16532016

RESUMO

Despite significant advances in prevention and therapy, cytomegalovirus (CMV) infection continues to be an important cause of morbidity and mortality in the hematopoietic stem cell transplant (HSCT) recipient. The standard drug for pre-emptive therapy is intravenous ganciclovir (GCV). Valganciclovir (VGC), the oral pro-drug of GCV, has excellent bioavailability and is ideal for oral therapy. Since March 2002, VGC was adopted in our center for outpatient pre-emptive therapy in all patients undergoing allogeneic HSCT. Fifty-two allogeneic HSCT recipients were followed weekly via Digene hybrid capture assay. Patients with a positive assay were treated with VGC 900 mg p.o. b.i.d. x 14 days followed by 900 mg p.o. QD until at least 7 days after a negative test. Eighteen patients (14 sib, four MUD) had 30 episodes of CMV DNA detection treated with oral VGC. Median duration of therapy was 21 days (range 10-21 days). The rate of response was 93% (28/30) as confirmed by a negative assay within 14 days. No significant toxicity was encountered. Two patients failed oral VGC. One case of CMV enteritis was diagnosed in a patient with acute GVHD. Pre-emptive therapy of CMV infection with oral VGC is safe and effective in allogeneic HSCT recipients.


Assuntos
Antivirais/uso terapêutico , Infecções por Citomegalovirus/prevenção & controle , Ganciclovir/análogos & derivados , Leucemia/terapia , Transplante de Células-Tronco/métodos , Administração Oral , Adulto , Antivirais/administração & dosagem , Antivirais/farmacocinética , Disponibilidade Biológica , Infecções por Citomegalovirus/tratamento farmacológico , Feminino , Ganciclovir/administração & dosagem , Ganciclovir/farmacocinética , Ganciclovir/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/terapia , Síndromes Mielodisplásicas/terapia , Estudos Retrospectivos , Transplante de Células-Tronco/efeitos adversos , Transplante Homólogo , Falha de Tratamento , Resultado do Tratamento , Valganciclovir , Irradiação Corporal Total
7.
Biochim Biophys Acta ; 551(2): 382-8, 1979 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-420841

RESUMO

A recent study by Blayney and co-workers (Blayney, L., Thomas, H., Muir, J. and Henderson, A. (1977) Biochim. Biophys. Acta 470, 128--133) purported to demonstrate that apparent spontaneous calcium release in sarcoplasmic reticulum is an artifact of the uptake of murexide dye. This report demonstrates that spontaneous calcium release (1) takes place despite equilibration of murexide sarcoplasmic reticulum to a stable baseline; (2) may be reversed by addition of ATP or oxalate after release has begun. The identical phenomenon can be demonstrated utilizing the indicator arsenazo III or Millipore filtration methods. The results suggest that equilibration of the murexide with sarcoplasmic reticulum vesicles must occur prior to ATP addition in order to achieve a stable baseline but that spontaneous calcium release is not an artifact.


Assuntos
Cálcio/metabolismo , Miocárdio/metabolismo , Retículo Sarcoplasmático/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Cães , Cinética , Oxalatos/farmacologia , Fosfatos/farmacologia , Retículo Sarcoplasmático/efeitos dos fármacos
8.
Biochim Biophys Acta ; 591(2): 251-65, 1980 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-7397124

RESUMO

Ca/+ transport and respiratory characteristics of two preparations of cardiac mitochondria (Palmer, J.W., Tandler, B. and Hoppel, C.L. (1977) J. Biol. Chem. 252, 8731-8739) isolated using polytron homogenization (subsarcolemmal mitochondria) and limited Nagarse exposure (intermyofibrillar mitochondria) are described. The Nagarse procedure yields mitochondria with 50% higher rates of oxidative phosphorylation than the polytron-prepared mitochondria in both rat and dog. Rat hear intermyofibrillar mitochondria contain 50% more cytochrome aa3 than the polytron preparation, whereas in the dog, cytochrome aa3 content is not significantly different. Cytochrome oxidase activities and cytochrome c, c1 and b contents were comparable in both populations of rat and dog heart mitochondria. The V of succinate-supported Ca2+ accumulation for Nagarse-prepared mitochondria from rat heart was 1.8-fold higher than the polytron-prepared mitochondria. In dog heart, the Nagarse preparation showed a 3.0-fold higher V for Ca2+ uptake compared to the polytron preparation. A lower apparent affinity for Ca2+ was demonstrated in the intermyofibrillar mitochondria for both species (Km is 2-2.5-fold higher). The Hill coefficient was 1 both mitochondrial types. Subsarcolemmal mitochondria from both species were treated with Nagarse to determine the role of this treatment on the observed differences. Nagarse did not alter any kinetic parameter of Ca2+ uptake. The properties of these mitochondria with reference to their presumed intracellular location may pertain to the role of mitochondria as an intracellular Ca2+ buffering mechanism in contractile tissue.


Assuntos
Cálcio/metabolismo , Mitocôndrias Cardíacas/metabolismo , Miofibrilas/metabolismo , Sarcolema/metabolismo , Absorção , Animais , Cães , Cinética , Fosforilação Oxidativa , Ratos , Especificidade da Espécie
9.
J Mol Biol ; 340(4): 797-808, 2004 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-15223321

RESUMO

EmrE is a multidrug transporter that utilises the proton gradient across bacterial cell membranes to pump hydrophobic cationic toxins out of the cell. The structure of EmrE is very unusual, because it is an asymmetric homodimer containing eight alpha-helices, six of which form the substrate-binding chamber and translocation pathway. Despite this structural information, the precise oligomeric order of EmrE in both the detergent-solubilised state and in vivo is unclear, although it must contain an even number of subunits to satisfy substrate-binding data. We have studied the oligomeric state of EmrE, purified in a functional form in dodecylmaltoside, by high-resolution size-exclusion chromatography (hrSEC) and by analytical ultracentrifugation. The data from equilibrium analytical ultracentrifugation were analysed using a measured density increment for the EmrE-lipid-detergent complex, which showed that the purified EmrE was predominantly a dimer. This value was consistent with the apparent mass for the EmrE-lipid-detergent complex (137 kDa) determined by hrSEC. EmrE was purified under different conditions using minimal concentrations of dodecylmaltoside, which would have maintained the structure of any putative higher oligomeric states: this EmrE preparation had an apparent mass of 206 kDa by hrSEC and equilibrium analytical ultracentrifugation showed unequivocally that EmrE was a dimer, although it was associated with a much larger mass of phospholipid. In addition, the effect of the substrate tetraphenylphosphonium on the oligomeric state was also analysed for both preparations of EmrE; velocity analytical ultracentrifugation showed that the substrate had no effect on the oligomeric state. Therefore, in the detergent dodecylmaltoside and under conditions where the protein is fully competent for substrate binding, EmrE is dimeric and there is no evidence from our data to suggest higher oligomeric states. These observations are discussed in relation to the recently published structures of EmrE from two- and three-dimensional crystals.


Assuntos
Detergentes/farmacologia , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/isolamento & purificação , Proteínas de Membrana Transportadoras/química , Proteínas de Membrana Transportadoras/isolamento & purificação , Aminoácidos/análise , Calibragem/normas , Cromatografia por Troca Iônica , Cromatografia em Camada Fina , Colorimetria , Dimerização , Resistência Microbiana a Medicamentos , Proteínas de Escherichia coli/metabolismo , Glucosídeos/farmacologia , Lipídeos/análise , Espectrometria de Massas , Proteínas de Membrana Transportadoras/metabolismo , Micelas , Peso Molecular , Fosfolipídeos/normas , Solubilidade , Ultracentrifugação
10.
Cardiovasc Res ; 27(12): 2222-8, 1993 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8313432

RESUMO

OBJECTIVE: The objective was to examine mitochondrial oxidative metabolism of long chain fatty acids and to compare it with glucose uptake and the generation of pressure-volume work in hearts from mature and aged rats. METHODS: Hearts from mature (8 to 15 months of age) and old (28 to 30 months) Fischer 344 rats were perfused as working hearts with either 10 mM glucose or glucose plus 1 mM oleic acid (2% bovine serum albumin) and rates of glucose extraction were determined. Hearts were subjected to a stepwise increase in work load. In separate experiments, mitochondria were isolated from mature and old rat hearts and assayed for respiratory function, carnitine exchange, carnitine palmitoyltransferase activities, and phospholipid content. RESULTS: Although there were no differences in peak work attained between the mature and old rats in the presence of either glucose alone or glucose plus oleic acid, glucose utilisation was significantly decreased by oleate in the mature animals only. No significant changes in either glutamate or succinate (+rotenone) supported respiration were found in heart mitochondria isolated from old rats compared with mature animals. In agreement with prior studies with the Wistar rat model of aging, significant decrements in the rates of palmitoylcarnitine oxidation and carnitine exchange were apparent in the old Fischer animals. A significant lowering of heart mitochondrial carnitine palmitoyltransferase I activity was also found in the old animals. A decrease in the amounts of carnitine loaded in mitochondria from old animals is consistent with reduced carnitine content in both mitochondria and whole hearts from aged Wistar and Fischer rats. A significant (23%) reduction in heart mitochondrial cardiolipin content from 30 month old Fischer rats suggests that this phospholipid may also contribute to the lower rates of carnitine and acylcarnitine transport across the mitochondrial inner membrane. CONCLUSION: The limitation in the delivery of fatty acyl units to beta oxidation as measured in isolated heart mitochondria from old rats has a physiological correlate in the intact heart. The well documented suppression of glucose oxidation by fatty acids seen in the adult rat heart is not seen in old hearts, supporting the in vitro finding of decreased oxidation of palmitoylcarnitine with senescence.


Assuntos
Envelhecimento/metabolismo , Ácidos Graxos/metabolismo , Mitocôndrias Cardíacas/metabolismo , Oxigênio/metabolismo , Animais , Carnitina/metabolismo , Carnitina O-Palmitoiltransferase/metabolismo , Glucose/metabolismo , Masculino , Mitocôndrias Cardíacas/enzimologia , Ácidos Oleicos/metabolismo , Perfusão , Fosfolipídeos/metabolismo , Ratos , Ratos Endogâmicos F344
11.
Oncogenesis ; 4: e168, 2015 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-26436950

RESUMO

Liver kinase B1 (LKB1), also known as serine/threonine kinase 11 (STK11), has been identified as a tumor suppressor in many cancers including breast. Low LKB1 expression has been associated with poor prognosis of breast cancer patients, and we report here a significant association between loss of LKB1 expression and reduced patient survival specifically in the basal subtype of breast cancer. Owing to the aggressive nature of the basal subtype as evidenced by high incidences of metastasis, the purpose of this study was to determine if LKB1 expression could regulate the invasive and metastatic properties of this specific breast cancer subtype. Induction of LKB1 expression in basal-like breast cancer (BLBC)/triple-negative breast cancer cell lines, MDA-MB-231 and BT-549, inhibited invasiveness in vitro and lung metastatic burden in an orthotopic xenograft model. Further analysis of BLBC cells overexpressing LKB1 by unbiased whole transcriptomics (RNA-sequencing) revealed striking regulation of metastasis-associated pathways, including cell adhesion, extracellular matrix remodeling, and epithelial-to-mesenchymal transition (EMT). In addition, LKB1 overexpression inhibited EMT-associated genes (CDH2, Vimentin, Twist) and induced the epithelial cell marker CDH1, indicating reversal of the EMT phenotype in the MDA-MB-231 cells. We further demonstrated marked inhibition of matrix metalloproteinase 1 expression and activity via regulation of c-Jun through inhibition of p38 signaling in LKB1-expressing cells. Taken together, these data support future development of LKB1 inducing therapeutics for the suppression of invasion and metastasis of BLBC.

12.
ACS Appl Mater Interfaces ; 7(15): 8188-99, 2015 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-25808481

RESUMO

Two isostructural low-band-gap small molecules that contain a one-atom substitution, S for Se, were designed and synthesized. The molecule 7,7'-[4,8-bis(2-ethylhexyloxy)benzo[1,2-b:4,5-b']dithiophene]bis[6-fluoro-4-(5'-hexyl-2,2'-bithiophen-5-yl)benzo[c][1,2,5]thiadiazole] (1) and its selenium analogue 7,7'-[4,8-bis(2-ethylhexyloxy)benzo[1,2-b:4,5-b']dithiophene]bis[6-fluoro-4-(5'-hexyl-2,2'-bithiophen-5-yl)benzo[c][1,2,5]selenodiazole] (2) are both based on the electron-rich central unit benzo[1,2-b:4,5-b']dithiophene. The aim of this work was to investigate the effect of one-atom substitution on the optoelectronic properties and photovoltaic performance of devices. Theoretical calculations revealed that this one-atom variation has a small but measurable effect on the energy of frontier molecular orbital (HOMO and LUMO), which, in turn, can affect the absorption profile of the molecules, both neat and when mixed in a bulk heterojunction (BHJ) with PC71BM. The Se-containing variant 2 led to higher efficiencies [highest power conversion efficiency (PCE) of 2.6%] in a standard organic photovoltaic architecture, when combined with PC71BM after a brief thermal annealing, than the S-containing molecule 1 (highest PCE of 1.0%). Studies of the resulting morphologies of BHJs based on 1 and 2 showed that one-atom substitution could engender important differences in the solubilities, which then influenced the crystal orientations of the small molecules within this thin layer. Brief thermal annealing resulted in rotation of the crystalline grains of both molecules to more energetically favorable configurations.

13.
Trends Biotechnol ; 14(11): 426-30, 1996 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8940772

RESUMO

G-protein-coupled receptors (GPCRs) are integral membrane proteins of great pharmacological importance owing to their central role in the regulation of cellular responses to external stimuli. Heterologous expression systems have been used to explore ligand binding, G protein and effector coupling, and structural aspects of the receptors. GPCRs can be expressed in a functional form in all expression systems, but with varying degrees of success because of differences in receptor and host cell characteristics. This article will discuss aspects related to the choice and suitability of expression systems for the intended analysis of GPCR properties.


Assuntos
Proteínas de Ligação ao GTP/metabolismo , Proteínas de Membrana/genética , Animais , Clonagem Molecular , Vetores Genéticos , Proteínas de Membrana/metabolismo
14.
Neurobiol Aging ; 16(2): 199-204, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-7777137

RESUMO

We examined gamma-aminobutyric acid (GABA), benzodiazepine and convulsant sites of postsynaptic GABA/benzodiazepine receptors (GBZR) in cerebral membranes of inbred Fischer 344 male rats as a function of age. In aged rats (23 to 24 months), the benzodiazepine binding site as determined by [3H]flunitrazepam was 47% and 43% lower than corresponding values in young adult (3 to 4 months) and mature (10 to 12 months) rats, respectively. The decrease was due to the loss of binding density rather than a change in affinity. No statistically significant age-related changes in [3H]muscimol binding were observed when 5 nM or 40 nM labeled muscimol were used. GABA produced a dose-dependent stimulation of flunitrazepam binding in all age groups, but the maximum stimulation in aged animals was significantly higher (24%) than in young and mature animals. The [35S]TBPS binding site, the convulsant site of GABA/benzodiazepine receptors, was unaffected with age. We also studied the effects of exercise on GBZR binding sites of aged rats. The decline of flunitrazepam binding sites and the high sensitivity of flunitrazepam binding to regulation by GABA in aged animals were reversed by 8 to 10 weeks of endurance exercise. Endurance exercise did not have any significant effect on muscimol or TBPS binding sites. Results suggest that there are aged-related alterations of GBZR binding sites and that these modifications can be reversed by exercise.


Assuntos
Envelhecimento/metabolismo , Química Encefálica/fisiologia , Compostos Bicíclicos Heterocíclicos com Pontes , Esforço Físico/fisiologia , Receptores de GABA-A/metabolismo , Animais , Benzodiazepinas/metabolismo , Compostos Bicíclicos com Pontes/metabolismo , Convulsivantes/metabolismo , Flunitrazepam/metabolismo , Cinética , Masculino , Membranas/metabolismo , Muscimol/metabolismo , Ensaio Radioligante , Ratos , Ratos Endogâmicos F344 , Ácido gama-Aminobutírico/metabolismo , Ácido gama-Aminobutírico/farmacologia
15.
FEBS Lett ; 504(3): 94-8, 2001 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-11532439

RESUMO

Recent successes in the determination of atomic resolution structures of integral membrane proteins have relied on purifying the proteins from abundant natural sources. In contrast, the majority of mammalian receptors, ion channels and transporters need to be overexpressed to obtain sufficient material for structural studies. This has often proved to be very difficult. Overexpression studies on a wide range of mammalian membrane proteins have shown that a few can be expressed functionally in bacteria, but many others require an insect or mammalian cell host for activity or high level expression. The serotonin transporter, which has been expressed in all the major hosts available, is a good example that has given insights into the problem of overexpressing mammalian membrane proteins for structural studies.


Assuntos
Membrana Celular/química , Proteínas de Membrana Transportadoras , Proteínas do Tecido Nervoso , Animais , Proteínas de Transporte/química , Membrana Celular/metabolismo , Cristalografia por Raios X , DNA Complementar/metabolismo , Humanos , Glicoproteínas de Membrana/química , Conformação Proteica , Estrutura Secundária de Proteína , Proteínas da Membrana Plasmática de Transporte de Serotonina
16.
FEBS Lett ; 564(3): 234-8, 2004 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-15111102

RESUMO

EmrE is a small multidrug transporter that contains 110 amino acid residues that form four transmembrane alpha-helices. The three-dimensional structure of EmrE has been determined from two-dimensional crystals by electron cryo-microscopy. EmrE is an asymmetric homo-dimer with one substrate molecule bound in a chamber accessible laterally from one leaflet of the lipid bilayer. Evidence from substrate binding analyses and analytical ultracentrifugation of detergent-solubilised EmrE shows that the minimum functional unit for substrate binding is a dimer. However, it is possible that EmrE exists as a tetramer in vivo and plausible models are suggested based upon analyses of two-dimensional crystals.


Assuntos
Antiporters/química , Proteínas de Escherichia coli/química , Proteínas de Membrana/química , Estrutura Quaternária de Proteína , Antiporters/metabolismo , Dimerização , Resistência Microbiana a Medicamentos , Proteínas de Escherichia coli/metabolismo , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismo , Proteínas de Membrana/metabolismo , Modelos Moleculares , Estrutura Secundária de Proteína
17.
J Med Chem ; 18(4): 344-51, 1975 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-1121000

RESUMO

The Free-Wilson equations are derived for the case of symmetrical substitution and are applied, in four modifications, to in vitro inhibitory activity of 77 organic disulfides against Histoplasma capsulatum. Substituent constants are listed to aid in the design of new inhibitory agents against this human pathogen (and perhaps other fungal organisms).


Assuntos
Dissulfetos/farmacologia , Histoplasma/efeitos dos fármacos , Cinética , Matemática , Testes de Sensibilidade Microbiana , Modelos Químicos , Análise de Regressão , Relação Estrutura-Atividade
18.
J Med Chem ; 20(8): 996-1001, 1977 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-330858

RESUMO

In an extension of promising inhibitory results in vitro against Histoplasma capsulatum, correlated earlier using substituent constants developed by regression analysis with 77 disulfides, one symmetrical and 14 unsymmetrical disulfides were prepared (3--17). About half were active in vitro against H. capsulatum (and one against Candida albicans). Groups that seemed most to lead to promising inhibition among the unsymmetrical disulfides were o-HO2CC6H4, (CH2)4SO2Na, Me2NC(S), p-ClC6H4, and perhaps p-CH3C6H4; the first two also might be used to increase solubility. Earlier inhibitory promise of the morpholino group did not materialize. None of the group 3--17 was significantly active in vivo. The unsymmetrical disulfides were prepared by reaction of thiols with sulfenyl chlorides or with acyclic or cyclic thiosulfonates. Two six-membered heterocyclic disulfides (5 and 6) were prepared by a novel cyclization, in which carbon disulfide reacted with an (N-alkylamino)ethyl Bunte salt, followed by ring closure; an explanation is suggested for formation of a thiazoline when the N-alkyl group is absent. One of the disulfides disproportionated with astonishing ease (31; 0.3--1 h at 25 degrees C).


Assuntos
Dissulfetos/síntese química , Histoplasma/efeitos dos fármacos , Anfotericina B/farmacologia , Animais , Candida albicans/efeitos dos fármacos , Candidíase/tratamento farmacológico , Dissulfetos/farmacologia , Dissulfetos/uso terapêutico , Histoplasmose/tratamento farmacológico , Camundongos , Relação Estrutura-Atividade
19.
J Am Geriatr Soc ; 44(5): 583-7, 1996 May.
Artigo em Inglês | MEDLINE | ID: mdl-8617910

RESUMO

OBJECTIVE: To examine the relationship between gender and specific types of behavior problems that occur in patients with Alzheimer's disease. DESIGN: This was an observational study using the Dementia Behavior Disturbance Scale to quantify and define behavioral problems encountered by caregivers. Multiple regressions were used to control for the possible influence of dementia severity as measured by the Mini-Mental State Examination and the duration of dementia. SETTING: Patients were sampled from the outpatient dementia clinics of Roger Williams Hospital and Miriam Hospital in Providence, Rhode Island. PARTICIPANTS: A total of 125 patients with probable Alzheimer's disease, defined by NINCDS-ADRDA diagnostic criteria, were included in the study. There were 75 women and 50 men. MAIN OUTCOME MEASURES: Caregivers rated the presence and frequency of 28 different behavior problems from the Dementia Behavior Disturbance Scale. Domains of behavior disturbance were then defined by a factor analysis of the data. RESULTS: Male and female groups were comparable for the demographic variables of age, education, and duration of dementia, as well as severity of depression, degree of cognitive impairment and overall severity of behavior disturbance. Among the six behavior factors that were defined, two were significantly related to gender. One factor, which included apathy and vegetative signs, was related to male gender; a second factor, which included reclusiveness and emotional lability, was related to female gender. CONCLUSIONS: Although overall severity of behavior disturbance in Alzheimer's disease may be related primarily to severity in dementia, significant differences in the types of behaviors manifested exist between males and females with the disease.


Assuntos
Doença de Alzheimer/psicologia , Comportamento , Caracteres Sexuais , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Análise de Regressão , Índice de Gravidade de Doença
20.
J Appl Physiol (1985) ; 81(4): 1488-94, 1996 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8904558

RESUMO

Aging is associated with a decreased cardiac responsiveness to beta-adrenergic stimulation. We examined the effect of endurance exercise training of old Fischer 344 male rates on beta-adrenergic stimulation of the function of isolated left ventricular papillary muscle. Three groups were examined: sedentary mature (SM; 12-mo old), sedentary old (SO; 23-24 mo old), and exercised old (EO; 23-24 mo old) that were treadmill trained for 4-8 wk. The isometric contractile properties were studied at 0.2 Hz and 0.75 mM calcium. Without beta-adrenergic stimulation, there were no group differences for peak tension, maximum rate of tension development (+dP/dt), or maximum rate of tension dissipation (-dP/dt). The time to peak tension was longer (P < 0.05) for both EO and SO than for SM rats. Half relaxation time (RT1/2) was prolonged (P < 0.05) for SO compared with SM and EO (which did not differ). The three groups did not differ in the beta-adrenergic stimulation by isoproterenol of peak tension, -dP/dt, time to peak tension, or contraction duration. The inotropic response (+dP/dt) of SM was greater (P < 0.05) than that in SO or EO rats (which did not differ); however, the lusitropic response (RT1/2) was lesser (P < 0.05) in SO than in SM or EO rats (which did not differ). Thus exercise training of old rats improved the lusitropic response to isoproterenol without altering the age-associated impairment in inotropic response.


Assuntos
Agonistas Adrenérgicos beta/farmacologia , Envelhecimento/fisiologia , Coração/fisiologia , Isoproterenol/farmacologia , Condicionamento Físico Animal , Animais , Cálcio/fisiologia , Coração/efeitos dos fármacos , Técnicas In Vitro , Contração Isométrica/efeitos dos fármacos , Masculino , Contração Miocárdica/efeitos dos fármacos , Contração Miocárdica/fisiologia , Músculos Papilares/efeitos dos fármacos , Músculos Papilares/fisiologia , Ratos , Ratos Endogâmicos F344
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