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1.
Nano Lett ; 23(19): 8940-8946, 2023 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-37733604

RESUMEN

A fundamental capability needed for any transmissive optical component is anti-reflection, yet this capability can be challenging to achieve in a cost-effective manner over longer infrared wavelengths. We demonstrate that Mie-resonant photonic structures can enable high transmission through a high-index optical component, allowing it to function effectively over long-wavelength infrared wavelengths. Using silicon as a model system, we demonstrate a resonant metasurface that enables a window optic with transmission up to 40% greater than that of unpatterned Si. Imaging comparisons with unpatterned Si and off-the-shelf germanium optics are shown as well as modulation transfer function measurements, showing excellent performance and suitability for imaging applications. Our results show how resonant photonic structures can be used to improve optical transmission through high-index optical components and highlight their possible use in infrared imaging applications.

2.
Nano Lett ; 22(1): 90-96, 2022 01 12.
Artículo en Inglés | MEDLINE | ID: mdl-34939817

RESUMEN

We argue that light sails with nanometer-scale thicknesses that are rapidly accelerated to relativistic velocities by lasers must be significantly curved in order to reduce their intrafilm mechanical stresses and avoid tears. Using an integrated opto-thermo-mechanical model, we show that the diameter and radius of curvature of a circular light sail should be comparable in magnitude, both on the order of a few meters, in optimal designs for gram-scale payloads. Moreover, we demonstrate that, when sufficient laser power is available, a sail's acceleration length decreases as its curvature increases. Our findings provide critical guidance for emerging light sail design programs, which herald a new era of interstellar space exploration to destinations such as the Oort cloud, the Alpha Centauri system, and beyond.


Asunto(s)
Rayos Láser
3.
Nano Lett ; 22(2): 594-601, 2022 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-35014534

RESUMEN

The Breakthrough Starshot Initiative aims to send a gram-scale probe to our nearest extrasolar neighbors using a laser-accelerated lightsail traveling at relativistic speeds. Thermal management is a key lightsail design objective because of the intense laser powers required but has generally been considered secondary to accelerative performance. Here, we demonstrate nanophotonic photonic crystal slab reflectors composed of 2H-phase molybdenum disulfide and crystalline silicon nitride, highlight the inverse relationship between the thermal band extinction coefficient and the lightsail's maximum temperature, and examine the trade-off between minimizing acceleration distance and setting realistic sail thermal limits, ultimately realizing a thermally endurable acceleration minimum distance of 23.3 Gm. We additionally demonstrate multiscale photonic structures featuring thermal-wavelength-scale Mie resonant geometries and characterize their broadband Mie resonance-driven emissivity enhancement and acceleration distance reduction. More broadly, our results highlight new possibilities for simultaneously controlling optical and thermal response over broad wavelength ranges in ultralight nanophotonic structures.

4.
Appl Opt ; 58(25): 6834-6840, 2019 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-31503653

RESUMEN

Phase retrieval is an attractive approach for sensor-less adaptive optics (AO) because of its relatively simple implementation. Recently, random phase diversity has shown fast convergence for phase retrieval algorithms. In this study, design optimization using random phase diversity is discussed with respect to a sensor-less AO system using a liquid-crystal-on-silicon (LCoS) spatial light modulator. The extrinsic phase disturbances studied are due to Kolmogorov turbulence. Simulation analysis shows that the size of super-pixel segments of the random phase patterns on the LCoS and the cropped image area of the phasorgrams are determined by Fried's parameter for high-Strehl-ratio and low-iteration-number reconstruction. AO experiments with an LCoS spatial light modulator confirm the simulation results.

5.
Br J Sports Med ; 49(1): 3-6, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25263651

RESUMEN

While the research base is limited, studies have consistently reported poor oral health in elite athletes since the first report from the 1968 Olympic Games. The finding is consistent both across selected samples attending dental clinics at major competitions and more representative sampling of teams and has led to calls from the International Olympic Committee for more accurate data on oral health. Poor oral health is an important issue directly as it can cause pain, negative effects on appearance and psychosocial effects on confidence and quality of life and may have long-term consequences for treatment burden. Self-reported evidence also suggests an impact on training and performance of athletes. There are many potential challenges to the oral health of athletes including nutritional, oral dehydration, exercise-induced immune suppression, lack of awareness, negative health behaviours and lack of prioritisation. However, in theory, oral diseases are preventable by simple interventions with good evidence of efficacy. The consensus statement aims to raise awareness of the issues of oral health in elite sport and recommends strategies for prevention and health promotion in addition to future research strategies.


Asunto(s)
Rendimiento Atlético/fisiología , Salud Bucal/normas , Consenso , Deshidratación/fisiopatología , Conducta Alimentaria/fisiología , Conductas Relacionadas con la Salud , Conocimientos, Actitudes y Práctica en Salud , Promoción de la Salud , Humanos , Enfermedades de la Boca/etiología , Enfermedades de la Boca/fisiopatología , Factores de Riesgo
6.
J Strength Cond Res ; 28(12): 3416-24, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24910953

RESUMEN

Precooling lowers skin (Tsk) and core temperature (Tre) and can improve performance in hot conditions, but has predominantly been studied in males. This study investigated the effects of precooling on self-paced 2,000-m rowing performance, within females, in hot, humid conditions. Eight physically active females (19.9 ± 1.5 years, 66.8 ± 3.1 kg, 30.0 ± 5.0% body fat) performed 2,000-m rows in a randomized order within 3 conditions {control (CONT) (20° C, 40% relative humidity [RH]); hot (HOT) (35° C, 60% RH); precooling (PREC) (35° C, 60% RH, preceded by precooling)}. The precooling condition consisted of 20-minute precooling with a cold water shower, followed by a 2,000-m row. In contrast, CONT and HOT consisted of 20-minute passive rest in place of precooling. Tre, Tsk, and power output were recorded every 100 m of the rows. Muscle temperature (Tmu) was recorded at baseline, after 20-minute passive rest/precooling and post-row. No differences were observed between conditions for performance time (CONT, 8.89 ± 0.45 minutes; HOT, 9.01 ± 0.55 minutes; PREC, 8.87 ± 0.48 minutes; p = 0.42). Mean Tre during the row was not different between conditions (CONT, 37.8 ± 0.2° C; HOT, 37.7 ± 0.3° C; PREC, 37.5 ± 0.2° C; p = 0.12; main effect), although lower Tre was observed at 1,600 and 1,800 m in PREC compared with HOT (p ≤ 0.05). Tmu was significantly reduced after precooling (p = 0.03). Precooling did not enhance 2,000-m rowing performance, despite differences in Tre, Tsk, and Tmu. The lack of observed improvement in rowing performance after cold shower precooling may have been due to the short exercise time. An improvement in performance may have been observed using an alternate method of precooling, which has been shown to be ergogenic in other sports.


Asunto(s)
Rendimiento Atlético/fisiología , Temperatura Corporal , Frío , Deportes/fisiología , Adolescente , Femenino , Calor , Humanos , Humedad , Músculo Esquelético/fisiología , Distribución Aleatoria , Temperatura Cutánea , Adulto Joven
7.
Res Sports Med ; 22(4): 425-37, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25295479

RESUMEN

Goal line officials (GLO) are exposed to extreme environmental conditions when employed to officiate in professional European soccer cup competitions. The present study aimed to investigate the effect of such environments on GLO decision-making ability. Thirteen male participants were exposed to three conditions: cold (-5°C, 50% relative humidity (RH)); temperate (18°C, 50% RH); and hot (30°C, 50% RH) for 90 min per condition, with a 15 min half-time break after 45 min. Decision-making ability was assessed throughout the 90 min exposure. Core and skin temperatures were recorded throughout. Decision making was improved during exposure to the temperate condition when compared with the cold (mean difference = 12.5%; 95% CI = 1.1%, 23.9%; P = 0.031). Regression analysis indicated that as skin temperature increases so does decision-making ability. Exposure to cold conditions diminished the decision-making ability of GLO.


Asunto(s)
Frío , Toma de Decisiones , Calor , Humedad , Fútbol , Temperatura Corporal , Humanos , Masculino , Pruebas Neuropsicológicas , Adulto Joven
8.
Eur J Appl Physiol ; 113(1): 109-15, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22592455

RESUMEN

Heat acclimation (HA) can improve thermoregulatory stability in able-bodied athletes in part by an enhanced sweat response. Athletes with spinal cord lesion are unable to sweat below the lesion and it is unknown if they can HA. Five paralympic shooting athletes with spinal cord lesion completed seven consecutive days HA in hot conditions (33.4 ± 0.6 °C, 64.8 ± 3.7 %rh). Each HA session consisted of 20 min arm crank exercise at 50 % [Formula: see text] followed by 40 min rest, or simulated shooting. Aural temperature (T (aur)) was recorded throughout. Body mass was assessed before and after each session and a sweat collection swab was fixed to T12 of the spine. Fingertip whole blood was sampled at rest on days 1 and 7 for estimation of the change in plasma volume. Resting T (aur) declined from 36.3 ± 0.2 °C on day 1 to 36.0 ± 0.2 °C by day 6 (P < 0.05). During the HA sessions mean, T (aur) declined from 37.2 ± 0.2 °C on day 1, to 36.7 ± 0.3 °C on day 7 (P < 0.05). Plasma volume increased from day 1 by 1.5 ± 0.6 % on day 7 (P < 0.05). No sweat secretion was detected or changes in body mass observed from any participant. Repeated hyperthermia combined with limited evaporative heat loss was sufficient to increase plasma volume, probably by alterations in fluid regulatory hormones. In conclusion, we found that although no sweat response was observed, athletes with spinal cord lesion could partially HA.


Asunto(s)
Aclimatación , Regulación de la Temperatura Corporal , Ejercicio Físico , Traumatismos de la Médula Espinal/fisiopatología , Deportes , Adulto , Calor , Humanos
10.
Ecol Evol ; 11(10): 5111-5120, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-34025995

RESUMEN

Trait differences among plant species can favor species coexistence. The role that such differences play in the assembly of diverse plant communities maintained by frequent fires remains unresolved. This lack of resolution results in part from the possibility that species with similar traits may coexist because none has a significant fitness advantage and in part from the difficulty of experimental manipulation of highly diverse assemblages dominated by perennial species. We examined a 65-year chronosequence of losses of herbaceous species following fire suppression (and subsequent encroachment by Pinus elliottii) in three wet longleaf pine savannas. We used cluster analysis, similarity profile permutation tests, and k-R cluster analysis to identify statistically significant functional groups. We then used randomization tests to determine if the absence of functional groups near pines was greater (or less) than expected by chance. We also tested whether tolerant and sensitive species were less (or more) likely to co-occur by chance in areas in savannas away from pines in accordance with predictions of modern coexistence theory. Functional group richness near pines was lower than expected from random species extirpations. Wetland perennials with thick rhizomes and high leaf water content, spring-flowering wetland forbs (including Drosera tracyi), orchids, Polygala spp., and club mosses were more likely to be absent near pines than expected by chance. C3 grasses and sedges with seed banks and tall, fall-flowering C4 grasses were less likely to be absent near pines than expected by chance. Species sensitive to pine encroachment were more likely to co-occur with other such species away from pines at two of the three sites. Results suggest that herb species diversity in frequently burned wet savannas is maintained in part by a weak fitness (e.g., competitive) hierarchy among herbs, and not as a result of trait differences among co-occurring species.

11.
Gen Comp Endocrinol ; 166(1): 19-24, 2010 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-19699742

RESUMEN

Vertebrates respond to perceived stressors through increased plasma concentrations of glucocorticoids. However, there is considerable variation within and across species in the circumstances and degree to which glucocorticoid levels are elevated. We measured baseline and acute stress-induced levels of corticosterone of free-living, black-legged kittiwake chicks (Rissa tridactyla) across four consecutive breeding seasons in the northern Gulf of Alaska to determine the effect of hatching order and brood size on corticosterone levels of chicks. We sampled 12- to 15-day-old chicks from intact broods (i.e., no brood reduction) at three colonies from 2002-2005 (n=164). Baseline and stress-induced levels of corticosterone did not vary by hatching order or brood size. These results suggest that the adrenocortical function of kittiwake chicks from broods that survive intact through 12-15 days is not affected by either hatching order or brood size.


Asunto(s)
Animales Recién Nacidos/sangre , Charadriiformes , Corticosterona/sangre , Comportamiento de Nidificación , Alaska , Animales , Animales Salvajes , Estrés Fisiológico
12.
Cureus ; 12(7): e9428, 2020 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-32864254

RESUMEN

A 77-year-old male with a history of cataract extraction and intraocular lens placement 5.5 years prior, was referred for idiopathic corneal edema of the right eye. Six months prior to initial consult with a Cornea specialist, the patient presented with acute onset cystoid macular edema (CME) and later developed anterior chamber (AC) cell. The cornea became diffusely edematous and decompensated on topical steroids and hypertonic drops. During the Descemet's membrane endothelial keratoplasty (DMEK) procedure, a sequestered retained lens fragment (RLF) migrated out of the posterior chamber and was aspirated. The remainder of the surgery and post-operative period was unremarkable. This case is the first reported in which a significantly delayed onset of inflammatory reaction from a sequestered RLF led to full corneal decompensation requiring keratoplasty. This case highlights the importance of RLF suspicion in delayed presentation, even when RLFs are not visible via slit-lamp or on gonioscopic view.

13.
ACS Appl Mater Interfaces ; 12(39): 44156-44162, 2020 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-32877159

RESUMEN

The adaptation of colloidal quantum dots loaded within a polymer for use in nondestructive testing can be used as an optical strain gauge due to the nanomaterial's strain sensing properties. In this paper, we utilized InP/ZnS colloidal quantum dots loaded within a polymer matrix applied onto the surface of a dog-bone foil precoated with an epoxy. By employing an empirical formula and a calibration factor, there is a propinquity between both the calculated optical strain and mechanical stress-strain reference data. Fluctuations are observed, which may be due to both additional strain responses not seen by the mechanical data and quantum dot blinking. These results and methods show the applied use of this novel optical nondestructive testing technique for a variety of structures, especially for structures that operate in harsh environments.

14.
J Mol Biol ; 371(1): 79-92, 2007 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-17560604

RESUMEN

Metalloregulators of the MerR family activate transcription upon metal binding by underwinding the operator-promoter DNA to permit open complex formation by pre-bound RNA polymerase. Historically, MerR's allostery has been monitored only indirectly via nuclease sensitivity or by fluorescent nucleotide probes and was very specific for Hg(II), although purified MerR binds several thiophilic metals. To observe directly MerR's ligand-induced behavior we made 2-fluorotyrosine-substituted MerR and found similar, minor changes in (19)F chemical shifts of tyrosine residues in the free protein exposed to Hg(II), Cd(II) or Zn(II). However, DNA binding elicits large chemical shift changes in MerR's tyrosine residues and in DNA-bound MerR Hg(II) provokes changes very distinct from those of Cd(II) or Zn(II). These chemical shift changes and other biophysical and phenotypic properties of wild-type MerR and relevant mutants reveal elements of an allosteric network that enables the coordination state of the metal binding site to direct metal-specific movements in the distant DNA binding site and the DNA-bound state also to affect the metal binding domain.


Asunto(s)
Regulación Bacteriana de la Expresión Génica , Secuencias Reguladoras de Ácidos Nucleicos , Tirosina/análogos & derivados , Regulación Alostérica , Secuencia de Aminoácidos , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Cadmio/química , Cadmio/metabolismo , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Radioisótopos de Flúor/química , Radioisótopos de Flúor/metabolismo , Mercurio/química , Mercurio/metabolismo , Modelos Moleculares , Datos de Secuencia Molecular , Mutagénesis Sitio-Dirigida , Resonancia Magnética Nuclear Biomolecular , Estructura Terciaria de Proteína , Alineación de Secuencia , Tirosina/química , Tirosina/metabolismo , Zinc/química , Zinc/metabolismo
15.
Protein Pept Lett ; 15(5): 516-20, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18537743

RESUMEN

Measurements of [theta](222) of E. coli phosphatase on heating from 20 degrees to 90 degrees and subsequent cooling to 20 degrees shows a gradual increase in [theta](222) on heating, while cooling shows a symmetric transition centered at 45 degrees . Reheating and cooling shows the same phenomenon. Enzyme heated and cooled once is fully active. The activity of the enzyme depends on its storage conditions (buffer and pH for example), but such changes are least to some extent reversible, especially by heating in different solvents. We conclude the enzyme exists in several forms which are in slow equilibrium with each other, so that the enzyme responds slowly when heated and hence is not at equilibrium during heating/cooling experiments.


Asunto(s)
Fosfatasa Alcalina/química , Escherichia coli/enzimología , Fosfatasa Alcalina/metabolismo , Frío , Estabilidad de Enzimas , Calor , Desnaturalización Proteica , Termodinámica
16.
Ecol Evol ; 7(12): 4377-4389, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28649349

RESUMEN

The factors responsible for maintaining diverse groundcover plant communities of high conservation value in frequently burned wet pine savannas are poorly understood. While most management involves manipulating extrinsic factors important in maintaining species diversity (e.g., fire regimes), most ecological theory (e.g., niche theory and neutral theory) examines how traits exhibited by the species promote species coexistence. Furthermore, although many ecologists focus on processes that maintain local species diversity, conservation biologists have argued that other indices (e.g., phylogenetic diversity) are better for evaluating assemblages in terms of their conservation value. I used a null model that employed beta-diversity calculations based on Raup-Crick distances to test for deterministic herbaceous species losses associated with a 65-year chronosequence of woody species encroachment within each of three localities. I quantified conservation value of assemblages by measuring taxonomic distinctness, endemism, and floristic quality of plots with and without woody encroachment. Reductions in herb species richness per plot attributable to woody encroachment were largely stochastic, as indicated by a lack of change in the mean or variance in beta-diversity caused by woody encroachment in the savannas studied here. Taxonomic distinctness, endemism, and floristic quality (when summed across all species) were all greater in areas that had not experienced woody encroachment. However, when corrected for local species richness, only average endemism and floristic quality of assemblages inclusive of herbs and woody plants were greater in areas that had not experienced woody encroachment, due to the more restricted ranges and habitat requirements of herbs. Results suggest that frequent fires maintain diverse assemblages of fire-dependent herb species endemic to the region. The stochastic loss of plant species, irrespective of their taxonomic distinctness, to woody encroachment suggests that the relevance of niche partitioning or phylogenetic diversity to the management of biodiversity in wet pine savannas is minimal.

17.
FEBS Lett ; 579(20): 4367-73, 2005 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-16054142

RESUMEN

Cellobiohydrolase A (CbhA) from Clostridium thermocellum is composed of an N-terminal carbohydrate-binding domain 4 (CBD4), an immunoglobulin-like domain (Ig), a glycoside hydrolase 9 (GH9), X1(1) and X1(2) domains, a CBD3, and a dockerin domain. All domains, except the Ig, bind Ca2+. The following constructs were made: X1(2), X1(1)X1(2), CBD3, X1(1)X1(2)-CBD3, Ig, GH9, Ig-GH9, Ig-GH9-X1(1)X1(2), and Ig-GH9-X1(1)X1(2)-CBD3. Interactions between domains in (1) buffer, (2) with Ca2+, or (3) ethylenediaminetetraacetic acid (EDTA) were studied by differential scanning calorimetry. Thermal unfoldings of all constructs were irreversible. Calcium increased T(d) and cooperativity of unfolding. Multi-domain constructs exhibited more cooperative unfolding in buffer and in the presence of EDTA than did individual domains. They denatured by mechanism simpler than expected from their modular architecture. The results indicate that domain coupling in thermophilic proteins constitutes a significant stabilizing factor.


Asunto(s)
Celulosa 1,4-beta-Celobiosidasa/química , Clostridium thermocellum/enzimología , Calcio/metabolismo , Desnaturalización Proteica , Pliegue de Proteína , Estructura Terciaria de Proteína
18.
J Mol Biol ; 341(4): 1015-21, 2004 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-15289101

RESUMEN

Human neuron-specific enolase (NSE) or isozyme gamma has been expressed with a C-terminal His-tag in Escherichia coli. The enzyme has been purified, crystallized and its crystal structure determined. In the crystals the enzyme forms the asymmetric complex NSE x Mg2 x SO4/NSE x Mg x Cl, where "/" separates the dimer subunits. The subunit that contains the sulfate (or phosphate) ion and two magnesium ions is in the closed conformation observed in enolase complexes with the substrate or its analogues; the other subunit is in the open conformation observed in enolase subunits without bound substrate or analogues. This indicates negative cooperativity for ligand binding between subunits. Electrostatic charge differences between isozymes alpha and gamma, -19 at physiological pH, are concentrated in the regions of the molecular surface that are negatively charged in alpha, i.e. surface areas negatively charged in alpha are more negatively charged in gamma, while areas that are neutral or positively charged tend to be charge-conserved.


Asunto(s)
Fosfopiruvato Hidratasa/metabolismo , Rastreo Diferencial de Calorimetría , Cristalografía por Rayos X , Dimerización , Humanos , Ligandos , Fosfopiruvato Hidratasa/química , Fosfopiruvato Hidratasa/aislamiento & purificación , Conformación Proteica
19.
Protein Eng Des Sel ; 17(11): 759-69, 2004 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-15596428

RESUMEN

Cellobiohydrolase CbhA from Clostridium thermocellum cellulosome is a multi-modular protein composed starting from the N-terminus of a carbohydrate-binding module (CBM) of family 4, an immunoglobulin(Ig)-like module, a catalytic module of family 9 glycoside hydrolases (GH9), X1(1) and X1(2) modules, a CBM of family 3 and a dockerin module. Deletion of the Ig-like module from the Ig-GH9 construct results in complete inactivation of the GH9 module. The crystal structure of the Ig-GH9 module pair reveals the existence of an extensive module interface composed of over 40 amino acid residues of both modules and maintained through a large number of hydrophilic and hydrophobic interactions. To investigate the importance of these interactions between the two modules, we compared the secondary and tertiary structures and thermostabilities of the individual Ig-like and GH9 modules and the Ig-GH9 module pair using both circular dichroism (CD) spectroscopy and differential scanning calorimetry (DSC). Thr230, Asp262 and Asp264 of the Ig-like module are located in the module interface of the Ig-GH9 module pair and are suggested to be important in 'communication' between the modules. These residues were mutated to alanyl residues. The structure, stability and catalytic properties of the native Ig-GH9 and its D264A and T230A/D262A mutants were compared. The results indicate that despite being able to fold relatively independently, the Ig-like and GH9 modules interact and these interactions affect the final fold and stability of each module. Mutations of one or two amino acid residues lead to destabilization and change of the mechanism of thermal unfolding of the polypeptides. The enzymatic properties of native Ig-GH9, D264A and T230A/D262A mutants are similar. The results indicate that inactivation of the GH9 module occurs as a result of multiple structural disturbances finally affecting the topology of the catalytic center.


Asunto(s)
Celulosa 1,4-beta-Celobiosidasa/metabolismo , Celulosomas/enzimología , Clostridium thermocellum/enzimología , Rastreo Diferencial de Calorimetría , Celulosa 1,4-beta-Celobiosidasa/química , Celulosa 1,4-beta-Celobiosidasa/genética , Dicroismo Circular , Clostridium thermocellum/genética , Calor , Cinética , Mutación , Desnaturalización Proteica , Estructura Terciaria de Proteína
20.
Hum Immunol ; 64(4): 440-52, 2003 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-12651070

RESUMEN

CD8(+) T-cell responses to three human cytomegalovirus (CMV) pp65 epitopes were studied in panels of healthy seropositive HLA-A*02/HLA-B*07 individuals, and HLA-A*02 donors mismatched for HLA-B*07. The majority of the latter had significant responses to a HLA-A*02-restricted epitope within the CMV pp65 antigen. By contrast, the strongest responses to CMV in the first group were to HLA-B*07-restricted epitopes. Similar immunodominance of HLA-B*07 over HLA-A*02 was found in two immunocompromised HIV-infected HLA-A*02/HLA-B*07 patients, and in the reconstituting immune system of three stem cell transplant recipients. In vitro stimulation of peripheral blood mononuclear cells (PBMC) from two immunocompetent HLA-A*02/HLA-B*07 individuals indicated that cytotoxic T lymphocyte (CTL) precursors specific for both HLA-A*02 and HLA-B*07 restricted epitopes were present and could be expanded by stimulation with the cognate peptides. However, if stimulation was performed by antigen presenting cells infected with recombinant vaccinia expressing full-length native pp65, only HLA-B*07 epitope-specific cells were seen. In one patient the HLA-B*07 dominance was partially broken by using recombinant vaccinia expressing ubiquitinated pp65, suggesting that enhanced protein processing can reveal weaker immune responses. Our results indicate that CMV-specific cellular immune responses restricted by HLA-B*07 dominate those restricted by HLA-A*02 in both immunocompetent and immunocompromised individuals. This may have significant consequences for the design of epitope-specific vaccines.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Fosfoproteínas/inmunología , Proteínas de la Matriz Viral/inmunología , Alelos , Citocinas/metabolismo , Infecciones por Citomegalovirus/genética , Infecciones por Citomegalovirus/inmunología , Antígeno HLA-B7 , Humanos , Epítopos Inmunodominantes/inmunología , Interleucina-2/metabolismo , Leucocitos Mononucleares/inmunología , Fragmentos de Péptidos/farmacología , Trasplante de Células Madre
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