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1.
Nature ; 620(7976): 965-970, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37648757

RESUMO

Subjecting a physical system to extreme conditions is one of the means often used to obtain a better understanding and deeper insight into its organization and structure. In the case of the atomic nucleus, one such approach is to investigate isotopes that have very different neutron-to-proton (N/Z) ratios than in stable nuclei. Light, neutron-rich isotopes exhibit the most asymmetric N/Z ratios and those lying beyond the limits of binding, which undergo spontaneous neutron emission and exist only as very short-lived resonances (about 10-21 s), provide the most stringent tests of modern nuclear-structure theories. Here we report on the first observation of 28O and 27O through their decay into 24O and four and three neutrons, respectively. The 28O nucleus is of particular interest as, with the Z = 8 and N = 20 magic numbers1,2, it is expected in the standard shell-model picture of nuclear structure to be one of a relatively small number of so-called 'doubly magic' nuclei. Both 27O and 28O were found to exist as narrow, low-lying resonances and their decay energies are compared here to the results of sophisticated theoretical modelling, including a large-scale shell-model calculation and a newly developed statistical approach. In both cases, the underlying nuclear interactions were derived from effective field theories of quantum chromodynamics. Finally, it is shown that the cross-section for the production of 28O from a 29F beam is consistent with it not exhibiting a closed N = 20 shell structure.

3.
Proc Biol Sci ; 289(1981): 20220840, 2022 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-35975439

RESUMO

Recent evidence has suggested environmental hyperoxia (O2 supersaturation) can boost cardiorespiratory performance in aquatic ectotherms, thereby increasing resilience to extreme heat waves associated with climate change. Here, using rainbow trout (Oncorhynchus mykiss) as a model species, we analysed whether improved cardiorespiratory performance can explain the increased thermal tolerance of fish in hyperoxia (200% air saturation). Moreover, we collated available literature data to assess the prevalence and magnitude of hyperoxia-induced thermal tolerance across fish species. During acute warming, O2 consumption rate was substantially elevated under hyperoxia relative to normoxia beyond 23°C. This was partly driven by higher cardiac output resulting from improved cardiac contractility. Notably, hyperoxia mitigated the rise in plasma lactate at temperatures approaching upper limits and elevated the critical thermal maximum (+0.87°C). Together, these findings show, at least in rainbow trout, that hyperoxia-induced thermal tolerance results from expanded tissue O2 supply capacity driven by enhanced cardiac performance. We show 50% of the fishes so far examined have increased critical thermal limits in hyperoxia (range: 0.4-1.8°C). This finding indicates environmental hyperoxia could improve the ability of a large number of fishes to cope with extreme acute warming, thereby increasing resilience to extreme heat wave events resulting from climate change.


Assuntos
Hiperóxia , Oncorhynchus mykiss , Animais , Peixes , Coração , Prevalência , Temperatura
4.
Biol Lett ; 18(11): 20220401, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36321431

RESUMO

Several studies have demonstrated that hyperoxia increases the maximal O2 consumption rate (MO2max) in fish, but exactly how this occurs remains to be explained. Here, we tested the hypothesis that hyperoxia improves arterial oxygenation in rainbow trout during exhaustive exercise. We demonstrate a 35% higher MO2max in hyperoxia (200% air saturation) relative to normoxia, which was achieved through a combined 15% increase in cardiac output due to elevated peak heart rate, and a 19% increase of the arterial-venous (A-V) O2 content difference. While arterial O2 partial pressure (PaO2) and O2 saturation of haemoglobin declined post-exhaustive exercise in normoxia, this did not occur in hyperoxia. This protective effect of hyperoxia on arterial oxygenation led to a 22% higher arterial O2 content post-exhaustive exercise, thereby allowing a higher A-V O2 content difference. These findings indicate that MO2max is gill diffusion limited in exhaustively exercised rainbow trout. Moreover, as previous studies in salmonids have demonstrated collapsing PaO2 in normoxia at maximal swimming speed and at acutely high temperatures, a diffusion limitation may constrain MO2 in other situations eliciting peak metabolic demand. These findings, along with the fact that hyperoxia increases MO2max in several other fishes, suggest that gill diffusion limitations of MO2max may be widespread in fishes.


Assuntos
Hiperóxia , Animais , Hiperóxia/metabolismo , Consumo de Oxigênio/fisiologia , Oxigênio/metabolismo , Brânquias , Peixes
5.
Phys Rev Lett ; 116(2): 022701, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26824536

RESUMO

Neutron-rich {96,98}Sr isotopes have been investigated by safe Coulomb excitation of radioactive beams at the REX-ISOLDE facility. Reduced transition probabilities and spectroscopic quadrupole moments have been extracted from the differential Coulomb excitation cross sections. These results allow, for the first time, the drawing of definite conclusions about the shape coexistence of highly deformed prolate and spherical configurations. In particular, a very small mixing between the coexisting states is observed, contrary to other mass regions where strong mixing is present. Experimental results have been compared to beyond-mean-field calculations using the Gogny D1S interaction in a five-dimensional collective Hamiltonian formalism, which reproduce the shape change at N=60.

7.
Acta Paediatr ; 104(4): 356-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25545583

RESUMO

AIM: It takes several minutes for infants to become pink after birth. Preductal oxygen saturation (SpO2) measurements are used to guide the delivery of supplemental oxygen to newly born infants, but pulse oximetry is not available in many parts of the world. We explored whether the pinkness of an infant's tongue provided a useful indication that supplemental oxygen was required. METHODS: This was a prospective observational study of infants delivered by Caesarean section. Simultaneous recording of SpO2 and visual assessment of whether the tongue was pink or not was made at 1-7 and 10 min after birth. RESULTS: The 38 midwives and seven paediatric trainees carried out 271 paired assessments on 68 infants with a mean (SD) birthweight of 3214 (545) grams and gestational age of 38 (2) weeks. When the infant did not have a pink tongue, this predicted SpO2 of <70% with a sensitivity of 26% and a specificity of 96%. CONCLUSION: Tongue colour was a specific but insensitive sign that indicated when SpO2 was <70%. When the tongue is pink, it is likely that an infant has an SpO2 of more than 70% and does not require supplemental oxygen.


Assuntos
Triagem Neonatal/métodos , Oxigenoterapia , Língua/anatomia & histologia , Cor , Salas de Parto , Feminino , Humanos , Recém-Nascido , Masculino , Estudos Prospectivos
8.
J Fish Biol ; 87(5): 1234-47, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26440307

RESUMO

The consequences of elevated temperature on body shape were investigated by comparing European perch Perca fluviatilis from the Forsmark area of the Baltic Sea to P. fluviatilis from a nearby Biotest enclosure. The Biotest is a man-made enclosure within the Baltic Sea that has received warm water from a nuclear power plant since 1980, resulting in temperatures that are elevated 5-10 °C relative to the surrounding Baltic Sea. Sampled fish ranged from young-of-the-year to 14 years. Geometric morphometrics and multivariate statistical analysis revealed significant morphological differences between individuals of P. fluviatilis from these two habitats. Most importantly, relative shape changed with size, with small individuals of P. fluviatilis from Biotest being characterized by a deeper body shape and a larger caudal peduncle than the smaller Baltic individuals. In large specimens, smaller differences were found with Biotest individuals being more slender than Baltic individuals. These results show that, in order to have a full understanding of the biological effects of elevated temperatures, studies that cover the entire size range of organisms will be important. Apart from the direct influence of temperature on growth rate and body shape, other ecological factors affected by temperature are discussed as possible contributors to the observed differences between the two populations.


Assuntos
Aquecimento Global , Temperatura Alta , Percas/anatomia & histologia , Percas/crescimento & desenvolvimento , Animais , Países Bálticos , Ecossistema , Feminino , Masculino , Temperatura , Água
9.
Phys Rev Lett ; 113(26): 262504, 2014 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-25615316

RESUMO

We optimize chiral interactions at next-to-next-to leading order to observables in two- and three-nucleon systems and compute Gamow-Teller transitions in 14C and (22,24)O using consistent two-body currents. We compute spectra of the daughter nuclei 14N and (22,24)F via an isospin-breaking coupled-cluster technique, with several predictions. The two-body currents reduce the Ikeda sum rule, corresponding to a quenching factor q2≈0.84-0.92 of the axial-vector coupling. The half-life of 14C depends on the energy of the first excited 1+ state, the three-nucleon force, and the two-body current.

10.
Phys Rev Lett ; 112(16): 162701, 2014 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-24815644

RESUMO

Coulomb-excitation experiments to study electromagnetic properties of radioactive even-even Hg isotopes were performed with 2.85 MeV/nucleon mercury beams from REX-ISOLDE. Magnitudes and relative signs of the reduced E2 matrix elements that couple the ground state and low-lying excited states in Hg182-188 were extracted. Information on the deformation of the ground and the first excited 0+ states was deduced using the quadrupole sum rules approach. Results show that the ground state is slightly deformed and of oblate nature, while a larger deformation for the excited 0+ state was noted in Hg182,184. The results are compared to beyond mean field and interacting-boson based models and interpreted within a two-state mixing model. Partial agreement with the model calculations was obtained. The presence of two different structures in the light even-mass mercury isotopes that coexist at low excitation energy is firmly established.

11.
Phys Rev Lett ; 110(19): 192502, 2013 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-23705702

RESUMO

We optimize the nucleon-nucleon interaction from chiral effective field theory at next-to-next-to-leading order (NNLO). The resulting new chiral force NNLO(opt) yields χ(2)≈1 per degree of freedom for laboratory energies below approximately 125 MeV. In the A=3, 4 nucleon systems, the contributions of three-nucleon forces are smaller than for previous parametrizations of chiral interactions. We use NNLO(opt) to study properties of key nuclei and neutron matter, and we demonstrate that many aspects of nuclear structure can be understood in terms of this nucleon-nucleon interaction, without explicitly invoking three-nucleon forces.

12.
Ann Oncol ; 22(2): 438-43, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20688844

RESUMO

BACKGROUND: To study the impact of the dietary antioxidant quercetin on risk of gastric adenocarcinoma. PATIENTS AND METHODS: Using data from a large Swedish population-based case-control study of gastric cancer (505 cases and 1116 controls), we studied the association between quercetin and risk of anatomic (cardia/noncardia) and histological (intestinal and diffuse) subtypes of gastric cancer. RESULTS: We found strong inverse associations between quercetin and the risk of noncardia gastric adenocarcinoma, with an adjusted odds ratio (OR) of 0.57 (95% confidence interval 0.40-0.83) for the highest quintile (≥11.9 mg) of daily quercetin intake relative to the lowest quintile of intake (<4 mg quercetin/day), supported by a significant decreasing linear trend (P value < 0.001). Similar findings were observed for the intestinal and diffuse subtype. For cardia cancer, we found a less evident and nonsignificant inverse relationship. The protection of quercetin appeared to be stronger among female smokers, with the OR leveled of at values <0.2 in quintiles 3-5 (>6 mg quercetin/day). CONCLUSIONS: High dietary quercetin intake is inversely related to the risk of noncardia gastric adenocarcinoma, and the protection appears to be particularly strong for women exposed to oxidative stress, such as tobacco smoking.


Assuntos
Adenocarcinoma/prevenção & controle , Antioxidantes/administração & dosagem , Suplementos Nutricionais , Quercetina/administração & dosagem , Neoplasias Gástricas/prevenção & controle , Adenocarcinoma/epidemiologia , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Neoplasias Gástricas/epidemiologia , Suécia/epidemiologia
13.
Philos Trans R Soc Lond B Biol Sci ; 376(1830): 20200214, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34121459

RESUMO

During spawning, adult Pacific salmonids (Oncorhynchus spp.) complete challenging upriver migrations during which energy and oxygen delivery must be partitioned into activities such as locomotion, maturation and spawning behaviours under the constraints of an individual's cardiac capacity. To advance our understanding of cardiac function in free-swimming fishes, we implanted migrating adult Chinook salmon (Oncorhynchus tshawytscha) collected near the mouth of the Sydenham River, Ontario, with heart rate (fH) biologgers that recorded fH every 3 min until these semelparous fish expired on spawning grounds several days later. Fundamental aspects of cardiac function were quantified, including resting, routine and maximum fH, as well as scope for fH (maximum-resting fH). Predictors of fH were explored using generalized least-squares regression, including water temperature, discharge, fish size and fish origin (wild versus hatchery). Heart rate was positively correlated with water temperature, which aligned closely with daily and seasonal shifts. Wild fish had slower resting heart rates than hatchery fish, which led to significantly higher scope for fH. Our findings suggest that wild salmon may have better cardiac capacity during migration than hatchery fish, potentially promoting migration success in wild fish. This article is part of the theme issue 'Measuring physiology in free-living animals (Part I)'.


Assuntos
Migração Animal/fisiologia , Frequência Cardíaca/fisiologia , Reprodução/fisiologia , Salmão/fisiologia , Comportamento Sexual Animal/fisiologia , Animais , Aquicultura , Masculino , Ontário
14.
Neuron ; 31(4): 631-8, 2001 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-11545721

RESUMO

In agreement with theories of sequence learning, hippocampal place representations expand asymmetrically during repeated route following. This behaviorally induced, experience-dependent expression of neuronal plasticity was blocked by the NMDA(R) antagonist CPP, suggesting that it may result from the temporal asymmetry and associative properties of LTP. NMDA(R) antagonism, however, had no effect on the range of the progressive shift of firing phase of hippocampal cells, relative to the theta rhythm, as the rat traverses the cell's "place field." Thus, when place fields normally expand with experience, the relationship between firing phase and position is altered, as predicted by models that account for "phase precession" on the basis of asymmetry of synaptic connection strengths. These effects of CPP mimic changes that occur during normal aging, suggesting mechanisms by which sequence learning deficits may arise in aged animals.


Assuntos
Antagonistas de Aminoácidos Excitatórios/farmacologia , Hipocampo/fisiologia , Piperazinas/farmacologia , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Percepção Espacial/fisiologia , Animais , Condicionamento Psicológico/fisiologia , Hipocampo/citologia , Memória/efeitos dos fármacos , Memória/fisiologia , Células Piramidais/fisiologia , Ratos , Ratos Endogâmicos F344 , Percepção Espacial/efeitos dos fármacos , Ritmo Teta
15.
Nurs Res Pract ; 2018: 9618036, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30533223

RESUMO

BACKGROUND: Research shows that first-time fathers want to take part in preparation for birth and parenthood but they describe being excluded by health professionals. AIM: The aim of this study was to illustrate first-time fathers' experiences of support from midwives in maternity clinics as a step in the validation of "The Father Perceived-Professional-Support" (The FaPPS) scale. METHODS: A qualitative content analysis with an inductive and deductive approach was used; seven first-time fathers were strategically selected and interviewed. In the inductive part the following open question was asked: "How did you perceive the support from the antenatal midwife/midwives?" In the deductive part, the fathers were asked to respond to the FaPPS scale, in order to receive their thoughts and understanding of the scale, inspired by the "Think-aloud" method. FINDINGS: The inductive results showed two main categories: Experience of not knowing what support they needed and Experience of being excluded. The fathers found support from other fathers in parental education classes, but they lack time to discuss. Overall it seems as if the fathers answered both from their own perspective and from the mothers' perspective. This was not evident in the deductive results. The FaPPs scale should therefore include professionals' ability to strengthen social support from other first-time fathers and professionals' ability to offer support to the mother. Conclusion and Clinical Implications. The fathers experienced exclusion both by themselves and also by midwives. Midwives should offer both parents the opportunity to pose questions. It is important for expectant fathers that time for discussion is planned in parental education classes. The FaPPS scale is useful but needs further development. Parts of our result are in line with earlier research, for decades; therefore it is necessary to focus more on support for fathers.

16.
J Natl Cancer Inst ; 91(9): 786-90, 1999 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-10328109

RESUMO

BACKGROUND: Reports of dramatic increases in gastric cardia cancer incidence warrant concern. However, the recent introduction of a separate diagnostic code, the lack of a consensus definition of the cardia area, and the accelerating interest in cardia cancer may affect classification practices. Little is known about the magnitude of cardia cancer misclassification in large cancer registries. METHODS: In a well-defined Swedish population (1.3 million), we uniformly classified all patients with newly diagnosed gastric adenocarcinoma (from 1989 through 1994) with respect to gastric subsite, and we used this patient group as our gold standard. We then evaluated the completeness of the Swedish Cancer Registry in registering gastric adenocarcinomas against this gold standard and, further, assessed the completeness of cardia cancer registration and the rate of falsely included cases to estimate the potential impact on observed incidence trends. RESULTS: Our gold standard contained 1337 case subjects with gastric adenocarcinoma. Overall, the Swedish Cancer Registry was 98% complete with regard to gastric adenocarcinomas and had a 4% rate of falsely included cases. The completeness of coding cardia cancer was only 69%, and the positive predictive value for cardia cancer was 82%, with no improvement over time. CONCLUSIONS: Although overall completeness of gastric cancer registration by the Swedish Cancer Registry was excellent, accuracy in registering cardia tumors was surprisingly low. Our estimates suggest that true cardia cancer incidence could be up to 45% higher or 15% lower than that reported in the Cancer Registry. This margin of error could accommodate the observed increase in cardia cancer in Sweden. Therefore, secular trends in cardia cancer incidence should be interpreted cautiously.


Assuntos
Adenocarcinoma/classificação , Adenocarcinoma/epidemiologia , Neoplasias Gástricas/classificação , Neoplasias Gástricas/epidemiologia , Adenocarcinoma/diagnóstico , Idoso , Cárdia , Diagnóstico Diferencial , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Neoplasias Gástricas/diagnóstico , Suécia/epidemiologia
17.
Cancer Res ; 59(23): 5932-7, 1999 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-10606238

RESUMO

Gastric cancer trends seem to follow improvements in the environment of blue-collar workers, but the etiological role of occupational exposures in gastric carcinogenesis is scantily investigated. The risk of gastric adenocarcinoma in 10 common occupational industries, and particularly the long-term effects of asbestos, organic solvents, impregnating agents, insecticides, and herbicides, were evaluated in a population-based case-control study, including data on most established risk factors. The study base included all individuals of ages 40-79, born in Sweden and living in either of two areas (total population, 1.3 million) with differing gastric cancer incidences, from February 1989 through January 1995. We interviewed 567 cases classified to site (cardia/noncardia) and histological type, and 1,165 population-based controls, frequency-matched for age and sex. Metal workers had a 46% excess gastric cancer risk [adjusted odds ratio (OR), 1.46; 95% confidence interval (CI), 1.10-1.94], increasing to 1.65 (95% CI, 1.17-2.32) for >10 years in the industry. The elevated risk after exposure to herbicides (OR, 1.56; 95% CI, 1.13-2.15) was attributable to phenoxyacetic acids (adjusted OR, 1.70; 95% CI, 1.16-2.48), similarly across tumor subtypes, and not modified by smoking, body mass index, or Helicobacter pylori. The absence of interaction was demonstrated by the pure multiplicative effect found among those exposed to both H. pylori and phenoxyacetic acids (OR, 3.42; 95% CI, 1.41-8.26). Organic solvents, insecticides, impregnating agents, and asbestos were not associated with gastric cancer risk. Employment in the metal industry and exposure to phenoxyacetic acids were both positively and independently associated with gastric cancer risk. The fractions of all gastric cancers attributable to these job-related exposures were small but not negligible (7 and 5%, respectively) in the Swedish population.


Assuntos
Adenocarcinoma/epidemiologia , Exposição Ocupacional , Neoplasias Gástricas/epidemiologia , Adenocarcinoma/classificação , Adenocarcinoma/etiologia , Adulto , Fatores Etários , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Incidência , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores Sexuais , Neoplasias Gástricas/classificação , Neoplasias Gástricas/etiologia , Suécia/epidemiologia
18.
J Neurosci ; 21(5): RC134, 2001 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-11222672

RESUMO

In neocortex, neighboring neurons frequently exhibit correlated encoding properties. There is conflicting evidence whether a similar phenomenon occurs in hippocampus. To assess this quantitatively, a comparison was made of the spatial and temporal firing correlations within and between local groups of hippocampal cells, spaced 350-1400 microm apart. No evidence of clustering was found in a sample of >3000 neurons. Moreover, cells active in two environments were uniformly interspersed at a scale of <100 microm, as assessed by the activity-induced gene Arc. Independence of encoding characteristics implies uncorrelated inputs, which could enhance the capacity of the hippocampus to store arbitrary associations.


Assuntos
Potenciais de Ação/fisiologia , Hipocampo/metabolismo , Células Piramidais/fisiologia , Animais , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Estimulação Elétrica , Eletrodos Implantados , Meio Ambiente , Hipocampo/citologia , Interneurônios/fisiologia , Masculino , Aprendizagem em Labirinto/fisiologia , Feixe Prosencefálico Mediano/fisiologia , Atividade Motora/fisiologia , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos F344 , Processamento de Sinais Assistido por Computador , Comportamento Espacial/fisiologia
19.
East Afr Med J ; 82(11): 579-85, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16463752

RESUMO

OBJECTIVE: To explore the methods, reasons and decision-making process for termination of pregnancy among adolescents and older women, in Mulago hospital, Kampala, Uganda. DESIGN: Comparative study. SUBJECTS: Nine hundred and forty two women seeking postabortion care, of which 333 had induced abortion (of whom 115 were adolescents). SETTING: The emergency gynaecological ward of Mulago Hospital, Kampala, Uganda from September 2003 through June 2004. RESULTS: Women with induced abortion were single, in polygamous marital relationships and of lower parity (p<0.001); had lower education and number of living children (p<0.05), reported more (p<0.001) mistimed, unplanned or unwanted pregnancies, and were 13 times more likely to have recent history of domestic violence. Relationship issues were the most common reason for pregnancy termination for both categories. Decision-making for induced abortion was influenced by socio-economic, educational and personal considerations. Instrumentation and use of local herbs in the genitalia were the most common methods for pregnancy termination. Neither methods used for pregnancy termination nor reasons differed when adolescents were compared with older women. CONCLUSION: Relationship issues influence the decision-making process for pregnancy termination. Neither methods used for pregnancy termination nor reasons for pregnancy termination differ when adolescents are compared with older women.


Assuntos
Aborto Induzido , Tomada de Decisões , Adolescente , Adulto , Violência Doméstica/estatística & dados numéricos , Feminino , Humanos , Estado Civil , Paridade , Gravidez , Fatores Socioeconômicos , Uganda
20.
Hum Immunol ; 53(2): 195-205, 1997 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-9129979

RESUMO

The HLA DQA1 locus is polymorphic. Haplotypes containing HLA DQA1*0501, but not HLA DQA1*0201, together with HLA DQB1*0201 are associated with Grave's disease and celiac sprue. In this report, we demonstrate a functional correlate of DQA1 polymorphism. T cells infiltrating a herpes simplex virus (HSV) lesion from a HLA DQ 2,7 individual yielded a virus-specific CD4+ clone restricted by DQ2. Presentation of viral peptide and protein segregated with DQA1 allele, because cell lines bearing DQA1*0501/DQB1*0201 heterodimers presented antigen in proliferation and cytotoxicity assays much more efficiently than cell lines bearing DQA1*0201/DQB1*0201. Binding of viral peptide to cell lines bearing DQA1*0201, in comparison to DQA1*0501, was only moderately reduced and may not explain this effect. Truncation and substitution analyses of peptide binding and T-cell activation were performed to determine which viral peptide residues contacting TCR might therefore be presented in an altered conformation by DQA1*0201/DQB1*0201. Residues 432, 435, 437, 438, and 440 (position P1, P4, P6, P7, and P9) contributed to DQ2 binding, whereas residues 431, 433, 434, and 436 (positions P 1, P2, P3, and P5) contributed to TCR contact. Differential presentation of peptide by HLA DQ2 heterodimers varying at the DQA1 locus may have relevance to host defense and the pathogenesis of HLA DQ2-associated autoimmune diseases.


Assuntos
Apresentação de Antígeno/genética , Antígenos Virais/imunologia , Linfócitos T CD4-Positivos/imunologia , Antígenos HLA-DQ/metabolismo , Herpesvirus Humano 2/imunologia , Alelos , Aminoácidos/análise , Antígenos Virais/metabolismo , Linhagem Celular Transformada , Antígenos HLA-DQ/genética , Cadeias alfa de HLA-DQ , Cadeias beta de HLA-DQ , Proteína Vmw65 do Vírus do Herpes Simples/imunologia , Proteína Vmw65 do Vírus do Herpes Simples/metabolismo , Humanos , Peptídeos/análise , Conformação Proteica , Receptores de Antígenos de Linfócitos T/metabolismo
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