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1.
J Community Psychol ; 48(2): 302-322, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31596962

RESUMEN

Rooted in multiracial feminist theory, this research investigated the roles of adults engaged in youth participatory action research (YPAR) projects focused on developing critical perspectives of gender, power, and critical hope with the youth of color. Across 10 weeks, two novice adult facilitators documented ethnographic observations (i.e., voice memos) of their experiences collaborating with youth in YPAR. Voice memos were transcribed and coded for emergent themes. Our findings highlight how we deconstructed adultism, prioritized humanizing youth, and integrated critical gender perspectives to understand gender as a mechanism of systemic oppression. Our purpose was to capture moments of breakthroughs, realizations, and tensions as scholars contending with inexperience in YPAR and share our journey with other researchers interested in YPAR. We provide recommendations for adults to develop pathways towards humanity for the youth of color, collective resistance and take social justice action steps towards a critically hopeful future.


Asunto(s)
Investigación Participativa Basada en la Comunidad , Investigación sobre Servicios de Salud , Derechos Humanos , Cambio Social , Adolescente , Femenino , Esperanza , Humanos , Relaciones Interpersonales , Masculino , Instituciones Académicas , Factores Sexuales , Adulto Joven
2.
Br J Sports Med ; 53(9): 547-553, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30262452

RESUMEN

OBJECTIVES: We aimed to identify the rate of seven comorbidities (mental health disorders, chronic pain, substance abuse disorders, cardiovascular disorders, metabolic syndrome, systemic arthropathy and sleep disorders) that occurred within 2 years after hip arthroscopy. METHODS: Data from individuals (ages 18-50 years) undergoing arthroscopic hip surgery between 2004 and 2013 were collected from the Military Health System (MHS) Data Repository (MDR). The MDR captures all healthcare encounters in all settings and locations for individuals within the MHS. Person-level data over 36 months were pulled and aggregated. Seven comorbidities related to poor outcomes from musculoskeletal disorders (mental health disorders, chronic pain, substance abuse disorders, cardiovascular disorders, metabolic syndrome, systemic arthropathy and sleep disorders) were examined 12 months prior and 24 months after surgery. Changes in frequencies were calculated as were differences in proportions between presurgery and postsurgery. RESULTS: 1870 subjects were identified (mean age 32.24 years; 55.5% men) and analysed. There were statistically significant increases (p<0.001) proportionally for all comorbidities after surgery. Relative to baseline, cases of mental health disorders rose 84%, chronic pain diagnoses increased 166%, substance abuse disorders rose 57%, cardiovascular disorders rose by 71%, metabolic syndrome cases rose 85.9%, systemic arthropathy rose 132% and sleep disorders rose 111%. CONCLUSIONS: Major (potentially 'hidden') clinical comorbidities increased substantially after elective arthroscopic hip surgery when compared with preoperative status. These comorbidities appear to have been overlooked in major studies evaluating the benefits and risks of arthroscopic hip surgery. LEVEL OF EVIDENCE: Prognostic, level III.


Asunto(s)
Artroscopía/efectos adversos , Comorbilidad , Articulación de la Cadera/cirugía , Adolescente , Adulto , Enfermedades Cardiovasculares/epidemiología , Dolor Crónico/epidemiología , Femenino , Humanos , Artropatías/epidemiología , Masculino , Trastornos Mentales/epidemiología , Síndrome Metabólico/epidemiología , Persona de Mediana Edad , Personal Militar , Estudios Retrospectivos , Trastornos del Sueño-Vigilia/epidemiología , Trastornos Relacionados con Sustancias/epidemiología , Adulto Joven
3.
Phys Rev Lett ; 121(24): 246801, 2018 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-30608739

RESUMEN

We demonstrate strain-induced coupling between a hole spin in a quantum dot and mechanical motion of a cantilever. The optical transitions of quantum dots integrated into GaAs mechanical resonators are measured synchronously with the motion of the driven resonators. In a Voigt magnetic field, both electron and hole spin splittings are measured, showing negligible change for the electron spin but a large change for the hole spin of up to 36%. This large effect is attributed to the stronger spin orbit interaction of holes compared to electrons.

4.
Phys Chem Chem Phys ; 20(46): 29558-29565, 2018 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-30457613

RESUMEN

Gold nanoparticles (AuNPs) of differing shapes are of great interest to researchers due to their unique optical properties, making them potentially powerful theranostic tools. The synthesis of AuNPs is performed frequently, however the assessment of biological activity for each nanoparticle is not always commonplace. While it is thought that physicochemical parameters such as shape may play an important role in dictating the outcomes of interactions which take place at the nano-bio interface, a systematic approach to the assessment of nanomaterials has not been widely adopted. In this study, the interaction between human serum albumin (HSA) and four similar sized but different shaped AuNPs (spherical, rod shaped, prismatic and cubic) synthesised using a common chemical surfactant (CTAB), is presented. Using fluorescence spectroscopy it is shown that all AuNPs exhibit static binding with HSA, however the shape affects both the affinity and strength of the binding. Rod shaped nanoparticles were found to have the highest binding strength and affinity. Conversely, shapes with large flat planar surfaces such as prisms and cubes were shown to have reduced accessibility to the site of the fluorophore within the structure of HSA. The differences observed help to provide a better understanding of the effect of shape on AuNP-protein interactions - knowledge which may be applied to the development of AuNPs for future biological applications.


Asunto(s)
Oro/química , Nanopartículas del Metal/química , Albúmina Sérica Humana/química , Humanos , Espectrometría de Fluorescencia , Tensoactivos/química
5.
N Z Vet J ; 65(3): 134-139, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28359226

RESUMEN

AIMS: To evaluate a vaccine containing type 1c bovine viral diarrhoea (BVD) virus for prevention of fetal infection in pregnant heifers when challenged with New Zealand BVD virus type 1a 6 months after vaccination, compared to unvaccinated heifers and heifers vaccinated with a vaccine containing type 1a BVD virus. METHODS: Fifty five crossbred Friesian heifers, free from BVD virus and antibody, were randomly allocated to three groups. Twenty five heifers were vaccinated twice with a vaccine containing type 1c BVD virus (T1c group), and 10 heifers with a vaccine containing type 1a BVD virus (T1a group), and 20 heifers were unvaccinated (NC group). After oestrus synchronisation the heifers were bred by artificial insemination followed by natural bull mating. Six months after booster vaccination 15 heifers from the T1c group, eight from the T1a group, and 15 from the NC group, were exposed to four calves that were persistently infected with type 1a BVD virus, for 4 weeks. At the beginning of the challenge phase 36/38 heifers were 72-74 days pregnant and 2/38 heifers were approximately 53 days pregnant. Approximately 52 days after the start of the challenge the heifers were subjected to euthanasia and fetal tissues were collected for the detection of BVD virus by ELISA in fetal heart blood and PCR in fetal tissues. RESULTS: Based on PCR results, BVD virus was detected in 15/15 fetuses in the NC group, compared to 4/14 fetuses in the T1c group and 3/8 fetuses in the T1a group. The proportion of BVD virus-positive fetuses was lower in both vaccinated groups compared to the NC group (p<0.002), but there was no difference in proportions between the vaccinated groups (p=1.00). Fetal protection, expressed as the prevented fraction, was 71.4 (95% CI=41.9-91.6)% and 62.5 (95% CI=24.5-91.5)% for the T1c and T1a groups, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The vaccines containing killed type 1c and type 1a BVD viruses significantly reduced fetal infection following challenge with a New Zealand type 1a BVD virus. Prevention of fetal infection by vaccination may not be 100%, and the risk of persistently infected calves being born to some vaccinated cattle should be acknowledged and managed as part of a BVD control programme.


Asunto(s)
Diarrea Mucosa Bovina Viral/prevención & control , Virus de la Diarrea Viral Bovina Tipo 1/clasificación , Transmisión Vertical de Enfermedad Infecciosa/veterinaria , Vacunas Virales/inmunología , Animales , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/metabolismo , Diarrea Mucosa Bovina Viral/transmisión , Bovinos , Virus de la Diarrea Viral Bovina Tipo 1/inmunología , Femenino , Feto/inmunología , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Embarazo
6.
BMC Musculoskelet Disord ; 17: 60, 2016 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-26846934

RESUMEN

BACKGROUND: As the prevalence of hip pathology in the younger athletic population rises, the medical community continues to investigate effective intervention options. Femoracetabular impingement is the morphologically abnormal articulation of the femoral head against the acetabulum, and often implicated in pre-arthritic hip conditions of musculoskeletal nature. Arthroscopic surgical decompression and non-surgical rehabilitation programs focused on strengthening and stability are common interventions. However, they have never been directly compared in clinical trials. The primary purpose of this study will be to assess the difference in outcomes between these 2 commonly utilized interventions for femoracetabular impingement. METHODS: The study will be a single site, non-inferiority, randomized controlled trial comparing two different treatment approaches (surgical and nonsurgical) for FAI. The enrollment goal is for a total of 80 subjects with a diagnosis of Femoracetabular impingement that are surgical candidates and have failed 6 weeks of conservative treatment. This will be a convenience sample of consecutive patients that are Tricare beneficiaries and seeking care at Madigan Army Medical Center. Patients that meet the criteria will be screened, provide written consent before enrollment, and then randomized into one of two arms (Group I = hip arthroscopy, Group II = physical therapy). Group I will undergo hip arthroscopy with or without labral repair. Group II will follow an impairment based physical therapy program consisting of 2 sessions per week for 6 weeks. The primary outcome will be the Hip Outcome Score and secondary measures will include the International Hip Outcome Tool and the Global Rating of Change. Measures will be taken at baseline, 6 months, 1 and 2 years. Hip-related healthcare utilization between both groups will also be assessed at the end of 2 years. DISCUSSION: The current evidence to support both surgical and conservative interventions for femoroacetabular impingement is based on low-level research. To date, none of these interventions have been directly compared in a randomized clinical trial. Clinical trials are needed to help establish the value of these interventions in the management of femoracetabular impingement and to help define appropriate clinical pathways. TRIAL REGISTRATION: NCT01993615 30 October 2013.


Asunto(s)
Artroscopía/tendencias , Pinzamiento Femoroacetabular/diagnóstico , Pinzamiento Femoroacetabular/terapia , Modalidades de Fisioterapia/tendencias , Adulto , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Método Simple Ciego , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
7.
Neuroimage ; 112: 160-168, 2015 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-25776213

RESUMEN

AIM: MR-based correction for photon attenuation in PET/MRI remains challenging, particularly for neurological applications requiring quantitation of data. Existing methods are either not sufficiently accurate or are limited by the computation time required. The goal of this study was to develop an MR-based attenuation correction method that accurately separates bone tissue from air and provides continuous-valued attenuation coefficients for bone. MATERIALS AND METHODS: PET/MRI and CT datasets were obtained from 98 subjects (mean age [±SD]: 66yrs [±9.8], 57 females) using an IRB-approved protocol and with informed consent. Subjects were injected with 352±29MBq of (18)F-Florbetapir tracer, and PET acquisitions were begun either immediately or 50min after injection. CT images of the head were acquired separately using a PET/CT system. Dual echo ultrashort echo-time (UTE) images and two-point Dixon images were acquired. Regions of air were segmented via a threshold of the voxel-wise multiplicative inverse of the UTE echo 1 image. Regions of bone were segmented via a threshold of the R2* image computed from the UTE echo 1 and UTE echo 2 images. Regions of fat and soft tissue were segmented using fat and water images decomposed from the Dixon images. Air, fat, and soft tissue were assigned linear attenuation coefficients (LACs) of 0, 0.092, and 0.1cm(-1), respectively. LACs for bone were derived from a regression analysis between corresponding R2* and CT values. PET images were reconstructed using the gold standard CT method and the proposed CAR-RiDR method. RESULTS: The RiDR segmentation method produces mean Dice coefficient±SD across subjects of 0.75±0.05 for bone and 0.60±0.08 for air. The CAR model for bone LACs greatly improves accuracy in estimating CT values (28.2%±3.0 mean error) compared to the use of a constant CT value (46.9%±5.8, p<10(-6)). Finally, the CAR-RiDR method provides a low whole-brain mean absolute percent-error (MAPE±SD) in PET reconstructions across subjects of 2.55%±0.86. Regional PET errors were also low and ranged from 0.88% to 3.79% in 24 brain ROIs. CONCLUSION: We propose an MR-based attenuation correction method (CAR-RiDR) for quantitative PET neurological imaging. The proposed method employs UTE and Dixon images and consists of two novel components: 1) accurate segmentation of air and bone using the inverse of the UTE1 image and the R2* image, respectively and 2) estimation of continuous LAC values for bone using a regression between R2* and CT-Hounsfield units. From our analysis, we conclude that the proposed method closely approaches (<3% error) the gold standard CT-scaled method in PET reconstruction accuracy.


Asunto(s)
Huesos/anatomía & histología , Huesos/diagnóstico por imagen , Imagen por Resonancia Magnética/estadística & datos numéricos , Neuroimagen/estadística & datos numéricos , Tomografía de Emisión de Positrones/estadística & datos numéricos , Tejido Adiposo/anatomía & histología , Anciano , Aire , Algoritmos , Compuestos de Anilina , Encéfalo/anatomía & histología , Encéfalo/diagnóstico por imagen , Glicoles de Etileno , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones/métodos , Radiofármacos , Cráneo/anatomía & histología , Cráneo/diagnóstico por imagen
8.
Arthroscopy ; 31(4): 680-3, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25522680

RESUMEN

PURPOSE: The purpose of this study was to determine the incidence of meniscal injury, specifically medial meniscal injury, in US Army soldiers undergoing revision anterior cruciate ligament (ACL) reconstruction. METHODS: A retrospective review was performed of all patients who underwent revision ACL reconstruction from 2002 to 2011 at our institution. A complete chart review was performed to identify the prevalence of meniscal pathology identified at the time of revision ACL surgery. Patient demographic data and meniscal injury patterns were analyzed. RESULTS: Sixty-seven patients were identified, with a mean age of 28 years. The mean time to revision reconstruction was 67 months. Most patients (64.1%) reported a distinct reinjury. Reinjury was reported as the cause for revision ACL reconstruction in 43 patients. In this subgroup the mean time from reinjury to revision surgery was 13.9 months. Meniscal pathology was identified in 50 patients (74.6%). Medial meniscal tears were noted in 38 patients (56.7%), a rate significantly greater than that previously described (P = .008). Lateral meniscal tears were noted in 26 patients (38.8%), which was similar to previously published data (P = .52). CONCLUSIONS: The prevalence of meniscal injury at the time of revision ACL reconstruction in active-duty US Army soldiers is nearly identical to that of previously published data looking at a civilian population (74.6% v 74%) in the Multicenter ACL Revision Study (MARS) cohort. However, the incidence of medial meniscal injury was greater in the active-duty population than in the civilian population (56.7% v 40%). The observed increase in the prevalence of medial meniscal pathology is likely multifactorial, relating to the unique demands on young military athletes in both combat and training environments, rate of reinjury, and various delays to treatment after reinjury. LEVEL OF EVIDENCE: Level IV, therapeutic case series.


Asunto(s)
Lesiones del Ligamento Cruzado Anterior , Reconstrucción del Ligamento Cruzado Anterior , Traumatismos en Atletas/cirugía , Traumatismos de la Rodilla/cirugía , Lesiones de Menisco Tibial , Adulto , Ligamento Cruzado Anterior/cirugía , Femenino , Humanos , Traumatismos de la Rodilla/diagnóstico , Masculino , Meniscos Tibiales/cirugía , Persona de Mediana Edad , Personal Militar , Prevalencia , Reoperación , Estudios Retrospectivos , Adulto Joven
9.
J Biol Chem ; 287(53): 44143-50, 2012 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-23148225

RESUMEN

Tumor necrosis factor receptor-associated factor 6 (TRAF6) and TGFß-activated kinase 1 (TAK1) are considered as key intermediates in Toll-like receptor (TLR) signaling. However, the role of TRAF6 and TAK1 in C-type lectin receptors (CLRs) in response to fungal infection has not been studied. In this study, we have utilized macrophages derived from TRAF6 knock-out mice and myeloid-specific TAK1-deficient mice and determined the role of TRAF6 and TAK1 in CLR-induced signal transduction events. We demonstrate that TRAF6 and TAK1 are required for NF-κB and JNK activation, and expression of proinflammatory cytokines in response to Candida albicans infection. Our results highlight TRAF6 and TAK1 as key components in the signaling cascade downstream of C-type lectin receptors and as critical mediators of the anti-fungal immune response. Therefore, our studies provide a mechanistic understanding of the host immune response to C. albicans, which has a significant impact for the development of anti-fungal therapeutics and in understanding risk-factors and determining susceptibility to C. albicans infection.


Asunto(s)
Candida albicans/fisiología , Candidiasis/inmunología , Lectinas Tipo C/inmunología , Quinasas Quinasa Quinasa PAM/inmunología , Transducción de Señal , Factor 6 Asociado a Receptor de TNF/inmunología , Animales , Candida albicans/inmunología , Candidiasis/enzimología , Candidiasis/genética , Células Cultivadas , Femenino , Humanos , Lectinas Tipo C/genética , Quinasas Quinasa Quinasa PAM/genética , Macrófagos/inmunología , Macrófagos/microbiología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Factor 6 Asociado a Receptor de TNF/genética
10.
Proc Natl Acad Sci U S A ; 107(29): 12919-24, 2010 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-20615976

RESUMEN

The transcription factor Osterix (Osx) is required for osteoblast differentiation and bone formation during embryonic development, but it is not known whether Osx has an essential function in postnatal bone growth and in bone homeostasis. Conditional deletion of Osx at several time points postnatally revealed that Osx was essential for osteoblast differentiation and new bone formation in growing and adult bones. Additionally, inactivation of Osx in bones severely disrupted the maturation, morphology, and function of osteocytes. These findings identify Osx as having an essential role in the cell-specific genetic program of osteocytes. Interestingly, Osx inactivation also led to the massive accumulation of unresorbed calcified cartilage in a large area below the growth plate of endochondral bones. This specific area was also marked by an unanticipated almost complete lack of bone marrow cells and a marked decrease in the density and size of osteoclasts. This diminished density of osteoclasts could contribute to the lack of resorption of mineralized cartilage. In addition, we speculate that the abnormally accumulated, mainly naked cartilage represents an unfavorable substrate for osteoclasts. Our study identifies Osx as an essential multifunctional player in postnatal bone growth and homeostasis.


Asunto(s)
Desarrollo Óseo , Homeostasis , Factores de Transcripción/metabolismo , Animales , Animales Recién Nacidos , Células de la Médula Ósea/citología , Células de la Médula Ósea/metabolismo , Huesos/metabolismo , Huesos/patología , Huesos/ultraestructura , Calcificación Fisiológica , Cartílago/metabolismo , Cartílago/patología , Diferenciación Celular , Ratones , Osteoblastos/citología , Osteoblastos/metabolismo , Osteoblastos/ultraestructura , Osteocitos/citología , Osteocitos/metabolismo , Osteocitos/ultraestructura , Osteogénesis , Fenotipo , Factor de Transcripción Sp7
11.
J Shoulder Elbow Surg ; 22(5): 595-601, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23177167

RESUMEN

HYPOTHESIS: The objective of this study was to compare the efficacy of subacromial injection of triamcinolone compared to injection of ketorolac in the treatment of external shoulder impingement syndrome. METHODS: Thirty-two patients diagnosed with external shoulder impingement syndrome were included in this double-blinded randomized controlled clinical trial. Each patient was randomized into the steroid group or nonsteroidal anti-inflammatory drugs (NSAID) group. The steroid syringe contained 40 mg triamcinolone; and the NSAID syringe contained 60 mg ketorolac. Each patient was evaluated in terms of arc of motion, visual analog scale (VAS) for evaluating pain, and the UCLA (The University of California at Los Angeles) shoulder rating scale. RESULTS: At 1 month follow-up, both treatment arms resulted in increased range of motion and decreased pain. The steroid group decreased in active abduction while the NSAID group increased (steroid: 134°, NSAID: 151°, P = .03). The mean improvement in the UCLA shoulder rating scale at 4 weeks was 7.15 for the NSAID group and 2.13 for the steroid group (P = .03). Subgroup analysis of the UCLA scale demonstrated an increase in both forward flexion strength (P = .04) and patient satisfaction (P = .03) in the NSAID group. No significant difference could be seen in all other outcome measures. CONCLUSION: In this study, an injection of ketorolac resulted in greater improvements in the UCLA shoulder rating scale than an injection of triamcinolone at 4 weeks follow-up. While both triamcinolone and ketorolac are effective in the treatment of isolated subacromial impingement, ketorolac appears to have equivalent if not superior efficacy; all the while decreasing patient exposure to the potential side-effects of corticosteroids.


Asunto(s)
Antiinflamatorios no Esteroideos/administración & dosificación , Glucocorticoides/administración & dosificación , Ketorolaco/administración & dosificación , Síndrome de Abducción Dolorosa del Hombro/tratamiento farmacológico , Triamcinolona/administración & dosificación , Adulto , Método Doble Ciego , Femenino , Humanos , Inyecciones Intraarticulares , Masculino , Persona de Mediana Edad , Adulto Joven
12.
J Biol Chem ; 286(26): 22814-24, 2011 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-21558270

RESUMEN

Tumor necrosis factor receptor 2 (TNFR2) activates transcription factor κB (NF-κB) and c-Jun N-terminal kinase (JNK). The mechanisms mediating these activations are dependent on the recruitment of TNF receptor-associated factor 2 (TRAF2) to the intracellular region of the receptor. TNFR2 also induces TRAF2 degradation. We show that in addition to the well characterized TRAF2 binding motif 402-SKEE-405, the human receptor contains another sequence located at the C-terminal end (amino acids 425-439), which also recruits TRAF2 and activates NF-κB. In addition to that, human TNFR2 contains a conserved region (amino acids 338-379) which is responsible for TRAF2 degradation and therefore of terminating NF-κB signaling. TRAF2 degradation and the lack of NF-κB activation when both TNFR1 and TNFR2 are co-expressed results in an enhanced ability of TNFR1 to induce cell death, showing that the cross-talk between both receptors is of a great biological relevance. Induction of TRAF2 degradation appears to be independent of TRAF2 binding to the receptor. Amino acids 343-TGSSDSS-349 are essential for inducing TRAF2 degradation because deletion mutants of this region or point mutations at serine residues 345 and 346 or 348 and 349 obliterate the ability of TNFR2 to induce TRAF2 degradation.


Asunto(s)
FN-kappa B/metabolismo , Receptores Tipo II del Factor de Necrosis Tumoral/metabolismo , Transducción de Señal/fisiología , Factor 2 Asociado a Receptor de TNF/metabolismo , Secuencias de Aminoácidos , Animales , Células HEK293 , Humanos , MAP Quinasa Quinasa 4/genética , MAP Quinasa Quinasa 4/metabolismo , FN-kappa B/genética , Receptores Tipo I de Factores de Necrosis Tumoral/genética , Receptores Tipo I de Factores de Necrosis Tumoral/metabolismo , Receptores Tipo II del Factor de Necrosis Tumoral/genética , Factor 2 Asociado a Receptor de TNF/genética
13.
J Biol Chem ; 286(35): 30806-30815, 2011 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-21690091

RESUMEN

DNA damage response is an important surveillance mechanism used to maintain the integrity of the human genome in response to genotoxic stress. Histone variant H2AX is a critical sensor that undergoes phosphorylation at serine 139 upon genotoxic stress, which provides a docking site to recruit the mediator of DNA damage checkpoint protein 1 (MDC1) and DNA repair protein complex to sites of DNA breaks for DNA repair. Here, we show that monoubiquitination of H2AX is induced upon DNA double strand breaks and plays a critical role in H2AX Ser-139 phosphorylation (γ-H2AX), in turn facilitating the recruitment of MDC1 to DNA damage foci. Mechanistically, we show that monoubiquitination of H2AX induced by RING finger protein 2 (RNF2) is required for the recruitment of active ataxia telangiectasia mutated to DNA damage foci, thus affecting the formation of γ-H2AX. Importantly, a defect in monoubiquitination of H2AX profoundly enhances ionizing radiation sensitivity. Our study therefore suggests that monoubiquitination of H2AX is an important step for DNA damage response and may have important clinical implications for the treatment of cancers.


Asunto(s)
Daño del ADN , Histonas/metabolismo , Neoplasias/metabolismo , Ubiquitina/química , Animales , Sitios de Unión , Línea Celular Tumoral , Reparación del ADN , Histonas/fisiología , Humanos , Ratones , Modelos Biológicos , Fosforilación , Radiación Ionizante , Transducción de Señal , Transfección , Ubiquitina/metabolismo
14.
S Afr J Sports Med ; 34(1): v34i1a13979, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36815918

RESUMEN

Sudden cardiac adverse events remain an area of concern in sport. The precise risk for netball athletes is unknown but the annual incidence of sudden cardiac death in sports is reported at 0.5-2 cases in 100 000 young competitive athletes between the ages of 12-35 years. Cardiac screening in the sport and exercise medicine context aims at identifying pathologies associated with catastrophic events when combined with physical activity. There is an ongoing debate relating to the standardisation of the pre-participatory medical assessment (PPMA). World Netball (WN) commissioned a cardiac screening policy (13 March 2022). The minimum PPMA recommended by World Netball is a history, physical examination, and a resting 12-lead electrocardiogram (ECG). ECGs should be interpreted in accordance with athlete-specific ECG interpretation criteria. Expansion of sports cardiology experience and infrastructure, in combination with universal emergency response planning for sudden cardiac arrest, is intended to safeguard athlete health and player welfare in WN.

15.
Phys Rev Lett ; 106(1): 018101, 2011 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-21231772

RESUMEN

We demonstrate a method for the fast, high-throughput characterization of the dynamics of active particles. Specifically, we measure the swimming speed distribution and motile cell fraction in Escherichia coli suspensions. By averaging over ∼10(4) cells, our method is highly accurate compared to conventional tracking, yielding a routine tool for motility characterization. We find that the diffusivity of nonmotile cells is enhanced in proportion to the concentration of motile cells.


Asunto(s)
Escherichia coli/citología , Escherichia coli/fisiología , Microscopía/métodos , Luz , Movimiento , Dispersión de Radiación
16.
J Immunol ; 182(12): 7718-28, 2009 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-19494296

RESUMEN

The Carma1-Bcl10-Malt1 signaling module bridges TCR signaling to the canonical IkappaB kinase (IKK)/NF-kappaB pathway. Covalent attachment of regulatory ubiquitin chains to Malt1 paracaspase directs TCR signaling to IKK activation. Further, the ubiquitin-editing enzyme A20 was recently suggested to suppress T cell activation, but molecular targets for A20 remain elusive. In this paper, we show that A20 regulates the strength and duration of the IKK/NF-kappaB response upon TCR/CD28 costimulation. By catalyzing the removal of K63-linked ubiquitin chains from Malt1, A20 prevents sustained interaction between ubiquitinated Malt1 and the IKK complex and thus serves as a negative regulator of inducible IKK activity. Upon T cell stimulation, A20 is rapidly removed and paracaspase activity of Malt1 has been suggested to cleave A20. Using antagonistic peptides or reconstitution of Malt1(-/-) T cells, we show that Malt1 paracaspase activity is required for A20 cleavage and optimal IL-2 production, but dispensable for initial IKK/NF-kappaB signaling in CD4(+) T cells. However, proteasomal inhibition impairs A20 degradation and impedes TCR/CD28-induced IKK activation. Taken together, A20 functions as a Malt1 deubiquitinating enzyme and proteasomal degradation and de novo synthesis of A20 contributes to balance TCR/CD28-induced IKK/NF-kappaB signaling.


Asunto(s)
Caspasas/metabolismo , Regulación hacia Abajo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , FN-kappa B/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares/metabolismo , Receptores de Antígenos de Linfocitos T/inmunología , Transducción de Señal/inmunología , Ubiquitina/metabolismo , Proteínas Adaptadoras de Señalización CARD/metabolismo , Caspasas/genética , Línea Celular , Proteínas de Unión al ADN , Activación Enzimática , Humanos , Quinasa I-kappa B/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Proteína 1 de la Translocación del Linfoma del Tejido Linfático Asociado a Mucosas , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Complejo de la Endopetidasa Proteasomal/metabolismo , Unión Proteica , ARN Interferente Pequeño/genética , Receptores de Antígenos de Linfocitos T/metabolismo , Proteína 3 Inducida por el Factor de Necrosis Tumoral alfa
17.
J Chem Phys ; 134(5): 054505, 2011 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-21303136

RESUMEN

Intermediate scattering functions are measured for colloidal hard sphere systems using both dynamic light scattering and x-ray photon correlation spectroscopy. We compare the techniques, and discuss the advantages and disadvantages of each. Both techniques agree in the overlapping range of scattering vectors. We investigate the scaling behavior found by Segré and Pusey [Phys. Rev. Lett. 77, 771 (1996)] but challenged by Lurio et al. [Phys. Rev. Lett. 84, 785 (2000)]. We observe a scaling behavior over several decades in time but not in the long-time regime. Moreover, we do not observe long-time diffusive regimes at scattering vectors away from the peak of the structure factor and so question the existence of long-time diffusion coefficients at these scattering vectors.

18.
J Chem Phys ; 133(11): 114906, 2010 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-20866156

RESUMEN

We report the results of dynamic light scattering measurements of the coherent intermediate scattering function (ISF) of glasses of colloidal hard spheres for several volume fractions and a range of scattering vectors around the primary peak of the static structure factor. The ISF shows a clear crossover from an initial fast decay to a slower nonstationary decay. Aging is quantified in several different ways. However, regardless of the method chosen, the perfect "aged" glass is approached in a power law fashion. In particular the coupling between the fast and slow decays, as measured by the degree of stretching of the ISF at the crossover, also decreases algebraically with waiting time. The nonstationarity of this coupling implies that even the fastest detectable processes are themselves nonstationary.

19.
Biochemistry ; 48(44): 10558-67, 2009 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-19810754

RESUMEN

TRAF proteins are intracellular signal transducers for a number of immune receptor superfamilies. Specifically, TRAF2 interacts with members of the TNF receptor superfamily and connects the receptors to downstream signaling proteins. It has been assumed that TRAF2 is a ubiquitin ligase like TRAF6 and mediates K63-linked polyubiquitination of RIP1, a kinase pivotal in TNFalpha-induced NF-kappaB activation. Here we report the crystal structure of the RING and the first zinc finger domains of TRAF2. We show that the TRAF2 RING structure is very different from the known TRAF6 RING structure. The differences are multifaceted, including amino acid differences at the critical Ubc13-interacting site, local conformational differences, and a unique nine-residue insertion between the RING domain and the first zinc finger in TRAF2. These structural differences prevent TRAF2 from interacting with Ubc13 and other related E2s via steric clash and unfavorable interfaces. Our structural observation should prompt a re-evaluation of the role of TRAF2 in TNFalpha signaling and may indicate that TRAF2-associated proteins such as cIAPs may be the ubiquitin ligases for NF-kappaB signaling.


Asunto(s)
Factor 2 Asociado a Receptor de TNF/química , Secuencia de Aminoácidos , Cristalografía por Rayos X , Humanos , Datos de Secuencia Molecular , Conformación Proteica , Homología de Secuencia de Aminoácido , Factor 2 Asociado a Receptor de TNF/metabolismo , Ubiquitinación
20.
Phys Rev Lett ; 103(25): 258302, 2009 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-20366293

RESUMEN

The current correlation function is determined from dynamic light scattering measurements of a suspension of particles with hard spherelike interactions. For suspensions in thermodynamic equilibrium we find scaling of the space and time variables of the current correlation function. This finding supports the notion that the movement of suspended particles can be described in terms of uncorrelated Brownian encounters. However, in the metastable fluid, at volume fractions above freezing, this scaling fails.

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