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1.
Clocks Sleep ; 6(1): 183-199, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38534801

RESUMO

Previous work has demonstrated the modest impact of environmental interventions that manipulate lighting, sound, or temperature on sleep inertia symptoms. The current study sought to expand on previous work and measure the impact of a multimodal intervention that collectively manipulated light, sound, and ambient temperature on sleep inertia. Participants slept in the lab for four nights and were awoken each morning by either a traditional alarm clock or the multimodal intervention. Feelings of sleep inertia were measured each morning through Psychomotor Vigilance Test (PVT) assessments and ratings of sleepiness and mood at five time-points. While there was little overall impact of the intervention, the participant's chronotype and the length of the lighting exposure on intervention mornings both influenced sleep inertia symptoms. Moderate evening types who received a shorter lighting exposure (≤15 min) demonstrated more lapses relative to the control condition, whereas intermediate types exhibited a better response speed and fewer lapses. Conversely, moderate evening types who experienced a longer light exposure (>15 min) during the intervention exhibited fewer false alarms over time. The results suggest that the length of the environmental intervention may play a role in mitigating feelings of sleep inertia, particularly for groups who might exhibit stronger feelings of sleep inertia, including evening types.

2.
Comput Methods Programs Biomed ; 245: 108035, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38290290

RESUMO

BACKGROUND AND OBJECTIVE: Biopsy stands as the gold standard for kidney transplant assessment, yet its invasive nature restricts frequent use. Shear wave elastography (SWE) is emerging as a promising alternative for kidney transplant monitoring. A parametric study involving 12 biopsy data sets categorized by standard biopsy scores (3 with normal histology, 3 with interstitial inflammation (i), 3 with interstitial fibrosis (ci), and 3 with tubular atrophy (ct)), was conducted to evaluate the interdependence between microstructural variations triggered by chronic allograft rejection and corresponding alterations in SWE measurements. METHODS: Heterogeneous shear wave motion simulations from segmented kidney cortex sections were performed employing the staggered-grid finite difference (SGFD) method. The SGFD method allows the mechanical properties to be defined on a pixel-basis for shear wave motion simulation. Segmentation techniques enabled the isolation of four histological constituents: glomeruli, tubules, interstitium, and fluid. Baseline ex vivo Kelvin-Voigt mechanical properties for each constituent were drawn from established literature. The parametric evaluation was then performed by altering the baseline values individually. Shear wave velocity dispersion curves were measured with the generalized Stockwell transform in conjunction with slant frequency-wavenumber analysis (GST-SFK) algorithm. By fitting the curve within the 100-400 Hz range to the Kelvin-Voigt model, the rheological parameters, shear elasticity (µ1) and viscosity (µ2), were estimated. A time-to-peak algorithm was used to estimate the group velocity. The resultant in silico models emulated the heterogeneity of kidney cortex within the shear wave speed (SWS) reconstructions. RESULTS: The presence of inflammation showed considerable spatial composition disparities compared to normal cases, featuring a 23 % increase in interstitial area and a 19 % increase in glomerular area. Concomitantly, there was a reduction of 12 % and 47 % in tubular and fluid areas, respectively. Consequently, mechanical changes induced by inflammation predominate in terms of rheological differentiation, evidenced by increased elasticity and viscosity. Mild tubular atrophy showed significant elevation in group velocity and µ1. Conversely, mild and moderate fibrosis exhibited negligible alterations across all parameters, compatible with relatively limited morphological impact. CONCLUSIONS: This proposed model holds promise in enabling patient-specific simulations of the kidney cortex, thus facilitating exploration into how pathologies altering cortical morphology correlates to modifications in SWE-derived rheological measurements. We demonstrated that inflammation caused substantial changes in measured mechanical properties.


Assuntos
Técnicas de Imagem por Elasticidade , Humanos , Técnicas de Imagem por Elasticidade/métodos , Biópsia , Inflamação , Glomérulos Renais , Fibrose , Atrofia
3.
Front Psychol ; 13: 897241, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35719506

RESUMO

Background: Work-related stress is one of the top sources of stress amongst working adults. Relaxation rooms are one organizational strategy being used to reduce workplace stress. Amongst healthcare workers, relaxation rooms have been shown to improve perceived stress levels after 15 min of use. However, few studies have examined physiological and cognitive changes after stress, which may inform why relaxation rooms reduce perceived stress. Understanding the biological mechanisms governing why perceived stress improves when using a relaxation room could lead to more effective strategies to address workplace stress. Objective: The purpose of this research study is to understand how physiological measures, cognitive performance, and perceived stress change after acute stress and whether certain sensory features of a relaxation room are more effective at promoting recovery from stress. Methods: 80 healthy adults will perform a stress induction task (Trier Social Stress Test, TSST) to evaluate how physiological and cognitive responses after stress are affected by sensory features of a relaxation room. After the stress induction task, participants will recover for 40 min in a MindBreaks™ relaxation room containing auditory and visual stimuli designed to promote relaxation. Participants will be randomized into four cohorts to experience auditory and visual stimuli; auditory stimuli; visual stimuli; or no stimuli in the room. Measures of heart rate and neural activity will be continuously monitored using wearable devices. Participants will perform working memory assessments and rate their perceived stress levels throughout the experiment. These measures will be compared before and after the stress induction task to determine how different sensory stimuli affect the rate at which individuals recover. Results: Recruitment started in December 2021 and will continue until December 2022 or until enrollment is completed. Final data collection and subsequent analysis are anticipated by December 2022. We expect all trial results will be available by early 2023. Discussion: Findings will provide data and information about which sensory features of a relaxation room are most effective at promoting recovery after acute stress. This information will be useful in determining how these features might be effective at creating individualized and organizational strategies for mitigating the effects of workplace stress.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33023141

RESUMO

As a critical factor in the built environment, lighting presents considerable influence on occupants. Previous research across static lighting conditions has found that both illuminance and correlated color temperature (CCT) affect occupants' physiological and psychological functioning. However, little research has been conducted on the non-visual impacts of dynamic lighting with daily variation in illuminance and CCT levels. The purpose of this study is to better understand the impact of dynamic lighting on office occupants' health, well-being and experience at a living lab. Fifteen participants were recruited to work in three office modules for four months. Four lighting conditions were designed and implemented in this study, including two static lighting conditions and two dynamic lighting conditions with a specific predefined control scheme. A prototype lighting system with enhanced control capabilities was configured and implemented to ensure the desired lighting environment protocol. Both objective methods and subjective surveys were used to assess the behavioral and physiological outcomes of interest, including mental stress, sleep, productivity, satisfaction, mood, visual comfort and perceived naturalness. The results showed that the daytime behavioral impacts were either positive or mixed. Specifically, a significant alertness increase was observed in the afternoon, indicating a potential solution to reduce the natural feelings of sleepiness during the workday. There was also a marginal benefit for mood. The nighttime impacts include a significant decrease in perceived sleep quality and sleep time after subjects were exposed to dynamic lighting. No significant differences were observed for mental stress, productivity, visual comfort, or perceived naturalness. The findings present additional insights into the non-visual impacts of dynamic lighting and give recommendations for further investigations.


Assuntos
Eficiência , Iluminação , Afeto , Humanos , Satisfação Pessoal , Sono
5.
Ann Glob Health ; 86(1): 39, 2020 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-32322537

RESUMO

Engineering technology plays a pivotal role in the delivery of health care in under-resourced countries by providing an infrastructure to improve patient outcomes. However, sustainability of these technologies is difficult in these settings oftentimes due to limited resources or training. The framework presented in this editorial focuses on establishing medical and laboratory equipment sustainability in developing countries and is comprised of four steps: 1) establishing reliable in-country relationships with stakeholders, 2) identifying needs for sustainable solutions locally, 3) exploring potential solutions and assessing their effort-to-impact ratios, and 4) working with strategic partners to implement solutions with clear performance metrics. By focusing on the sustainability of donated equipment instead of the equipment itself, this method presented distinguishes itself from other philanthropic endeavors in the field by seeking to establish preventive maintenance habits that can impact clinical outcomes of a community long term. Application of this methodology is reported in the Original Research Article "A Low-Cost Humidity Control System to Protect Microscopes in a Tropical Climate" by Asp et. al.


Assuntos
Países em Desenvolvimento , Equipamentos e Provisões , Recursos em Saúde , Avaliação de Programas e Projetos de Saúde , Utilização de Equipamentos e Suprimentos , Humanos , Manutenção , Avaliação das Necessidades , Organizações sem Fins Lucrativos , Participação dos Interessados , Ensino
6.
Artigo em Inglês | MEDLINE | ID: mdl-29389651

RESUMO

Currently, dynamic elastography techniques estimate the linear elastic shear modulus of different body tissues. New methods that investigate other properties of soft tissues such as anisotropy, viscosity, and shear nonlinearity would provide more information about the structure and function of the tissue and might provide a better contrast than tissue stiffness and hence provide more effective diagnostic tools for some diseases. It has previously been shown that shear wave velocity in a medium changes due to an applied stress, a phenomenon called acoustoelasticity (AE). Applying a stress to compress a medium while measuring the shear wave velocity versus strain provides data with which the third-order nonlinear shear modulus can be estimated. To evaluate the feasibility of estimating , we evaluated ten ex vivo porcine kidneys embedded in 10% porcine gelatin to mimic the case of a transplanted kidney. Under assumptions of an elastic incompressible medium for AE measurements, the shear modulus was quantified at each compression level and the applied strain was assessed by measuring the change in the thickness of the kidney cortex. Finally, was calculated by applying the AE theory. Our results demonstrated that it is possible to estimate a nonlinear shear modulus by monitoring the changes in strain and due to kidney deformation. The magnitudes of are higher when the compression is performed progressively and when using a plate attached to the transducer. Nevertheless, the values obtained for are similar to those previously reported in the literature for breast tissue.


Assuntos
Módulo de Elasticidade/fisiologia , Técnicas de Imagem por Elasticidade/métodos , Rim/diagnóstico por imagem , Animais , Anisotropia , Feminino , Dinâmica não Linear , Suínos , Viscosidade
7.
Artigo em Inglês | MEDLINE | ID: mdl-26742131

RESUMO

Elasticity is measured by shear wave elasticity imaging (SWEI) methods using acoustic radiation force to create the shear waves. Phase aberration and tissue attenuation can hamper the generation of shear waves for in vivo applications. In this study, the effects of phase aberration and attenuation in ultrasound focusing for creating shear waves were explored. This includes the effects of phase shifts and amplitude attenuation on shear wave characteristics such as shear wave amplitude, shear wave speed, shear wave center frequency, and bandwidth. Two samples of swine belly tissue were used to create phase aberration and attenuation experimentally. To explore the phase aberration and attenuation effects individually, tissue experiments were complemented with ultrasound beam simulations using fast object-oriented C++ ultrasound simulator (FOCUS) and shear wave simulations using finite-element-model (FEM) analysis. The ultrasound frequency used to generate shear waves was varied from 3.0 to 4.5 MHz. Results: The measured acoustic pressure and resulting shear wave amplitude decreased approximately 40%-90% with the introduction of the tissue samples. Acoustic intensity and shear wave displacement were correlated for both tissue samples, and the resulting Pearson's correlation coefficients were 0.99 and 0.97. Analysis of shear wave generation with tissue samples (phase aberration and attenuation case), measured phase screen, (only phase aberration case), and FOCUS/FEM model (only attenuation case) showed that tissue attenuation affected the shear wave generation more than tissue aberration. Decreasing the ultrasound frequency helped maintain a focused beam for creation of shear waves in the presence of both phase aberration and attenuation.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Modelos Biológicos , Abdome/diagnóstico por imagem , Acústica , Animais , Análise de Elementos Finitos , Processamento de Imagem Assistida por Computador , Suínos
8.
Artigo em Inglês | MEDLINE | ID: mdl-28948043

RESUMO

Esophageal cancer is a malignant neoplasm with poor outcomes. Determination of local disease progression is a major determining factor in treatment modality, radiation dose, radiation field and subsequent surgical therapy. Discrimination of true tumor extent is difficult given the similarity of soft tissues of the malignancy compared to non-malignant tissues using current imaging modalities. A possible method to discriminate between these tissues may be to exploit mechanical properties to diagnostic advantage, as malignant tissues tend to be stiffer relative to normal adjacent tissue. Shear waves propagate faster in stiffer tissues relative to softer tissues. This may be measured by using ultrasound based shear wave vibrometry. In this method, acoustic radiation force is used to create a shear wave in the tissue of interest and ultrafast ultrasound imaging is used to track the propagating wave to measure the wave velocity and estimate the shear moduli. In this study we created simulated malignant lesions (1.5 cm length) using radiofrequency ablation in ex vivo esophageal samples with varied progression (partial thickness n = 4, and full thickness n = 5) and used normal regions of the same esophageal specimen as controls. Shear wave vibrometry was used to measure shear wave group velocity and shear wave phase velocity in the ex vivo specimens. These values were used to estimate shear moduli using an elastic shear wave model and elastic and viscoelastic Lamb wave models. Our results show that the group and phase velocities increase due to both full and mucosal ablation, and that discrimination may be provided by higher order analysis using viscoelastic Lamb wave fitting. This technique may have application for determination of extent of early esophageal malignancy and warrants further investigation using in vivo approaches to determine performance compared to current imaging modalities.

9.
Artigo em Inglês | MEDLINE | ID: mdl-26067038

RESUMO

Tissues such as skeletal muscle and kidneys have well-defined structure that affects the measurements of mechanical properties. As an approach to characterize the material properties of these tissues, different groups have assumed that they are transversely isotropic (TI) and measure the shear wave velocity as it varies with angle with respect to the structural architecture of the organ. To refine measurements in these organs, it is desirable to have tissue-mimicking phantoms that exhibit similar anisotropic characteristics. Some approaches involve embedding fibers into a material matrix. However, if a homogeneous solid is under compression due to a static stress, an acoustoelastic effect can manifest that makes the measured wave velocities change with the compression stress. We propose to exploit this characteristic to demonstrate that stressed tissue mimicking phantoms can be characterized as a TI material. We tested six phantoms made with different concentrations of gelatin and agar. Stress was applied by the weight of a water container centered on top of a plate on top of the phantom. A linear array transducer and a V-1 Verasonics system were used to induce and measure shear waves in the phantoms. The shear wave motion was measured using a compound plane wave imaging technique. Autocorrelation was applied to the received in-phase/quadrature data. The shear wave velocity, c, was estimated using a Radon transform method. The transducer was mounted on a rotating stage so measurements were made every 10° over a range of 0° to 360°, where the stress is applied along 0° to 180° direction. The shear moduli were estimated. A TI model was fit to the data and the fractional anisotropy was evaluated. This approach can be used to explore many configurations of transverse isotropy with the same phantom, simply by applying stress to the tissue-mimicking phantom.


Assuntos
Técnicas de Imagem por Elasticidade/instrumentação , Modelos Biológicos , Imagens de Fantasmas , Ágar/química , Técnicas de Imagem por Elasticidade/métodos , Gelatina/química
10.
Phys Med Biol ; 60(3): 1289-306, 2015 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-25591921

RESUMO

In this paper, we propose a method to model the shear wave propagation in transversely isotropic, viscoelastic and incompressible media. The targeted application is ultrasound-based shear wave elastography for viscoelasticity measurements in anisotropic tissues such as the kidney and skeletal muscles. The proposed model predicts that if the viscoelastic parameters both across and along fiber directions can be characterized as a Voigt material, then the spatial phase velocity at any angle is also governed by a Voigt material model. Further, with the aid of Taylor expansions, it is shown that the spatial group velocity at any angle is close to a Voigt type for weakly attenuative materials within a certain bandwidth. The model is implemented in a finite element code by a time domain explicit integration scheme and shear wave simulations are conducted. The results of the simulations are analyzed to extract the shear wave elasticity and viscosity for both the spatial phase and group velocities. The estimated values match well with theoretical predictions. The proposed theory is further verified by an ex vivo tissue experiment measured in a porcine skeletal muscle by an ultrasound shear wave elastography method. The applicability of the Taylor expansion to analyze the spatial velocities is also discussed. We demonstrate that the approximations from the Taylor expansions are subject to errors when the viscosities across or along the fiber directions are large or the maximum frequency considered is beyond the bandwidth defined by radii of convergence of the Taylor expansions.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Acústica , Animais , Anisotropia , Bovinos , Simulação por Computador , Cães , Análise de Elementos Finitos , Ondas de Choque de Alta Energia , Humanos , Modelos Teóricos , Resistência ao Cisalhamento , Suínos , Ultrassom , Viscosidade
11.
Phys Med Biol ; 59(24): 7735-52, 2014 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-25419697

RESUMO

Ultrasound radiation force-based methods can quantitatively evaluate tissue viscoelastic material properties. One of the limitations of the current methods is neglecting the inherent anisotropy nature of certain tissues. To explore the phenomenon of anisotropy in a laboratory setting, we created two phantom designs incorporating fibrous and fishing line material with preferential orientations. Four phantoms were made in a cube-shaped mold; both designs were arranged in multiple layers and embedded in porcine gelatin using two different concentrations (8%, 14%). An excised sample of pork tenderloin was also studied. Measurements were made in the phantoms and the pork muscle at different angles by rotating the phantom with respect to the transducer, where 0° and 180° were defined along the fibers, and 90° and 270° across the fibers. Shear waves were generated and measured by a Verasonics ultrasound system equipped with a linear array transducer. For the fibrous phantom, the mean and standard deviations of the shear wave speeds along (0°) and across the fibers (90°) with 8% gelatin were 3.60  ±  0.03 and 3.18  ±  0.12 m s(-1) and with 14% gelatin were 4.10  ±  0.11 and 3.90  ±  0.02 m s(-1). For the fishing line material phantom, the mean and standard deviations of the shear wave speeds along (0°) and across the fibers (90°) with 8% gelatin were 2.86  ±  0.20 and 2.44  ±  0.24 m s(-1) and with 14% gelatin were 3.40  ±  0.09 and 2.84  ±  0.14 m s(-1). For the pork muscle, the mean and standard deviations of the shear wave speeds along the fibers (0°) at two different locations were 3.83  ±  0.16 and 3.86  ±  0.12 m s(-1) and across the fibers (90°) were 2.73  ±  0.18 and 2.70  ±  0.16 m s(-1), respectively. The fibrous and fishing line gelatin-based phantoms exhibited anisotropy that resembles that observed in the pork muscle.


Assuntos
Materiais Biomiméticos/química , Técnicas de Imagem por Elasticidade/instrumentação , Técnicas de Imagem por Elasticidade/métodos , Músculo Esquelético/diagnóstico por imagem , Imagens de Fantasmas , Algoritmos , Animais , Óleo de Rícino/química , Gelatina/química , Músculo Esquelético/efeitos da radiação , Resistência ao Cisalhamento , Suínos , Ultrassom , Viscosidade
12.
Sci Rep ; 4: 4464, 2014 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-24662985

RESUMO

Protein Disulfide Isomerase-Like protein of the Testis (PDILT) is a testis-specific member of the PDI family. PDILT displays similar domain architecture to PDIA1, the founding member of this protein family, but lacks catalytic cysteines needed for oxidoreduction reactions. This suggests special importance of chaperone activity of PDILT, but how it recognizes misfolded protein substrates is unknown. Here, we report the high-resolution crystal structure of the b' domain of human PDILT. The structure reveals a conserved hydrophobic pocket, which is likely a principal substrate-binding site in PDILT. In the crystal, this pocket is occupied by side chains of tyrosine and tryptophan residues from another PDILT molecule, suggesting a preference for binding exposed aromatic residues in protein substrates. The lack of interaction of the b' domain with the P-domains of calreticulin-3 and calmegin hints at a novel way of interaction between testis-specific lectin chaperones and PDILT. Further studies of this recently discovered PDI member would help to understand the important role that PDILT plays in the differentiation and maturation of spermatozoids.


Assuntos
Diferenciação Celular/genética , Isomerases de Dissulfetos de Proteínas/química , Estrutura Terciária de Proteína , Testículo/química , Sequência de Aminoácidos , Sítios de Ligação , Cristalografia por Raios X , Humanos , Interações Hidrofóbicas e Hidrofílicas , Lectinas/química , Masculino , Ligação Proteica , Isomerases de Dissulfetos de Proteínas/genética , Espermatozoides/crescimento & desenvolvimento
13.
Protein Sci ; 23(5): 618-26, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24549644

RESUMO

Protein disulfide isomerases (PDIs) are responsible for catalyzing the proper oxidation and isomerization of disulfide bonds of newly synthesized proteins in the endoplasmic reticulum (ER). Here, it is shown that human PDI (PDIA1) dimerizes in vivo and proposed that the dimerization of PDI has physiological relevance by autoregulating its activity. The crystal structure of the dimeric form of noncatalytic bb' domains of human PDIA1 determined to 2.3 Å resolution revealed that the formation of dimers occludes the substrate binding site and may function as a mechanism to regulate PDI activity in the ER.


Assuntos
Pró-Colágeno-Prolina Dioxigenase/química , Isomerases de Dissulfetos de Proteínas/química , Multimerização Proteica , Sítios de Ligação , Cristalografia por Raios X , Retículo Endoplasmático/metabolismo , Humanos , Modelos Moleculares , Pró-Colágeno-Prolina Dioxigenase/metabolismo , Isomerases de Dissulfetos de Proteínas/metabolismo , Estrutura Terciária de Proteína , Tiorredoxinas/química
14.
Phys Med Biol ; 56(20): 6723-38, 2011 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-21970846

RESUMO

Characterization of the viscoelastic material properties of soft tissue has become an important area of research over the last two decades. Our group has been investigating the feasibility of using a shear wave dispersion ultrasound vibrometry (SDUV) method to excite Lamb waves in organs with plate-like geometry to estimate the viscoelasticity of the medium of interest. The use of Lamb wave dispersion ultrasound vibrometry to quantify the mechanical properties of viscoelastic solids has previously been reported. Two organs, the heart wall and the spleen, can be readily modeled using plate-like geometries. The elasticity of these two organs is important because they change in pathological conditions. Diastolic dysfunction is the inability of the left ventricle (LV) of the heart to supply sufficient stroke volumes into the systemic circulation and is accompanied by the loss of compliance and stiffening of the LV myocardium. It has been shown that there is a correlation between high splenic stiffness in patients with chronic liver disease and strong correlation between spleen and liver stiffness. Here, we investigate the use of the SDUV method to quantify the viscoelasticity of the LV free-wall myocardium and spleen by exciting Rayleigh waves on the organ's surface and measuring the wave dispersion (change of wave velocity as a function of frequency) in the frequency range 40­500 Hz. An equation for Rayleigh wave dispersion due to cylindrical excitation was derived by modeling the excised myocardium and spleen with a homogenous Voigt material plate immersed in a nonviscous fluid. Boundary conditions and wave potential functions were solved for the surface wave velocity. Analytical and experimental convergence between the Lamb and Rayleigh waves is reported in a finite element model of a plate in a fluid of similar density, gelatin plate and excised porcine spleen and left-ventricular free-wall myocardium.


Assuntos
Elasticidade , Ultrassom/métodos , Animais , Ecocardiografia , Gelatina , Miocárdio/citologia , Baço/citologia , Baço/diagnóstico por imagem , Suínos , Viscosidade
15.
J Biol Chem ; 285(49): 38612-20, 2010 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-20880849

RESUMO

The calnexin cycle is a process by which glycosylated proteins are subjected to folding cycles in the endoplasmic reticulum lumen via binding to the membrane protein calnexin (CNX) or to its soluble homolog calreticulin (CRT). CNX and CRT specifically recognize monoglucosylated Glc(1)Man(9)GlcNAc(2) glycans, but the structural determinants underlying this specificity are unknown. Here, we report a 1.95-Å crystal structure of the CRT lectin domain in complex with the tetrasaccharide α-Glc-(1→3)-α-Man-(1→2)-α-Man-(1→2)-Man. The tetrasaccharide binds to a long channel on CRT formed by a concave ß-sheet. All four sugar moieties are engaged in the protein binding via an extensive network of hydrogen bonds and hydrophobic contacts. The structure explains the requirement for glucose at the nonreducing end of the carbohydrate; the oxygen O(2) of glucose perfectly fits to a pocket formed by CRT side chains while forming direct hydrogen bonds with the carbonyl of Gly(124) and the side chain of Lys(111). The structure also explains a requirement for the Cys(105)-Cys(137) disulfide bond in CRT/CNX for efficient carbohydrate binding. The Cys(105)-Cys(137) disulfide bond is involved in intimate contacts with the third and fourth sugar moieties of the Glc(1)Man(3) tetrasaccharide. Finally, the structure rationalizes previous mutagenesis of CRT and lays a structural groundwork for future studies of the role of CNX/CRT in diverse biological pathways.


Assuntos
Oligossacarídeos/química , Proteína G de Ligação ao Cálcio S100/química , Animais , Calbindina 2 , Cristalografia por Raios X , Dissulfetos , Humanos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Camundongos , Estrutura Terciária de Proteína , Relação Estrutura-Atividade
16.
J Biol Chem ; 285(46): 35551-7, 2010 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-20801878

RESUMO

Little is known about how chaperones in the endoplasmic reticulum are organized into complexes to assist in the proper folding of secreted proteins. One notable exception is the complex of ERp57 and calnexin that functions as part the calnexin cycle to direct disulfide bond formation in N-glycoproteins. Here, we report three new complexes composed of the peptidyl prolyl cis-trans-isomerase cyclophilin B and any of the lectin chaperones: calnexin, calreticulin, or calmegin. The 1.7 Å crystal structure of cyclophilin with the proline-rich P-domain of calmegin reveals that binding is mediated by the same surface that binds ERp57. We used NMR titrations and mutagenesis to measure low micromolar binding of cyclophilin to all three lectin chaperones and identify essential interfacial residues. The immunosuppressant cyclosporin A did not affect complex formation, confirming the functional independence of the P-domain binding and proline isomerization sites of cyclophilin. Our results reveal the P-domain functions as a unique protein-protein interaction domain and implicate a peptidyl prolyl isomerase as a new element in the calnexin cycle.


Assuntos
Calnexina/química , Calreticulina/química , Ciclofilinas/química , Isomerases de Dissulfetos de Proteínas/química , Estrutura Terciária de Proteína , Animais , Sítios de Ligação/genética , Proteínas de Ligação ao Cálcio/química , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Calnexina/genética , Calnexina/metabolismo , Calreticulina/genética , Calreticulina/metabolismo , Cristalografia por Raios X , Ciclofilinas/genética , Ciclofilinas/metabolismo , Humanos , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Chaperonas Moleculares/química , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Mutagênese Sítio-Dirigida , Mutação , Prolina/química , Prolina/genética , Prolina/metabolismo , Ligação Proteica , Isomerases de Dissulfetos de Proteínas/genética , Isomerases de Dissulfetos de Proteínas/metabolismo
17.
Rev. enferm. UERJ ; 9(1): 19-25, jan.-abr. 2001.
Artigo em Espanhol | LILACS, BDENF - Enfermagem | ID: lil-284367

RESUMO

Este artigo tem por objetivo utilizar o enfoque de intervençäo em Saúde da Família como instrumento para o manejo de pacientes terminais, aceitando-se que as relaçöes intrafamiliares desempenham uma fuçäo estratégica no aspecto psicológico individual e na preparaçäo da família para a luta...


Assuntos
Humanos , Cuidados Paliativos na Terminalidade da Vida/psicologia , Doente Terminal/psicologia , Saúde da Família
18.
Invest. educ. enferm ; 15(1): 81-92, mar. 1997.
Artigo em Espanhol | LILACS, BDENF - Enfermagem | ID: lil-354079

RESUMO

Para el estudio del maltrato infantiles fundamental que se aísle metodológicamente la causa de tal violencia. El presente artículo asboza una tipificación de las causas del maltrato infantil intrafamiliar en dos vías. En primer lugar, un enfoque microscópico o de carácter inductivo, en el que se analizan los factores intrafamiliares, surgidos de la incapacidad de los cuidadores para desempeñar normalmente su rol psicológico y personal. De otro lado, un enfoque de índole deductivo o macroscópico; en éste la explicación del malltrato infantil se desarrolla a partir de factores extrafamiliares, es decir, de causas generadas en el contexto social que rodea a la familia. los causales típicos de maltrato infantil intrafamiliar son: 1)autoritarismo, 2)marianismo, 3)necesidades basicas insatisfechas, 4)estrés, 5)vínculo filial indeseado, 6)disfunción conyugal, 7)marginalidad de las familias y 8)objetualización. Los extrafamiliares son aquellos que se derivan de la influencia de los aparatos ideológicos estatales y de la reproduccion de la violencia a través de un ciclo de enseñanza- aprendizaje denominado de pedagogía negra. Entre los aparatos ideológicos estatales se encuentran la escuela, la iglesia, los pares, la calle y los medios de comunicación. la pedagogía negra, por su parte, es un ciclo recurrente de reproducción del problema que declina en modelos de organización social autoritaria basado en los procesos de trasmición de hábitos y valores. Algunas posibles soluciones se apoyan en que el analista de salud familiar debe atender a un diagnóstico transdisciplinario que permita un tipo de intercvención en la familia en el sentido de identificar y reducir las causas del síndrome de maltrato infantil, en los sistemas familiar y social, que permita la ruptura de este ciclo de violencia.


Assuntos
Violência , Colômbia , Maus-Tratos Infantis , Violência Doméstica
19.
Invest. educ. enferm ; 14(2): 119-129, sept. 1996.
Artigo em Espanhol | LILACS, BDENF - Enfermagem | ID: lil-457863

RESUMO

Los cambios de la sociedad colombiana han generado un efecto de medios de masas que incorpora nuevos valores con aumento de los abusos derivados de la conjunción de la personalidad violenta del individuo colombiano con su sexualidad. Se necesita un colombiano dueño de una sexualidad integral, acorde con los requerimientos de pareja y familia, pues los nuevos modelos sociales cargan con el peso histórico de un proceso evolutivo tardío, con características anómalas de personalidad traducidos en comportamientos artificiosos. Se gira alrededor de una subcultura de la corpolatria, adoración del cuerpo y de sus características juveniles, alimentada por medios de masas, la realización en pareja sólo se justifica por el coito entre seres que se sienten solitarios. El sexo ha sido relacionado con vicios, delitos, violencia de todo género, amoralidad y problemática de la etapa juvenil. Colombia presenta las mismas características de toda sociedad en proceso de modernidad, en la que la democracia se traduce como un relativismo frente al bien y el mal. Ello significa un sistema cultural postradicional, en el cual la modernidad y la posmodernidad tardía que genera un problema sicosocioafectivo, ya no fisiosanitarioanatómico. Se debe pasar a un sistema mental abierto, en el que se parta de una visión general y múltiple con mejor comprensión del sexo.


Assuntos
Sexualidade , Educação Sexual
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