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Find video protocols related to scientific articles indexed in Pubmed.
Flexible Single Crystal Silicon Nanomembrane Photonic Crystal Cavity.
ACS Nano
PUBLISHED: 11-20-2014
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Flexible inorganic electronic devices promise numerous applications, especially in fields that could not be covered satisfactorily by conventional rigid devices. Benefits on a similar scale are also foreseeable for silicon photonic components. However, the difficulty in transferring intricate silicon photonic devices has deterred widespread development. In this paper, we demonstrate a flexible single crystal silicon nanomembrane photonic crystal microcavity through a bonding and substrate removal approach. The transferred cavity shows a quality factor of 2.2×10^4, and could be bended to a curvature of 5 mm radius without deteriorating the performance compared to its counterparts on rigid substrates. A thorough characterization of the device reveals that the resonant wavelength is a linear function of the bending-induced strain. The device also shows a curvature-independent sensitivity to the ambient index variation.
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Constrained TpV Minimization for Enhanced Exploitation of Gradient Sparsity: Application to CT Image Reconstruction.
IEEE J Transl Eng Health Med
PUBLISHED: 11-18-2014
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Exploiting sparsity in the image gradient magnitude has proved to be an effective means for reducing the sampling rate in the projection view angle in computed tomography (CT). Most of the image reconstruction algorithms, developed for this purpose, solve a nonsmooth convex optimization problem involving the image total variation (TV). The TV seminorm is the ? 1 norm of the image gradient magnitude, and reducing the ? 1 norm is known to encourage sparsity in its argument. Recently, there has been interest in employing nonconvex ?p quasinorms with 0
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?-catenin mediates stress resilience through Dicer1/microRNA regulation.
Nature
PUBLISHED: 10-20-2014
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?-catenin is a multi-functional protein that has an important role in the mature central nervous system; its dysfunction has been implicated in several neuropsychiatric disorders, including depression. Here we show that in mice ?-catenin mediates pro-resilient and anxiolytic effects in the nucleus accumbens, a key brain reward region, an effect mediated by D2-type medium spiny neurons. Using genome-wide ?-catenin enrichment mapping, we identify Dicer1-important in small RNA (for example, microRNA) biogenesis-as a ?-catenin target gene that mediates resilience. Small RNA profiling after excising ?-catenin from nucleus accumbens in the context of chronic stress reveals ?-catenin-dependent microRNA regulation associated with resilience. Together, these findings establish ?-catenin as a critical regulator in the development of behavioural resilience, activating a network that includes Dicer1 and downstream microRNAs. We thus present a foundation for the development of novel therapeutic targets to promote stress resilience.
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All-optical switching with 1-ps response time in a DDMEBT enabled silicon grating coupler/resonator hybrid device.
Opt Express
PUBLISHED: 10-17-2014
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An amorphous film of the third-order nonlinear optical material DDMEBT was spun onto silicon chips for the first time, filling 80 nm lithographic features. A 710 ?m2 device was designed, fabricated, and tested that acts both as a nonlinear resonator switch and as an input/output grating coupler to a perfectly vertical single mode fiber. Autocorrelation and spectral measurements indicate the device has <1 ps response time, 4 nm of switching bandwidth, and 4 dB of on/off contrast. With sufficient power, this all-optical device can potentially modulate a single optical carrier frequency in excess of 1 THz.
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Task-based optimization of dedicated breast CT via Hotelling observer metrics.
Med Phys
PUBLISHED: 10-06-2014
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The purpose of this work is to develop and demonstrate a set of practical metrics for CT systems optimization. These metrics, based on the Hotelling observer (HO) figure of merit, are task-based. The authors therefore take the specific example of optimizing a dedicated breast CT system, including the reconstruction algorithm, for two relevant tasks, signal detection and Rayleigh discrimination.
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Balloon-assisted endovascular treatment of intracranial dural arteriovenous fistulas.
Turk Neurosurg
PUBLISHED: 10-01-2014
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Most dural arteriovenous fistulas (DAVFs) can be treated safely and effectively with endovascular Onyx embolization. Balloon-assisted endovascular Onyx embolization of intracranial DAVFs is especially suitable for arterial protection and arterial flow reduction in complicated DAVFs. We systemically report our experience in the use of arterial balloon for Onyx embolization of DAVF and evaluate the clinical outcomes.
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Production of carbon occluded in phytolith is season-dependent in a bamboo forest in subtropical China.
PLoS ONE
PUBLISHED: 09-04-2014
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Carbon (C) occluded in phytolith (PhytOC) is a stable form of C; when PhytOC is returned to the soil through litterfall it is stored in the soil which can be an effective way for long-term C sequestration. However, few estimates on the rate of PhytOC input to the soil are available. To better understand the seasonal dynamics of PhytOC production and the annual rate of stable C sequestration through PhytOC input, we quantified the monthly litterfall, phytolith and PhytOC return to the soil over a year in a typical Lei bamboo (Phyllostachys praecox) forest in subtropical China. The monthly litterfall ranged between 14.81 and 131.18 g m(-2), and the phytolith concentration in the monthly litterfall samples ranged between 47.21 and 101.68 g kg(-1) of litter mass, with the PhytOC concentration in the phytolith ranged between 29.4 and 44.9 g kg(-1) of phytolith, equivalent to 1.8-3.6 g kg(-1) of PhytOC in the litterfall (based on litterfall dry mass). The amount of phytolith input to the soil system was 292.21 ± 69.12 (mean ± SD) kg ha(-1) yr(-1), sequestering 41.45 ± 9.32 kg CO2-e ha(-1) yr(-1) of C in the studied Lei bamboo forest. This rate of C sequestration through the formation of PhytOC found in this study falls within the range of rates for other grass-type species reported in the literature. We conclude that return of C occluded in phytolith to the soil can be a substantial source of stable soil C and finding means to increase PhytOC storage in the soil should be able to play a significant role in mitigating the rapidly increasing atmospheric CO2 concentration.
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X-ray tomography system to investigate granular materials during mechanical loading.
Rev Sci Instrum
PUBLISHED: 09-01-2014
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We integrate a small and portable medical x-ray device with mechanical testing equipment to enable in situ, non-invasive measurements of a granular material's response to mechanical loading. We employ an orthopedic C-arm as the x-ray source and detector to image samples mounted in the materials tester. We discuss the design of a custom rotation stage, which allows for sample rotation and tomographic reconstruction under applied compressive stress. We then discuss the calibration of the system for 3D computed tomography, as well as the subsequent image reconstruction process. Using this system to reconstruct packings of 3D-printed particles, we resolve packing features with 0.52?mm resolution in a (60 mm)(3) field of view. By analyzing the performance bounds of the system, we demonstrate that the reconstructions exhibit only moderate noise.
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Global variation in the effects of ambient temperature on mortality: a systematic evaluation.
Epidemiology
PUBLISHED: 08-29-2014
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Studies have examined the effects of temperature on mortality in a single city, country, or region. However, less evidence is available on the variation in the associations between temperature and mortality in multiple countries, analyzed simultaneously.
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Combination Approaches to Attenuate Hemorrhagic Transformation After tPA Thrombolytic Therapy in Patients with Poststroke Hyperglycemia/Diabetes.
Adv. Pharmacol.
PUBLISHED: 08-22-2014
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To date, tissue type plasminogen activator (tPA)-based thrombolytic stroke therapy is the only FDA-approved treatment for achieving vascular reperfusion and clinical benefit, but this agent is given to only about 5% of stroke patients in the USA. This may be related, in part, to the elevated risk of symptomatic intracranial hemorrhage, and consequently limited therapeutic time window. Clinical investigations demonstrate that poststroke hyperglycemia is one of the most important risk factors that cause intracerebral hemorrhage and worsen neurological outcomes. There is a knowledge gap in understanding the underlying molecular mechanisms, and lack of effective therapeutics targeting the severe complication. This short review summarizes clinical observations and experimental investigations in preclinical stroke models of the field. The data strongly suggest that interactions of multiple pathogenic factors including hyperglycemia-mediated vascular oxidative stress and inflammation, ischemic insult, and tPA neurovascular toxicity in concert contribute to the BBB damage-intracerebral hemorrhagic transformation process. Development of combination approaches targeting the multiple pathological cascades may help to attenuate the hemorrhagic complication.
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A new approach to asymmetric synthesis of infectocaryone.
Org. Biomol. Chem.
PUBLISHED: 08-22-2014
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A useful and flexible strategy for synthesis of (-)- and (+)-infectocaryone from commercial sugars is developed. The key step of the synthesis is a new-type Diels-Alder reaction with good chemoselectivity and stereoselectivity, in which a mixture of alkene regioisomers in a dynamic equilibrium is employed as chiral dienophiles for the first time.
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Pollution and skin: From epidemiological and mechanistic studies to clinical implications.
J. Dermatol. Sci.
PUBLISHED: 07-31-2014
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In recent years, the health effects associated with air pollution have been intensively studied. Most studies focus on air pollution effects on the lung and the cardiovascular system. More recently, however, epidemiological and mechanistic studies suggest that air pollution is also affecting skin integrity. This state-of-the-art review focuses on this latter aspect; it was developed with the collaboration of European and Chinese board of experts with specific interests in environmental health, clinical and basic research in dermatology and cosmetic dermatology. A literature review limited to pollution and health effects and (sensitive) skin was performed using PubMed. Review and original articles were chosen. We summarize the existing scientific evidence that air pollution exerts detrimental effects on human skin, discuss potential clinical implications and suggest specific and unspecific cosmetic protective measures.
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Association of the paired box 2 gene polymorphism with the susceptibility and pathogenesis of Henoch?Schönlein purpura in children.
Mol Med Rep
PUBLISHED: 07-01-2014
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The present study aimed to investigate the distribution of paired box 2 (PAX2) gene polymorphisms in healthy populations and in patients with Henoch?Schönlein purpura (HSP), focusing on the association between PAX2 gene polymorphisms and the susceptibility and clinical characteristics of HSP. Genomic DNA was extracted from the peripheral venous blood of 100 healthy children (mean age: 5±1.9 years) and 118 children with HSP (mean age: 10.2±2.3 years). Polymerase chain reaction (PCR) was used to amplify exons 1?12 of the PAX2 gene. Denaturing high performance liquid chromatography and DNA sequencing analysis were conducted for screening of mutations in the PAX2 gene in the PCR products. No genetic polymorphism of the PAX2 gene was identified in exons 1?7, 9, 10 or 12. Two single nucleotide polymorphisms (SNPs), which presented as complete linkage haplotype 798C>T/909A>C, were identified in exon 8. An SNP (1164T>A) was also identified in exon 11. No significant difference in the allele and genotype frequency distribution of exon 8 (798C>T) or 11 (1164T>A) of the PAX2 gene was identified between the HSP and control groups (P>0.05). However, the frequency of the PAX2 heterozygous genotype 798C>T in the HSP with nephritis (HSPN) group was significantly higher than those in the controls and in the HSP without nephritis group (P<0.05). Furthermore, no significant correlation was identified between the PAX2 gene exon 8 polymorphism (798 C>T) and the renal pathology of children with HSPN. An SNP (1164T>A) was identified in exon 11. The PAX2 heterozygous genotype 798C>T did not increase susceptibility to HSP, however, it may be used clinically as a screening indicator for HSP in children with a high risk of renal involvement.
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Grating-coupled silicon-on-sapphire integrated slot waveguides operating at mid-infrared wavelengths.
Opt Lett
PUBLISHED: 07-01-2014
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We demonstrate subwavelength bidirectional grating (SWG) coupled slot waveguide fabricated in silicon-on-sapphire for transverse electric polarized wave operation at 3.4 ?m wavelength. Coupling efficiency of 29% for SWG coupler is experimentally achieved. Propagation loss of 11??dB/cm has been experimentally obtained for slot waveguides. Two-step taper mode converters with an insertion loss of 0.13 dB are used to gradually convert the strip waveguide mode into slot waveguide mode.
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Simvastatin attenuates angiotensin II?induced inflammation and oxidative stress in human mesangial cells.
Mol Med Rep
PUBLISHED: 06-20-2014
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Chronic kidney disease (CKD) is an intractable disease in which inflammation and oxidative stress are important. In the present study, the effect of simvastatin on inflammation and oxidative stress induced by angiotensin II (Ang II) in human mesangial cells (HMCs) and its corresponding mechanism was examined. In the in vitro experiment, HMCs were pretreated either without additives (control group) or with simvastatin at different concentrations (0, 0.1, 1 or 10 µM) for 1 h and were then stimulated by Ang II (1 µM) for 24 h. Following stimulation, the cells were collected for analysis using quantitative polymerase chain reaction, western blotting and dihydroethidium staining. The supernatant of the cells was collected and analyzed using an enzyme?linked immunosorbent assay. The results demonstrated that simvastatin suppressed the increased mRNA expression of monocyte chemoattractant protein?1, tumor necrosis factor??, interleukin (IL)?1? and IL?6 and the content of reactive oxygen species induced by Ang II in a dose?dependent manner. In addition, simvastatin decreased the protein expression of cyclooxygenase?2 (COX?2), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and protein kinase C (PKC) as well as the content of prostaglandin E2 and the phosphorylation level of nuclear factor??B (NF??B) p65 in a dose?dependent manner. Furthermore, simvastatin significantly increased the protein expression of peroxisome proliferator?activated receptor ? (PPAR?). Therefore, simvastatin suppressed inflammation and oxidative stress in Ang II?stimulated HMCs via COX?2, PPAR?, NF??B, NADPH oxidase and PKCs, thereby exerting a protective effect on CKD.
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Separation and enrichment of enantiopure from racemic compounds using magnetic levitation.
Chem. Commun. (Camb.)
PUBLISHED: 05-31-2014
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Crystallization of a solution with high enantiomeric excess can generate a mixture of crystals of the desired enantiomer and the racemic compound. Using a mixture of S-/RS-ibuprofen crystals as a model, we demonstrated that magnetic levitation (MagLev) is a useful technique for analysis, separation and enantioenrichment of chiral/racemic products.
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Natural Higgs mass in supersymmetry from nondecoupling effects.
Phys. Rev. Lett.
PUBLISHED: 05-14-2014
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The Higgs mass implies fine-tuning for minimal theories of weak-scale supersymmetry (SUSY). Nondecoupling effects can boost the Higgs mass when new states interact with the Higgs boson, but new sources of SUSY breaking that accompany such extensions threaten naturalness. We show that two singlets with a Dirac mass can increase the Higgs mass while maintaining naturalness in the presence of large SUSY breaking in the singlet sector. We explore the modified Higgs phenomenology of this scenario, which we call the "Dirac next-to-minimal supersymmetric standard model."
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Investigation of iterative image reconstruction in low-dose breast CT.
Phys Med Biol
PUBLISHED: 05-01-2014
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There is interest in developing computed tomography (CT) dedicated to breast-cancer imaging. Because breast tissues are radiation-sensitive, the total radiation exposure in a breast-CT scan is kept low, often comparable to a typical two-view mammography exam, thus resulting in a challenging low-dose-data-reconstruction problem. In recent years, evidence has been found that suggests that iterative reconstruction may yield images of improved quality from low-dose data. In this work, based upon the constrained image total-variation minimization program and its numerical solver, i.e., the adaptive steepest descent-projection onto the convex set (ASD-POCS), we investigate and evaluate iterative image reconstructions from low-dose breast-CT data of patients, with a focus on identifying and determining key reconstruction parameters, devising surrogate utility metrics for characterizing reconstruction quality, and tailoring the program and ASD-POCS to the specific reconstruction task under consideration. The ASD-POCS reconstructions appear to outperform the corresponding clinical FDK reconstructions, in terms of subjective visualization and surrogate utility metrics.
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Chronic cocaine-regulated epigenomic changes in mouse nucleus accumbens.
Genome Biol.
PUBLISHED: 04-22-2014
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Increasing evidence supports a role for altered gene expression in mediating the lasting effects of cocaine on the brain, and recent work has demonstrated the involvement of chromatin modifications in these alterations. However, all such studies to date have been restricted by their reliance on microarray technologies that have intrinsic limitations.
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Low Al-composition p-GaN/Mg-doped Al0.25Ga0.75N/n+-GaN polarization-induced backward tunneling junction grown by metal-organic chemical vapor deposition on sapphire substrate.
Sci Rep
PUBLISHED: 04-17-2014
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Low Al-composition p-GaN/Mg-doped Al0.25Ga0.75N/n(+)-GaN polarization-induced backward tunneling junction (PIBTJ) was grown by metal-organic chemical vapor deposition on sapphire substrate. A self-consistent solution of Poisson-Schrödinger equations combined with polarization-induced theory was used to model PIBTJ structure, energy band diagrams and free carrier concentrations distribution. The PIBTJ displays reliable and reproducible backward tunneling with a current density of 3?A/cm(2) at the reverse bias of -1?V. The absence of negative differential resistance behavior of PIBTJ at forward bias can mainly be attributed to the hole compensation centers, including C, H and O impurities, accumulated at the p-GaN/Mg-doped AlGaN heterointerface.
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An atomic model of the tropomyosin cable on F-actin.
Biophys. J.
PUBLISHED: 04-17-2014
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Tropomyosin regulates a wide variety of actin filament functions and is best known for the role that it plays together with troponin in controlling muscle activity. For effective performance on actin filaments, adjacent 42-nm-long tropomyosin molecules are joined together by a 9- to 10-residue head-to-tail overlapping domain to form a continuous cable that wraps around the F-actin helix. Yet, despite the apparent simplicity of tropomyosin's coiled-coil structure and its well-known periodic association with successive actin subunits along F-actin, the structure of the tropomyosin cable on actin is uncertain. This is because the conformation of the overlap region that joins neighboring molecules is poorly understood, thus leaving a significant gap in our understanding of thin-filament structure and regulation. However, recent molecular-dynamics simulations of overlap segments defined their overall shape and provided unique and sufficient cues to model the whole actin-tropomyosin filament assembly in atomic detail. In this study, we show that these MD structures merge seamlessly onto the ends of tropomyosin coiled-coils. Adjacent tropomyosin molecules can then be joined together to provide a comprehensive model of the tropomyosin cable running continuously on F-actin. The resulting complete model presented here describes for the first time (to our knowledge) an atomic-level structure of ??-striated muscle tropomyosin bound to an actin filament that includes the critical overlap domain. Thus, the model provides a structural correlate to evaluate thin-filament mechanics, self-assembly mechanisms, and the effect of disease-causing mutations.
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The impact of ambient particle pollution during extreme-temperature days in guangzhou city, china.
Asia Pac J Public Health
PUBLISHED: 04-14-2014
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The aim of this study is to explore whether the effect of PM10 (particulate matter with an aerodynamic diameter of <10 µm) on daily mortality was modified by extreme temperatures in Guangzhou from 2005 to 2009. The present study used time-series analysis to explore the modification effects of temperature on the association between PM10 and the cause-specific mortalities for cardiovascular, respiratory, cardiopulmonary, and nonaccidental mortality. The interactions between PM10 and temperature were statistically significant on respiratory mortality. The effect estimates per 10-µg/m(3) increase in PM10 concentrations at the moving average of lags of 0 and 1 day on high-temperature days were 2.34% (95% confidence interval = 0.55, 4.16) for nonaccidental, 1.35% (-1.69, 4.48) for cardiovascular, 6.09% (2.42, 9.89) for respiratory, and 3.36% (0.92, 5.86) for cardiopulmonary mortalities. The results suggest that it is important to control and reduce the emission of air particles in Guangzhou, particularly on extreme-high-temperature days.
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Thermal-triggerd proteinquake leads to disassembly of DegP hexamer as an imperative activation step.
Sci Rep
PUBLISHED: 04-11-2014
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The Escherichia coli DegP has been reported to function both as molecular chaperone and protease for the quality control of outer membrane protein biogenesis. Activation of the inactive DegP hexamers was believed to occur via their disassembly into trimeric units and subsequent reassembly into larger oligomers (12-mers and 24-mers). Here, we analyzed the thermal stability and the unfolding dynamics of the different secondary structure components of the DegP hexamers using Fourier transform infrared spectroscopy and temperature-jump nanosecond time-resolved IR difference absorbance spectroscopy. We found that the interfacial secondary structure components possess a degreed thermal stability, with the disassembly of the DegP hexamers follows a "proteinquake" manner, such that the fully exposed parts of the interfacial ?-sheets serving as the temperature sensor and epicenter to drive the sequential unfolding/disassembly process that finishes within about 134?ns at room temperature.
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The association between ambient temperature and children's lung function in Baotou, China.
Int J Biometeorol
PUBLISHED: 04-10-2014
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The objective of this study is to examine the association between ambient temperature and children's lung function in Baotou, China. We recruited 315 children (8-12 years) from Baotou, China in the spring of 2004, 2005, and 2006. They performed three successive forced expiratory measurements three times daily (morning, noon, and evening) for about 5 weeks. The highest peak expiratory flow (PEF) was recorded for each session. Daily data on ambient temperature, relative humidity, and air pollution were monitored during the same period. Mixed models with a distributed lag structure were used to examine the effects of temperature on lung function while adjusting for individual characteristics and environmental factors. Low temperatures were significantly associated with decreases in PEF. The effects lasted for lag 0-2 days. For all participants, the cumulative effect estimates (lag 0-2 days) were -1.44 (-1.93, -0.94) L/min, -1.39 (-1.92, -0.86) L/min, -1.40 (-1.97, -0.82) L/min, and -1.28 (-1.69, -0.88) L/min for morning, noon, evening, and daily mean PEF, respectively, associated with 1 °C decrease in daily mean temperature. Generally, the effects of temperature were slightly stronger in boys than in girls for noon, evening, and daily mean PEF, while the effects were stronger in girls for morning PEF. PM2.5 had joint effects with temperature on children's PEF. Higher PM2.5 increased the impacts of low temperature. Low ambient temperatures are associated with lower lung function in children in Baotou, China. Preventive health policies will be required for protecting children from the cold weather.
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Intravenous administration of Honokiol provides neuroprotection and improves functional recovery after traumatic brain injury through cell cycle inhibition.
Neuropharmacology
PUBLISHED: 03-30-2014
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Recently, increasing evidence has shown that cell cycle activation is a key factor of neuronal death and neurological dysfunction after traumatic brain injury (TBI). This study aims to investigate the effects of Honokiol, a cell cycle inhibitor, on attenuating the neuronal damage and facilitating functional recovery after TBI in rats, in an attempt to unveil its underlying molecular mechanisms in TBI. This study suggested that delayed intravenous administration of Honokiol could effectively ameliorate TBI-induced sensorimotor and cognitive dysfunctions. Meanwhile, Honokiol treatment could also reduce the lesion volume and increase the neuronal survival in the cortex and hippocampus. The neuronal degeneration and apoptosis in the cortex and hippocampus were further significantly attenuated by Honokiol treatment. In addition, the expression of cell cycle-related proteins, including cyclin D1, CDK4, pRb and E2F1, was significantly increased and endogenous cell cycle inhibitor p27 was markedly decreased at different time points after TBI. And these changes were significantly reversed by post-injury Honokiol treatment. Furthermore, the expression of some of the key cell cycle proteins such as cyclin D1 and E2F1 and the associated apoptosis in neurons were both remarkably attenuated by Honokiol treatment. These results show that delayed intravenous administration of Honokiol could effectively improve the functional recovery and attenuate the neuronal cell death, which is probably, at least in part, attributed to its role as a cell cycle inhibitior. This might give clues to developing attractive therapies for future clinical trials.
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The effects of ambient temperature on cerebrovascular mortality: an epidemiologic study in four climatic zones in China.
Environ Health
PUBLISHED: 03-26-2014
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Little evidence is available about the association between temperature and cerebrovascular mortality in China. This study aims to examine the effects of ambient temperature on cerebrovascular mortality in different climatic zones in China.
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Analysis of ultra-high sensitivity configuration in chip-integrated photonic crystal microcavity bio-sensors.
Appl Phys Lett
PUBLISHED: 03-13-2014
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We analyze the contributions of quality factor, fill fraction, and group index of chip-integrated resonance microcavity devices, to the detection limit for bulk chemical sensing and the minimum detectable biomolecule concentration in biosensing. We analyze the contributions from analyte absorbance, as well as from temperature and spectral noise. Slow light in two-dimensional photonic crystals provide opportunities for significant reduction of the detection limit below 1?×?10(-7) RIU (refractive index unit) which can enable highly sensitive sensors in diverse application areas. We demonstrate experimentally detected concentration of 1 fM (67 fg/ml) for the binding between biotin and avidin, the lowest reported till date.
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Role of vitamin D3 in regulation of T helper cell 17 and regulatory T-cell balance in rats with immunoglobulin a nephropathy.
Iran J Kidney Dis
PUBLISHED: 03-08-2014
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Dysregulation of CD4+ T cell subsets participates in the pathogenesis of immunoglobulin A nephropathy (IgAN). Vitamin D has immunomodulatory functions. This study aims to investigate the regulatory effect of vitamin D3 on T helper- regulatory T (Th17-Treg) cells balance in rats with IgAN.
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On-chip silicon optical phased array for two-dimensional beam steering.
Opt Lett
PUBLISHED: 02-25-2014
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A 16-element optical phased array integrated on chip is presented for achieving two-dimensional (2D) optical beam steering. The device is fabricated on the silicon-on-insulator platform with a 250 nm silicon device layer. Steering is achieved via a combination of wavelength tuning and thermo-optic phase shifting with a switching power of P(?)=20??mW per channel. Using a silicon waveguide grating with a polycrystalline silicon overlay enables narrow far field beam widths while mitigating the precise etching needed for conventional shallow etch gratings. Using this system, 2D steering across a 20°×15° field of view is achieved with a sidelobe level better than 10 dB and with beam widths of 1.2°×0.5°.
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Structure and flexibility of the tropomyosin overlap junction.
Biochem. Biophys. Res. Commun.
PUBLISHED: 02-12-2014
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To be effective as a gatekeeper regulating the access of binding proteins to the actin filament, adjacent tropomyosin molecules associate head-to-tail to form a continuous super-helical cable running along the filament surface. Chimeric head-to-tail structures have been solved by NMR and X-ray crystallography for N- and C-terminal segments of smooth and striated muscle tropomyosin spliced onto non-native coiled-coil forming peptides. The resulting 4-helix complexes have a tight coiled-coil N-terminus inserted into a separated pair of C-terminal helices, with some helical unfolding of the terminal chains in the striated muscle peptides. These overlap complexes are distinctly curved, much more so than elsewhere along the superhelical tropomyosin cable. To verify whether the non-native protein adducts (needed to stabilize the coiled-coil chimeras) perturb the overlap, we carried out Molecular Dynamics simulations of head-to-tail structures having only native tropomyosin sequences. We observe that the splayed chains all refold and become helical. Significantly, the curvature of both the smooth and the striated muscle overlap domain is reduced and becomes comparable to that of the rest of the tropomyosin cable. Moreover, the measured flexibility across the junction is small. This and the reduced curvature ensure that the super-helical cable matches the contours of F-actin without manifesting localized kinking and excessive flexibility, thus enabling the high degree of cooperativity in the regulation of myosin accessibility to actin filaments.
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ngs.plot: Quick mining and visualization of next-generation sequencing data by integrating genomic databases.
BMC Genomics
PUBLISHED: 02-04-2014
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Understanding the relationship between the millions of functional DNA elements and their protein regulators, and how they work in conjunction to manifest diverse phenotypes, is key to advancing our understanding of the mammalian genome. Next-generation sequencing technology is now used widely to probe these protein-DNA interactions and to profile gene expression at a genome-wide scale. As the cost of DNA sequencing continues to fall, the interpretation of the ever increasing amount of data generated represents a considerable challenge.
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Directed neurite growth of rat dorsal root ganglion neurons and increased colocalization with Schwann cells on aligned poly(methyl methacrylate) electrospun nanofibers.
Brain Res.
PUBLISHED: 02-04-2014
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Electrospun nanofibers are promising scaffolds for peripheral and central nervous system repair. The aim of this study was to examine the details of neurite growth of rat dorsal root ganglion neurons (DRGn) on randomly oriented and aligned poly(methyl methacrylate) (PMMA) nanofibers and the relationship between neurites and nanofibers on each substrate. Our substrate design involved electrospinning PMMA nanofibers directly onto bare glass coverslips with acceptable biocompatibility. We cocultured DRGn and Schwann cells on PMMA nanofibers and evaluated their response to each substrate. Compared with neurons cultured on PMMA film and randomly oriented nanofibers, DRGn on aligned PMMA nanofibers formed longer, parallel neurites in accordance with the orientation of the substrate nanofibers, although the average neurite number did not differ among the three groups. Regarding the relationship between neurites and nanofibers, the neurites of DRGn were in close contact with the substrate nanofibers, and the neurites seemed to follow aligned nanofibers more than randomly oriented nanofibers. Coculturing DRGn and Schwann cells on PMMA nanofibers revealed that on aligned nanofibers, neurites and Schwann cells had a higher chance of colocalization than on randomly oriented nanofibers or film; this colocalization may be beneficial during the process of myelination that follows. The results of this study enhance our understanding of the ability of aligned electrospun nanofibers to provide contact guidance to neural cells and strengthen the rationale for future in vivo studies.
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A rapid and efficient access to renieramycin-type alkaloids featuring a temperature-dependent stereoselective cyclization.
Org. Biomol. Chem.
PUBLISHED: 01-30-2014
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A flexible and practical protocol for the asymmetric synthesis of renieramycin-type antitumor alkaloids is described, in which the stereoselective Pictet-Spengler cyclization of amino ester 16 and aldehyde 15 by regulating temperature and the automatic lactamization after N-deprotection of the cyclization product are exploited to rapidly construct the common pentacyclic framework. (-)-Renieramycin G and (-)-jorunnamycin A, as representative members of the two subgroup renieramycin-type alkaloids, are obtained in 19 steps from l-tyrosine with 15.8% and 14.3% overall yield respectively.
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Reward inference by primate prefrontal and striatal neurons.
J. Neurosci.
PUBLISHED: 01-24-2014
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The brain contains multiple yet distinct systems involved in reward prediction. To understand the nature of these processes, we recorded single-unit activity from the lateral prefrontal cortex (LPFC) and the striatum in monkeys performing a reward inference task using an asymmetric reward schedule. We found that neurons both in the LPFC and in the striatum predicted reward values for stimuli that had been previously well experienced with set reward quantities in the asymmetric reward task. Importantly, these LPFC neurons could predict the reward value of a stimulus using transitive inference even when the monkeys had not yet learned the stimulus-reward association directly; whereas these striatal neurons did not show such an ability. Nevertheless, because there were two set amounts of reward (large and small), the selected striatal neurons were able to exclusively infer the reward value (e.g., large) of one novel stimulus from a pair after directly experiencing the alternative stimulus with the other reward value (e.g., small). Our results suggest that although neurons that predict reward value for old stimuli in the LPFC could also do so for new stimuli via transitive inference, those in the striatum could only predict reward for new stimuli via exclusive inference. Moreover, the striatum showed more complex functions than was surmised previously for model-free learning.
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Liquid-metal electrode to enable ultra-low temperature sodium-beta alumina batteries for renewable energy storage.
Nat Commun
PUBLISHED: 01-22-2014
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Commercial sodium-sulphur or sodium-metal halide batteries typically need an operating temperature of 300-350?°C, and one of the reasons is poor wettability of liquid sodium on the surface of beta alumina. Here we report an alloying strategy that can markedly improve the wetting, which allows the batteries to be operated at much lower temperatures. Our combined experimental and computational studies suggest that addition of caesium to sodium can markedly enhance the wettability. Single cells with Na-Cs alloy anodes exhibit great improvement in cycling life over those with pure sodium anodes at 175 and 150?°C. The cells show good performance even at as low as 95?°C. These results demonstrate that sodium-beta alumina batteries can be operated at much lower temperatures with successfully solving the wetting issue. This work also suggests a strategy to use liquid metals in advanced batteries that can avoid the intrinsic safety issues associated with dendrite formation.
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Transmission and evolution of hepatitis C virus in HCV seroconverters in HIV infected subjects.
Virology
PUBLISHED: 01-15-2014
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HIV/HCV co-infection provides a model to determine the role of immunity on HCV transmission and evolution. In this study HCV transmission and evolution were evaluated in 6 HCV seroconverters in HIV-infected subjects with a wide range of CD4 cell count. The HCV envelope E1/E2 sequences were analyzed for transmission bottleneck, viral diversity/divergence, immune pressure, and mutations of HLA class I/II restricted epitopes. HCV infection started with transmission bottleneck in all HIV-infected individuals. During the 1.0-2.0 years of infection there was a shift of viral quasispecies in majority of the subjects from one to next visit. However, HCV diversity, divergence, mutations in HLA class I/II restricted and virus neutralizing epitopes were similar in all subjects regardless of CD4 cell count at the time of HCV infection. Our results suggest that HCV transmission and evolution in HIV-infected subjects may not be influenced by host CD4 cell count at the time of infection.
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Association between particulate matter and its chemical constituents of urban air pollution and daily mortality or morbidity in Beijing City.
Environ Sci Pollut Res Int
PUBLISHED: 01-05-2014
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Recent time series studies have indicated that daily mortality and morbidity are associated with particulate matters. However, about the relative effects and its seasonal patterns of fine particulate matter constituents is particularly limited in developing Asian countries. In this study, we examined the role of particulate matters and its key chemical components of fine particles on both mortality and morbidity in Beijing. We applied several overdispersed Poisson generalized nonlinear models, adjusting for time, day of week, holiday, temperature, and relative humidity, to investigate the association between risk of mortality or morbidity and particulate matters and its constituents in Beijing, China, for January 2005 through December 2009. Particles and several constituents were associated with multiple mortality or morbidity categories, especially on respiratory health. For a 3-day lag, the nonaccident mortality increased by 1.52, 0.19, 1.03, 0.56, 0.42, and 0.32 % for particulate matter (PM)2.5, PM10, K(+), SO4 (2-), Ca(2+), and NO3 (-) based on interquartile ranges of 36.00, 64.00, 0.41, 8.75, 1.43, and 2.24 ?g/m(3), respectively. The estimates of short-term effects for PM2.5 and its components in the cold season were 1?~?6 times higher than that in the full year on these health outcomes. Most of components had stronger adverse effects on human health in the heavy PM2.5 mass concentrations, especially for K(+), NO3 (-), and SO4 (2-). This analysis added to the growing body of evidence linking PM2.5 with mortality or morbidity and indicated that excess risks may vary among specific PM2.5 components. Combustion-related products, traffic sources, vegetative burning, and crustal component and resuspended road dust may play a key role in the associations between air pollution and public health in Beijing.
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The burden of air pollution on years of life lost in Beijing, China, 2004-08: retrospective regression analysis of daily deaths.
BMJ
PUBLISHED: 12-11-2013
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To better understand the burden of air pollution on deaths, we examined the effects of air pollutants on years of life lost (YLL) in Beijing, China.
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Enhanced insulin secretion responsiveness and islet adrenergic desensitization after chronic norepinephrine suppression is discontinued in fetal sheep.
Am. J. Physiol. Endocrinol. Metab.
PUBLISHED: 11-19-2013
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Intrauterine growth-restricted (IUGR) fetuses experience prolonged hypoxemia, hypoglycemia, and elevated norepinephrine (NE) concentrations, resulting in hypoinsulinemia and ?-cell dysfunction. Previously, we showed that acute adrenergic blockade revealed enhanced insulin secretion responsiveness in the IUGR fetus. To determine whether chronic exposure to NE alone enhances ?-cell responsiveness afterward, we continuously infused NE into fetal sheep for 7 days and, after terminating the infusion, evaluated glucose-stimulated insulin secretion (GSIS) and glucose-potentiated arginine-induced insulin secretion (GPAIS). During treatment, NE-infused fetuses had greater (P < 0.05) plasma NE concentrations and exhibited hyperglycemia (P < 0.01) and hypoinsulinemia (P < 0.01) compared with controls. GSIS during the NE infusion was also reduced (P < 0.05) compared with pretreatment values. GSIS and GPAIS were approximately fourfold greater (P < 0.01) in NE fetuses 3 h after the 7 days that NE infusion was discontinued compared with age-matched controls or pretreatment GSIS and GPAIS values of NE fetuses. In isolated pancreatic islets from NE fetuses, mRNA concentrations of adrenergic receptor isoforms (?1D, ?2A, ?2C, and ?1), G protein subunit-?i-2, and uncoupling protein 2 were lower (P < 0.05) compared with controls, but ?-cell regulatory genes were not different. Our findings indicate that chronic exposure to elevated NE persistently suppresses insulin secretion. After removal, NE fetuses demonstrated a compensatory enhancement in insulin secretion that was associated with adrenergic desensitization and greater stimulus-secretion coupling in pancreatic islets.
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LSD 2.0: an update of the leaf senescence database.
Nucleic Acids Res.
PUBLISHED: 10-31-2013
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This manuscript describes an update of the leaf senescence database (LSD) previously featured in the 2011 NAR Database Issue. LSD provides comprehensive information concerning senescence-associated genes (SAGs) and their corresponding mutants. We have made extensive annotations for these SAGs through both manual and computational approaches. Recently, we updated LSD to a new version LSD 2.0 (http://www.eplantsenescence.org/), which contains 5356 genes and 322 mutants from 44 species, an extension from the previous version containing 1145 genes and 154 mutants from 21 species. In the current version, we also included several new features: (i) Primer sequences retrieved based on experimental evidence or designed for high-throughput analysis were added; (ii) More than 100 images of Arabidopsis SAG mutants were added; (iii) Arabidopsis seed information obtained from The Arabidopsis Information Resource (TAIR) was integrated; (iv) Subcellular localization information of SAGs in Arabidopsis mined from literature or generated from the SUBA3 program was presented; (v) Quantitative Trait Loci information was added with links to the original database and (vi) New options such as primer and miRNA search for database query were implemented. The updated database will be a valuable and informative resource for basic research of leaf senescence and for the manipulation of traits of agronomically important plants.
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Essential role of SIRT1 signaling in the nucleus accumbens in cocaine and morphine action.
J. Neurosci.
PUBLISHED: 10-11-2013
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Sirtuins (SIRTs), class III histone deacetylases, are well characterized for their control of cellular physiology in peripheral tissues, but their influence in brain under normal and pathological conditions remains poorly understood. Here, we establish an essential role for SIRT1 and SIRT2 in regulating behavioral responses to cocaine and morphine through actions in the nucleus accumbens (NAc), a key brain reward region. We show that chronic cocaine administration increases SIRT1 and SIRT2 expression in the mouse NAc, while chronic morphine administration induces SIRT1 expression alone, with no regulation of all other sirtuin family members observed. Drug induction of SIRT1 and SIRT2 is mediated in part at the transcriptional level via the drug-induced transcription factor ?FosB and is associated with robust histone modifications at the Sirt1 and Sirt2 genes. Viral-mediated overexpression of SIRT1 or SIRT2 in the NAc enhances the rewarding effects of both cocaine and morphine. In contrast, the local knockdown of SIRT1 from the NAc of floxed Sirt1 mice decreases drug reward. Such behavioral effects of SIRT1 occur in concert with its regulation of numerous synaptic proteins in NAc as well as with SIRT1-mediated induction of dendritic spines on NAc medium spiny neurons. These studies establish sirtuins as key mediators of the molecular and cellular plasticity induced by drugs of abuse in NAc, and of the associated behavioral adaptations, and point toward novel signaling pathways involved in drug action.
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Ultralow-loss silicon waveguide crossing using Bloch modes in index-engineered cascaded multimode-interference couplers.
Opt Lett
PUBLISHED: 10-10-2013
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We investigate the loss mechanism in three-moded multimode-interference couplers that are the building blocks of a compact and low-loss waveguide crossing structure. Broadband silicon waveguide crossing arrays with <0.01??dB insertion loss per crossing are proposed using cascaded multimode-interference couplers, where lateral subwavelength nanostructures are used to reduce the insertions loss. We design and fabricate a 101×101 waveguide crossing array with a pitch of 3.08 ?m. Insertion loss of ?0.02??dB per crossing and crosstalk <-40??dB at 1550 nm operating wavelength and a broad transmission spectrum ranging from 1520 to 1610 nm are experimentally demonstrated.
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Colorless grating couplers realized by interleaving dispersion engineered subwavelength structures.
Opt Lett
PUBLISHED: 10-10-2013
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We investigate the waveguide dispersion of subwavelength structures, and propose that the waveguide dispersion can be reduced by reducing the period of subwavelength structures. A 3 dB bandwidth increment of 20% has been observed by introducing this concept into previously demonstrated grating couplers. To fully exploit the bandwidth merits of the structures, gratings with interleaved subwavelength structures were designed and fabricated. Two typical types of interleaving geometries have been investigated. Both demonstrated a 1 dB bandwidth ?70??nm, a 3 dB bandwidth ?117??nm, and a peak efficiency ?-5.1??dB at 1570 nm for transverse-electric polarized light. The simulation confirms that the dispersion engineering adds an extra 12 nm to the 1 dB bandwidth.
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Rheumatoid Arthritis-Associated MicroRNA-155 Targets SOCS1 and Upregulates TNF-? and IL-1? in PBMCs.
Int J Mol Sci
PUBLISHED: 09-25-2013
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miR-155 plays a crucial role in proinflammatory activation. This study was carried out to assess the association of abnormal expression of miR-155 in peripheral blood of patients with Rheumatoid arthritis with the expression of TNF-? and IL-1?. Release of TNF-? and IL-1?, and expression of miR-155 were determined in RA peripheral blood or peripheral blood macrophages, followed by correlation analysis of the cytokines release and miR-155 expression. Furthermore, in vitro studies indicate that miR-155 inhibited the expression of SOCS1. Our results suggest that there is a correlation between the high-level expression of miR-155 and the enhanced expression of TNF-? and IL-1?. miR-155 targets and suppresses the expression of SOCS1, and the decrease of SOCS1 may lead to the upregulation of TNF-? and IL-1?.
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Asymmetric total synthesis of (-)-jorunnamycins A and C and (-)-jorumycin from L-tyrosine.
J. Nat. Prod.
PUBLISHED: 08-27-2013
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Three renieramycin-type antitumor alkaloids, (-)-jorunnamycins A (1) and C (2) and (-)-jorumycin (3), have been synthesized by a new convergent approach, which features a highly regio- and stereoselective Pictet-Spengler cyclization to couple the isoquinoline and the trisubstituted phenylalaninol partners. This synthetic strategy opens an economical access to these important antitumor alkaloids with high yields: (-)-jorunnamycin A, as a common precursor to other renieramycin-type alkaloids and their analogues, is obtained with 18.1% overall yield from l-tyrosine.
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Controversies and evolving new mechanisms in subarachnoid hemorrhage.
Prog. Neurobiol.
PUBLISHED: 08-09-2013
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Despite decades of study, subarachnoid hemorrhage (SAH) continues to be a serious and significant health problem in the United States and worldwide. The mechanisms contributing to brain injury after SAH remain unclear. Traditionally, most in vivo research has heavily emphasized the basic mechanisms of SAH over the pathophysiological or morphological changes of delayed cerebral vasospasm after SAH. Unfortunately, the results of clinical trials based on this premise have mostly been disappointing, implicating some other pathophysiological factors, independent of vasospasm, as contributors to poor clinical outcomes. Delayed cerebral vasospasm is no longer the only culprit. In this review, we summarize recent data from both experimental and clinical studies of SAH and discuss the vast array of physiological dysfunctions following SAH that ultimately lead to cell death. Based on the progress in neurobiological understanding of SAH, the terms "early brain injury" and "delayed brain injury" are used according to the temporal progression of SAH-induced brain injury. Additionally, a new concept of the vasculo-neuronal-glia triad model for SAH study is highlighted and presents the challenges and opportunities of this model for future SAH applications.
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Effects of airborne metals on lung function in inner Mongolian schoolchildren.
J. Occup. Environ. Med.
PUBLISHED: 08-02-2013
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To evaluate the effects of particles and their components on lung function.
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Dyna-CT-assisted percutaneous microballoon compression for trigeminal neuralgia.
J Neurointerv Surg
PUBLISHED: 07-31-2013
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Percutaneous microballoon compression (PMC) for trigeminal neuralgia (TN) is a well-established technique. However, complications from cannulating the foramen ovale (FO) have been reported because direct puncture of the FO is sometimes difficult. Here we report our experience with Dyna-CT-assisted PMC for TN in cannulating the FO and determining the position and volume of the balloon.
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The structural dynamics of ?-tropomyosin on F-actin shape the overlap complex between adjacent tropomyosin molecules.
Arch. Biochem. Biophys.
PUBLISHED: 07-30-2013
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Coiled-coil tropomyosin, localized on actin filaments in virtually all eukaryotic cells, serves as a gatekeeper regulating access of the motor protein myosin and other actin-binding proteins onto the thin filament surface. Tropomyosins modular pseudo-repeating pattern of approximately 39 amino acid residues is designed to allow binding of the coiled-coil to successive actin subunits along thin filaments. Even though different tropomyosin isoforms contain varying numbers of repeat modules, the pseudo-repeat length, in all cases, matches that of a single actin subunit. Thus, the seven pseudo-repeats of 42nm long muscle tropomyosin bind to seven successive actin subunits along thin filaments, while simultaneously bending into a super-helical conformation that is preshaped to the actin filament helix. In order to form a continuous cable on thin filaments that is free of gaps, adjacent tropomyosin molecules polymerize head-to-tail by means of a short (?9 residue) overlap. Several laboratories have engineered peptides to mimic the N- and C-terminal tropomyosin association and to characterize the overlap structure. All overlapping domains examined show a compact N-terminal coiled-coil inserting into a partially opened C-terminal partner, where the opposing coiled-coils at the overlap junction face each other at up to ?90° twist angles. Here, Molecular Dynamics (MD) simulations were carried out to determine constraints on the formation of the tropomyosin overlap complex and to assess the amount of twisting exhibited by full-length tropomyosin when bound to actin. With the exception of the last 20-40 C- and N-terminal residues, we find that the average tropomyosin structure closely resembles a "canonical" model proposed in the classic work of McLachlan and Stewart, displaying perfectly symmetrical supercoil geometry matching the F-actin helix with an integral number of coiled-coil turns, a coiled-coil helical pitch of 137Å, a superhelical pitch of 770Å, and no localized pseudo-rotation. Over the middle 70% of tropomyosin, the average twisting of the coiled-coil deviates only by 10° from the canonical model and the torsional freedom is very small (std. dev. of 7°). This small degree of twisting cannot yield the orthogonal N- and C-termini configuration observed experimentally. In marked contrast, considerable coiled-coil unfolding, splaying and twisting at N- and C-terminal ends is observed, providing the conformational plasticity needed for head-to-tail nexus formation.
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Mutations in repeating structural motifs of tropomyosin cause gain of function in skeletal muscle myopathy patients.
Hum. Mol. Genet.
PUBLISHED: 07-25-2013
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The congenital myopathies include a wide spectrum of clinically, histologically and genetically variable neuromuscular disorders many of which are caused by mutations in genes for sarcomeric proteins. Some congenital myopathy patients have a hypercontractile phenotype. Recent functional studies demonstrated that ACTA1 K326N and TPM2 ?K7 mutations were associated with hypercontractility that could be explained by increased myofibrillar Ca(2+) sensitivity. A recent structure of the complex of actin and tropomyosin in the relaxed state showed that both these mutations are located in the actin-tropomyosin interface. Tropomyosin is an elongated molecule with a 7-fold repeated motif of around 40 amino acids corresponding to the 7 actin monomers it interacts with. Actin binds to tropomyosin electrostatically at two points, through Asp25 and through a cluster of amino acids that includes Lys326, mutated in the gain-of-function mutation. Asp25 interacts with tropomyosin K6, next to K7 that was mutated in the other gain-of-function mutation. We identified four tropomyosin motifs interacting with Asp25 (K6-K7, K48-K49, R90-R91 and R167-K168) and three E-E/D-K/R motifs interacting with Lys326 (E139, E181 and E218), and we predicted that the known skeletal myopathy mutations ?K7, ?K49, R91G, ?E139, K168E and E181K would cause a gain of function. Tests by an in vitro motility assay confirmed that these mutations increased Ca(2+) sensitivity, while mutations not in these motifs (R167H, R244G) decreased Ca(2+) sensitivity. The work reported here explains the molecular mechanism for 6 out of 49 known disease-causing mutations in the TPM2 and TPM3 genes, derived from structural data of the actin-tropomyosin interface.
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Distribution of infused umbilical cord mesenchymal stem cells in a rat model of renal interstitial fibrosis.
Ren Fail
PUBLISHED: 07-23-2013
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Stem cell transplantation for the treatment of kidney diseases is dependent on choice of transplant pathway. We evaluated the safety of human umbilical cord mesenchymal stem cells through peripheral infusion and their distribution in a rat model of renal interstitial fibrosis (RIF).
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Bone marrow stroma-mediated resistance to FLT3 inhibitors in FLT3-ITD AML is mediated by persistent activation of extracellular regulated kinase.
Br. J. Haematol.
PUBLISHED: 06-17-2013
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A consistent pattern of response has been observed when FMS-like tyrosine kinase 3 (FLT3) tyrosine kinase inhibitors (TKIs) have been used as monotherapy to treat patients with relapsed or refractory FLT3- internal tandem duplication (ITD) acute myeloid leukaemia (AML). Circulating blasts are cleared from the peripheral blood, while bone marrow blasts are either unaffected or are cleared from the marrow at a much slower rate. We used an in vitro model of FLT3-ITD AML blasts co-cultured with normal human bone marrow stromal cells to investigate the basis for this dichotomous response pattern to FLT3 inhibitors. We have found that in blasts on stroma, potent FLT3 inhibition predominantly results in cell cycle arrest rather than apoptosis. The anti-apoptotic effect is mediated through a combination of direct cell-cell contact and soluble factors. The addition of exogenous FLT3 ligand (FL) augments the protection, primarily by shifting the 50% inhibitory concentration for FLT3 inhibition upwards. Cytokine-activated extracellular regulated kinase (ERK), rather than STAT5, appears to be the most important downstream signalling protein mediating the protective effect, and inhibition of MEK significantly abrogates stromal-mediated resistance. These findings explain the phenomenon of peripheral blood versus bone marrow blast responses and suggest that the combination of potent FLT3 inhibition and MEK inhibition is a promising strategy for the treatment of FLT3-ITD AML.
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Polymorphism in tropomyosin structure and function.
J. Muscle Res. Cell. Motil.
PUBLISHED: 05-16-2013
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Tropomyosins (Tm) in humans are expressed from four distinct genes and by alternate splicing >40 different Tm polypeptide chains can be made. The functional Tm unit is a dimer of two parallel polypeptide chains and these can be assembled from identical (homodimer) or different (heterodimer) polypeptide chains provided both chains are of the same length. Since most cells express multiple isoforms of Tm, the number of different homo and heterodimers that can be assembled becomes very large. We review the mechanism of dimer assembly and how preferential assembly of some heterodimers is driven by thermodynamic stability. We examine how in vitro studies can reveal functional differences between Tm homo and heterodimers (stability, actin affinity, flexibility) and the implication for how there could be selection of Tm isomers in the assembly on to an actin filament. The role of Tm heterodimers becomes more complex when mutations in Tm are considered, such as those associated with cardiomyopathies, since mutations can appear in only one of the chains.
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The acute effects of fine particles on respiratory mortality and morbidity in Beijing, 2004-2009.
Environ Sci Pollut Res Int
PUBLISHED: 03-26-2013
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Recent epidemiological and toxicological studies have shown associations between particulate matter and human health. However, the estimates of adverse health effects are inconsistent across many countries and areas. The stratification and interaction models were employed within the context of the generalized additive Poisson regression equation to examine the acute effects of fine particles on respiratory health and to explore the possible joint modification of temperature, humidity, and season in Beijing, China, for the period 2004-2009. The results revealed that the respiratory health damage threshold of the PM2.5 concentration was mainly within the range of 20-60 ?g/m(3), and the adverse effect of excessively high PM2.5 concentration maintained a stable level. In the most serious case, an increase of 10 ?g/m(3) PM2.5 results in an elevation of 4.60 % (95 % CI 3.84-4.60 %) and 4.48 % (95 % CI 3.53-5.41 %) with a lag of 3 days, values far higher than the average level of 0.69 % (95 % CI 0.54-0.85 %) and 1.32 % (95 % CI 1.02-1.61 %) for respiratory mortality and morbidity, respectively. There were strong seasonal patterns of adverse effects with the seasonal variation of temperature and humidity. The growth rates of respiratory mortality and morbidity were highest in winter. And, they increased 1.4 and 1.8 times in winter, greater than in the full year as PM2.5 increased 10 ?g/m(3).
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Gestalt-Binding of tropomyosin on actin during thin filament activation.
J. Muscle Res. Cell. Motil.
PUBLISHED: 03-12-2013
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Our thesis is that thin filament function can only be fully understood and muscle regulation then elucidated if atomic structures of the thin filament are available to reveal the positions of tropomyosin on actin in all physiological states. After all, it is tropomyosin influenced by troponin that regulates myosin-crossbridge cycling on actin and therefore controls contraction in all muscles. In addition, we maintain that a complete appreciation of thin filament activation also requires that the mechanical properties of tropomyosin itself are recognized and then related to the effect of myosin-association on actin. Taking the Gestalt-binding of tropomyosin into account, coupled with our electron microscopy structures and computational chemistry, we propose a comprehensive mechanism for tropomyosin regulatory movement over the actin filament surface that explains the cooperative muscle activation process. In fact, well-known point mutations of critical amino acids on the actin-tropomyosin binding interface disrupt Gestalt-binding and are associated with a number of inherited myopathies. Moreover, dysregulation of tropomyosin may also be a factor that interferes with the gatekeeping operation of non-muscle tropomyosin in the controlling interactions of a wide variety of cellular actin-binding proteins. The clinical relevance of Gestalt-binding is discussed in articles by the Marston and the Gunning groups in this special journal issue devoted to the impact of tropomyosin on biological systems.
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First-order convex feasibility algorithms for x-ray CT.
Med Phys
PUBLISHED: 03-08-2013
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Iterative image reconstruction (IIR) algorithms in computed tomography (CT) are based on algorithms for solving a particular optimization problem. Design of the IIR algorithm, therefore, is aided by knowledge of the solution to the optimization problem on which it is based. Often times, however, it is impractical to achieve accurate solution to the optimization of interest, which complicates design of IIR algorithms. This issue is particularly acute for CT with a limited angular-range scan, which leads to poorly conditioned system matrices and difficult to solve optimization problems. In this paper, we develop IIR algorithms which solve a certain type of optimization called convex feasibility. The convex feasibility approach can provide alternatives to unconstrained optimization approaches and at the same time allow for rapidly convergent algorithms for their solution-thereby facilitating the IIR algorithm design process.
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Comparison of human and Hotelling observer performance for a fan-beam CT signal detection task.
Med Phys
PUBLISHED: 03-08-2013
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A human observer study was performed for a signal detection task for the case of fan-beam x-ray computed tomography. Hotelling observer (HO) performance was calculated for the same detection task without the use of efficient channels. By considering the full image covariance produced by the filtered backprojection (FBP) algorithm and avoiding the use of channels in the computation of HO performance, the authors establish an absolute upper bound on signal detectability. Therefore, this study serves as a baseline for relating human and ideal observer performance in the case of fan-beam CT.
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Genetic analysis of a 12-year-old boy with X-linked ichthyosis in association with sclerosing glomerulonephritis.
Mol Med Rep
PUBLISHED: 02-22-2013
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In this study, we report the case of a 12-year-old male with X-linked ichthyosis (XLI) in association with glomerular sclerosis, and our investigation into the deletion pattern of the STS gene and the flanking regions in DNA samples of family members. We observed no features typical of renal osteodystrophy or rickets, with the exception of short stature, in the three afffected male family members. Audiometry, visual acuity and olfactory sensation were normal. By performing PCR analysis of the steroid sulfatase (STS) gene and flanking regions on our patients, we discovered a complete deletion that involved the entire region from DXS1139 to DXF22S1. Further studies are required to determine whether the STS gene or the co-deleted flanking sequences are the cause of renal disease associated with XLI.
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Size-fractioned particulate air pollution and cardiovascular emergency room visits in Beijing, China.
Environ. Res.
PUBLISHED: 01-30-2013
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Although short-term exposure to ambient particulate matter has increasingly been linked with cardiovascular diseases, it is not quite clear how physical characteristics of particles, such as particle size may be responsible for the association. This study aimed at investigating whether daily changes in number or mass concentrations of accurately size-segregated particles in the range of 3nm-10?m are associated with daily cardiovascular emergency room visits in Beijing, China.
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Effect of gene transfecting at different times on mandibular distraction osteogenesis.
J Craniofac Surg
PUBLISHED: 01-26-2013
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Recently, numerous research of gene therapy for mandibular distraction has been published. Based on previous study, the authors used New Zealand rabbits bilateral mandibular distraction model and used electroporation mediate gene therapy at different time, to explore the optimal time for gene therapy and obtain a better effect.
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The correlation between lateralization of intracerebral hemorrhage in basal ganglia and handedness.
Acta Cir Bras
PUBLISHED: 01-18-2013
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To investigate the correlation between lateralization of cerebral basal ganglia hemorrhage and handedness.
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Modified laparoscopic sacrocolpopexy with mesh for severe pelvic organ prolapse.
Int J Gynaecol Obstet
PUBLISHED: 01-14-2013
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To evaluate anatomic and sexual outcomes among patients with severe pelvic organ prolapse, defined as stage III or higher by Pelvic Organ Prolapse Quantification (POP-Q), who underwent modified laparoscopic sacrocolpopexy.
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A Novel Phosphopeptide Microarray Based Interactome Map in Breast Cancer Cells Reveals Phosphoprotein-GRB2 Cell Signaling Networks.
PLoS ONE
PUBLISHED: 01-01-2013
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The architecture of cellular proteins connected to form signaling pathways in response to internal and external cues is much more complex than a group of simple protein-protein interactions. Post translational modifications on proteins (e.g., phosphorylation of serine, threonine and tyrosine residues on proteins) initiate many downstream signaling events leading to protein-protein interactions and subsequent activation of signaling cascades leading to cell proliferation, cell differentiation and cell death. As evidenced by a rapidly expanding mass spectrometry database demonstrating protein phosphorylation at specific motifs, there is currently a large gap in understanding the functional significance of phosphoproteins with respect to their specific protein connections in the signaling cascades. A comprehensive map that interconnects phospho-motifs in pathways will enable identification of nodal protein interactions that are sensitive signatures indicating a disease phenotype from the physiological hemostasis and provide clues into control of disease. Using a novel phosphopeptide microarray technology, we have mapped endogenous tyrosine-phosphoproteome interaction networks in breast cancer cells mediated by signaling adaptor protein GRB2, which transduces cellular responses downstream of several RTKs through the Ras-ERK signaling cascade. We have identified several previously reported motif specific interactions and novel interactions. The peptide microarray data indicate that various phospho-motifs on a single protein are differentially regulated in various cell types and shows global downregulation of phosphoprotein interactions specifically in cells with metastatic potential. The study has revealed novel phosphoprotein mediated signaling networks, which warrants further detailed analysis of the nodes of protein-protein interaction to uncover their biomarker or therapeutic potential.
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diffReps: detecting differential chromatin modification sites from ChIP-seq data with biological replicates.
PLoS ONE
PUBLISHED: 01-01-2013
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ChIP-seq is increasingly being used for genome-wide profiling of histone modification marks. It is of particular importance to compare ChIP-seq data of two different conditions, such as disease vs. control, and identify regions that show differences in ChIP enrichment. We have developed a powerful and easy to use program, called diffReps, to detect those differential sites from ChIP-seq data, with or without biological replicates. In addition, we have developed two useful tools for ChIP-seq analysis in the diffReps package: one for the annotation of the differential sites and the other for finding chromatin modification "hotspots". diffReps is developed in PERL programming language and runs on all platforms as a command line script. We tested diffReps on two different datasets. One is the comparison of H3K4me3 between two human cell lines from the ENCODE project. The other is the comparison of H3K9me3 in a discrete region of mouse brain between cocaine- and saline-treated conditions. The results indicated that diffReps is a highly sensitive program in detecting differential sites from ChIP-seq data.
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Chronic pulsatile hyperglycemia reduces insulin secretion and increases accumulation of reactive oxygen species in fetal sheep islets.
J. Endocrinol.
PUBLISHED: 12-19-2011
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Children from diabetic pregnancies have a greater incidence of type 2 diabetes. Our objective was to determine if exposure to mild-moderate hyperglycemia, by modeling managed diabetic pregnancies, affects fetal ?-cell function. In sheep fetuses, ?-cell responsiveness was examined after 2 weeks of sustained hyperglycemia with 3 pulses/day, mimicking postprandial excursions, and compared to saline-infused controls (n = 10). Two pulsatile hyperglycemia (PHG) treatments were studied: mild (mPHG, n = 5) with +15% sustained and +55% pulse; and moderate (PHG, n = 10) with +20% sustained and +100% pulse. Fetal glucose-stimulated insulin secretion and glucose-potentiated arginine insulin secretion were lower (P < 0.05) in PHG (0.86 ± 0.13 and 2.91 ± 0.39 ?ng/ml plasma insulin) but not in mPHG fetuses (1.21 ± 0.08 and 4.25 ± 0.56 ?ng/ml) compared to controls (1.58 ± 0.25 and 4.51 ± 0.56 ?ng/ml). Islet insulin content was 35% lower in PHG and 35% higher in mPHG vs controls (P < 0.01). Insulin secretion and maximally stimulated insulin release were also reduced (P < 0.05) in PHG islets due to lower islet insulin content. Isolated PHG islets also had 63% greater (P < 0.01) reactive oxygen species (ROS) accumulation at 11.1 ?mmol/l glucose than controls (P < 0.01), but oxidative damage was not detected in islet proteins. PHG fetuses showed evidence of oxidative damage to skeletal muscle proteins (P < 0.05) but not insulin resistance. Our findings show that PHG induced dysregulation of islet ROS handling and decreased islet insulin content, but these outcomes are independent. The ?-cell outcomes were dependent on the severity of hyperglycemia because mPHG fetuses had no distinguishable impairments in ROS handling or insulin secretion but greater insulin content.
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CHOP silencing reduces acute brain injury in the rat model of subarachnoid hemorrhage.
Stroke
PUBLISHED: 12-15-2011
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Endoplasmic reticulum stress triggers apoptotic cascades in neurons of the central nervous system after subarachnoid hemorrhage. The aim of this work was to study the mechanism of neuroprotection conferred by targeting cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in the acute brain injury following subarachnoid hemorrhage.
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Structural analysis of smooth muscle tropomyosin ? and ? isoforms.
J. Biol. Chem.
PUBLISHED: 11-27-2011
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A large number of tropomyosin (Tm) isoforms function as gatekeepers of the actin filament, controlling the spatiotemporal access of actin-binding proteins to specialized actin networks. Residues ?40-80 vary significantly among Tm isoforms, but the impact of sequence variation on Tm structure and interactions with actin is poorly understood, because structural studies have focused on skeletal muscle Tm?. We describe structures of N-terminal fragments of smooth muscle Tm? and Tm? (sm-Tm? and sm-Tm?). The 2.0-? structure of sm-Tm?81 (81-aa) resembles that of skeletal Tm?, displaying a similar super-helical twist matching the contours of the actin filament. The 1.8-? structure of sm-Tm?98 (98-aa) unexpectedly reveals an antiparallel coiled coil, with the two chains staggered by only 4 amino acids and displaying hydrophobic core interactions similar to those of the parallel dimer. In contrast, the 2.5-? structure of sm-Tm?98, containing Gly-Ala-Ser at the N terminus to mimic acetylation, reveals a parallel coiled coil. None of the structures contains coiled-coil stabilizing elements, favoring the formation of head-to-tail overlap complexes in four of five crystallographically independent parallel dimers. These complexes show similarly arranged 4-helix bundles stabilized by hydrophobic interactions, but the extent of the overlap varies between sm-Tm?98 and sm-Tm?81 from 2 to 3 helical turns. The formation of overlap complexes thus appears to be an intrinsic property of the Tm coiled coil, with the specific nature of hydrophobic contacts determining the extent of the overlap. Overall, the results suggest that sequence variation among Tm isoforms has a limited effect on actin binding but could determine its gatekeeper function.
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Group-index independent coupling to band engineered SOI photonic crystal waveguide with large slow-down factor.
Opt Express
PUBLISHED: 11-24-2011
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Group-index independent coupling to a silicon-on-insulator (SOI) based band-engineered photonic crystal (PCW) waveguide is presented. A single hole size is used for designing both the PCW coupler and the band-engineered PCW to improve fabrication yield. Efficiency of several types of PCW couplers is numerically investigated. An on-chip integrated Fourier transform spectral interferometry device is used to experimentally determine the group-index while excluding the effect of the couplers. A low-loss, low-dispersion slow light transmission over 18 nm bandwidth under the silica light line with a group index of 26.5 is demonstrated, that corresponds to the largest slow-down factor of 0.31 ever demonstrated for a PCW with oxide bottom cladding.
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Structural implications of conserved aspartate residues located in tropomyosins coiled-coil core.
Bioarchitecture
PUBLISHED: 10-09-2011
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Polar residues lying between adjacent ?-helical chains of coiled-coils often contribute to coiled-coil curvature and flexibility, while more typical core hydrophobic residues anneal the chains together. In tropomyosins, ranging from smooth and skeletal muscle to cytoplasmic isoforms, a highly conserved Asp at residue 137 places negative charges within the tropomyosin coiled-coil core in a position which may affect the conformation needed for tropomyosin binding and regulatory movements on actin. Proteolytic susceptibility suggested that substituting a canonical Leu for the naturally occurring Asp at residue 137 increases inter-chain rigidity by stabilizing the tropomyosin coiled-coil. Using molecular dynamics, we now directly assess changes in coiled-coil curvature and flexibility caused by such mutants. Although the coiled-coil flexibility is modestly diminished near the residue 137 mutation site, as expected, a delocalized increase in flexibility along the overall coiled-coil is observed. Even though the average shape of the D137L tropomyosin is straighter than that of wild-type tropomyosin, it is still capable of binding actin due to this increase in flexibility. We conclude that the conserved, non-canonical Asp-137 destabilizes the local structure resulting in a local flexible region in the middle of tropomyosin that normally is important for tropomyosin steady-state equilibrium position on actin.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.