分类: 生物学 >> 生物物理学 >> 生物物理、生物化学与分子生物学 提交时间: 2016-05-11
摘要: It has been established that exposure in the hypomagnetic field (HMF), which is one of the environmental factor of outer space, has adverse effects on animal and human behavior and brain function. Thus, it is necessary to develop appropriate counteract strategy to avoid the HMF-induced risks to the health of the astronauts during long-term and long-distance manned space mission. However, the physical and mental effects of the HMF in details still await systematic evaluation and the underlying mechanism remains elusive, so far. In this study, we constructed an HMF animal rearing system (<500 nT) and examined the effects of one-month HMF exposure on the circadian behavior, pain response and emotions in adult male C57BL/6 mice (4 similar to 6 weeks old, (20 +/- 2) g). The control animals were reared in the geomagnetic field (GMF). The HMF-exposed animals exhibited a prolonged alteration of the circadian drinking rhythm and a decrease in general activity, accompanied with an increase in thermal hyperalgesia. But the HMF did not induce obvious depression-like and anxiety-related behaviors. The serum noradrenalin concentration in HMF-exposed mice significantly decreased. These findings indicate that the HMF disturbs the behavior rhythm and the function of endocrine system, which probably leads to the subsequently weakened activities of the animal.
分类: 生物学 >> 生物物理学 >> 细胞生物学 提交时间: 2016-05-12
摘要: Type 2 diabetes mellitus (T2DM) is regarded as one of the serious risk factors for age-related cognitive impairment; however, a causal link between these two diseases has so far not been established. It was recently discovered that, apart from high D-glucose levels, T2DM patients also display abnormally high concentrations of uric D-ribose. Here, we show for the first time that the administration of D-ribose, the most active glycator among monosaccharides, produces high levels of advanced glycation end products (AGEs) and, importantly, triggers hyperphosphorylation of Tau in the brain of C57BL/6 mouse and neuroblastoma N2a cells. However, the administration of D-glucose showed no significant changes in Tau phosphorylation under the same experimental conditions. Crucially, suppression of AGE formation using an AGEs inhibitor (aminoguanidine) effectively prevents hyperphosphorylation of Tau protein. Further study shows AGEs resulted from ribosylation activate calcium-/calmodulin-dependent protein kinase type II (CaMKII), a key kinase responsible for Tau hyperphosphorylation. These data suggest that there is indeed a mechanistic link between ribosylation and Tau hyperphosphorylation. Targeting ribosylation by inhibiting AGE formation may be a promising therapeutic strategy to prevent Alzheimer's disease-like Tau hyperphosphorylation and diabetic encephalopathies.
分类: 地球科学 >> 空间物理学 提交时间: 2016-12-22
摘要: In 2012 March the Sun exhibited extraordinary activities. In particular, the active region NOAA AR 11429 emitted a series of large coronal mass ejections (CMEs) which were imaged by the Solar Terrestrial Relations Observatory as it rotated with the Sun from the east to west. These sustained eruptions are expected to generate a global shell of disturbed material sweeping through the heliosphere. A cluster of shocks and interplanetary CMEs were observed near the Earth, and are propagated outward from 1 AU using an MHD model. The transient streams interact with each other, which erases memory of the source and results in a large merged interaction region (MIR) with a preceding shock. The MHD model predicts that the shock and MIR would reach 120 AU around 2013 April 22, which agrees well with the period of radio emissions and the time of a transient disturbance in galactic cosmic rays detected by Voyager 1. These results are important for understanding the "fate" of CMEs in the outer heliosphere and provide confidence that the heliopause is located around 120 AU from the Sun.
分类: 生物学 >> 生物物理学 >> 生物物理、生物化学与分子生物学 提交时间: 2016-05-11
摘要: A cinetobacter baumannii is a new threat in intensive care units (ICUs) for its multiresistance to antibiotics, but little is known about this bacterium. Nucleoside diphosphate kinase (NDK) is an evolutionarily conserved enzyme that catalyzes phosphoryl transformation between nucleosides. In our study, the crystal structure of wild type A cinetobacter baumannii NDK along with its mutant generated through truncation of the C-terminal arginine-threonine-arginine (RTR) residues, were solved. In comparison with Myxococcus xanthus NDK structure, we speculated that A cinetobacter baumannii NDK shared a similar catalytic mechanism with Myxococcus xanthus. Activity assay and CD spectra analysis revealed that E28A mutant might interrupt the secondary structure of the protein leading to declined enzymatic activity. Truncation of the C-terminal RTR residues would lead to the instability of the tertiary structure resulting in reduced kinase activity. Lys33 was a key residue for maintaining dimer interaction when RTR residues were truncated but was not sufficient to keep efficient enzymatic reaction. The structural data can provide a potential target to develop novel therapeutic approaches to overcome multiresistance of the bacterium against antibiotics.
分类: 地球科学 >> 空间物理学 提交时间: 2016-05-12
摘要: We study the role of the coronal magnetic field configuration of an active region (AR) in determining the propagation direction of a coronal mass ejection (CME). The CME occurred in the AR 11944 (S09W01) near the disk center on 2014 January 7 and was associated with an X1.2 flare. A new CME reconstruction procedure based on a polarimetric technique is adopted, which shows that the CME changed its propagation direction by around 28 degrees in latitude within 2.5 R-circle dot and 43 degrees in longitude within 6.5 R-circle dot with respect to the CME source region. This significant non-radial motion is consistent with the finding of Mostl et al. We use nonlinear force-free field and potential field source surface extrapolation methods to determine the configurations of the coronal magnetic field. We also calculate the magnetic energy density distributions at different heights based on the extrapolations. Our results show that the AR coronal magnetic field has a strong influence on the CME propagation direction. This is consistent with the "channeling" by the AR coronal magnetic field itself, rather than deflection by nearby structures. These results indicate that the AR coronal magnetic field configuration has to be taken into account in order to determine CME propagation direction correctly.
分类: 地球科学 >> 空间物理学 提交时间: 2016-12-26
摘要: We study the solar energetic particle (SEP) event associated with the 2012 July 23 extreme solar storm, for which Solar Terrestrial Relations Observatory (STEREO) and the spacecraft at L1 provide multi-point remote sensing and in situ observations. The extreme solar storm, with a superfast shock and extremely enhanced ejecta magnetic fields observed near 1 au at STEREO A, was caused by the combination of successive coronal mass ejections (CMEs). Meanwhile, energetic particles were observed by STEREO and near-Earth spacecraft such as the Advanced Composition Explorer and SOlar and Heliospheric Observatory, suggesting a wide longitudinal spread of the particles at 1 au. Combining the SEP observations with in situ plasma and magnetic field measurements, we investigate the longitudinal distribution of the SEP event in connection with the associated shock and CMEs. Our results underscore the complex magnetic configuration of the inner heliosphere formed by solar eruptions. Examination of particle intensities, proton anisotropy distributions, element abundance ratios, magnetic connectivity, and spectra also gives important clues for particle acceleration, transport, and distribution.
分类: 地球科学 >> 空间物理学 提交时间: 2016-05-12
摘要: Voyager 2 (V2) observed multiple crossings of the heliospheric termination shock (TS) on 2007 August 31-September 1 at a distance of 84 AU from the Sun. Here, for the first time, we present two-dimensional particle-incell (PIC) simulations of the TS self-consistently including pickup ions (PUIs), and compare the simulation results with V2 observations. We find that (1) PUIs play a key role in the energy dissipation of the TS, and most of the incident ion kinetic energy is transferred to the thermal energy of PUIs. The PIC simulation indicates that, for the upstream parameters chosen for V2 conditions, the density of PUIs is about 25% and the PUIs gain the largest fraction (approximately 86.6%) of downstream thermal pressure. (2) The simulated heliosheath ion distribution function is a superposition of a cold core formed by transmitted solar wind ions (SWIs), with the shoulders contributed by the hot reflected SWIs and directly transmitted PUIs, and the wings of the distribution dominated by the very hot reflected PUIs. The V2 Faraday cups observed the cool core of the distribution, and so they only saw the tip of the iceberg. (3) The nonstationarity of the shock front is mainly caused by ripples along the shock front which form even if the percentage of PUIs is high. These simulation results agree reasonably well with the V2 experimental data. The relevance of the shock front ripples to the multiple TS crossings observed by V2 is also discussed in this paper.
分类: 生物学 >> 生物物理学 >> 衰老生物学 提交时间: 2016-05-11
摘要: Background: Hedgehog (Hh) signals are instrumental to the dorsoventral patterning of the vertebrate eye, promoting optic stalk and ventral retinal fates and repressing dorsal retinal identity. There has been limited analysis, however, of the critical window during which Hh molecules control eye polarity and of the temporal changes in the responsiveness of eye cells to these signals. Results: In this study, we used pharmacological and molecular tools to perform stage-specific manipulations of Hh signalling in the developing Xenopus eye. In gain-of-function experiments, most of the eye was sensitive to ventralization when the Hh pathway was activated starting from gastrula/neurula stages. During optic vesicle stages, the dorsal eye became resistant to Hh-dependent ventralization, but this pathway could partially upregulate optic stalk markers within the retina. In loss-of-function assays, inhibition of Hh signalling starting from neurula stages caused expansion of the dorsal retina at the expense of the ventral retina and the optic stalk, while the effects of Hh inhibition during optic vesicle stages were limited to the reduction of optic stalk size. Conclusions: Our results suggest the existence of two competence windows during which the Hh pathway differentially controls patterning of the eye region. In the first window, between the neural plate and the optic vesicle stages, Hh signalling exerts a global influence on eye dorsoventral polarity, contributing to the specification of optic stalk, ventral retina and dorsal retinal domains. In the second window, between optic vesicle and optic cup stages, this pathway plays a more limited role in the maintenance of the optic stalk domain. We speculate that this temporal regulation is important to coordinate dorsoventral patterning with morphogenesis and differentiation processes during eye development.
分类: 地球科学 >> 空间物理学 提交时间: 2016-05-12
摘要: We present high-resolution observations of a quiescent solar prominence that consists of a vertical and a horizontal foot encircled by an overlying spine and has ubiquitous counter-streaming mass flows. While the horizontal foot and the spine were connected to the solar surface, the vertical foot was suspended above the solar surface and was supported by a semicircular bubble structure. The bubble first collapsed, then reformed at a similar height, and finally started to oscillate for a long time. We find that the collapse and oscillation of the bubble boundary were tightly associated with a flare-like feature located at the bottom of the bubble. Based on the observational results, we propose that the prominence should be composed of an overlying horizontal spine encircling a low-lying horizontal and vertical foot, in which the horizontal foot consists of shorter field lines running partially along the spine and has ends connected to the solar surface, while the vertical foot consists of piling-up dips due to the sagging of the spine fields and is supported by a bipolar magnetic system formed by parasitic polarities (i.e., the bubble). The upflows in the vertical foot were possibly caused by the magnetic reconnection at the separator between the bubble and the overlying dips, which intruded into the persistent downflow field and formed the picture of counter-streaming mass flows. In addition, the counter-streaming flows in the horizontal foot were possibly caused by the imbalanced pressure at the both ends.
分类: 生物学 >> 生物物理学 提交时间: 2016-05-12
摘要: Tyrosine kinase inhibitors (TKIs) are mostly used in non-small cell lung cancer (NSCLC) treatment. Unfortunately, treatment with Gefitinib for a period of time will result in drug resistance and cause treatment failure in clinic. Therefore, exploring novel compounds to overcome this resistance is urgently required. Here we investigated the antitumor effect of homoharringtonine (HHT), a natural compound extracted from Cephalotaxus harringtonia, on Gefitinib-resistant NSCLC cell lines in vitro and in vivo. NCI-H1975 cells with EGFR T790M mutation are more sensitive to HHT treatment compared with that of A549 cells with wild type EGFR. HHT inhibited cells growth, cell viability and colony formation, as well as induced cell apoptosis through mitochondria pathway. Furthermore, we explored the mechanism of HHT inhibition on NSCLC cells. Higher level of interleukin-6 (IL-6) existed in lung cancer patients and mutant EGFR and TGF beta signal requires the upregulation of IL-6 through the gp130/JAK pathway to overactive STAT3, an oncogenic protein which has been considered as a potential target for cancer therapy. HHT reversiblely inhibited IL-6-induced STAT3 Tyrosine 705 phosphorylation and reduced anti-apoptotic proteins expression. Gefitinib-resistant NSCLC xenograft tests also confirmed the antitumor effect of HHT in vivo. Consequently, HHT has the potential in Gefitinib-resistant NSCLC treatment.
分类: 地球科学 >> 空间物理学 提交时间: 2016-12-26
摘要: As a follow-up study on Sun-to-Earth propagation of fast coronal mass ejections (CMEs), we examine the Sun-to-Earth characteristics of slow CMEs combining heliospheric imaging and in situ observations. Three events of particular interest, the 2010 June 16, 2011 March 25, and 2012 September 25 CMEs, are selected for this study. We compare slow CMEs with fast and intermediate-speed events, and obtain key results complementing the attempt of Liu et al. to create a general picture of CME Sun-to-Earth propagation: (1) the Sun-to-Earth propagation of a typical slow CME can be approximately described by two phases, a gradual acceleration out to about 20-30 solar radii, followed by a nearly invariant speed around the average solar wind level; (2) comparison between different types of CMEs indicates that faster CMEs tend to accelerate and decelerate more rapidly and have shorter cessation distances for the acceleration and deceleration; (3) both intermediate-speed and slow CMEs would have speeds comparable to the average solar wind level before reaching 1 au; (4) slow CMEs have a high potential to interact with other solar wind structures in the Sun-Earth space due to their slow motion, providing critical ingredients to enhance space weather; and (5) the slow CMEs studied here lack strong magnetic fields at the Earth but tend to preserve a flux-rope structure with an. axis generally perpendicular to the radial direction from the Sun. We also suggest a "best" strategy for the application of a triangulation concept in determining CME Sun-to-Earth kinematics, which helps to clarify confusions about CME geometry assumptions in the triangulation and to improve CME analysis and observations.
分类: 地球科学 >> 空间物理学 提交时间: 2016-05-12
摘要: The largest geomagnetic storms of solar cycle 24 so far occurred on 2015 March 17 and June 22 with D-st minima of -223 and -195 nT, respectively. Both of the geomagnetic storms show a multi-step development. We examine the plasma and magnetic field characteristics of the driving coronal mass ejections (CMEs) in connection with the development of the geomagnetic storms. A particular effort is to reconstruct the in situ structure using a Grad-Shafranov technique and compare the reconstruction results with solar observations, which gives a larger spatial perspective of the source conditions than one-dimensional in situ measurements. Key results are obtained concerning how the plasma and magnetic field characteristics of CMEs control the geomagnetic storm intensity and variability: (1) a sheath-ejecta-ejecta mechanism and a sheath-sheath-ejecta scenario are proposed for the multi-step development of the 2015 March 17 and June 22 geomagnetic storms, respectively;(2) two contrasting cases of how the CME flux-rope characteristics generate intense geomagnetic storms are found, which indicates that a southward flux-rope orientation is not a necessity for a strong geomagnetic storm;and (3) the unexpected 2015 March 17 intense geomagnetic storm resulted from the interaction between two successive CMEs plus the compression by a high-speed stream from behind, which is essentially the "perfect storm" scenario proposed by Liu et al. (i.e., a combination of circumstances results in an event of unusual magnitude), so the "perfect storm" scenario may not be as rare as the phrase implies.
分类: 生物学 >> 生物物理学 >> 肿瘤学 提交时间: 2016-05-15
摘要: Tumor necrosis factor receptor-associated protein 1 (TRAP1) is abnormally expressed in many cancers. In this study, we showed that TRAP1 is aberrantly upregulated in breast tumors compared to control tissues. TRAP1 knockdown downregulates mitochondrial aerobic respiratory, sensitizes cells to lethal stimuli, and inhibited tumor growth in MDA-MB-231 and MCF-7 breast cancer cells in vivo. TRAP1 overexpression, however, enhances the capacity to cope with stress conditions. These evidences suggested that TRAP1 is required for tumorigenesis. We also found that TRAP1 regulates the mitochondrial morphology. Relatively lower TRAP1 levels are associated with the rod-shaped mitochondrial phenotype in invasive and metastatic MDA-MB-231 breast cancer cells; on the contrary, higher TRAP1 levels are associated with the tubular network-shaped mitochondrial phenotype in non-invasive MCF-7 cells. Interestingly, the expression of TRAP1 in human breast cancer specimens inversely correlates with tumor grade. Overexpression of TRAP1 in MDA-MB-231 cells causes mitochondrial fusion, triggers mitochondria to form tubular networks, and suppresses cell migration and invasion in vitro and in vivo. These data link TRAP1-regulated mitochondrial dynamics and function with tumorigenesis of breast cancer and suggested that TRAP1 may therefore be a potential target for breast cancer drug development.
分类: 生物学 >> 生物物理学 >> 肿瘤学 提交时间: 2016-05-11
摘要: In addition to D-Glucose, D-Ribose is also abnormally elevated in the urine of type 2 diabetic patients, establishing a positive correlation between the concentration of uric D-Ribose and the severity of diabetes. Intraperitoneal injection of D-Ribose causes memory loss and brain inflammation in mice. To simulate a chronic progression of age-related cognitive impairment, we orally administered D-Ribose by gavage at both a low and high dose to 8 week-old male C57BL/6J mice daily for a total of 6 months, followed by behavioral, histological and biochemical analysis. We found that long-term oral administration of D-Ribose impairs spatial learning and memory, accompanied by anxiety-like behavior. Tau was hyperphosphorylated at AT8, S396, S214 and T181 in the brain. A beta-like deposition was also found in the hippocampus for the high dose group. D-Glucose-gavaged mice did not show significant memory loss and anxiety-like behavior under the same experimental conditions. These results demonstrate that a long-term oral administration of D-Ribose not only induces memory loss with anxiety-like behavior, but also elevates A beta-like deposition and Tau hyperphosphorylation, presenting D-Ribose-gavaged mouse as a model for agerelated cognitive impairment and diabetic encephalopathy.
分类: 生物学 >> 生物物理学 提交时间: 2016-05-11
摘要: Cyanohydrin derivatives as enterovirus 71 (EV71) 3C protease (3C(pro)) inhibitors have been synthesized and assayed for their biochemical and antiviral activities. Compared with the reported inhibitors, cyanohydrins (1S,2S,2'S,5S)-16 and (1R,2S,2'S,5S)-16 exhibited significantly improved activity and attractive selectivity profiles against other proteases, which were a result of the specific interactions between the cyanohydrin moiety and the catalytic site of 3C(pro). Cyanohydrin as an anchoring group with high selectivity and excellent inhibitory activity represents a useful choice for cysteine protease inhibitors.
分类: 生物学 >> 生物物理学 提交时间: 2016-05-05
摘要: Nicotine addiction is associated with risky behaviors and abnormalities in local brain areas related to risky decision-making such as the dorsal anterior cingulate cortex (dACC), anterior insula (AI), and thalamus. Although these brain abnormalities are anatomically separated, they may in fact belong to one neural network. However, it is unclear whether circuit-level abnormalities lead to risky decision-making in smokers. In the current study, we used task-based functional magnetic resonance imaging (fMRI) and examined resting-state functional connectivity (RSFC) to study how connectivity between the dACC, insula, and thalamus influence risky decision-making in nicotine addicts. We found that an increase in risky decision-making was associated with stronger nicotine dependence and stronger RSFC of the dACC-rAI (right AI), the dACC-thalamus, the dACC-lAI (left AI), and the rAI-lAI, but that risky decision-making was not associated with risk level-related activation. Furthermore, the severity of nicotine dependence positively correlated with RSFC of the dACC-thalamus but was not associated with risk level-related activation. Importantly, the dACC-thalamus coupling fully mediated the effect of nicotine-dependent severity on risky decision-making. These results suggest that circuit-level connectivity may be a critical neural link between risky decision-making and severity of nicotine dependence in smokers.
分类: 地球科学 >> 空间物理学 提交时间: 2016-05-04
摘要: The severe geomagnetic effects of solar storms or coronal mass ejections (CMEs) are to a large degree determined by their propagation direction with respect to Earth. There is a lack of understanding of the processes that determine their non-radial propagation. Here we present a synthesis of data from seven different space missions of a fast CME, which originated in an active region near the disk centre and, hence, a significant geomagnetic impact was forecasted. However, the CME is demonstrated to be channelled during eruption into a direction + 37 +/- 10 degrees (longitude) away from its source region, leading only to minimal geomagnetic effects. In situ observations near Earth and Mars confirm the channelled CME motion, and are consistent with an ellipse shape of the CME-driven shock provided by the new Ellipse Evolution model, presented here. The results enhance our understanding of CME propagation and shape, which can help to improve space weather forecasts.
分类: 生物学 >> 生物物理学 提交时间: 2016-05-11
摘要: Hippocampus-related topographic amnesia is the most common symptom of memory disorders in Alzheimer's disease (AD) patients. Recent studies have revealed that experience-mediated DNA methylation, which is regulated by enzymes with DNA methyltransferase (DNMT) activity, is required for the formation of recent memory as well as the maintenance of remote memory. Notably, overexpression of DNMT3a in the hippocampus can reverse spatial memory deficits in aged mice. However, a decline in global DNA methylation was found in the autopsied hippocampi of patients with AD. Exactly, what endogenous factors that affect DNA methylation still remain to be elucidated. Here, we report a marked increase in endogenous formaldehyde levels is associated with a decline in global DNA methylation in the autopsied hippocampus from AD patients. In vitro and in vivo results show that formaldehyde in excess of normal physiological levels reduced global DNA methylation by interfering DNMTs. Interestingly, intrahippocampal injection of excess formaldehyde before spatial learning in healthy adult rats can mimic the learning difficulty of early stage of AD. Moreover, injection of excess formaldehyde after spatial learning can mimic the loss of remote spatial memory observed in late stage of AD. These findings suggest that aging-associated formaldehyde contributes to topographic amnesia in AD patients. (C) 2015 Elsevier Inc. All rights reserved.
分类: 生物学 >> 生物物理学 提交时间: 2016-05-12
摘要: Novelty seeking (NS) is a personality trait reflecting excitement in response to novel stimuli. High NS is usually a predictor of risky behaviour such as drug abuse. However, the relationships between NS and risk-related cognitive processes, including individual risk preference and the brain activation associated with risk prediction, remain elusive. In this fMRI study, participants completed the Tridimensional Personality Questionnaire to measure NS and performed a probabilistic decision making task. Using a mathematical model, we estimated individual risk preference. Brain regions associated with risk prediction were determined via fMRI. The NS score showed a positive correlation with risk preference and a negative correlation with the activation elicited by risk prediction in the right posterior insula (r-PI), left anterior insula (l-AI), right striatum (r-striatum) and supplementary motor area (SMA). Within these brain regions, only the activation associated with risk prediction in the r-PI showed a correlation with NS after controlling for the effect of risk preference. Resting-state functional connectivity between the r-PI and r-striatum/l-AI was negatively correlated with NS. Our results suggest that high NS may be associated with less aversion to risk and that the r-PI plays an important role in relating risk prediction to NS.
分类: 物理学 >> 普通物理:统计和量子力学,量子信息等 提交时间: 2017-05-02
摘要: Detection of malignant cells from malignant effusion is crucial to establish or adjust therapies of patients with cancer. The conventional qualitative detection in malignant pleuroperitoneal effusion is cytological analysis, which is time-consuming and complicated. Therefore, a faster and more convenient detection strategy is urgently needed. In this study, we report a rapid method to detect malignant cells from malignant pleuroperitoneal effusion (hydrothorax and ascites) of patients using IR-808, a tumor-targeted near-infrared (NIR) fluorescent heptamethine dye (tNRI dye), which exhibited superior labeling efficacy without specific conjugation to biomarkers. The targeted imaging performance toward malignant cells using IR-808 was confirmed by comparing with normal cells, and the fluorescence stability assay of IR- 808 in malignant effusion was performed from 1 h to 48 h. In order to save time and dose, the incubation time and concentration were optimized to 10 min and 5 mM, which were used to detect malignant cells from 28 clinical samples of malignant pleuroperitoneal effusion. The results revealed that IR-808 could be internalized selectively by malignant cells of samples, and these malignant cells could be easily distinguished from normal cells under a fluorescence microscope. The positive rates between cytological analysis and the IR-808 staining method were 86% (24/28) and 79% (22/28), respectively. An excellent concordance level (Kappa 1⁄4 0.752, P < 0.001) was observed between the two methods. Our results indicated that IR-808, a new NIR fluorescent heptamethine dye with unique optical imaging and tumor targeting properties, could provide a fast and simple way to detect a broad spectrum of malignant cells from malignant pleuroperitoneal effusion in patients.