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Find video protocols related to scientific articles indexed in Pubmed.
Dual-functional probes for sequential thiol and redox homeostasis sensing in live cells.
Analyst
PUBLISHED: 11-20-2014
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A new type of resorufin-based dual-functional fluorescent probe whose fluorescence emission features are sensitive to thiol compounds and redox homeostasis was developed. Thiols-triggered nucleophilic substitution of the probes converts the nonfluorescent probe to the highly fluorescent resorufin moiety; the released resorufin not only enables fluorescence signaling specific for thiol compounds but functions as a redox indicator with sensitive colorimetric and fluorescence emission change upon redox variation. Preliminary fluorescence imaging experiments have revealed the biocompatibility of the as-prepared probes and validated their practicability for thiol sensing and redox homeostasis mapping in living cells.
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[Risk factors of the occurence and death of acute respiratory distress syndrome: a prospective multicenter cohort study].
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
PUBLISHED: 11-18-2014
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To explore the risk factors of the occurence and 28-day death of acute respiratory distress syndrome (ARDS) in intensive care unit (ICU).
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Intracranial inertial cavitation threshold and thermal ablation lesion creation using MRI-guided 220-kHz focused ultrasound surgery: preclinical investigation.
J. Neurosurg.
PUBLISHED: 11-08-2014
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OBJECT In biological tissues, it is known that the creation of gas bubbles (cavitation) during ultrasound exposure is more likely to occur at lower rather than higher frequencies. Upon collapsing, such bubbles can induce hemorrhage. Thus, acoustic inertial cavitation secondary to a 220-kHz MRI-guided focused ultrasound (MRgFUS) surgery is a serious safety issue, and animal studies are mandatory for laying the groundwork for the use of low-frequency systems in future clinical trials. The authors investigate here the in vivo potential thresholds of MRgFUS-induced inertial cavitation and MRgFUS-induced thermal coagulation using MRI, acoustic spectroscopy, and histology. METHODS Ten female piglets that had undergone a craniectomy were sonicated using a 220-kHz transcranial MRgFUS system over an acoustic energy range of 5600-14,000 J. For each piglet, a long-duration sonication (40-second duration) was performed on the right thalamus, and a short sonication (20-second duration) was performed on the left thalamus. An acoustic power range of 140-300 W was used for long-duration sonications and 300-700 W for short-duration sonications. Signals collected by 2 passive cavitation detectors were stored in memory during each sonication, and any subsequent cavitation activity was integrated within the bandwidth of the detectors. Real-time 2D MR thermometry was performed during the sonications. T1-weighted, T2-weighted, gradient-recalled echo, and diffusion-weighted imaging MRI was performed after treatment to assess the lesions. The piglets were killed immediately after the last series of posttreatment MR images were obtained. Their brains were harvested, and histological examinations were then performed to further evaluate the lesions. RESULTS Two types of lesions were induced: thermal ablation lesions, as evidenced by an acute ischemic infarction on MRI and histology, and hemorrhagic lesions, associated with inertial cavitation. Passive cavitation signals exhibited 3 main patterns identified as follows: no cavitation, stable cavitation, and inertial cavitation. Low-power and longer sonications induced only thermal lesions, with a peak temperature threshold for lesioning of 53°C. Hemorrhagic lesions occurred only with high-power and shorter sonications. The sizes of the hemorrhages measured on macroscopic histological examinations correlated with the intensity of the cavitation activity (R2 = 0.74). The acoustic cavitation activity detected by the passive cavitation detectors exhibited a threshold of 0.09 V·Hz for the occurrence of hemorrhages. CONCLUSIONS This work demonstrates that 220-kHz ultrasound is capable of inducing a thermal lesion in the brain of living swines without hemorrhage. Although the same acoustic energy can induce either a hemorrhage or a thermal lesion, it seems that low-power, long-duration sonication is less likely to cause hemorrhage and may be safer. Although further study is needed to decrease the likelihood of ischemic infarction associated with the 220-kHz ultrasound, the threshold established in this work may allow for the detection and prevention of deleterious cavitations.
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Stereotactic radiosurgery for facial nerve schwannomas: A preliminary assessment and review of the literature.
Br J Neurosurg
PUBLISHED: 11-06-2014
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Objective. Facial nerve schwannomas (FNS) are rare tumors, and their appropriate management remains the subject of considerable debate. This report details the results of a series of patients with FNS treated with stereotactic radiosurgery (SRS) at the University of Virginia. Methods. We performed a retrospective review of the clinical and imaging outcomes of 5 patients who underwent Gamma Knife RS (GKRS) for small-to-medium-sized (< 5 mL) FNS at our institution. The study population consisted of 3 males and 2 females with a median age of 35 years. All patients presented with varying degrees of facial palsy and/or hearing dysfunction. Tumor volumes at GKRS ranged from 0.1 to 5 (median = 0.8) mL. The median maximum radiosurgical dose and tumor margin dose were 24 Gy and 12 Gy, respectively. Results. After a median follow-up period of 12 (range, 6-36) months, three tumors were radiographically smaller and two remained stable. Facial function improved in three patients, remained stable in one patient, and slightly declined from House-Brackmann grade I to II in one patient. Hearing function was preserved in three patients and deteriorated in two patients, one from Gardner-Robertson grade I to II and the other from serviceable hearing grade II to III. Conclusion. SRS appears to offer a reasonable rate of facial nerve preservation and tumor control for patients with small-to-medium-sized FNS. Considering the published outcomes achieved with resection, RS may be the preferred first-line treatment for these tumors.
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Rapid Screening of Peptide Probes through In Situ Single-Bead Sequencing Microarray.
Anal. Chem.
PUBLISHED: 11-06-2014
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Peptide ligands as targeting probes for in vivo imaging and drug delivery have attracted great interest in the biomedical community. However, high affinity and specificity screening of large peptide libraries remains a tedious process. Here, we report a continuous-flow microfluidic method for one-bead-one-compound (OBOC) combinatorial peptide library screening. We screened a library with 2 × 10(5) peptide beads within 4 h and discovered 140 noncanonical peptide hits targeting the tumor marker, aminopeptidase N (APN). Using the Clustal algorithm, we identified the conserved sequence Tyr-XX-Tyr in the N terminal. We demonstrated that the novel sequence YVEYHLC peptides have both nanomolar affinity and high specificity for APN in ex vivo and in vivo models. We envision that the successful demonstration of this integrated novel nanotechnology for peptide screening and identification open a new avenue for rapid discovery of new peptide-based reagents for disease diagnostics and therapeutics.
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Cauda equina-derived extracellular matrix for fabrication of nano-structured hybrid scaffolds applied to neural tissue engineering.
Tissue Eng Part A
PUBLISHED: 11-05-2014
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Extracellular matrix (ECM) components have become important candidate materials as neural scaffolds for neural tissue engineering. In this study, we prepared cauda equina-derived ECM material for producing scaffolds. Natural porcine cauda equina was decellularized with use of TritonX-100 and sodium deoxycholate, then physically shattered and made into a suspension by differential centrifugation. The decellularization procedure resulted in the removal of > 94% nuclear material and well preserved the extracellular collagen, sulfated glycosaminoglycan (sGAG). Immunofluorescence staining confirmed the presence of collagen type I, laminin, and fibronectin in ECM. Cauda equina ECM was blended with poly(l-lactide-co-glycolide) (PLGA) to fabricate nano-structured scaffolds by electrospinning. The incorporation of ECM increased the hydrophilicity of scaffolds. Fourier transform infrared spectroscopy and multiphoton-induced autofluorescence images showed the presence of ECM in the scaffolds. ECM/PLGA scaffolds were beneficial to the survival of Schwann cells as compared with PLGA-alone scaffolds, and aligned fibers could regulate cell morphologic features by inducing cell orientation. Axons in dorsal root ganglia explants extended to a greater extent along ECM/PLGA than PLGA-alone fibers. Cauda equina ECM may be promising material of scaffolds for neural tissue engineering.
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Investigating the molecular genetic basis of heterosis for internode expansion in maize by microRNA transcriptomic deep sequencing.
Funct. Integr. Genomics
PUBLISHED: 11-03-2014
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Heterosis has been used widely in the breeding of maize and other crops and plays an important role in increasing yield, improving quality, and enhancing stress resistance, but its molecular mechanism is far from clear. To determine whether microRNA (miRNA)-dependent gene regulation is responsible for heterosis of elongating internodes below the ear and ear height in maize, a deep-sequencing strategy was applied to the elite hybrid Xundan20, which is currently cultivated widely in China, and its two parents. RNA was extracted from the eighth internode because it shows clear internode length heterosis. A total of 99 conserved maize miRNAs were detected in both the hybrid and parental lines. Most of these miRNAs were expressed nonadditively in the hybrid compared with its parental lines. These results indicated that miRNAs might participate in heterosis during internode expansion in maize and exert an influence on ear and plant height via the repression of their target genes. In total, eight novel miRNAs belonging to four miRNA families were predicted in the expanding internode. Global repression of miRNAs in the hybrid, which might result in enhanced gene expression, might be one reason why the hybrid shows longer internodes and taller seedlings compared with its parental lines.
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Lipolysaccharide-Induced Neuroinflammation Is Associated with Alzheimer-Like Amyloidogenic Axonal Pathology and Dendritic Degeneration in Rats.
Adv Alzheimer Dis
PUBLISHED: 11-01-2014
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Chronic neuroinflammation is thought to play an etiological role in Alzheimer's disease (AD), which is characterized pathologically by amyloid and tau formation, as well as neuritic dystrophy and synaptic degeneration. The causal relationship between these pathological events is a topic of ongoing research and discussion. Recent data from transgenic AD models point to a tight spatiotemporal link between neuritic and amyloid pathology, with the obligatory enzyme for ?-amyloid (A?) production, namely ?-secretase-1 (BACE1), is overexpressed in axon terminals undergoing dystrophic change. However, the axonal pathology inherent with BACE1 elevation seen in transgenic AD mice may be secondary to increased soluble A? in these genetically modified animals. Here we explored the occurrence of the AD-like axonal and dendritic pathology in adult rat brain affected by LPS-induced chronic neuroinflammation. Unilateral intracerebral LPS injection induced prominent inflammatory response in glial cells in the ipsilateral cortex and hippocampal formation. BACE1 protein levels were elevated the ipsilateral hippocampal lysates in the LPS treated animals relative to controls. BACE1 immunoreactive dystrophic axons appeared in the LPS-treated ipsilateral cortex and hippocampal formation, colocalizing with increased ?-amyloid precursor protein and A? antibody (4G8) immunolabeling. Quantitative Golgi studies revealed reduction of dendritic branching points and spine density on cortical layer III and hippocampal CA3 pyramidal neurons in the LPS-treated ipsilateral cerebrum. These findings suggest that Alzheimer-like amyloidogenic axonal pathology and dendritic degeneration occur in wildtype mammalian brain in partnership with neuroinflammation following LPS injection.
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[Effects of lentivirus-mediated epidermal growth factor-like domain 7 silencing on proliferation and invasion of human laryngeal carcinoma Hep-2 cells].
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 10-30-2014
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To explore the effects of epidermal growth factor-like domain 7 (EGFL7) gene silencing on the proliferation and invasion ablity of laryngeal carcinoma cells.
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Flow-through cell electroporation microchip integrating dielectrophoretic viable cell sorting.
Anal. Chem.
PUBLISHED: 10-06-2014
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Microfluidics based continuous cell electroporation is an appealing approach for high-throughput cell transfection, but cell viability of existing methods is usually compromised by adverse electrical or hydrodynamic effects. Here we present the validation of a flow-through cell electroporation microchip, in which dielectrophoretic force was employed to sort viable cells. By integrating parallel electroporation electrodes and dielectrophoresis sorting electrodes together in a simple straight microfluidic channel, sufficient electrical pulses were applied for efficient electroporation, and a proper sinusoidal electrical field was subsequently utilized to exclude damaged cells by dielectrophoresis. Thus, the difficulties for seeking the fine balance between electrotransfection efficiency and cell viability were steered clear. After careful investigation and optimization of the DEP behaviors of electroporated cells, efficient electrotransfection of plasmid DNA was demonstrated in vulnerable neuron cells and several hard-to-transfect primary cell types with excellent cell viability. This microchip constitutes a novel way of continuous cell transfection to significantly improve the cell viability of existing methodologies.
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Covalent Functionalization of Graphene Oxide with Biocompatible Poly(ethylene glycol) for Delivery of Paclitaxel.
ACS Appl Mater Interfaces
PUBLISHED: 09-18-2014
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Graphene oxide (GO), a novel 2D nanomaterial prepared by the oxidation of natural graphite, has been paid much attention in the area of drug delivery due to good biocompatibility and low toxicity. In the present work, 6-armed poly(ethylene glycol) was covalently introduced into the surface of GO sheets via a facile amidation process under mild conditions, making the modified GO, GO-PEG (PEG: 65 wt %, size: 50-200 nm), stable and biocompatible in physiological solution. This nanosized GO-PEG was found to be nontoxic to human lung cancer A549 and human breast cancer MCF-7 cells via cell viability assay. Furthermore, paclitaxel (PTX), a widely used cancer chemotherapy drug, was conjugated onto GO-PEG via ?-? stacking and hydrophobic interactions to afford a nanocomplex of GO-PEG/PTX with a relatively high loading capacity for PTX (11.2 wt %). This complex could quickly enter into A549 and MCF-7 cells evidenced by inverted fluorescence microscopy using Fluorescein isothiocyanate as a probe, and it also showed remarkably high cytotoxicity to A549 and MCF-7 cells in a broad range of concentration of PTX and time compared to free PTX. This kind of nanoscale drug delivery system on the basis of PEGylated GO may find potential application in biomedicine.
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A flexible microneedle array as low-voltage electroporation electrodes for in vivo DNA and siRNA delivery.
Lab Chip
PUBLISHED: 09-04-2014
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In vivo electroporation is an appealing method to deliver nucleic acid into living tissues, but the clinical application of such a method was limited due to severe tissue damage and poor coverage of the tissue surface. Here we present the validation of a novel flexible microneedle array electrode (MNAE) chip, in which the microneedle array and the flexible substrate are integrated together to simultaneously facilitate low-voltage electroporation and accomplish good coverage of the tissue surface. The efficient delivery of both DNA and siRNA was demonstrated on mice. Upon penetrating the high-resistance stratum corneum, the electroporation voltage was reduced to about 35 V, which was generally recognized safe for humans. Also, a pathological analysis of the microneedle-electroporated tissues was carried out to thoroughly assess the skin damage, which is an important consideration in pre-clinical studies of electroporation devices. This MNAE constitutes a novel way of in vivo delivery of siRNA and DNA to certain tissues or organs with satisfactory efficiency and good adaptation to the tissue surface profile as well as minimum tissue damage, thus avoiding the disadvantages of existing electroporation methods.
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Volume-staged versus dose-staged radiosurgery outcomes for large intracranial arteriovenous malformations.
Neurosurg Focus
PUBLISHED: 09-02-2014
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The aim in this paper was to compare the outcomes of dose-staged and volume-staged stereotactic radio-surgery (SRS) in the treatment of large (> 10 cm(3)) arteriovenous malformations (AVMs).
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Seizure outcomes following radiosurgery for cerebral arteriovenous malformations.
Neurosurg Focus
PUBLISHED: 09-02-2014
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Seizures are a common presentation of cerebral arteriovenous malformations (AVMs). The authors evaluated the efficacy of stereotactic radiosurgery (SRS) for the management of seizures associated with AVMs and identified factors influencing seizure outcomes following SRS for AVMs.
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Involvement of the left-flipper-to-dorsal-fin interface of the zebrafish P2X4 receptor in ATP binding and structural rearrangement.
Neurosci. Lett.
PUBLISHED: 08-29-2014
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P2X receptors are trimeric ATP-activated non-selective cation channels. The ATP binding pocket is positioned between two neighboring subunits. Accompanying ligand binding, subunit-subunit contacts are most likely involved in receptor function and drive a conformational change to open the ion permeation pathway. In this way, we sought to determine the function of side chains of the zebrafish P2X4 receptor ectodomain left-flipper-to-dorsal-fin interface residues in ligand binding. By combining site-directed mutagenesis and electrophysiology methods, we showed that cysteine substitutions of I212, S215, Y216 and L217 resulted in decreased sensitivity to ATP. In addition, the ATP induced current at L217C was completely inhibited by sodium (2-sulfonatoethyl) methanethiosulfonate (MTSES(-)), indicating a role for this residue in ATP action. Deletion of residues 285-293 from the zebrafish P2X4 receptor abolished channel function. However, insertion of the same sequence frame into a homologous position of the rat P2X6 receptor did not rescue channel function, suggesting that these residues are necessary but not sufficient for achieving the correct ATP-induced conformation.
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Betaine homocysteine methyltransferase (BHMT) as a specific and sensitive blood marker for acute liver injury.
Biomarkers
PUBLISHED: 08-21-2014
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Abstract We developed a high-performance ELISA assay and measured serum BHMT levels in healthy individuals and patients with acute liver injury (ALI). The detection range of this ELISA assay was from 1.56 to 100?ng/ml. BHMT levels are significantly higher in ALI groups. In the healthy group (n?=?244), the median value (interquartile range, IQR 0-56.40) was 1.83?ng/ml. In the ALI group (n?=?42), the median value of BHMT was 748.48?ng/ml (IQR, 0-51095.92). ROC curve analysis demonstrated good sensitivity (0.86) and specificity (0.98). In addition, in five ALI cases with time course samples available, BHMT and ALT both followed the "rise and fall" temporal pattern with the disease progression. However, the slopes of BHMT curves were steeper than ALT curves. And in three out of the five cases, BHMT levels peaked 1 day earlier than ALT levels be a sensitive marker with good prognostic value.
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Effect of low estrogen on neurons in the preoptic area of hypothalamus of ovariectomized rats.
Acta Histochem.
PUBLISHED: 08-18-2014
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The purpose of this study was to investigate the difference in neuronal activity in the preoptic area of the hypothalamus (POAH) under low estrogen condition induced by ovariectomy. One hundred and twenty sham-operated (SHAM) and ovariectomized (OVX) rats were placed in different temperatures for 2h. Twelve rats from each group were stimulated by 4°C, 10°C, 25°C, 33°C and 38°C, respectively. c-Fos expression in the POAH was detected by immunohistochemistry. Following exposure to warm and cold stimuli, there were markedly lower c-Fos-positive cell densities in the OVX group compared with the SHAM group in the median preoptic nucleus (MnPO) at 4°C, 10°C, 33°C and 38°C, in the medial preoptic area (MPA) at 25°C and 38°C, in the ventromedial preoptic nucleus (VMPO) at 4°C, 10°C and 38°C and in the ventrolateral preoptic nucleus (VLPO) at 4°C and 38°C. Both temperature and surgery had an impact on c-Fos expression by two-way ANOVA method except in the lateral preoptic area (LPO). c-Fos expression differed within different nuclei of the two groups in the same and different temperature stimuli. This indicated that the temperature-sensitive nuclei in the POAH exhibited lower and different activities during temperature stimuli following ovariectomy, which possibly resulted in abnormal thermoregulation and menopausal symptoms.
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Label-free quantitative detection of tumor-derived exosomes through surface plasmon resonance imaging.
Anal. Chem.
PUBLISHED: 08-11-2014
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Exosomes are endosome-derived membrane vesicles carrying proteins and nucleic acids that are involved in cellular functions such as intercellular communication, protein and RNA secretion, and antigen presentation. Therefore, exosomes serve as potential biomarkers for many diseases including cancer. Because exosomes are difficult to enrich or purify from biofluids, quantification of exosomes is tedious and inaccurate. Here, we present a real-time, label-free, and quantitative method to detect and characterize tumor-derived exosomes without enrichment or purification. Utilizing surface plasmon resonance imaging (SPRi) in combination with antibody microarrays specific to the extracellular domains of exosome membrane proteins, exosomes in tumor cell culture medium can be quantitatively detected. We found a positive correlation between the metastatic potential of tumor cell lines and exosome secretion. This method provides an easy, efficient, and novel way to detect exosome secretion and thus an avenue toward the diagnosis and prognosis prediction of cancer.
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Critical role of all-trans retinoic acid in stabilizing human natural regulatory T cells under inflammatory conditions.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 08-06-2014
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Recent studies have demonstrated that thymus-derived naturally occurring CD4(+)Foxp3(+) regulatory T cells (Tregs) in human and mouse may be unstable and dysfunctional in the presence of proinflammatory cytokines. All-trans RA (atRA), the active derivative of vitamin A, has been shown to regulate Treg and T effector cell differentiation. We hypothesize atRA stabilizes human natural Tregs (nTregs) under inflammatory conditions. atRA prevents human nTregs from converting to Th1 and/or Th17 cells and sustains their Foxp3 expression and suppressive function in vitro or in vivo following encounters with IL-1 and IL-6. Interestingly, adoptive transfer of human nTregs pretreated with atRA significantly enhanced their suppressive effects on xenograft-vs.-host diseases (xGVHDs), and atRA- but not rapamycin-pretreated nTregs sustained the functional activity against xGVHD after stimulation with IL-1/IL-6. atRA suppresses IL-1 receptor (IL-1R) up-regulation, accelerates IL-6R down-regulation, and diminishes their signaling events as well as prevents the up-regulation of STIP1 homology and U-Box containing protein 1 on Foxp3(+) cells following IL-1/IL-6 stimulation. atRA also increases histone acetylation on Foxp3 gene promoter and CpG demethylation in the region of Foxp3 locus (i.e., Treg-specific demethylated region). These results strongly implicate that nTregs primed with atRA may represent a novel treatment strategy to control established chronic immune-mediated autoimmune and inflammatory diseases.
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PIM1 kinase phosphorylates the human transcription factor FOXP3 at serine 422 to negatively regulate its activity under inflammation.
J. Biol. Chem.
PUBLISHED: 08-05-2014
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Previous reports have suggested that human CD4(+) CD25(hi)FOXP3(+) T regulatory cells (Tregs) have functional plasticity and may differentiate into effector T cells under inflammation. The molecular mechanisms underlying these findings remain unclear. Here we identified the residue serine 422 of human FOXP3 as a phosphorylation site that regulates its function, which is not present in murine Foxp3. PIM1 kinase, which is highly expressed in human Tregs, was found to be able to interact with and to phosphorylate human FOXP3 at serine 422. T cell receptor (TCR) signaling inhibits PIM1 induction, whereas IL-6 promotes PIM1 expression in in vitro expanded human Tregs. PIM1 negatively regulates FOXP3 chromatin binding activity by specifically phosphorylating FOXP3 at Ser(422). Our data also suggest that phosphorylation of FOXP3 at the Ser(418) site could prevent FOXP3 phosphorylation at Ser(422) mediated by PIM1. Knockdown of PIM1 in in vitro expanded human Tregs promoted FOXP3-induced target gene expression, including CD25, CTLA4, and glucocorticoid-induced tumor necrosis factor receptor (GITR), or weakened FOXP3-suppressed IL-2 gene expression and enhanced the immunosuppressive activity of Tregs. Furthermore, PIM1-specific inhibitor boosted FOXP3 DNA binding activity in in vitro expanded primary Tregs and also enhanced their suppressive activity toward the proliferation of T effector cells. Taken together, our findings suggest that PIM1 could be a new potential therapeutic target in the prevention and treatment of human-specific autoimmune diseases because of its ability to modulate the immunosuppressive activity of human Tregs.
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The E3 deubiquitinase USP17 is a positive regulator of retinoic acid-related orphan nuclear receptor ?t (ROR?t) in Th17 cells.
J. Biol. Chem.
PUBLISHED: 07-28-2014
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Stable retinoic acid-related orphan nuclear receptor ?t (ROR?t) expression is pivotal for the development and function of Th17 cells. Here we demonstrate that expression of the transcription factor ROR?t can be regulated through deubiquitination, which prevents proteasome-mediated degradation. We establish that USP17 stabilizes ROR?t protein expression by reducing ROR?t polyubiquitination at its Lys-360 residue. In contrast, knockdown of endogenous USP17 in Th17 cells resulted in decreased ROR?t protein levels and down-regulation of Th17-related genes. Furthermore, USP17 expression was up-regulated in CD4(+) T cells from systemic lupus erythematosus patients. Our data reveal a molecular mechanism in which ROR?t expression in Th17 cells can be positively regulated by USP17, thereby modulating Th17 cell functions.
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Laser ranging at few-photon level by photon-number-resolving detection.
Appl Opt
PUBLISHED: 07-01-2014
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Sensitive laser ranging was demonstrated at few-photon level using photon-number-resolving (PNR) detectors. The reflected photon pulses from a non-cooperation remote target were distinguished in a sunlight environment of 2.5×103??lx by setting the discrimination threshold at 5-photon level. By comparing the detected photon numbers, two remote targets with different reflection coefficients were well recognized. PNR detection facilitated remote laser ranging of few-photon sensitivity with similar capabilities of linear optical detectors. This technique avoids photon-counting saturation and is important for ultra-long distance LIDAR and 3D imaging at a few photon level.
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A novel self-lipid antigen targets human T cells against CD1c(+) leukemias.
J. Exp. Med.
PUBLISHED: 06-16-2014
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T cells that recognize self-lipids presented by CD1c are frequent in the peripheral blood of healthy individuals and kill transformed hematopoietic cells, but little is known about their antigen specificity and potential antileukemia effects. We report that CD1c self-reactive T cells recognize a novel class of self-lipids, identified as methyl-lysophosphatidic acids (mLPAs), which are accumulated in leukemia cells. Primary acute myeloid and B cell acute leukemia blasts express CD1 molecules. mLPA-specific T cells efficiently kill CD1c(+) acute leukemia cells, poorly recognize nontransformed CD1c-expressing cells, and protect immunodeficient mice against CD1c(+) human leukemia cells. The identification of immunogenic self-lipid antigens accumulated in leukemia cells and the observed leukemia control by lipid-specific T cells in vivo provide a new conceptual framework for leukemia immune surveillance and possible immunotherapy.
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Stereotactic radiosurgery for acromegaly: outcomes by adenoma subtype.
Pituitary
PUBLISHED: 06-14-2014
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The subtypes of somatotroph-cell pituitary adenomas have been correlated with clinical and histopathological variables. Densely granulated somatotroph-cell (DG) adenomas are typically highly responsive to somatostatin analog drugs, whereas sparsely granulated somatotroph-cell (SG) are less responsive. The aim of the study is to determine the effect of stereotactic radiosurgery (SRS) on remission and development of new pituitary deficiency according to the different subtypes of growth hormone (GH) secreting adenomas.
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Critical exponents of the superfluid-Bose-glass transition in three dimensions.
Phys. Rev. Lett.
PUBLISHED: 06-03-2014
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Recent experimental and numerical studies of the critical-temperature exponent ? for the superfluid-Bose-glass universality in three-dimensional systems report strong violations of the key quantum critical relation, ?=?z, where z and ? are the dynamic and correlation-length exponents, respectively; these studies question the conventional scaling laws for this quantum critical point. Using Monte Carlo simulations of the disordered Bose-Hubbard model, we demonstrate that previous work on the superfluid-to-normal-fluid transition-temperature dependence on the chemical potential (or the magnetic field, in spin systems), T_{c}?(?-?_{c})^{?}, was misinterpreting transient behavior on approach to the fluctuation region with the genuine critical law. When the model parameters are modified to have a broad quantum critical region, simulations of both quantum and classical models reveal that the ?=?z law [with ?=2.7(2), z=3, and ?=0.88(5)] holds true, resolving the ?-exponent "crisis."
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Multisession Gamma Knife Radiosurgery: A Preliminary Experience with a Non-invasive, Relocatable Frame.
World Neurosurg
PUBLISHED: 06-02-2014
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To evaluate our preliminary outcomes for a cohort of patients who were treated with multisession Gamma Knife radiosurgery (GKRS) using the new non-invasive vacuum-assisted immobilization system.
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Single-fluorophore-based fluorescent probes enable dual-channel detection of Ag? and Hg²? with high selectivity and sensitivity.
Anal. Chim. Acta
PUBLISHED: 06-02-2014
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A new type of fluorescent probe capable of detecting Ag(+) and Hg(2+) in two independent channels was developed in the present work. Specifically, in CH3CN-MOPS mixed solvents with CH3CN/MOPS ratio (v/v) of 15/85, this type of probe fluoresced weakly, and the addition of Ag(+) remarkably induced fluorescence enhancement of the probe. In CH3CN-MOPS mixed solvents with the percentage of CH3CN increased up to 65%, the probe was highly fluorescent and addition of Hg(2+) dramatically induced the fluorescence quenching. Thus, using such single-fluorophore-based probe and tuning the polarity of the mixed solvent, Ag(+), and Hg(2+) can be detected in independent channels with high selectivity and sensitivity. As a result, the mutual interference usually encountered in most cases of Ag(+) and Hg(2+) sensing owing to the similar fluorescence response that these two ions induced, can be effectively circumvented by using the probes developed herein.
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Whole-sellar stereotactic radiosurgery for functioning pituitary adenomas.
Neurosurgery
PUBLISHED: 05-29-2014
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Functioning pituitary adenomas (FPAs) can be difficult to delineate on postoperative magnetic resonance imaging, making them difficult targets for stereotactic radiosurgery (SRS). In such cases, radiation delivery to the entire sella has been utilized as a radiosurgical equivalent of a total hypophysectomy.
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Nanostructured hybrid layered-spinel cathode material synthesized by hydrothermal method for lithium-ion batteries.
ACS Appl Mater Interfaces
PUBLISHED: 05-27-2014
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Nanostructured spinel LiMn1.5Ni0.5O4, layered Li1.5Mn0.75Ni0.25O2.5 and layered-spinel hybrid particles have been successfully synthesized by hydrothermal methods. It is found that the nanostructured hybrid cathode contains both spinel and layered components, which could be expressed as Li1.13Mn0.75Ni0.25O2.32. Diffraction-contrast bright-field (BF) and dark-field (DF) images illustrate that the hybrid cathode has well dispersed spinel component. Electrochemical measurements reveal that the first-cycle efficiency of the layered-spinel hybrid cathode is greatly improved (up to 90%) compared with that of the layered material (71%) by integrating spinel component. Our investigation demonstrates that the spinel containing hybrid material delivers a high capacity of 240 mAh g(-1) with good cycling stability between 2.0 and 4.8 V at a current rate of 0.1 C.
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[Detection of polA gene in whole blood samples and preliminary observations with molecular subtyping of Treponema pallidum].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 05-24-2014
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To detect Treponema pallidum (T.pallidum) DNA with polymerase chain reaction (PCR) in whole blood samples of syphilis patients and analyze their features of sub-genotypes.
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Neurod1 Modulates Opioid Antinociceptive Tolerance via Two Distinct Mechanisms.
Biol. Psychiatry
PUBLISHED: 05-20-2014
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The activity of neurogenic differentiation 1 (Neurod1) decreases after morphine administration, which leads to impairments of the stability of dendritic spines in primary hippocampal neurons, adult neurogenesis in mouse hippocampi, and drug-associated contextual memory. The current study examined whether Neurod1 could affect the development of opioid tolerance.
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Arsenic mobility in the arsenic-contaminated Yangzonghai Lake in China.
Ecotoxicol. Environ. Saf.
PUBLISHED: 05-19-2014
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Coagulation-precipitation techniques have been used successfully in the remediation of arsenic (As) contamination, but insufficient data exist to evaluate the side effects on lake environments (especially secondary pollution). Yangzonghai Lake, a deep lake located in southwest China that was treated with flocculants after an accident resulted in As-contamination, was selected as a case study. We attempted to elucidate how As migrates and transforms in the lake based on water simulation experiments. The results were expected to facilitate evaluation of the suitability and safety of the technology when used in a natural water body. The results showed that the As that had already been precipitated into the sediment by FeCl3 would be released again into the water body due to the increasing activity of anaerobic microorganisms, thereby causing secondary pollution. This phenomenon was especially evident during summer because water temperature stratification reduced the dissolved oxygen (DO) at the sediment surface and led to anaerobic conditions, which enhanced the anaerobic activity at the bottom of the lake. In summer, the concentration of As in the water column increased with increasing depth. In contrast, during winter, the concentration of As was quite similar at all depths of the lake because the water temperature was uniform during this period. As was released from sediments to the aqueous phase in the form of trivalent As [As(III)] upon anaerobic incubation and was oxidized gradually into pentavalent As [As(V)] by the higher DO in the upper layers of the lake water. Contrary to expectation, the disturbance (turnover in the fall) did not increase, but rather decreased the As concentration in the lake, which might result in further coagulation and precipitation through intensive mixture of the unsaturated flocculants from the sediments.
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Silent Corticotroph Adenomas After Stereotactic Radiosurgery: A Case-Control Study.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 05-08-2014
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To investigate the safety and effectiveness of stereotactic radiosurgery (SRS) in patients with a silent corticotroph adenoma (SCA) compared with patients with other subtypes of non-adrenocorticotropic hormone staining nonfunctioning pituitary adenoma (NFA).
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Four new species of pholcine spiders (Araneae: Pholcidae) from Southeast Asia.
Zootaxa
PUBLISHED: 04-29-2014
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Four new species belonging to four genera of the subfamily Pholcinae are reported from Southeast Asia: Belisana protumida spec. nov. (male, female), Khorata bayeri spec. nov. (male), Pholcus schawalleri spec. nov. (male), and Uthina khaosokensis spec. nov. (male).
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The Effect of the Left Stellate Ganglion on Sympathetic Neural Remodeling of the Left Atrium in Rats Following Myocardial Infarction.
Pacing Clin Electrophysiol
PUBLISHED: 04-25-2014
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The neural remodeling of the atrium plays an important role in the initiation of atrial fibrillation after myocardial infarction (MI); however, the effects of the left stellate ganglion (LSG) on the neural remodeling of the atrium remain incompletely understood. Thus, this study investigated the mechanism by which the LSG mediates sympathetic neural remodeling of the left atrium (LA) in rats after MI.
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LSECtin expressed on melanoma cells promotes tumor progression by inhibiting antitumor T-cell responses.
Cancer Res.
PUBLISHED: 04-25-2014
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Therapeutic antibodies that target T-cell co-inhibitory molecules display potent antitumor effects in multiple types of cancer. LSECtin is a cell surface lectin of the DC-SIGN family expressed in dendritic cells that inhibits T-cell responses. LSECtin limits T-cell activity in infectious disease, but it has not been studied in cancer. Here we report the finding that LSECtin is expressed commonly in melanomas where it blunts tumor-specific T-cell responses. When expressed in B16 melanoma cells, LSECtin promoted tumor growth, whereas its blockade slowed tumor growth in either wild-type or LSECtin-deficient mice. The tumor-promoting effects of LSECtin were abrogated in Rag1(-/-) mice or in response to CD4(+) or CD8(+) T-cell depletion. Mechanistic investigations determined that LSECtin inhibited the proliferation of tumor-specific effector T cells by downregulating the cell cycle kinases CDK2, CDK4, and CDK6. Accordingly, as expressed in B16, tumor cells LSECtin inhibited tumor-specific T-cell responses relying upon proliferation in vitro and in vivo. Notably, LSECtin interacted with the co-regulatory molecule LAG-3, the blockade of which restored IFN? secretion that was reduced by melanoma-derived expression of LSECtin. Together, our findings reveal that common expression of LSECtin in melanoma cells engenders a mechanism of immune escape, with implications for novel immunotherapeutic combination strategies.
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Preparation and characterization of fullerene (C60) amino acid nanoparticles for liver cancer cell treatment.
J Nanosci Nanotechnol
PUBLISHED: 04-18-2014
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The properties of an ideal photosensitizer are water solubility, low cytotoxicity in the dark, high ability to produce reactive oxygen species (ROS). The characteristics of water-soluble fullerene (C60) amino acid nanoparticles as a photosensitizer were evaluated. C60 modified with l-phenylalanine (C60-phe) or glycine (C60-gly) was very efficient to carry out photodynamic activity leading to cleavage of plasmid DNA in vitro. These C60 amino acid nanoparticles were the most active photosensitizer against human Liver cancer cells and induced cancer cells apoptosis after illumination. However, these derivatives exhibited no significant cytotoxicity in dark. It produced diffuse intracellular fluorescence when 2',7'-dichlorfluorescein-diacetate (DCFH-DA) was added as an ROS probe, suggesting phototoxicity of these derivatives related with the generation of intracellular ROS. These findings indicate that these fullerene derivatives may be excellent candidate PDT enhancing agents.
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Higher FOXP3-TSDR demethylation rates in adjacent normal tissues in patients with colon cancer were associated with worse survival.
Mol. Cancer
PUBLISHED: 04-06-2014
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The influence of natural regulatory T cells (nTregs) on the patients with colon cancer is unclear. Demethylated status of the Treg-specific demethylated region (TSDR) of the FOXP3 gene was reported to be a potential biomarker for the identification of nTregs.
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Application of diffusion-weighted magnetic resonance imaging to predict the intracranial metastatic tumor response to gamma knife radiosurgery.
J. Neurooncol.
PUBLISHED: 04-05-2014
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To evaluate the effect of stereotactic radiosurgery (SRS) on intracranial metastases with diffusion-weighted imaging/apparent diffusion coefficient maps. A total of 107 patients with 144 metastases larger than 1 cm in diameter were retrospectively reviewed. We calculated the DWI(Tumor/white matter) ratios (DWI(T/WM) ratio) between the metastases and the normal, contralateral frontal white matter at each time point. We also recorded the ADC values for metastases (ADCT values). The DWI(T/WM) ratio and ADCT values were assessed for correlation with the patients' tumor response, brain edema, and survival. A decrease in DWI(T/WM) ratios was seen in the controlled metastases, and an increase in the DWI(T/WM) ratio were seen in the metastases with poor tumor control. On the other hand, an increase in ADCT values was seen in the controlled metastases, and a decrease in ADCT values was seen in the metastases with poor control. The differences were significant (p value: 0.001 and 0.002, respectively). Sensitivity of a decrease in the DWI(T/WM) ratio to make an early prediction of tumor control was 83.9%, and specificity was 88.5%. When using the initial ADCT values of metastases to predict tumor response, sensitivity and specificity were 85.5 and 72.7%, respectively. DWI/ADC is a practical method for studying the efficacy of SRS and predicting early metastases response progression. A decrease signal on DWI and increased ADC values are indicators of good tumor control, and reflect the beneficial effect of SRS.
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Generation of the SCN1A epilepsy mutation in hiPS cells using the TALEN technique.
Sci Rep
PUBLISHED: 03-26-2014
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Human induced pluripotent stem cells (iPSC) can be used to understand the pathological mechanisms of human disease. These cells are a promising source for cell-replacement therapy. However, such studies require genetically defined conditions. Such genetic manipulations can be performed using the novel Transcription Activator-Like Effector Nucleases (TALENs), which generate site-specific double-strand DNA breaks (DSBs) with high efficiency and precision. Combining the TALEN and iPSC methods, we developed two iPS cell lines by generating the point mutation A5768G in the SCN1A gene, which encodes the voltage-gated sodium channel Nav1.1 ? subunit. The engineered iPSC maintained pluripotency and successfully differentiated into neurons with normal functional characteristics. The two cell lines differ exclusively at the epilepsy-susceptibility variant. The ability to robustly introduce disease-causing point mutations in normal hiPS cell lines can be used to generate a human cell model for studying epileptic mechanisms and for drug screening.
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Bimodal imprint chips for peptide screening: integration of high-throughput sequencing by MS and affinity analyses by surface plasmon resonance imaging.
Anal. Chem.
PUBLISHED: 03-24-2014
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Peptide probes and drugs have widespread applications in disease diagnostics and therapy. The demand for peptides ligands with high affinity and high specificity toward various targets has surged in the biomedical field in recent years. The traditional peptide screening procedure involves selection, sequencing, and characterization steps, and each step is manual and tedious. Herein, we developed a bimodal imprint microarray system to embrace the whole peptide screening process. Silver-sputtered silicon chip fabricated with microwell array can trap and pattern the candidate peptide beads in a one-well-one-bead manner. Peptides on beads were photocleaved in situ. A portion of the peptide in each well was transferred to a gold-coated chip to print the peptide array for high-throughput affinity analyses by surface plasmon resonance imaging (SPRi), and the peptide left in the silver-sputtered chip was ready for in situ single bead sequencing by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Using the bimodal imprint chip system, affinity peptides toward AHA were efficiently screened out from the 7 × 10(4) peptide library. The method provides a solution for high efficiency peptide screening.
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Radiosurgery for ruptured intracranial arteriovenous malformations.
J. Neurosurg.
PUBLISHED: 03-21-2014
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Ruptured intracranial arteriovenous malformations (AVMs) are at a significantly greater risk for future hemorrhage than unruptured lesions, thereby necessitating treatment in the majority of cases. In a retrospective, single-center study, the authors describe the outcomes after radiosurgery in a large cohort of patients with ruptured AVMs.
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Amylocyclicin, a novel circular bacteriocin produced by Bacillus amyloliquefaciens FZB42.
J. Bacteriol.
PUBLISHED: 03-07-2014
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Bacillus amyloliquefaciens FZB42 is a Gram-positive plant growth-promoting bacterium with an impressive capacity to synthesize nonribosomal secondary metabolites with antimicrobial activity. Here we report on a novel circular bacteriocin which is ribosomally synthesized by FZB42. The compound displayed high antibacterial activity against closely related Gram-positive bacteria. Transposon mutagenesis and subsequent site-specific mutagenesis combined with matrix-assisted laser desorption ionization-time of flight mass spectroscopy revealed that a cluster of six genes covering 4,490 bp was responsible for the production, modification, and export of and immunity to an antibacterial compound, here designated amylocyclicin, with a molecular mass of 6,381 Da. Peptide sequencing of the fragments obtained after tryptic digestion of the purified peptide revealed posttranslational cleavage of an N-terminal extension and head-to-tail circularization of the novel bacteriocin. Homology to other putative circular bacteriocins in related bacteria let us assume that this type of peptide is widespread among the Bacillus/Paenibacillus taxon.
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Radiosurgery for low-grade intracranial arteriovenous malformations.
J. Neurosurg.
PUBLISHED: 03-07-2014
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Low-grade, or Spetzler-Martin (SM) Grades I and II, arteriovenous malformations (AVMs) are associated with lower surgical morbidity rates than higher-grade lesions. While radiosurgery is now widely accepted as an effective treatment approach for AVMs, the risks and benefits of the procedure for low-grade AVMs, as compared with microsurgery, remain poorly understood. The authors of this study present the outcomes for a large cohort of low-grade AVMs treated with radiosurgery.
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Design and optimization of a modal- independent linear ultrasonic motor.
IEEE Trans Ultrason Ferroelectr Freq Control
PUBLISHED: 02-27-2014
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To simplify the design of the linear ultrasonic motor (LUSM) and improve its output performance, a method of modal decoupling for LUSMs is proposed in this paper. The specific embodiment of this method is decoupling of the traditional LUSM stator's complex vibration into two simple vibrations, with each vibration implemented by one vibrator. Because the two vibrators are designed independently, their frequencies can be tuned independently and frequency consistency is easy to achieve. Thus, the method can simplify the design of the LUSM. Based on this method, a prototype modal- independent LUSM is designed and fabricated. The motor reaches its maximum thrust force of 47 N, maximum unloaded speed of 0.43 m/s, and maximum power of 7.85 W at applied voltage of 200 Vpp. The motor's structure is then optimized by controlling the difference between the two vibrators' resonance frequencies to reach larger output speed, thrust, and power. The optimized results show that when the frequency difference is 73 Hz, the output force, speed, and power reach their maximum values. At the input voltage of 200 Vpp, the motor reaches its maximum thrust force of 64.2 N, maximum unloaded speed of 0.76 m/s, maximum power of 17.4 W, maximum thrust-weight ratio of 23.7, and maximum efficiency of 39.6%.
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Testing for association with multiple traits in generalized estimation equations, with application to neuroimaging data.
Neuroimage
PUBLISHED: 02-14-2014
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There is an increasing need to develop and apply powerful statistical tests to detect multiple traits-single locus associations, as arising from neuroimaging genetics and other studies. For example, in the Alzheimer's Disease Neuroimaging Initiative (ADNI), in addition to genome-wide single nucleotide polymorphisms (SNPs), thousands of neuroimaging and neuropsychological phenotypes as intermediate phenotypes for Alzheimer's disease, have been collected. Although some classic methods like MANOVA and newly proposed methods may be applied, they have their own limitations. For example, MANOVA cannot be applied to binary and other discrete traits. In addition, the relationships among these methods are not well understood. Importantly, since these tests are not data adaptive, depending on the unknown association patterns among multiple traits and between multiple traits and a locus, these tests may or may not be powerful. In this paper we propose a class of data-adaptive weights and the corresponding weighted tests in the general framework of generalized estimation equations (GEE). A highly adaptive test is proposed to select the most powerful one from this class of the weighted tests so that it can maintain high power across a wide range of situations. Our proposed tests are applicable to various types of traits with or without covariates. Importantly, we also analytically show relationships among some existing and our proposed tests, indicating that many existing tests are special cases of our proposed tests. Extensive simulation studies were conducted to compare and contrast the power properties of various existing and our new methods. Finally, we applied the methods to an ADNI dataset to illustrate the performance of the methods. We conclude with the recommendation for the use of the GEE-based Score test and our proposed adaptive test for their high and complementary performance.
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Bone marrow mesenchymal stem cells with Nogo-66 receptor gene silencing for repair of spinal cord injury.
Neural Regen Res
PUBLISHED: 02-08-2014
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We hypothesized that RNA interference to silence Nogo-66 receptor gene expression in bone marrow mesenchymal stem cells before transplantation might further improve neurological function in rats with spinal cord transection injury. After 2 weeks, the number of neurons and BrdU-positive cells in the Nogo-66 receptor gene silencing group was higher than in the bone marrow mesenchymal stem cell group, and significantly greater compared with the model group. After 4 weeks, behavioral performance was significantly enhanced in the model group. After 8 weeks, the number of horseradish peroxidase-labeled nerve fibers was higher in the Nogo-66 receptor gene silencing group than in the bone marrow mesenchymal stem cell group, and significantly higher than in the model group. The newly formed nerve fibers and myelinated nerve fibers were detectable in the central transverse plane section in the bone marrow mesenchymal stem cell group and in the Nogo-66 receptor gene silencing group.
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PEGylated liposomes with NGR ligand and heat-activable cell-penetrating peptide-doxorubicin conjugate for tumor-specific therapy.
Biomaterials
PUBLISHED: 01-30-2014
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Cell-penetrating peptides (CPPs) mediated tumor-oriented nanocarriers have been widely studied by researchers recently. However, applications of CPPs in vivo were usually hampered by their loss in untargeted tissues and enzymatic degradation. These shortfalls required strategies to camouflage CPPs before their arrival at the targeted site. In this work, we constructed a thermosensitive liposome (TSL) containing Asparagines-Glycine-Arginine (NGR) peptide as the targeting moiety and heat-activable cell-penetrating peptide-doxorubicin conjugate for enhancing specific cancer therapy. Different to the masking strategies of CPPs reported, CPPs existing in conjugation form of CPPs and doxorubicin (CPP-Dox) were hidden in TSL to cloak and protect CPPs. Meanwhile, NGR moiety and local tumor hyperthermia were utilized to achieve specific targeting of CPPs to the tumor. The nanocarrier (CPP-Dox/NGR-TSL) prepared in this work possessed suitable physiochemical properties such as small particle size of about 90 nm, high drug encapsulation efficiency of approximately 95%, good stability in the medium containing 10% fetal bovine serum (FBS) and so on. In vitro experiments on Human fibrosarcoma cells (HT-1080) and human breast adenocarcinoma cells (MCF-7) verified the specific targeting ability and enhanced intracellular drug delivery of the liposomes to HT-1080 cells. Furthermore, comparing with NGR-targeted TSL containing Dox (Dox/NGR-TSL), the results of intravenous administration showed CPP-Dox/NGR-TSL significantly inhibited tumor growth in nude mice xenografted HT-1080 tumors and excellent body safety. In conclusion, the nanocarrier constructed in this study would be a safe and efficiently drug delivery system for specific cancer treatment.
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Stereotactic radiosurgery for acromegaly.
J. Clin. Endocrinol. Metab.
PUBLISHED: 01-28-2014
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The role of stereotactic radiosurgery (SRS) in acromegaly is being assessed.
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Inhibition of HERG potassium channels by domiphen bromide and didecyl dimethylammonium bromide.
Eur. J. Pharmacol.
PUBLISHED: 01-26-2014
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Domiphen bromide and didecyl dimethylammonium bromide were widely used environmental chemicals with potent activity on blockade of human ether-a-go-go related gene (HERG) channels. But the mechanism of their action is not clear. The kinetics of block of HERG channels by domiphen bromide and didecyl dimethylammonium bromide was studied in order to characterize the inhibition of HERG currents by these quaternary ammonium compounds (QACs). Domiphen bromide and didecyl dimethylammonium bromide inhibited HERG channel currents in a dose-dependent manner with IC50 values of 9nM and 5nM, respectively. Block of HERG channel by domiphen bromide and didecyl dimethylammonium bromide was voltage-dependent and use-dependent. Domiphen bromide and didecyl dimethylammonium bromide caused substantial negative shift of the activation curves, accelerated activated process, but had no effects on the deactivation and reactivation processes. The docking models implied that these two compounds bound to PAS domain of HERG channels and inhibited its function. Our data demonstrated that domiphen bromide and didecyl dimethylammonium bromide blocked the HERG channel with a preference for the activated channel state.
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Radiosurgery for Spetzler-Martin Grade III arteriovenous malformations.
J. Neurosurg.
PUBLISHED: 01-24-2014
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Intracranial arteriovenous malformations (AVMs) are most commonly classified based on their Spetzler-Martin grades. Due to the composition of the Spetzler-Martin grading scale, Grade III AVMs are the most heterogeneous, comprising 4 distinct lesion subtypes. The management of this class of AVMs and the optimal treatment approach when intervention is indicated remain controversial. The authors report their experience with radiosurgery for the treatment of Grade III AVMs in a large cohort of patients.
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Graphene networks anchored with sn@graphene as lithium ion battery anode.
ACS Nano
PUBLISHED: 01-13-2014
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A facile and scalable in situ chemical vapor deposition (CVD) technique using metal precursors as a catalyst and a three-dimensional (3D) self-assembly of NaCl particles as a template is developed for one-step fabrication of 3D porous graphene networks anchored with Sn nanoparticles (5-30 nm) encapsulated with graphene shells of about 1 nm (Sn@G-PGNWs) as a superior lithium ion battery anode. In the constructed architecture, the CVD-synthesized graphene shells with excellent elasticity can effectively not only avoid the direct exposure of encapsulated Sn to the electrolyte and preserve the structural and interfacial stabilization of Sn nanoparticles but also suppress the aggregation of Sn nanoparticles and buffer the volume expansion, while the interconnected 3D porous graphene networks with high electrical conductivity, large surface area, and high mechanical flexibility tightly pin the core-shell structure of Sn@G and thus lead to remarkably enhanced electrical conductivity and structural integrity of the overall electrode. As a consequence, this 3D hybrid anode exhibits very high rate performance (1022 mAh/g at 0.2 C, 865 mAh/g at 0.5 C, 780 mAh/g at 1 C, 652 mAh/g at 2 C, 459 mAh/g at 5 C, and 270 mAh/g at 10 C, 1 C = 1 A/g) and extremely long cycling stability even at high rates (a high capacity of 682 mAh/g is achieved at 2 A/g and is maintained approximately 96.3% after 1000 cycles). As far as we know, this is the best rate capacity and longest cycle life ever reported for a Sn-based lithium ion battery anode.
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Initial Gamma Knife radiosurgery for nonfunctioning pituitary adenomas.
J. Neurosurg.
PUBLISHED: 01-03-2014
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Nonfunctioning pituitary adenomas (NFAs) are the most common type of pituitary adenoma and, when symptomatic, typically require surgical removal as an initial means of management. Gamma Knife radiosurgery (GKRS) is an alternative therapeutic strategy for patients whose comorbidities substantially increase the risks of resection. In this report, the authors evaluated the efficacy and safety of initial GKRS for NFAs.
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The development and amino acid binding ability of nano-materials based on azo derivatives: theory and experiment.
Mater Sci Eng C Mater Biol Appl
PUBLISHED: 01-02-2014
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Two nano-material-containing azo groups have been designed and developed, and the binding ability of nano-materials with various amino acids has been characterized by UV-vis and fluorescence titrations. Results indicated that two nano-materials showed the strongest binding ability for homocysteine among twenty normal kinds of amino acids (alanine, valine, leucine, isoleucine, methionine, aspartic acid, glutamic acid, arginine, glycine, serine, threonine, asparagine, phenylalanine, histidine, tryptophan, proline, lysine, glutamine, tyrosine and homocysteine). The reason for the high sensitivity for homocysteine was that two nano-materials containing an aldehyde group reacted with SH in homocysteine and afforded very stable thiazolidine derivatives. Theoretical investigation further illustrated the possible binding mode in host-guest interaction and the roles of molecular frontier orbitals in molecular interplay. Thus, the two nano-materials can be used as optical sensors for the detection of homocysteine.
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Tumor size of breast invasive ductal cancer measured with contrast-enhanced ultrasound predicts regional lymph node metastasis and N stage.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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This study aimed to determine the role of breast invasive ductal cancer (BIDC) size measured with Contrast-enhanced Ultrasound (CEUS) in the prediction of regional lymph node metastasis (LNM) and N stage.
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Epidemiology of hepatitis e virus in china: results from the third national viral hepatitis prevalence survey, 2005-2006.
PLoS ONE
PUBLISHED: 01-01-2014
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In China, hepatitis E virus (HEV) is prevalent and causes disease, but its epidemiological profile is not well understood. We used a commercial enzyme-linked immunosorbent assay to detect total antibodies to hepatitis E virus in 15,862 serum samples collected during the Third National Viral Hepatitis Prevalence Survey. The results were analyzed to calculate estimates of HEV seroprevalence and to examine the effects of some putative risk factors. The seroprevalence of HEV in the general Chinese population during the period from 2005 through 2006 was 23.46% (95% confidence interval [CI], 18.41%-28.50%). The farming population, the age group of 15-60 year olds, and those living in the Midwest or Mideast region and in Xinjiang province had the highest seroprevalence estimates. The prevalence of HEV is high in China. The seroprevalence rate of HEV shows an unbalanced distribution among areas with different geographic location and economic development levels. The characteristics of the distribution associated may be due to the route of HEV transmission (via contaminated water or animal reservoirs). Within the same region, the seroprevalence of HEV is generally increased with age.
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Quantitative trait loci for mercury accumulation in maize (Zea mays L.) identified using a RIL population.
PLoS ONE
PUBLISHED: 01-01-2014
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To investigate the genetic mechanism of mercury accumulation in maize (Zea mays L.), a population of 194 recombinant inbred lines derived from an elite hybrid Yuyu 22, was used to identify quantitative trait loci (QTLs) for mercury accumulation at two locations. The results showed that the average Hg concentration in the different tissues of maize followed the order: leaves > bracts > stems > axis > kernels. Twenty-three QTLs for mercury accumulation in five tissues were detected on chromosomes 1, 4, 7, 8, 9 and 10, which explained 6.44% to 26.60% of the phenotype variance. The QTLs included five QTLs for Hg concentration in kernels, three QTLs for Hg concentration in the axis, six QTLs for Hg concentration in stems, four QTLs for Hg concentration in bracts and five QTLs for Hg concentration in leaves. Interestingly, three QTLs, qKHC9a, qKHC9b, and qBHC9 were in linkage with two QTLs for drought tolerance. In addition, qLHC1 was in linkage with two QTLs for arsenic accumulation. The study demonstrated the concentration of Hg in Hg-contaminated paddy soil could be reduced, and maize production maintained simultaneously by selecting and breeding maize Hg pollution-safe cultivars (PSCs).
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Longitudinal analysis is more powerful than cross-sectional analysis in detecting genetic association with neuroimaging phenotypes.
PLoS ONE
PUBLISHED: 01-01-2014
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Most existing genome-wide association analyses are cross-sectional, utilizing only phenotypic data at a single time point, e.g. baseline. On the other hand, longitudinal studies, such as Alzheimer's Disease Neuroimaging Initiative (ADNI), collect phenotypic information at multiple time points. In this article, as a case study, we conducted both longitudinal and cross-sectional analyses of the ADNI data with several brain imaging (not clinical diagnosis) phenotypes, demonstrating the power gains of longitudinal analysis over cross-sectional analysis. Specifically, we scanned genome-wide single nucleotide polymorphisms (SNPs) with 56 brain-wide imaging phenotypes processed by FreeSurfer on 638 subjects. At the genome-wide significance level P < 1.8 x 10(9)) or a less stringent level (e.g. P < 10(7)), longitudinal analysis of the phenotypic data from the baseline to month 48 identified more SNP-phenotype associations than cross-sectional analysis of only the baseline data. In particular, at the genome-wide significance level, both SNP rs429358 in gene APOE and SNP rs2075650 in gene TOMM40 were confirmed to be associated with various imaging phenotypes in multiple regions of interests (ROIs) by both analyses, though longitudinal analysis detected more regional phenotypes associated with the two SNPs and indicated another significant SNP rs439401 in gene APOE. In light of the power advantage of longitudinal analysis, we advocate its use in current and future longitudinal neuroimaging studies.
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Susceptibility-weighted imaging for the noncontrast evaluation of hepatocellular carcinoma: a prospective study with histopathologic correlation.
PLoS ONE
PUBLISHED: 01-01-2014
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Specific morphologic features of hepatocellular carcinoma (HCC) on imaging have identifiable pathologic correlates as well as implications for altering surgical management and defining prognosis. In this study, we compared susceptibility-weighted imaging (SWI) to conventional techniques and correlated our findings with histopathology to determine the role of SWI in assessing morphologic features of HCC without using a contrast agent.
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Utility of R2* obtained from T2*-weighted imaging in differentiating hepatocellular carcinomas from cavernous hemangiomas of the liver.
PLoS ONE
PUBLISHED: 01-01-2014
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To evaluate the feasibility of applying R2* values to differentiate hepatocellular carcinomas (HCC) from cavernous hemangiomas of the liver (CHL).
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QTL analysis of Kernel-related traits in maize using an immortalized F2 population.
PLoS ONE
PUBLISHED: 01-01-2014
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Kernel size and weight are important determinants of grain yield in maize. In this study, multivariate conditional and unconditional quantitative trait loci (QTL), and digenic epistatic analyses were utilized in order to elucidate the genetic basis for these kernel-related traits. Five kernel-related traits, including kernel weight (KW), volume (KV), length (KL), thickness (KT), and width (KWI), were collected from an immortalized F2 (IF2) maize population comprising of 243 crosses performed at two separate locations over a span of two years. A total of 54 unconditional main QTL for these five kernel-related traits were identified, many of which were clustered in chromosomal bins 6.04-6.06, 7.02-7.03, and 10.06-10.07. In addition, qKL3, qKWI6, qKV10a, qKV10b, qKW10a, and qKW7a were detected across multiple environments. Sixteen main QTL were identified for KW conditioned on the other four kernel traits (KL, KWI, KT, and KV). Thirteen main QTL were identified for KV conditioned on three kernel-shape traits. Conditional mapping analysis revealed that KWI and KV had the strongest influence on KW at the individual QTL level, followed by KT, and then KL; KV was mostly strongly influenced by KT, followed by KWI, and was least impacted by KL. Digenic epistatic analysis identified 18 digenic interactions involving 34 loci over the entire genome. However, only a small proportion of them were identical to the main QTL we detected. Additionally, conditional digenic epistatic analysis revealed that the digenic epistasis for KW and KV were entirely determined by their constituent traits. The main QTL identified in this study for determining kernel-related traits with high broad-sense heritability may play important roles during kernel development. Furthermore, digenic interactions were shown to exert relatively large effects on KL (the highest AA and DD effects were 4.6% and 6.7%, respectively) and KT (the highest AA effects were 4.3%).
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Quantitative liver-specific protein fingerprint in blood: a signature for hepatotoxicity.
Theranostics
PUBLISHED: 01-01-2014
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We discuss here a new approach to detecting hepatotoxicity by employing concentration changes of liver-specific blood proteins during disease progression. These proteins are capable of assessing the behaviors of their cognate liver biological networks for toxicity or disease perturbations. Blood biomarkers are highly desirable diagnostics as blood is easily accessible and baths virtually all organs. Fifteen liver-specific blood proteins were identified as markers of acetaminophen (APAP)-induced hepatotoxicity using three proteomic technologies: label-free antibody microarrays, quantitative immunoblotting, and targeted iTRAQ mass spectrometry. Liver-specific blood proteins produced a toxicity signature of eleven elevated and four attenuated blood protein levels. These blood protein perturbations begin to provide a systems view of key mechanistic features of APAP-induced liver injury relating to glutathione and S-adenosyl-L-methionine (SAMe) depletion, mitochondrial dysfunction, and liver responses to the stress. Two markers, elevated membrane-bound catechol-O-methyltransferase (MB-COMT) and attenuated retinol binding protein 4 (RBP4), report hepatic injury significantly earlier than the current gold standard liver biomarker, alanine transaminase (ALT). These biomarkers were perturbed prior to onset of irreversible liver injury. Ideal markers should be applicable for both rodent model studies and human clinical trials. Five of these mouse liver-specific blood markers had human orthologs that were also found to be responsive to human hepatotoxicity. This panel of liver-specific proteins has the potential to effectively identify the early toxicity onset, the nature and extent of liver injury and report on some of the APAP-perturbed liver networks.
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VEGFR, RET, and RAF/MEK/ERK pathway take part in the inhibition of osteosarcoma MG63 cells with sorafenib treatment.
Cell Biochem. Biophys.
PUBLISHED: 01-01-2014
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Osteosarcoma (OS) is the leading primary malignant bone tumor in children and young adults. It is response for a high mortality rate. Nowadays, few researches have been performed on sorafenib against OS and no tools are available to guide the use of sorafenib in the OS treatment. In this study, we aim to investigate the effect of sorafenib on OS cell MG63 and figure the potential effective molecular pathway of its function. In the present study, we performed assays of cell proliferation, RT-PCR, and western blot to investigate the effect of sorafenib on OS MG63 cells and to elucidate the molecular actions of sorafenib against RTKs VEGFR2 and RET, as well as MEK/ERK signaling pathway. The present study confirmed that sorafenib could inhibit the proliferation of OS MG63 cells and caused a series of biomolecule effects, including the change of VEGFR2 and ERK gene expression, and the phosphorylation alteration of VEGFR2, RET, and MEK1 proteins. VEGFR2, RET, and MEK/ERK signaling pathway are involved in the pharmacological mechanism of sorafenib. They are potential candidate targets for OS treatment.
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Outcomes following single-session radiosurgery for high-grade intracranial arteriovenous malformations.
Br J Neurosurg
PUBLISHED: 12-27-2013
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Introduction. The management of Spetzler-Martin Grade-IV and -V arteriovenous malformations (AVMs) is controversial due to their uncertain natural history, the high rate of morbidity and mortality associated with microsurgical resection, and the relatively low rate of successful obliteration from less invasive approaches such as radiosurgery and embolization. We present our radiosurgical results for high-grade AVMs. Methods. We identified all patients with Spetzler-Martin Grade-IV and -V AVMs treated with single-session radiosurgery at the University of Virginia between 1989 and 2009. Patients with less than 2 years of follow-up without obliteration were excluded. This yielded 110 patients with a median age 27.6 years. The median AVM volume was 5.7 cc and prescription dose was 19 Gy. The median radiographic and clinical follow-up intervals were 88 and 97 months, respectively. Results. Complete AVM obliteration was identified on MRI only in 11 patients (10%) and confirmed by DSA in 38 patients (34%) for a cumulative obliteration rate of 44%. The actuarial rates of obliteration at 3 and 5 years were 10% and 23%, respectively. The mean and median times to obliteration were 60 months and 43 months, respectively. Significant independent predictors of obliteration were no pre-radiosurgery embolization (P = 0.008), superficial location (P = 0.001), and higher prescription dose (P = 0.028). The annual rate of post-radiosurgery hemorrhage was 3.0%, and symptomatic RIC was observed in 12% of patients. Unruptured AVMs were more likely to have RIC (P = 0.005). The rates of temporary and permanent post-radiosurgery clinical deterioration were 9% and 10%, respectively. Conclusion. Single-session radiosurgery is an acceptable treatment option for select patients harboring high-grade AVMs for which microsurgery or conservative management are associated with an unacceptably high risk of adverse outcomes.
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The machinery of macroautophagy.
Cell Res.
PUBLISHED: 12-24-2013
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Autophagy is a primarily degradative pathway that takes place in all eukaryotic cells. It is used for recycling cytoplasm to generate macromolecular building blocks and energy under stress conditions, to remove superfluous and damaged organelles to adapt to changing nutrient conditions and to maintain cellular homeostasis. In addition, autophagy plays a critical role in cytoprotection by preventing the accumulation of toxic proteins and through its action in various aspects of immunity including the elimination of invasive microbes and its participation in antigen presentation. The most prevalent form of autophagy is macroautophagy, and during this process, the cell forms a double-membrane sequestering compartment termed the phagophore, which matures into an autophagosome. Following delivery to the vacuole or lysosome, the cargo is degraded and the resulting macromolecules are released back into the cytosol for reuse. The past two decades have resulted in a tremendous increase with regard to the molecular studies of autophagy being carried out in yeast and other eukaryotes. Part of the surge in interest in this topic is due to the connection of autophagy with a wide range of human pathophysiologies including cancer, myopathies, diabetes and neurodegenerative disease. However, there are still many aspects of autophagy that remain unclear, including the process of phagophore formation, the regulatory mechanisms that control its induction and the function of most of the autophagy-related proteins. In this review, we focus on macroautophagy, briefly describing the discovery of this process in mammalian cells, discussing the current views concerning the donor membrane that forms the phagophore, and characterizing the autophagy machinery including the available structural information.
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Potential energy profile of colloidal nanoparticles in optical confinement.
Opt Lett
PUBLISHED: 12-11-2013
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An optical bottle method is developed to determine the potential-energy profile of colloidal Rayleigh nanoparticles in an optical trap. The three-dimensional distribution of fluorescent particles in the trap is measured by laser scanning confocal fluorescence microscopy. At sufficiently low concentrations at which interactions between the particles are negligible, the single-particle trapping potential-energy profile is determined from the equilibrium number-density profile by use of the Boltzmann distribution. Fluorescence imaging as well as calculations based on a discrete dipole approximation show that effects due to scattering forces are negligible for polystyrene particles of size less than 10% of the wavelength of the trapping laser, thus justifying the assumption of conservative forces in the equilibrium potential-energy determinations. The new optical bottle method measures the entire two-dimensional trapping-potential profile for an individual nanoparticle without the restriction that only one particle be contained in the trap, thus obviating the need for high laser power.
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Impact of target location on the response of trigeminal neuralgia to stereotactic radiosurgery.
J. Neurosurg.
PUBLISHED: 12-06-2013
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Object The authors evaluate the impact of target location on the rate of pain relief (PR) in patients with intractable trigeminal neuralgia (TN) undergoing stereotactic radiosurgery (SRS). Methods The authors conducted a retrospective review of 99 patients with idiopathic TN who were identified from a prospectively maintained database and were treated with SRS targeting the dorsal root entry zone with a maximum dose of 80 Gy. Targeting of the more proximal portion of a trigeminal nerve with the 50% isodose line overlapping the brainstem was performed in 36 patients (proximal group). In a matched group, 63 patients received SRS targeting the 20% isodose line tangential to the emergence of the brainstem (distal group). The median follow-up time was 33 months (range 6-124 months). Results The actuarial rate of maintenance of Barrow Neurological Institute (BNI) Pain Score I-IIIa was attained in 89% of patients at 1 year, 81% at 2 years, and 69% at 4 years, respectively, after SRS. Kaplan-Meier analysis revealed that durability of PR was only associated with the proximal location of the radiosurgical target (log-rank test, p = 0.018). Radiosurgery-induced facial numbness (BNI Score II or III) developed in 35 patients, which was significantly more frequent in the proximal group (19 patients [53%] compared with 16 [25%] in the distal group [p = 0.015]). Conclusions The radiosurgical target appears to affect the duration of pain relief in patients with idiopathic trigeminal neuralgia with the target closer to the brainstem affording extended pain relief. However, the proximal SRS target was also associated with an increased risk of mild to moderate facial numbness.
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Highly enantioselective addition of phenylethynylzinc to aldehydes catalyzed by chiral cyclopropane-based amino alcohols.
Molecules
PUBLISHED: 11-18-2013
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The enantioselective addition of phenylethynylzinc to aldehydes catalyzed by a series of cyclopropane-based amino alcohol ligands 7 was investigated. The reactions afforded chiral propargylic alcohols in high yields (up to 96%) and with excellent enantioselectivities (up to 98% ee) under mild conditions. Furthermore, studies on the structural relationship show that the matching of the chiral center configuration is crucial to obtain the high enantioselectivity.
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Substrate-induced effects on the optical properties of individual ZnO nanorods with different diameters.
Nanoscale
PUBLISHED: 11-13-2013
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We present the influence of a substrate on the properties of well-dispersed individual ZnO nanorods (NRs) with different diameters, especially on the photoluminescence (PL) properties. The studied ZnO NRs were partially supported by the quartz substrate and partially suspended in air. Continuous redshift and intensity decrease of the near band-edge emission (NBE) were observed along the suspended segment of the ZnO NRs due to the increasing temperature under UV laser excitation, suggesting that the presence of the substrate can effectively enhance the heat-sinking capability of ZnO NRs. Based on the PL measurements on individual suspended ZnO NRs with diameters from 86 nm to 2.35 ?m, the redshift of NBE along the suspended segment was more obvious for ZnO NRs with a smaller diameter, indicating that the thermal conductive ability increases as diameter increases. Additionally, by combining the experimental and simulation results, we found that the presence of the substrate also quenched the whispering gallery modes (WGMs) of the ZnO NRs with a diameter above about 350 nm due to the symmetry breaking induced by the quartz substrate which has a larger refractive index compared with air. Our studies confirm that the substrate significantly influences the properties of ZnO NRs. To fully utilize the potential properties of nanomaterials for applications in nanodevices, the substrate-induced effects should be considered thoughtfully.
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