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Find video protocols related to scientific articles indexed in Pubmed.
Lithium-Sulfur Batteries: Dendrite-Free Nanostructured Anode: Entrapment of Lithium in a 3D Fibrous Matrix for Ultra-Stable Lithium-Sulfur Batteries (Small 21/2014).
Small
PUBLISHED: 11-08-2014
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The entrapment of free-lithium in a 3D fibrous Li7 B6 framework produces a LiB nanostructured anode with a stable interface. This structure is demonstrated by Q. Zhang and co-workers on page 4257. The nanostructured anode not only reduces the areal current density that lowers the growth velocity of lithium deposits, but also limits the final size of the deposited lithium, which leads to a dendrite-free morphology at the macroscale.
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Lithium-Sulfur Batteries: Hierarchical Vine-Tree-Like Carbon Nanotube Architectures: In-Situ CVD Self-Assembly and Their Use as Robust Scaffolds for Lithium-Sulfur Batteries (Adv. Mater. 41/2014).
Adv. Mater. Weinheim
PUBLISHED: 11-04-2014
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Hierarchical vine-tree-like carbon nanotube architectures composed of vine-like single-walled carbon nanotubes wrapping around the tree-like multi-walled carbon nanotubes are represented that are fabricated through in-situ chemical vapor deposition self-assembly, as reported by Q. Zhang, F. Wei, and co-workers on page 7051. Such biomimetic nanoarchitectures exhibit excellent performance when employed as the cathode scaffolds for lithium-sulfur batteries.
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Genetic association analyses of fast plasma glucose level in pre-menopausal Chinese women: potential interaction between osteocalcin and oestrogen receptor ?
Ann. Hum. Biol.
PUBLISHED: 10-30-2014
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Abstract Background: Fasting plasma glucose (FPG) levels are usually tightly regulated within a narrow physiologic range. Variation of FPG levels is clinically important and is strongly heritable. Several lines of evidence suggest the importance of the oestrogen receptor ? (ER-?) and osteocalcin (also known as BGP, for bone Gla protein) in determining FPG; however, whether their polymorphisms are associated with FPG variation is not well understood. Aim: To investigate whether ER-a PvuII and BGP HindIII genetic polymorphisms and their potential interaction are associated with FPG variation. Subjects and methods: The study subjects were 328 unrelated pre-menopausal Chinese women aged 21 years and over (mean age?±?SD, 33.2?±?5.9 years), with an average FPG of 4.92 (SD?=?0.81). All subjects were genotyped at the ER-? PvuII and BGP HindIII loci using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Results: The ER-? PvuII genotypes were significantly associated with FPG (p?=?0.007). In addition, a significant interaction was observed of the ER-? PvuII polymorphism with BGP HindIII polymorphism on FPG variation (p?=?0.013), although the BGP HindIII polymorphism was not shown to be individually associated with FPG. Conclusion: The PvuII polymorphism of the ER-? gene and its potential interaction with the HindIII polymorphism of the BGP gene were associated with FPG in pre-menopausal Chinese women.
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Catalytic Self-Limited Assembly at Hard Templates: A Mesoscale Approach to Graphene Nanoshells for Lithium-Sulfur Batteries.
ACS Nano
PUBLISHED: 10-23-2014
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Hollow nanostructures afford intriguing structural features ranging from large surface area and fully exposed active sites to kinetically favorable mass transportation and tunable surface permeability. The unique properties and potential applications of graphene nanoshells with well-defined small cavities and delicately designed graphene shells are strongly considered. Herein, a mesoscale approach to fabricate graphene nanoshells with a single or few graphene layers and quite small diameters through a catalytic self-limited assembly of nanographene on in situ formed nanoparticles was proposed. The graphene nanoshells with a diameter of ca. 10-30 nm and a pore volume of 1.98 cm(3) g(-1) were employed as hosts to accommodate the sulfur for high-rate lithium-sulfur batteries. A very high initial discharge capacity of 1520 mAh g(-1), corresponding to 91% sulfur utilization rate at 0.1 C, was achieved on a graphene nanoshell/sulfur composite with 62 wt % loading. A very high retention of 70% was maintained when the current density increased from 0.1 C to 2.0 C, and an ultraslow decay rate of 0.06% per cycle during 1000 cycles was detected.
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[Effect of dangua recipe on glycolipid metabolism and VCAM-1 and its mRNA expression level in Apo E(-/-) mice with diabetes mellitus].
Zhongguo Zhong Xi Yi Jie He Za Zhi
PUBLISHED: 10-23-2014
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To study the effect of Dangua Recipe (DGR) on glycolipid metabolism, vascular cell adhesion molecule-1 (VCAM-1) and its mRNA expression level of transgenic Apo E(-/-) mouse with spontaneous atherosclerosis, thus revealing its partial mechanism for curing diabetes mellitus (DM) with angiopathy.
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Plk1 inhibition enhances the efficacy of androgen signaling blockade in castration-resistant prostate cancer.
Cancer Res.
PUBLISHED: 09-24-2014
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Prostate cancer is thought to be driven by oxidative stress, lipid metabolism, androgen receptor (AR) signaling, and activation of the PI3K-AKT-mTOR pathway, but it is uncertain how they may become coordinated during progression to castration-resistant disease that remains incurable. The mitotic kinase polo-like kinase 1 (Plk1) is elevated in prostate cancer, where its expression is linked to tumor grade. Notably, Plk1 signaling and lipid metabolism were identified recently as two of the top five most upregulated pathways in a mouse xenograft model of human prostate cancer. Herein, we show that oxidative stress activates both the PI3K-AKT-mTOR pathway and AR signaling in a Plk1-dependent manner in prostate cells. Inhibition of the PI3K-AKT-mTOR pathway prevented oxidative stress-induced activation of AR signaling. Plk1 modulation also affected cholesteryl ester accumulation in prostate cancer via the SREBP pathway. Finally, Plk1 inhibition enhanced cellular responses to androgen signaling inhibitors (ASI) and overcame ASI resistance in both cultured prostate cancer cells and patient-derived tumor xenografts. Given that activation of AR signaling and the PI3K-AKT-mTOR pathway is sufficient to elevate SREBP-dependent expression of key lipid biosynthesis enzymes in castration-resistant prostate cancer (CRPC), our findings argued that Plk1 activation was responsible for coordinating and driving these processes to promote and sustain the development of this advanced stage of disease. Overall, our results offer a strong mechanistic rationale to evaluate Plk1 inhibitors in combination drug trials to enhance the efficacy of ASIs in CRPC. Cancer Res; 74(22); 6635-47. ©2014 AACR.
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A novel osmolality-shift fermentation strategy for improving acarbose production and concurrently reducing byproduct component C formation by Actinoplanes sp. A56.
J. Ind. Microbiol. Biotechnol.
PUBLISHED: 09-16-2014
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Component C (Acarviosy-1,4-Glc-1,1-Glc) was a highly structural acarbose analog, which could be largely formed during acarbose fermentation process, resulting in acarbose purification being highly difficult. By choosing osmolality level as the key fermentation parameter of acarbose-producing Actinoplanes sp. A56, this paper successfully established an effective and simplified osmolality-shift strategy to improve acarbose production and concurrently reduce component C formation. Firstly, the effects of various osmolality levels on acarbose fermentation were firstly investigated in a 50-l fermenter. It was found that 400-500 mOsm/kg of osmolality was favorable for acarbose biosynthesis, but would exert a negative influence on the metabolic activity of Actinoplanes sp. A56, resulting in an obviously negative increase of acarbose and a sharp formation of component C during the later stages of fermentation (144-168 h). Based on this fact, an osmolality-shift fermentation strategy (0-48 h: 250-300 mOsm/kg; 49-120 h: 450-500 mOsm/kg; 121-168 h: 250-300 mOsm/kg) was further carried out. Compared with the osmolality-stat (450-500 mOsm/kg) fermentation process, the final accumulation amount of component C was decreased from 498.2 ± 27.1 to 307.2 ± 9.5 mg/l, and the maximum acarbose yield was increased from 3,431.9 ± 107.7 to 4,132.8 ± 111.4 mg/l.
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Hierarchical Vine-Tree-Like Carbon Nanotube Architectures: In-Situ CVD Self-Assembly and Their Use as Robust Scaffolds for Lithium-Sulfur Batteries.
Adv. Mater. Weinheim
PUBLISHED: 09-01-2014
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Hierarchical vine-tree-like carbon nanotube architectures composed of vine-like single-walled carbon nanotubes wrapping around the tree-like multi-walled carbon nanotubes are fabricated through in-situ chemical vapor deposition self-assembly. The vine-tree-like nanoarchitectures exhibit excellent cycling stability and rate performance when employed as the cathode scaffolds for lithium-sulfur batteries.
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Biphasic influence of dexamethasone exposure on embryonic vertebrate skeleton development.
Toxicol. Appl. Pharmacol.
PUBLISHED: 08-31-2014
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Dexamethasone (Dex) has anti-inflammatory and immunomodulatory properties against many conditions. There is a potential teratogenic risk, however, for pregnant women receiving Dex treatment. It has been claimed that Dex exposure during pregnancy could affect osteogenesis in the developing embryo, which still remains highly controversial. In this study, we employed chick embryos to investigate the effects of Dex exposure on skeletal development using combined in vivo and in vitro approach. First, we demonstrated that Dex (10(-8)-10(-6)?mol/egg) exposure resulted in a shortening of the developing long bones of chick embryos, and it accelerated the deposition of calcium salts. Secondly, histological analysis of chick embryo phalanxes exhibited Dex exposure inhibited the proliferation of chondrocytes, increased apoptosis of chondrocytes and osteocytes, and led to atypical arranged hypertrophic chondrocytes. The expression of genes related to skeletogenesis was also analyzed by semi-quantitative RT-PCR. The expression of ALP, Col1a2 and Col2a1 was decreased in the Dex treated phalanxes. A detectable increase was observed in Runx-2 and Mmp-13 expression. We next examined how Dex affected the different stages of skeletogenesis in vitro. Utilizing limb bud mesenchyme micromass cultures, we determined that Dex exposure exerted no effect on apoptosis but impaired chondrogenic cell proliferation. Interestingly, low dose of Dex moderately prompted nodule formation as revealed by alcian blue staining, but higher doses of Dex significantly inhibited similar chondrogenic differentiation. Dex exposure did not induce apoptosis when the chondrogenic precursors were still at the mesenchymal stage, however, cell viability was suppressed when the mesenchyme differentiated into chondrocytes. Alizarin red staining revealed that the capacity to form mineralized bone nodules was correspondingly enhanced as Dex concentrations increased. The mRNA level of Sox-9 was slightly increased in mesenchymal cell mass treated by low concentration of Dex. Mmp-13 expression was obviously up-regulated by Dex in both mesenchymal cells and primary chondrocyte cultures. And Col10a1 expression was also increased by Dex exposure in chondrocyte. In summary, we have revealed that different concentrations of Dex exposure during early gestation could exert a biphasic effect on vertebrate skeletal development.
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A comparison of the different 3D CT scanning modes on the GTV delineation for the solitary pulmonary lesion.
Radiat Oncol
PUBLISHED: 08-28-2014
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Objectives: To investigate the impacts of the different three-dimensional CT (3DCT) scanning modes on the GTV delineation for solitary pulmonary lesion (SPL) based on four-dimensional CT (4DCT), and to evaluate the feasibility of using the spiral CT scan in CT simulation.Materials and methods: Twenty-one patients with SPL underwent axial CT scan, spiral CT scan and 4DCT simulation scan during free-breathing, respectively. The same clinical radiation oncologist delineated the gross tumor volume (GTV) under the same CT window setting. GTVA and GTVS were created from the axial and spiral images, respectively. ITVMIP was created from the maximum intensity projection (MIP) reconstructed 4D images. The target volumes and position between GTVA, GTVS and ITVMIP were compared. The matching index (MI) between GTVA and GTVS, and the correlation between MI and GTVS were evaluated.
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Pharmacological inhibition of O-GlcNAcase (OGA) prevents cognitive decline and amyloid plaque formation in bigenic tau/APP mutant mice.
Mol Neurodegener
PUBLISHED: 08-27-2014
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Amyloid plaques and neurofibrillary tangles (NFTs) are the defining pathological hallmarks of Alzheimer's disease (AD). Increasing the quantity of the O-linked N-acetylglucosamine (O-GlcNAc) post-translational modification of nuclear and cytoplasmic proteins slows neurodegeneration and blocks the formation of NFTs in a tauopathy mouse model. It remains unknown, however, if O-GlcNAc can influence the formation of amyloid plaques in the presence of tau pathology.
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Improvement of the fermentative activity of lactic Acid bacteria starter culture by the addition of mn(2+).
Appl. Biochem. Biotechnol.
PUBLISHED: 08-22-2014
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Production of lactic acid bacteria (LAB) starter with raw material has received much scientific investigation, but little information is available on the influences of some trace elements on the growth and fermentative activity of LAB. Based on this fact, this paper aimed to investigate the effects of Mn(2+) on the performance of Lactobacillus plantarum CX-15 starter with Jerusalem artichoke (JA) as the main medium substrate. The results showed that Mn(2+) addition had a significant beneficial affect on the fermentative activity of L. plantarum CX-15 starter. In contrast, the lack of Mn(2+) would cause the subsequent fermentation significantly slower, whether the cell density in starter culture was higher or lower. The possible mechanism of these phenomenons was further elucidated by the time course analysis of the specific activities of metabolism key enzymes during the culture processes of L. plantarum CX-15 starter. Compared to the fermentation processes without Mn(2+) addition, it was found that Mn(2+) addition would enhance the lactate dehydrogenase (LDH) activity but reduce the activities of pyruvate dehydrogenase (PDH) and ATPase activity. Therefore, it could be concluded that the improvement of L. plantarum starter fermentative activity was probably a consequence of Mn(2+) acting as "metabolic switch," which regulated the metabolic flux from pyruvic acid to lactic acid and other metabolism pathway.
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Insulin sensitizers improve learning and attenuate tau hyperphosphorylation and neuroinflammation in 3xTg-AD mice.
J Neural Transm
PUBLISHED: 08-13-2014
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Sporadic Alzheimer's disease (AD) is a multifactorial metabolic brain disorder characterized by progressive neurodegeneration. Decreased brain energy and glucose metabolism occurs before the appearance of AD symptoms and worsens while the disease progresses. Deregulated brain insulin signaling has also been found in AD recently. To restore brain insulin sensitivity and glucose metabolism, pioglitazone and rosiglitazone, two insulin sensitizers commonly used for treating type 2 diabetes, have been studied and shown to have some beneficial effects in AD mouse models. However, the molecular mechanisms of the beneficial effects remain elusive. In the present study, we treated the 3xTg-AD mice, a widely used mouse model of AD, with pioglitazone and rosiglitazone for 4 months and studied the effects of the treatments on cognitive performance and AD-related brain alterations. We found that the chronic treatment improved spatial learning, enhanced AKT signaling, and attenuated tau hyperphosphorylation and neuroinflammation. These findings shed new light on the possible mechanisms by which these two insulin sensitizers might be useful for treating AD and support further clinical trials evaluating the efficacy of these drugs.
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Lightweight monitoring and control system for coal mine safety using REST style.
ISA Trans
PUBLISHED: 08-07-2014
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The complex environment of a coal mine requires the underground environment, devices and miners to be constantly monitored to ensure safe coal production. However, existing coal mines do not meet these coverage requirements because blind spots occur when using a wired network. In this paper, we develop a Web-based, lightweight remote monitoring and control platform using a wireless sensor network (WSN) with the REST style to collect temperature, humidity and methane concentration data in a coal mine using sensor nodes. This platform also collects information on personnel positions inside the mine. We implement a RESTful application programming interface (API) that provides access to underground sensors and instruments through the Web such that underground coal mine physical devices can be easily interfaced to remote monitoring and control applications. We also implement three different scenarios for Web-based, lightweight remote monitoring and control of coal mine safety and measure and analyze the system performance. Finally, we present the conclusions from this study and discuss future work.
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Dan-gua Fang () improves glycolipid metabolic disorders by promoting hepatic adenosine 5'-monophosphate activated protein kinase expression in diabetic Goto-Kakizaki rats.
Chin J Integr Med
PUBLISHED: 08-07-2014
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To investigate the effect of Dan-gua Fang () on adenosine 5'-monophosphate (AMP) activated protein kinase (AMPK) ? expression in liver and subsequent improvement of glucose and lipid metabolism.
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Passive immunization targeting the N-terminal projection domain of tau decreases tau pathology and improves cognition in a transgenic mouse model of Alzheimer disease and tauopathies.
J Neural Transm
PUBLISHED: 07-30-2014
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Intraneuronal accumulation of abnormally hyperphosphorylated tau in the brain is a histopathological hallmark of Alzheimer's disease and a family of related neurodegenerative disorders collectively called tauopathies. At present there is no effective treatment available for these progressive neurodegenerative diseases which are clinically characterized by dementia in mid to old-age. Here we report the treatment of 14-17-months-old 3xTg-AD mice with tau antibodies 43D (tau 6-18) and 77E9 (tau 184-195) to the N-terminal projection domain of tau or mouse IgG as a control by intraperitoneal injection once a week for 4 weeks, and the effects of the passive immunization on reduction of hyperphosphorylated tau, A? accumulation and cognitive performance in these animals. We found that treatment with tau antibodies 43D and 77E9 reduced total tau level, decreased tau hyperphosphorylated at Ser199, Ser202/Thr205 (AT8), Thr205, Ser262/356 (12E8), and Ser396/404 (PHF-1) sites, and a trend to reduce A? pathology. Most importantly, targeting N-terminal tau especially by 43D (tau 6-18) improved reference memory in the Morris water maze task in 3xTg-AD mice. We did not observe any abnormality in general physical characteristics of the treated animals with either of the two antibodies during the course of this study. Taken together, our studies demonstrate for the first time (1) that passive immunization targeting normal tau can effectively clear the hyperphosphorylated protein and possibly reduce A? pathology from the brain and (2) that targeting N-terminal projection domain of tau containing amino acid 6-18 is especially beneficial. Thus, targeting selective epitopes of N-terminal domain of tau may present a novel effective therapeutic opportunity for Alzheimer disease and other tauopathies.
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Direct Visualization of De novo Lipogenesis in Single Living Cells.
Sci Rep
PUBLISHED: 07-25-2014
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Increased de novo lipogenesis is being increasingly recognized as a hallmark of cancer. Despite recent advances in fluorescence microscopy, autoradiography and mass spectrometry, direct observation of de novo lipogenesis in living systems remains to be challenging. Here, by coupling stimulated Raman scattering (SRS) microscopy with isotope labeled glucose, we were able to trace the dynamic metabolism of glucose in single living cells with high spatial-temporal resolution. As the first direct visualization, we observed that glucose was largely utilized for lipid synthesis in pancreatic cancer cells, which occurs at a much lower rate in immortalized normal pancreatic epithelial cells. By inhibition of glycolysis and fatty acid synthase (FAS), the key enzyme for fatty acid synthesis, we confirmed the deuterium labeled lipids in cancer cells were from de novo lipid synthesis. Interestingly, we also found that prostate cancer cells exhibit relatively lower level of de novo lipogenesis, but higher fatty acid uptake compared to pancreatic cancer cells. Together, our results demonstrate a valuable tool to study dynamic lipid metabolism in cancer and other disorders.
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High-speed Intravascular Photoacoustic Imaging of Lipid-laden Atherosclerotic Plaque Enabled by a 2-kHz Barium Nitrite Raman Laser.
Sci Rep
PUBLISHED: 07-09-2014
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Lipid deposition inside the arterial wall is a key indicator of plaque vulnerability. An intravascular photoacoustic (IVPA) catheter is considered a promising device for quantifying the amount of lipid inside the arterial wall. Thus far, IVPA systems suffered from slow imaging speed (~50?s per frame) due to the lack of a suitable laser source for high-speed excitation of molecular overtone vibrations. Here, we report an improvement in IVPA imaging speed by two orders of magnitude, to 1.0?s per frame, enabled by a custom-built, 2-kHz master oscillator power amplifier (MOPA)-pumped, barium nitrite [Ba(NO3)2] Raman laser. This advancement narrows the gap in translating the IVPA technology to the clinical setting.
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From Chronic Cerebral Hypoperfusion to Alzheimer-Like Brain Pathology and Neurodegeneration.
Cell. Mol. Neurobiol.
PUBLISHED: 07-01-2014
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Chronic cerebral hypoperfusion (CCH) is a common consequence of various cerebral vascular disorders and hemodynamic and blood changes. Recent studies have revealed an important role of CCH in neurodegeneration and dementia, including vascular dementia and Alzheimer's disease (AD). This article reviews the recent advances in understanding CCH-induced neurodegeneration and AD-related brain pathology and cognitive impairment. We discuss the causes and assessment of CCH, the possible mechanisms by which CCH promotes Alzheimer-like pathology and neurodegeneration, and animal models of CCH. It appears that CCH promotes neurodegeneration and AD through multiple mechanisms, including induction of oxidative stress, A? accumulation and aggravation, tau hyperphosphorylation, synaptic dysfunction, neuronal loss, white matter lesion, and neuroinflammation. Better understanding of the mechanisms of CCH will help develop therapeutic strategies for preventing and treating neurodegeneration, including sporadic AD and vascular dementia, caused by CCH.
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Dendrite-Free Nanostructured Anode: Entrapment of Lithium in a 3D Fibrous Matrix for Ultra-Stable Lithium-Sulfur Batteries.
Small
PUBLISHED: 06-23-2014
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Entrapment of free lithium in a 3D fibrous Li7 B6 framework allows LiB nanostructured anodes with stable interfaces between the electrolyte and the electrode, which retards the formation of lithium dendrites. A lithium-sulfur cell with a nanostructured anode is created with a high Coulombic efficiency and high capacity retention rate of 36.3% after 2000 cycles.
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Imaging Lipid Metabolism in Live Caenorhabditis elegans Using Fingerprint Vibrations.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 06-08-2014
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Quantitation of lipid storage, unsaturation, and oxidation in live C.?elegans has been a long-standing obstacle. The combination of hyperspectral stimulated Raman scattering imaging and multivariate analysis in the fingerprint vibration region represents a platform that allows the quantitative mapping of fat distribution, degree of fat unsaturation, lipid oxidation, and cholesterol storage in?vivo in the whole worm. Our results reveal for the first time that lysosome-related organelles in intestinal cells are sites for storage of cholesterol in C.?elegans.
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Fast vibrational imaging of single cells and tissues by stimulated Raman scattering microscopy.
Acc. Chem. Res.
PUBLISHED: 05-28-2014
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Traditionally, molecules are analyzed in a test tube. Taking biochemistry as an example, the majority of our knowledge about cellular content comes from analysis of fixed cells or tissue homogenates using tools such as immunoblotting and liquid chromatography-mass spectrometry. These tools can indicate the presence of molecules but do not provide information on their location or interaction with each other in real time, restricting our understanding of the functions of the molecule under study. For real-time imaging of labeled molecules in live cells, fluorescence microscopy is the tool of choice. Fluorescent labels, however, are too bulky for small molecules such as fatty acids, amino acids, and cholesterol. These challenges highlight a critical need for development of chemical imaging platforms that allow in situ or in vivo analysis of molecules. Vibrational spectroscopy based on spontaneous Raman scattering is widely used for label-free analysis of chemical content in cells and tissues. However, the Raman process is a weak effect, limiting its application for fast chemical imaging of a living system. With high imaging speed and 3D spatial resolution, coherent Raman scattering microscopy is enabling a new approach for real-time vibrational imaging of single cells in a living system. In most experiments, coherent Raman processes involve two excitation fields denoted as pump at ?p and Stokes at ?s. When the beating frequency between the pump and Stokes fields (?p - ?s) is resonant with a Raman-active molecular vibration, four major coherent Raman scattering processes occur simultaneously, namely, coherent anti-Stokes Raman scattering (CARS) at (?p - ?s) + ?p, coherent Stokes Raman scattering (CSRS) at ?s - (?p - ?s), stimulated Raman gain (SRG) at ?s, and stimulated Raman loss (SRL) at ?p. In SRG, the Stokes beam experiences a gain in intensity, whereas in SRL, the pump beam experiences a loss. Both SRG and SRL belong to stimulated Raman scattering (SRS), in which the energy difference between the pump and Stokes fields is transferred to the molecule for vibrational excitation. The SRS signal appears at the same wavelengths as the excitation fields and is commonly extracted through a phase-sensitive detection scheme. The detected intensity change because of a Raman transition is proportional to Im[?(3)]IpIs, where ?(3) represents the third-order nonlinear susceptibility, Ip and Is stand for the intensity of the pump and Stokes fields. In this Account, we discuss the most recent advances in the technical development and enabling applications of SRS microscopy. Compared to CARS, the SRS contrast is free of nonresonant background. Moreover, the SRS intensity is linearly proportional to the density of target molecules in focus. For single-frequency imaging, an SRS microscope offers a speed that is ?1000 times faster than a line-scan Raman microscope and 10,000 times faster than a point-scan Raman microscope. It is important to emphasize that SRS and spontaneous Raman scattering are complementary to each other. Spontaneous Raman spectroscopy covers the entire window of molecular vibrations, which allows extraction of subtleties via multivariate analysis. SRS offers the speed advantage by focusing on either a single Raman band or a defined spectral window of target molecules. Integrating single-frequency SRS imaging and spontaneous Raman spectroscopy on a single platform allows quantitative compositional analysis of objects inside single live cells.
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Assessment of White Matter Loss Using Bond-Selective Photoacoustic Imaging in a Rat Model of Contusive Spinal Cord Injury.
J. Neurotrauma
PUBLISHED: 05-23-2014
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Abstract White matter (WM) loss is a critical event after spinal cord injury (SCI). Conventionally, such loss has been measured with histological and histochemical approaches, although the procedures are complex and may cause artifact. Recently, coherent Raman microscopy has been proven to be an emerging technology to study de- and remyelination of the injured spinal cord; however, limited penetration depth and small imaging field prevent it from comprehensive assessments of large areas of damaged tissues. Here, we report the use of bond-selective photoacoustic (PA) imaging with 1730-nm excitation, where the first overtone vibration of CH2 bond is located, to assess WM loss after a contusive SCI in adult rats. By employing the first overtone vibration of CH2 bond as the contrast, the mapping of the WM in an intact spinal cord was achieved in a label-free three-dimensional manner, and the physiological change of the spinal cord before and after injury was observed. Moreover, the recovery of the spinal cord from contusive injury with the treatment of a neuroprotective nanomedicine ferulic-acid-conjugated glycol chitosan (FA-GC) was also observed. Our study suggests that bond-selective PA imaging is a valuable tool to assess the progression of WM pathology after SCI as well as neuroprotective therapeutics in a label-free manner.
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Caffeic acid phenethyl ester, a major component of propolis, suppresses high fat diet-induced obesity through inhibiting adipogenesis at the mitotic clonal expansion stage.
J. Agric. Food Chem.
PUBLISHED: 05-05-2014
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In the present study, we aimed to investigate the antiobesity effect of CAPE in vivo, and the mechanism by which CAPE regulates body weight in vitro. To confirm the antiobesity effect of CAPE in vivo, mice were fed with a high fat diet (HFD) with different concentrations of CAPE for 5 weeks. CAPE significantly reduced body weight gain and epididymal fat mass in obese mice fed a HFD. In accordance with in vivo results, Oil red O staining results showed that CAPE significantly suppressed MDI-induced adipogenesis of 3T3-L1 preadipocytes. FACS analysis results showed that CAPE delayed MDI-stimulated cell cycle progression, thereby contributing to inhibit mitotic clonal expansion (MCE), which is a prerequisite step for adipogenesis. Also, CAPE regulated the expression of cyclin D1 and the phosphorylation of ERK and Akt, which are upstream of cyclin D1. These results suggest that CAPE exerts an antiobesity effect in vivo, presumably through inhibiting adipogenesis at an early stage of adipogenesis.
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An Early Cretaceous pterosaur with an unusual mandibular crest from China and a potential novel feeding strategy.
Sci Rep
PUBLISHED: 04-25-2014
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The Aptian Jiufotang Formation of northeast China is a Konservat Lagerstätte particularly rich in pterosaurs, notably azhdarchoids. Here we describe a new genus and species of toothed pteranodontoid pterosaur, Ikrandraco avatar gen. et sp. nov., based on two laterally flattened specimens. Ikrandraco avatar is diagnosed by a suite of features, including a very low and elongate skull, strongly inclined quadrate, and a deep, blade-like bony mandibular crest with a hook-like process on its posterior edge, an unusual structure so far unique to this taxon. The particular skull shape hints at a distinct feeding habit for pterosaurs that potentially includes temporary skimming and an extensible skin acting as a throat pouch that was more developed than in any other pterosaur known so far. The presence of two other taxa of purported piscivorous pterosaurs in the Jiufotang Formation suggests distinct resource exploitation in this part of China during the Early Cretaceous.
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Targeting TNF: a therapeutic strategy for Alzheimer's disease.
Drug Discov. Today
PUBLISHED: 04-04-2014
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Tumor necrosis factor (TNF), a ligand cytokine, is involved in systemic inflammation. Apart from the well-known pharmacological effects of TNF inhibitors on autoimmune disorders, interest in the effects of TNF in neurodegenerative disorders such as Alzheimer disease (AD) is increasing. TNF and its type 1 receptor (TNFRI) are not only involved in AD-related brain neuroinflammation, but also contribute to amyloidogenesis via ?-secretase regulation, suggesting TNF as a promising candidate for future AD therapy. Although the potential adverse effects of TNF-based AD therapies have been of concerns, here we summarize recent discoveries relating to TNF and TNFRI-mediated signal transduction as potential therapeutic targets in AD pathology and clinical investigations.
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Cross talk between PI3K-AKT-GSK-3? and PP2A pathways determines tau hyperphosphorylation.
Neurobiol. Aging
PUBLISHED: 03-20-2014
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Glycogen synthase kinase-3? (GSK-3?) and protein phosphatase 2A (PP2A) are the important enzymes controlling tau hyperphosphorylation. The relationship between these two enzymes and its impact on tau hyperphosphorylation are not well understood. In the present study, we determined the cross talk between PI3K-AKT-GSK-3? and PP2A pathways and found that the former regulated the methylation of PP2Ac via GSK-3?. Upregulation of GSK-3? led to an increase in the methylation and activity of PP2Ac through suppression of protein phosphatase methylesterase-1 expression and phosphorylation of leucine carboxyl methyltransferase 1. PP2A also regulated GSK-3? phosphorylation. Downregulation of PP2A enhanced Ser9 phosphorylation of GSK-3? and inhibited its kinase activity. Thus, GSK-3? and PP2A regulate each other and control tau phosphorylation both directly and indirectly through each other. Reduction of tau phosphorylation by inhibition of GSK-3? may be more than offset by inhibition of PP2A through a shift in phosphatase methylesterase-1/leucine carboxyl methyltransferase 1 balance; PP2A regulates phosphorylation of tau at Ser262/356, a required site for tau pathology. These findings suggest targeting PP2A rather than GSK-3? to inhibit tau pathology.
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Nitrogen-doped aligned carbon nanotube/graphene sandwiches: facile catalytic growth on bifunctional natural catalysts and their applications as scaffolds for high-rate lithium-sulfur batteries.
Adv. Mater. Weinheim
PUBLISHED: 03-19-2014
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Nitrogen-doped aligned CNT/graphene sandwiches are rationally designed and in-situ fabricated by a facile catalytic growth on bifunctional natural catalysts that exhibit high-rate performances as scaffolds for lithium-sulfur batteries, with a high initial capacity of 1152 mA h g(-1) at 1.0 C. A remarkable capacity of 770 mA h g(-1) can be achieved at 5.0 C. Such a design strategy for materials opens up new perspectives to novel advanced functional composites, especially interface-modified hierarchical nanocarbons for broad applications.
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Label-free real-time imaging of myelination in the Xenopus laevis tadpole by in vivo stimulated Raman scattering microscopy.
J Biomed Opt
PUBLISHED: 03-16-2014
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The myelin sheath plays an important role as the axon in the functioning of the neural system, and myelin degradation is a hallmark pathology of multiple sclerosis and spinal cord injury. Electron microscopy, fluorescent microscopy, and magnetic resonance imaging are three major techniques used for myelin visualization. However, microscopic observation of myelin in living organisms remains a challenge. Using a newly developed stimulated Raman scattering microscopy approach, we report noninvasive, label-free, real-time in vivo imaging of myelination by a single-Schwann cell, maturation of a single node of Ranvier, and myelin degradation in the transparent body of the Xenopus laevis tadpole.
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Intranasal insulin restores insulin signaling, increases synaptic proteins, and reduces A? level and microglia activation in the brains of 3xTg-AD mice.
Exp. Neurol.
PUBLISHED: 03-10-2014
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Decreased brain insulin signaling has been found recently in Alzheimer's disease (AD). Intranasal administration of insulin, which delivers the drug directly into the brain, improves memory and cognition in both animal studies and small clinical trials. However, the underlying mechanisms are unknown. Here, we treated 9-month-old 3xTg-AD mice, a commonly used mouse model of AD, with daily intranasal administration of insulin for seven days and then studied brain abnormalities of the mice biochemically and immunohistochemically. We found that intranasal insulin restored insulin signaling, increased the levels of synaptic proteins, and reduced A?40 level and microglia activation in the brains of 3xTg-AD mice. However, this treatment did not affect the levels of glucose transporters and O-GlcNAcylation or tau phosphorylation. Our findings provide a mechanistic insight into the beneficial effects of intranasal insulin treatment and support continuous clinical trials of intranasal insulin for the treatment of AD.
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Self-propagating high-temperature synthesis for compound thermoelectrics and new criterion for combustion processing.
Nat Commun
PUBLISHED: 02-20-2014
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The existing methods of synthesis of thermoelectric (TE) materials remain constrained to multi-step processes that are time and energy intensive. Here we demonstrate that essentially all compound thermoelectrics can be synthesized in a single-phase form at a minimal cost and on the timescale of seconds using a combustion process called self-propagating high-temperature synthesis. We illustrate this method on Cu2Se and summarize key reaction parameters for other materials. We propose a new empirically based criterion for sustainability of the combustion reaction, where the adiabatic temperature that represents the maximum temperature to which the reacting compact is raised as the combustion wave passes through, must be high enough to melt the lower melting point component. Our work opens a new avenue for ultra-fast, low-cost, large-scale production of TE materials, and provides new insights into combustion process, which greatly broaden the scope of materials that can be successfully synthesized by this technique.
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Phenylbutyric acid protects against spatial memory deficits in a model of repeated electroconvulsive therapy.
Curr Neurovasc Res
PUBLISHED: 01-28-2014
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Repeated electroconvulsive therapy (rECT) is widely applied in the treatment of refractory depression. Among the side effects of rECT, memory impairment is noticeable and needs effective protection. In this study, by employing a recognized repeated electroconvulsive shock (rECS) rat model, we found that rECS induced the significant spatial memory retention deficits with the simultaneous decreases in long-term potential (LTP), enhanced excitable postsynaptic potentials (EPSP), population spike (PS) and input/output curve in perforant pathway-dentate gyrus (PP-DG), but had no obvious neuron loss or dentritic spine loss in the brain by Nissle or Golgi stainings. Furthermore, the increased synaptic proteins of NR2A/B, PSD93, PSD95, the immediate early gene c-Fos and CREB protein were detected in hippocampus of rECS rats. rECS was also found to cause enhanced axon reorganization in DG region of hippocampus by Timm staining. Intraperitoneal injection of phenylbutyric acid (PBA), an aromatic short chain fatty acid acting as a molecule chaperon, could prevent rats from the rECS-induced memory deficits and synaptic potential enhancement by decreasing the levels of the abnormally increased memory-associated proteins and enhanced axon reorganization in hippocampus. Our data suggested that PBA might be potentially used to attenuate the rECS-induced memory impairment.
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Cholesteryl ester accumulation induced by PTEN loss and PI3K/AKT activation underlies human prostate cancer aggressiveness.
Cell Metab.
PUBLISHED: 01-23-2014
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Altered lipid metabolism is increasingly recognized as a signature of cancer cells. Enabled by label-free Raman spectromicroscopy, we performed quantitative analysis of lipogenesis at single-cell level in human patient cancerous tissues. Our imaging data revealed an unexpected, aberrant accumulation of esterified cholesterol in lipid droplets of high-grade prostate cancer and metastases. Biochemical study showed that such cholesteryl ester accumulation was a consequence of loss of tumor suppressor PTEN and subsequent activation of PI3K/AKT pathway in prostate cancer cells. Furthermore, we found that such accumulation arose from significantly enhanced uptake of exogenous lipoproteins and required cholesterol esterification. Depletion of cholesteryl ester storage significantly reduced cancer proliferation, impaired cancer invasion capability, and suppressed tumor growth in mouse xenograft models with negligible toxicity. These findings open opportunities for diagnosing and treating prostate cancer by targeting the altered cholesterol metabolism.
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Losartan-induced hypotension leads to tau hyperphosphorylation and memory deficit.
J. Alzheimers Dis.
PUBLISHED: 01-23-2014
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Recent studies have reported a correlation between dementia and low blood pressure. How hypotension is associated with the increased risk of Alzheimer's disease (AD) remains unclear. Here we show that one month treatment of losartan, an angiotensin II type 1 (AT1) receptor antagonist, causes chronic and sustained hypotension, along with oxidative stress in adult male Sprague-Dawley rats. Furthermore, we show that losartan treatment increases the level of inactivated protein phosphatase 2A (PP2A) and the hyperphosphorylation of tau at Ser 199 and Ser 396. Rats treated with losartan present memory deficits and decreases in spine-density. These findings suggest that losartan-induced hypotension may increase the risk of AD-like pathological alteration and behavioral impairment through oxidative stress which leads to tau hyperphosphorylation and loss of dendritic spines.
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The negative impact of Wnt signaling on megakaryocyte and primitive erythroid progenitors derived from human embryonic stem cells.
Stem Cell Res
PUBLISHED: 01-14-2014
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The Wnt gene family consists of structurally related genes encoding secreted signaling molecules that have been implicated in many developmental processes, including regulation of cell fate and patterning during embryogenesis. Previously, we found that Wnt signaling is required for primitive or yolk sac-derived-erythropoiesis using the murine embryonic stem cell (ESC) system. Here, we examine the effect of Wnt signaling on the formation of early hematopoietic progenitors derived from human ESCs. The first hematopoietic progenitor cells in the human ESC system express the pan-hematopoietic marker CD41 and the erythrocyte marker, glycophorin A or CD235. We have developed a novel serum-free, feeder-free, adherent differentiation system that can efficiently generate large numbers of CD41+CD235+ cells. We demonstrate that this cell population contains progenitors not just for primitive erythroid and megakaryocyte cells but for the myeloid lineage as well and term this population the primitive common myeloid progenitor (CMP). Treatment of mesoderm-specified cells with Wnt3a led to a loss of hematopoietic colony-forming ability while the inhibition of canonical Wnt signaling with DKK1 led to an increase in the number of primitive CMPs. Canonical Wnt signaling also inhibits the expansion and/or survival of primitive erythrocytes and megakaryocytes, but not myeloid cells, derived from this progenitor population. These findings are in contrast to the role of Wnt signaling during mouse ESC differentiation and demonstrate the importance of the human ESC system in studying species-specific differences in development.
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Excess ROS induced by AAPH causes myocardial hypertrophy in the developing chick embryo.
Int. J. Cardiol.
PUBLISHED: 01-11-2014
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The developing embryo is very sensitive to oxidative stress and excess reactive oxygen species (ROS) generation is often associated with cardiovascular malformation. However, little is known about the adverse effects of ROS during heart morphogenesis, especially during the formation of the atria and ventricles.
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Deregulation of brain insulin signaling in Alzheimer's disease.
Neurosci Bull
PUBLISHED: 01-03-2014
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Contrary to the previous belief that insulin does not act in the brain, studies in the last three decades have demonstrated important roles of insulin and insulin signal transduction in various functions of the central nervous system. Deregulated brain insulin signaling and its role in molecular pathogenesis have recently been reported in Alzheimer's disease (AD). In this article, we review the roles of brain insulin signaling in memory and cognition, the metabolism of amyloid ? precursor protein, and tau phosphorylation. We further discuss deficiencies of brain insulin signaling and glucose metabolism, their roles in the development of AD, and recent studies that target the brain insulin signaling pathway for the treatment of AD. It is clear now that deregulation of brain insulin signaling plays an important role in the development of sporadic AD. The brain insulin signaling pathway also offers a promising therapeutic target for treating AD and probably other neurodegenerative disorders.
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Microtubule-associated protein tau as a therapeutic target in Alzheimer's disease.
Expert Opin. Ther. Targets
PUBLISHED: 01-03-2014
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Alzheimer's disease (AD) is a major public health problem in modern society and as yet, other than a few symptomatic drugs, there is no disease-modifying treatment for this disease available.
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Alzheimer disease therapeutics: focus on the disease and not just plaques and tangles.
Biochem. Pharmacol.
PUBLISHED: 01-02-2014
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The bulk of AD research during the last 25 years has been A?-centric based on a strong faith in the Amyloid Cascade Hypothesis which is not supported by the data on humans. To date, A?-based therapeutic clinical trials on sporadic cases of AD have been negative. Although most likely the major reason for the failure is that A? is not an effective therapeutic target for sporadic AD, initiation of the treatment at mild to moderate stages of the disease is blamed as too late to be effective. Clinical trials on presymptomatic familial AD cases have been initiated with the logic that A? is a trigger of the disease and hence initiation of the A? immunotherapies several years before any clinical symptoms would be effective. There is an urgent need to explore targets other than A?. There is now increasing interest in inhibiting tau pathology, which does have a far more compelling rationale than A?. AD is multifactorial and over 99% of the cases are the sporadic form of the disease. Understanding of the various etiopathogenic mechanisms of sporadic AD and generation of the disease-relevant animal models are required to develop rational therapeutic targets and therapies. Treatment of AD will require both inhibition of neurodegeneration and regeneration of the brain.
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Apolipoprotein e gene polymorphisms are associated with primary hyperuricemia in a chinese population.
PLoS ONE
PUBLISHED: 01-01-2014
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Primary hyperuricemia, an excess of uric acid in the blood, is a major public health problem. In addition to the morbidity that is attributable to gout, hyperuricemia is also associated with metabolic syndrome, hypertension, and cardiovascular disease. This study aims to assess the genetic associations between Apolipoprotein E (APOE) polymorphisms and hyperuricemia in a Chinese population.
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Representation of pheromones, interspecific signals, and plant odors in higher olfactory centers; mapping physiologically identified antennal-lobe projection neurons in the male heliothine moth.
Front Syst Neurosci
PUBLISHED: 01-01-2014
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The arrangement of anatomically separated systems for information about general and pheromone odorants is well documented at the initial levels of the olfactory pathway both in vertebrates and insects. In the primary olfactory center of the moth brain, for example, a few enlarged glomeruli situated dorsally, at the entrance of the antennal nerve, are devoted to information about female-produced substances whereas a set of more numerous ordinary glomeruli (OG) receives input about general odorants. Heliothine moths are particularly suitable for studying central chemosensory mechanisms not only because of their anatomically separated systems for plant odors and pheromones but also due to their use of female-produced substances in communication across the species. Thus, the male-specific system of heliothine moths includes two sub-arrangements, one ensuring attraction and mating behavior by carrying information about pheromones released by conspecifics, and the other inhibition of attraction via signal information emitted from heterospecifics. Based on previous tracing experiments, a general chemotopic organization of the male-specific glomeruli has been demonstrated in a number of heliothine species. As compared to the well explored organization of the moth antennal lobe (AL), demonstrating a non-overlapping representation of the biologically relevant stimuli, less is known about the neural arrangement residing at the following synaptic level, i.e., the mushroom body calyces and the lateral horn. In the study presented here, we have labeled physiologically characterized antennal-lobe projection neurons in males of the two heliothine species, Heliothis virescens and Helicoverpa assulta, for the purpose of mapping their target regions in the protocerebrum. In order to compare the representation of plant odors, pheromones, and interspecific signals in the higher brain regions of each species, we have created standard brain atlases and registered three-dimensional models of distinct uniglomerular projection neuron types into the relevant atlas.
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Intranasal insulin prevents anesthesia-induced hyperphosphorylation of tau in 3xTg-AD mice.
Front Aging Neurosci
PUBLISHED: 01-01-2014
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It is well documented that elderly individuals are at increased risk of cognitive decline after anesthesia. General anesthesia is believed to be a risk factor for Alzheimer's disease (AD). Recent studies suggest that anesthesia may increase the risk for cognitive decline and AD through promoting abnormal hyperphosphorylation of tau, which is crucial to neurodegeneration seen in AD.
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Central projections of gustatory receptor neurons in the medial and the lateral sensilla styloconica of Helicoverpa armigera larvae.
PLoS ONE
PUBLISHED: 01-01-2014
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Food selection behavior of lepidopteran larvae is predominantly governed by the activation of taste neurons present in two sensilla styloconica located on the galea of the maxilla. In this study, we present the ultrastructure of the sensilla styloconica and the central projection pattern of their associated receptor neurons in larvae of the heliothine moth, Helicoverpa armigera. By means of light microscopy and scanning electron microscopy, the previous findings of two morphologically fairly similar sensilla comprising a socketed conic tip inserted into a large peg were confirmed. However, the peg size of the medial sensillum was found to be significantly bigger than that of the lateral sensillum. The sensory neurons derived from each sensillum styloconicum were mapped separately using anterograde staining experiments combined with confocal laser-scanning microscopy. For determining the afferents' target regions relative to each other, we reconstructed the labeled axons and placed them into a common reference framework. The sensory axons from both sensilla projected via the ipsilateral maxillary nerve to the suboesophageal ganglion and further through the ipsilateral circumoesophageal connective to the brain. In the suboesophageal ganglion, the sensory projections targeted two areas of the ipsilateral maxillary neuropil, one located in the ventrolateral neuromere and the other adjacent to the neuromere midline. In the brain, the axon terminals targeted the dorso-anterior area of the ipsilateral tritocerebrum. As confirmed by the three-dimensional reconstructions, the target regions of the neural projections originating from each of the two sensilla styloconica were identical.
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Chronic cerebral hypoperfusion causes decrease of O-GlcNAcylation, hyperphosphorylation of tau and behavioral deficits in mice.
Front Aging Neurosci
PUBLISHED: 01-01-2014
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Chronic cerebral hypoperfusion (CCH) is one of the causes of vascular dementia (VaD) and is also an etiological factor for Alzheimer's disease (AD). However, how CCH causes cognitive impairment and contributes to Alzheimer's pathology is poorly understood. Here we produced a mouse model of CCH by unilateral common carotid artery occlusion (UCCAO) and studied the behavioral changes and brain abnormalities in mice 2.5 months after UCCAO. We found that CCH caused significant short-term memory deficits and mild long-term spatial memory impairment, as well as decreased level of protein O-GlcNAcylation, increased level of tau phosphorylation, dysregulated synaptic proteins and insulin signaling, and selective neurodegeneration in the brain. These findings provide mechanistic insight into the effects of CCH on memory and cognition and the likely link between AD and VaD.
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Otopetrin 1 protects mice from obesity-associated metabolic dysfunction through attenuating adipose tissue inflammation.
Diabetes
PUBLISHED: 12-30-2013
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Chronic low-grade inflammation is emerging as a pathogenic link between obesity and metabolic disease. Persistent immune activation in white adipose tissue (WAT) impairs insulin sensitivity and systemic metabolism in part through the actions of proinflammatory cytokines. Whether obesity engages an adaptive mechanism to counteract chronic inflammation in adipose tissues has not been elucidated. Here we identified Otopetrin 1 (Otop1) as a component of a counter-inflammatory pathway that is induced in WAT during obesity. Otop1 expression is markedly increased in obese mouse WAT and is stimulated by TNF? in cultured adipocytes. Otop1 mutant mice respond to high-fat diet with pronounced insulin resistance and hepatic steatosis, accompanied by augmented adipose tissue inflammation. Otop1 attenuates interferon ? (IFN?) signaling in adipocytes through selective downregulation of the transcription factor STAT1. Using a tagged vector, we found that Otop1 physically interacts with endogenous STAT1. Thus, Otop1 defines a unique target of cytokine signaling that attenuates obesity-induced adipose tissue inflammation and plays an adaptive role in maintaining metabolic homeostasis in obesity.
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[Effect of fermented cordyceps powder and prednisone on the Notch2/Hes-1 signaling activation in the kidney tubules of rats with acute aristolochic acid nephropathy].
Zhongguo Zhong Xi Yi Jie He Za Zhi
PUBLISHED: 12-12-2013
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To investigate the effect of both fermented Cordyceps powder (CS) and prednisone on the Notch2/hes-1 signaling activation in the kidney tubules of rats with acute aristolochic acid nephropathy (AAAN).
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Vibrational Photoacoustic Tomography: Chemical Imaging beyond the Ballistic Regime.
J Phys Chem Lett
PUBLISHED: 11-14-2013
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Proof-of-concept of vibrational photoacoustic tomography is demonstrated with a homebuilt Raman laser generating greater than 100 mJ of energy per pulse at 1197 nm wavelength. We employed this system for excitation of second overtone transition of C-H bonds. Vibrational photoacoustic signal from C-H rich polyethylene tube phantom placed under 3 cm thick chicken breast tissue was obtained with a signal to noise ratio of 2.5. Further, we recorded photoacoustic image of a polyethylene ring placed under 5 mm chicken tissue with excellent contrast. This development opens new opportunities of performing label free vibrational imaging in the deep tissue regime.
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Neuroprotective ferulic acid (FA)-glycol chitosan (GC) nanoparticles for functional restoration of traumatically injured spinal cord.
Biomaterials
PUBLISHED: 10-10-2013
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An urgent unmet need exists for early-stage treatment of spinal cord injury (SCI). Currently methylprednisolone is the only therapeutic agent used in clinics, for which the efficacy is controversial and the side effect is well-known. We demonstrated functional restoration of injured spinal cord by self-assembled nanoparticles composed of ferulic acid modified glycol chitosan (FA-GC). Chitosan and ferulic acid are strong neuroprotective agents but their systemic delivery is difficult. Our data has shown a prolonged circulation time of the FA-GC nanoparticles allowing for effective delivery of both chitosan and ferulic acid to the injured site. Furthermore, the nanoparticles were found both in the gray matter and white matter. The in vitro tests demonstrated that nanoparticles protected primary neurons from glutamate-induced excitotoxicity. Using a spinal cord contusion injury model, significant recovery in locomotor function was observed in rats that were intravenously administered nanoparticles at 2 h post injury, as compared to non-improvement by methylprednisolone administration. Histological analysis revealed that FA-GC treatment significantly preserved axons and myelin and also reduced cavity volume, astrogliosis, and inflammatory response at the lesion site. No obvious adverse effects of nanoparticles to other organs were found. The restorative effect of FA-GC presents a promising potential for treating human SCIs.
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Imaging cytoplasmic lipid droplets in enterocytes and assessing dietary fat absorption.
Methods Cell Biol.
PUBLISHED: 10-09-2013
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The primary function of the small intestine is digesting and absorbing nutrients from consumed food. Because of this, the small intestine is often thought of as a nutrient thoroughfare-enterocytes taking up nutrients on the apical side and then secreting nutrients from the basolateral side. The small intestine is not commonly thought of as a lipid storage organ; however, when meals and diets containing high amounts of fat are consumed, some dietary fat is stored in cytoplasmic lipid droplets (CLDs). The balance between storage and secretion of dietary fat by enterocytes is important in determining the physiological fate of dietary fat, including regulating blood lipid concentrations and energy balance. The existence of CLDs within enterocytes has likely evolved for three important physiological functions: (i) to allow the small intestine to efficiently absorb large amounts of energy dense fat, (ii) to control the rate of dietary fat entering circulation, and (iii) to alleviate lipotoxicity to enterocytes induced by high concentrations of free fatty acids, especially when a high fat meal is consumed. The purpose of this chapter is to provide methods for imaging CLDs in enterocytes and assessing different aspects of dietary fat absorption.
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Biaxial deformation of collagen and elastin fibers in coronary adventitia.
J. Appl. Physiol.
PUBLISHED: 10-03-2013
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The microstructural deformation-mechanical loading relation of the blood vessel wall is essential for understanding the overall mechanical behavior of vascular tissue in health and disease. We employed simultaneous mechanical loading-imaging to quantify in situ deformation of individual collagen and elastin fibers on unstained fresh porcine coronary adventitia under a combination of vessel inflation and axial extension loading. Specifically, the specimens were imaged under biaxial loads to study microscopic deformation-loading behavior of fibers in conjunction with morphometric measurements at the zero-stress state. Collagen fibers largely orientate in the longitudinal direction, while elastin fibers have major orientation parallel to collagen, but with additional orientation angles in each sublayer of the adventitia. With an increase of biaxial load, collagen fibers were uniformly stretched to the loading direction, while elastin fibers gradually formed a network in sublayers, which strongly depended on the initial arrangement. The waviness of collagen decreased more rapidly at a circumferential stretch ratio of ?? = 1.0 than at ?? = 1.5, while most collagen became straightened at ?? = 1.8. These microscopic deformations imply that the longitudinally stiffer adventitia is a direct result of initial fiber alignment, and the overall mechanical behavior of the tissue is highly dependent on the corresponding microscopic deformation of fibers. The microstructural deformation-loading relation will serve as a foundation for micromechanical models of the vessel wall.
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Spectroscopic Imaging of Deep Tissue through Photoacoustic Detection of Molecular Vibration.
J Phys Chem Lett
PUBLISHED: 09-28-2013
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The quantized vibration of chemical bonds provides a way of imaging target molecules in a complex tissue environment. Photoacoustic detection of harmonic vibrational transitions provides an approach to visualize tissue content beyond the ballistic photon regime. This method involves pulsed laser excitation of overtone transitions in target molecules inside a tissue. Fast relaxation of the vibrational energy into heat results in a local temperature rise on the order of mK and a subsequent generation of acoustic waves detectable with an ultrasonic transducer. In this perspective, we review recent advances that demonstrate the advantages of vibration-based photoacoustic imaging and illustrate its potential in diagnosing cardiovascular plaques. An outlook into future development of vibrational photoacoustic endoscopy and tomography is provided.
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The nature of peptide interactions with acid end-group PLGAs and facile aqueous-based microencapsulation of therapeutic peptides.
J Control Release
PUBLISHED: 08-29-2013
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An important poorly understood phenomenon in controlled-release depots involves the strong interaction between common cationic peptides and low Mw free acid end-group poly(lactic-co-glycolic acids) (PLGAs) used to achieve continuous peptide release kinetics. The kinetics of peptide sorption to PLGA was examined by incubating peptide solutions of 0.2-4mM octreotide or leuprolide acetate salts in a 0.1M HEPES buffer, pH7.4, with polymer particles or films at 4-37°C for 24h. The extent of absorption/loading of peptides in PLGA particles/films was assayed by two-phase extraction and amino acid analysis. Confocal Raman microspectroscopy, stimulated Raman scattering (SRS) and laser scanning confocal imaging, and microtome sectioning techniques were used to examine peptide penetration into the polymer phase. The release of sorbed peptide from leuprolide-PLGA particles was evaluated both in vitro (PBST+0.02% sodium azide, 37°C) and in vivo (male Sprague-Dawley rats). We found that when the PLGA-COOH chains are sufficiently mobilized, therapeutic peptides not only bind at the surface, a common belief to date, but also can be internalized and distributed throughout the polymer phase at physiological temperature forming a salt with low-molecular weight PLGA-COOH. Importantly, absorption of leuprolide into low MW PLGA-COOH particles yielded ~17wt.% leuprolide loading in the polymer (i.e., ~70% of PLGA-COOH acids occupied), and the absorbed peptide was released from the polymer for >2weeks in a controlled fashion in vitro and as indicated by sustained testosterone suppression in male Sprague-Dawley rats. This new approach, which bypasses the traditional encapsulation method and associated production cost, opens up the potential for facile production of low-cost controlled-release injectable depots for leuprolide and related peptides.
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Autophagy deficiency by hepatic FIP200 deletion uncouples steatosis from liver injury in NAFLD.
Mol. Endocrinol.
PUBLISHED: 08-19-2013
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Nonalcoholic fatty liver disease is a metabolic disorder commonly associated with obesity. A subset of nonalcoholic fatty liver disease patients further develops nonalcoholic steatohepatitis that is characterized by chronic liver injury, inflammation, and fibrosis. Recent work has implicated the autophagy pathway in the mobilization and oxidation of triglycerides from lipid droplets. However, whether impaired autophagy in hepatocytes drives excess fat accumulation in the liver remains controversial. In addition, the role of autophagy in protecting the liver from gut endotoxin-induced injury has not been elucidated. Here we generated mice with liver-specific autophagy deficiency by the conditional deletion of focal adhesion kinase family kinase-interacting protein of 200 kDa (also called Rb1cc1), a core subunit of the mammalian autophagy related 1 complex. To our surprise, mice lacking FIP200 in hepatocytes were protected from starvation- and high-fat diet-induced fat accumulation in the liver and had decreased expression of genes involved in lipid metabolism. Activation of the de novo lipogenic program by liver X receptor was impaired in FIP200-deficient livers. Furthermore, liver autophagy was stimulated by exposure to low doses of lipopolysaccharides and its deficiency-sensitized mice to endotoxin-induced liver injury. Together these studies demonstrate that hepatocyte-specific autophagy deficiency per se does not exacerbate hepatic steatosis. Instead, autophagy may play a protective role in the liver after exposure to gut-derived endotoxins and its blockade may accelerate nonalcoholic steatohepatitis progression.
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FRET Imaging Reveals Different Cellular Entry Routes of Self-Assembled and Disulfide Bonded Polymeric Micelles.
Mol. Pharm.
PUBLISHED: 08-15-2013
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Although nanocarriers hold promise for cancer chemotherapy, their intracellular drug delivery pathways are not fully understood. In particular, the influence of nanocarrier stability on cellular uptake is still uncertain. By physically loading hydrophobic FRET probes, we revealed different intracellular drug delivery routes of self-assembled and disulfide bonded micelles. The self-assembled micelles were structurally dissociated by micelle-membrane interactions, and the hydrophobic probes were distributed on the plasma membrane. Alternatively, intact disulfide bonded micelles carrying hydrophobic probes were internalized into cancer cells via multiple endocytic pathways. Following internalization, disulfide bonded micelles were decomposed in early endosomes by glutathione-mediated disulfide bond reduction, exposing the probes to intracellular organelles.
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Nanomedicine for treating spinal cord injury.
Nanoscale
PUBLISHED: 08-14-2013
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Spinal cord injury results in significant mortality and morbidity, lifestyle changes, and difficult rehabilitation. Treatment of spinal cord injury is challenging because the spinal cord is both complex to treat acutely and difficult to regenerate. Nanomaterials can be used to provide effective treatments; their unique properties can facilitate drug delivery to the injury site, enact as neuroprotective agents, or provide platforms to stimulate regrowth of damaged tissues. We review recent uses of nanomaterials including nanowires, micelles, nanoparticles, liposomes, and carbon-based nanomaterials for neuroprotection in the acute phase. We also review the design and neural regenerative application of electrospun scaffolds, conduits, and self-assembling peptide scaffolds.
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Label-free quantitative imaging of cholesterol in intact tissues by hyperspectral stimulated Raman scattering microscopy.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 07-17-2013
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A finger on the pulse: Current molecular analysis of cells and tissues routinely relies on separation, enrichment, and subsequent measurements by various assays. Now, a platform of hyperspectral stimulated Raman scattering microscopy has been developed for the fast, quantitative, and label-free imaging of biomolecules in intact tissues using spectroscopic fingerprints as the contrast mechanism.
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Prevalence of hyperuricemia and its related risk factors in healthy adults from Northern and Northeastern Chinese provinces.
BMC Public Health
PUBLISHED: 07-15-2013
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Hyperuricemia (HUA) is a potential risk factor for developing insulin resistance, hypertension, dyslipidemia and cardiovascular disease. Therefore, we studied the prevalence of HUA and associated risk factors in the population of two provinces in northern China.
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Inhibition of protein synthesis alters protein degradation through activation of protein kinase B (AKT).
J. Biol. Chem.
PUBLISHED: 07-10-2013
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The homeostasis of protein metabolism is maintained and regulated by the rates of protein biosynthesis and degradation in living systems. Alterations of protein degradation may regulate protein biosynthesis through a feedback mechanism. Whether a change in protein biosynthesis modulates protein degradation has not been reported. In this study, we found that inhibition of protein biosynthesis induced phosphorylation/activation of AKT and led to phosphorylation of AKT target substrates, including FoxO1, GSK3?/?, p70S6K, AS160, and the E3 ubiquitin ligase MDM2. Phosphorylation of ribosomal protein S6 was also modulated by inhibition of protein biosynthesis. The AKT phosphorylation/activation was mediated mainly through the PI3K pathway because it was blocked by the PI3K inhibitor LY294002. The activated AKT phosphorylated MDM2 at Ser(166) and promoted degradation of the tumor suppressor p53. These findings suggest that inhibition of protein biosynthesis can alter degradation of some proteins through activation of AKT. This study reveals a novel regulation of protein degradation and calls for caution in blocking protein biosynthesis to study the half-life of proteins.
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Intracerebroventricular Streptozotocin Exacerbates Alzheimer-Like Changes of 3xTg-AD Mice.
Mol. Neurobiol.
PUBLISHED: 07-01-2013
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Alzheimers disease (AD) involves several possible molecular mechanisms, including impaired brain insulin signaling and glucose metabolism. To investigate the role of metabolic insults in AD, we injected streptozotocin (STZ), a diabetogenic compound if used in the periphery, into the lateral ventricle of the 6-month-old 3xTg-AD mice and studied the cognitive function as well as AD-like brain abnormalities, such as tau phosphorylation and A? accumulation, 3-6 weeks later. We found that STZ exacerbated impairment of short-term and spatial reference memory in 3xTg-AD mice. We also observed an increase in tau hyperphosphorylation and neuroinflammation, a disturbance of brain insulin signaling, and a decrease in synaptic plasticity and amyloid ? peptides in the brain after STZ treatment. The expression of 20 AD-related genes, including those involved in the processing of amyloid precursor protein, cytoskeleton, glucose metabolism, insulin signaling, synaptic function, protein kinases, and apoptosis, was altered, suggesting that STZ disturbs multiple metabolic and cell signaling pathways in the brain. These findings provide experimental evidence of the role of metabolic insult in AD.
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Cyclic AMP-Dependent Protein Kinase Enhances SC35-Promoted Tau Exon 10 Inclusion.
Mol. Neurobiol.
PUBLISHED: 06-25-2013
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Alternative splicing of tau exon 10 generates tau with three or four microtubule-binding repeats (3R-tau or 4R-tau). The ratio of 3R-tau to 4R-tau is approximately 1:1 in the adult normal human brain. Disturbances in the ratio result in neurodegenerative tauopathies. Splicing factor SC35 acts on a SC35-like element located at the 5 end of tau exon 10 and promotes tau exon 10 inclusion. Here, we report that protein kinase (PKA) was able to interact and phosphorylate SC35. Activation or overexpression of PKA catalytic subunits promoted SC35-mediated tau exon 10 inclusion. Four PKA catalytic subunits, ?1, ?2, ?1, and ?2, all enhanced SC35-promoted tau exon 10 inclusion. SC35 has four putative PKA phosphorylation sites, Ser121, Ser128, Ser130, and Ser171. Pseudophosphorylation (SC354E) and blockage (SC354A) of phosphorylation of SC35 at these four sites increased and decreased, respectively, SC35s ability to promote tau exon 10 inclusion. Moreover, PKA catalytic subunits no longer further enhanced tau exon 10 inclusion when these four were mutated to either alanine or glutamate. These results suggest that PKA interacts with and phosphorylates SC35 and enhances SC35-promoted tau exon 10 inclusion. In Alzheimers brain, down-regulation of the PKA pathway could lead to dysregulation of tau exon 10, contributing to tau pathogenesis.
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Spectrally modulated stimulated Raman scattering imaging with an angle-to-wavelength pulse shaper.
Opt Express
PUBLISHED: 06-06-2013
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The stimulated Raman scattering signal is often accompanied by unwanted background arising from other pump-probe modalities. We demonstrate an approach to overcome this challenge based on spectral domain modulation, enabled by a compact, cost-effective angle-to-wavelength pulse shaper. The pulse shaper switches between two spectrally narrow windows, which are cut out of a broadband femtosecond pulse and selected for on- and off- Raman resonance excitation, at 2.1 MHz frequency for detection of stimulated Raman scattering signal. Such spectral modulation reduced the unwanted pump-probe signals by up to 20 times and enabled stimulated Raman scattering imaging of molecules in a pigmented environment.
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Sound-sensitive neurons innervate the ventro-lateral protocerebrum of the heliothine moth brain.
Cell Tissue Res.
PUBLISHED: 05-15-2013
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Many noctuid moth species perceive ultrasound via tympanic ears that are located at the metathorax. Whereas the neural processing of auditory information is well studied at the peripheral and first synaptic level, little is known about the features characterizing higher order sound-sensitive neurons in the moth brain. During intracellular recordings from the lateral protocerebrum in the brain of three noctuid moth species, Heliothis virescens, Helicoverpa armigera and Helicoverpa assulta, we found an assembly of neurons responding to transient sound pulses of broad bandwidth. The majority of the auditory neurons ascended from the ventral cord and ramified densely within the anterior region of the ventro-lateral protocerebrum. The physiological and morphological characteristics of these auditory neurons were similar. We detected one additional sound-sensitive neuron, a brain interneuron with its soma positioned near the calyces of mushroom bodies and with numerous neuronal processes in the ventro-lateral protocerebrum. Mass-staining of ventral-cord neurons supported the assumption that the ventro-lateral region of the moth brain was the main target for the auditory projections ascending from the ventral cord.
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Stimulated Raman scattering imaging by continuous-wave laser excitation.
Opt Lett
PUBLISHED: 05-02-2013
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We demonstrate a low-cost-stimulated Raman scattering (SRS) microscope using continuous-wave (cw) lasers as excitation sources. A dual modulation scheme is used to remove the electronic background. The cw-SRS imaging of lipids in fatty liver is demonstrated by excitation of C?H stretch vibration.
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Intestinal acyl-CoA:diacylglycerol acyltransferase 2 overexpression enhances postprandial triglyceridemic response and exacerbates high fat diet-induced hepatic triacylglycerol storage.
Biochim. Biophys. Acta
PUBLISHED: 04-24-2013
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Intestinal acyl-CoA:diacylglycerol acyltransferase 2 (DGAT2) is important in the cellular and physiological responses to dietary fat. To determine the effect of increased intestinal DGAT2 on cellular and physiological responses to acute and chronic dietary fat challenges, we generated mice with intestine-specific overexpression of DGAT2 and compared them with intestine-specific overexpression of DGAT1 and wild-type (WT) mice. We found that when intestinal DGAT2 is present in excess, triacylglycerol (TG) secretion from enterocytes is enhanced compared to WT mice; however, TG storage within enterocytes is similar compared to WT mice. We found that when intestinal DGAT2 is present in excess, mRNA levels of genes involved in fatty acid oxidation were reduced. This result suggests that reduced fatty acid oxidation may contribute to increased TG secretion by overexpression of DGAT2 in intestine. Furthermore, this enhanced supply of TG for secretion in Dgat2(Int) mice may be a significant contributing factor to the elevated fasting plasma TG and exacerbated hepatic TG storage in response to a chronic HFD. These results highlight that altering fatty acid and TG metabolism within enterocytes has the capacity to alter systemic delivery of dietary fat and may serve as an effective target for preventing and treating metabolic diseases such as hepatic steatosis.
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Compact high power barium nitrite crystal-based Raman laser at 1197 nm for photoacoustic imaging of fat.
J Biomed Opt
PUBLISHED: 03-29-2013
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Photoacoustic imaging employing molecular overtone vibration as a contrast mechanism opens a new avenue for bond-selective imaging of deep tissues. Broad use of this modality is, however, hampered by the extremely low conversion efficiency of optical parametric oscillators at the overtone transition wavelengths. To overcome such a barrier, we demonstrate the construction and use of a compact, barium nitrite crystal-based Raman laser for photoacoustic imaging of C-H overtone vibrations. Using a 5-ns Nd?YAG laser as the pumping source, up to 21.4 mJ pulse energy at 1197 nm was generated, corresponding to a conversion efficiency of 34.8%. Using the 1197 nm pulses, three-dimensional photoacoustic imaging of intramuscular fat was demonstrated.
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Serum gamma-glutamyltransferase and uric acid levels are associated with impaired fasting glucose in adults from Inner Mongolia, China.
BMC Public Health
PUBLISHED: 03-26-2013
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BACKGROUND: Serum gamma-glutamyltransferase (GGT) and uric acid (UA) levels are elevated in patients with diabetes or cardiovascular disease. Prediabetes, characterized by impaired glucose tolerance, is an important risk factor for overt diabetes as well as cardiovascular disease. Therefore, the aim of this study was to explore the relationship between GGT, UA and prediabetes in a Chinese population, and provide a scientific basis for the early prevention and treatment of diabetes. METHODS: We performed a cross-sectional population-based study in a cohort of 2694 subjects (1211 men and 1483 women, aged 35--86 years). Questionnaires and physical examinations were performed using standardized procedures. Fasting blood was collected to measure glucose and other biochemical parameters. The subjects were divided into two groups with either normal fasting glucose (NFG) or impaired fasting glucose (IFG), according to international diagnostic criteria. Logistic regression analysis was performed to estimate odds ratios (OR) and 95% confidence intervals. RESULTS: Compared with the NFG group, the IFG group had significantly higher blood pressure but lower high-density lipoprotein--cholesterol in women. Body mass index, waist circumference, triglyceride, glucose, GGT, and UA levels were significantly higher in males and females in the IFG group than those in the NFG group. Logistic regression analysis revealed that the OR for prediabetes increased with increasing serum GGT quartiles and UA quartiles. GGT and UA were positively associated with prediabetes in men and women, independent of age, ethnicity, smoking, alcohol consumption, blood pressure, physical labor, and other confounders. CONCLUSIONS: We found that serum GGT and UA levels were positively associated with prediabetes in men and women living in areas inhabited by Chinese ethnic minorities. As elevated GGT and UA levels were associated with significantly increased risk of prediabetes, they may be used as sensitive biological markers of prediabetes.
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A multisensory centrifugal neuron in the olfactory pathway of heliothine moths.
J. Comp. Neurol.
PUBLISHED: 03-09-2013
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We have characterized, by intracellular recording and staining, a unique type of centrifugal neuron in the brain olfactory center of two heliothine moth species; one in Heliothis virescens and one in Helicoverpa armigera. This unilateral neuron, which is not previously described in any moth, has fine processes in the dorsomedial region of the protocerebrum and extensive neuronal branches with blebby terminals in all glomeruli of the antennal lobe. Its soma is located dorsally of the central body close to the brain midline. Mass-fills of antennal-lobe connections with protocerebral regions showed that the centrifugal neuron is, in each brain hemisphere, one within a small group of neurons having their somata clustered. In both species the neuron was excited during application of non-odorant airborne signals, including transient sound pulses of broad bandwidth and air velocity changes. Additional responses to odors were recorded from the neuron in Heliothis virescens. The putative biological significance of the centrifugal antennal-lobe neuron is discussed with regard to its morphological and physiological properties. In particular, a possible role in multisensory processes underlying the moths ability to adapt its odor-guided behaviors according to the sound of an echo-locating bat is considered.
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A metabolite of daidzein, 6,7,4-trihydroxyisoflavone, suppresses adipogenesis in 3T3-L1 preadipocytes via ATP-competitive inhibition of PI3K.
Mol Nutr Food Res
PUBLISHED: 02-16-2013
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Daidzein is one of the major soy isoflavones. Following ingestion, daidzein is readily metabolized in the liver and converted into hydroxylated metabolites. One such metabolite is 6,7,4-trihydroxyisoflavone (6,7,4-THIF), which has been the focus of recent studies due to its various health benefits, however, its anti-adipogenic activity has not been investigated. Our objective was to determine the effects of 6,7,4-THIF on adipogenesis in 3T3-L1 preadipocytes and elucidate the mechanisms of action involved.
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Fine structure and primary sensory projections of sensilla located in the labial-palp pit organ of Helicoverpa armigera (Insecta).
Cell Tissue Res.
PUBLISHED: 02-16-2013
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The fine structure and primary sensory projections of sensilla located in the labial-palp pit organ of the cotton bollworm Helicoverpa armigera (Insecta, Lepidoptera) are investigated by scanning electron and transmission electron microscopy combined with confocal laser scanning microscopy. The pit organ located on the third segment of the labial palp is about 300 ?m deep with a 60-?m-wide opening, each structure containing about 1200 sensilla. Two sensillum types have been found, namely hair-shaped and club-shaped sensilla, located on the upper and lower half of the pit, respectively. Most sensilla possess a single dendrite. The dendrite housed by the club-shaped sensilla is often split into several branches or becomes lamellated in the outer segment. As reported previously, the sensory axons of the sensilla in the labial pit organ form a bundle entering the ipsilateral side of the subesophageal ganglion via the labial palp nerve and project to three distinct areas: the labial pit organ glomerulus in each antennal lobe, the subesophageal ganglion and the ventral nerve cord. In the antennal lobe, the labial pit organ glomerulus is innervated by sensory axons from the labial pit organ only; no antennal afferents target this unit. One neuron has been found extending fine processes into the subesophageal ganglion and innervating the labial palp via one branch passing at the base of the labial palp nerve. The soma of this assumed motor neuron is located in the ipsilateral cell body layer of the subesophageal ganglion. Our results provide valuable knowledge concerning the neural circuit encoding information about carbon dioxide and should stimulate further investigations directed at controlling pest species such as H. armigera.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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