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1.
Sensors (Basel) ; 24(1)2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38203134

ABSTRACT

In ocean remote sensing missions, recognizing an underwater acoustic target is a crucial technology for conducting marine biological surveys, ocean explorations, and other scientific activities that take place in water. The complex acoustic propagation characteristics present significant challenges for the recognition of underwater acoustic targets (UATR). Methods such as extracting the DEMON spectrum of a signal and inputting it into an artificial neural network for recognition, and fusing the multidimensional features of a signal for recognition, have been proposed. However, there is still room for improvement in terms of noise immunity, improved computational performance, and reduced reliance on specialized knowledge. In this article, we propose the Residual Attentional Convolutional Neural Network (RACNN), a convolutional neural network that quickly and accurately recognize the type of ship-radiated noise. This network is capable of extracting internal features of Mel Frequency Cepstral Coefficients (MFCC) of the underwater ship-radiated noise. Experimental results demonstrate that the proposed model achieves an overall accuracy of 99.34% on the ShipsEar dataset, surpassing conventional recognition methods and other deep learning models.

2.
Opt Express ; 31(24): 40658-40674, 2023 Nov 20.
Article in English | MEDLINE | ID: mdl-38041360

ABSTRACT

Metasurfaces have enabled precise electromagnetic (EM) wave manipulation with strong potential to obtain unprecedented functionalities and multifunctional behavior in flat optical devices. One promising aspect to achieve multifunction is polarization-dependent metadevices enabled by simultaneous phase control over orthogonally polarized waves. Among these, metasurfaces with geometric phase shows their natural and robust phase control ability over different circularly polarized waves. However, the phase responses under the circularly polarized incidence are locked to be opposite with each other, resulting in limited multifunctionality. In this study, we propose what we believe to be a novel transmission-type microwave metadevice constructed by linear-to-circular metasurface and spin-decoupled metasurface. By endowing independent phase adjustment capability to each unit structure in a spin-decoupled metasurface, the metadevice can reconfigure arbitrary phase wavefronts under orthogonal polarization state incidence, thereby achieving flexible multifunctionality. As a proof-of-concept, the feasibility and reliability of proposed metasurfaces were verified by simulating multifunctional directional deflection, off-axis focusing, and focused vortex beam generation. Finally, the multifunctional manipulation capability of the metadevice is successfully demonstrated by actually measuring the generation of orbital angular momentum modes. This work is expected to drive the application development of metasurface devices in wireless communication.

3.
Opt Express ; 30(13): 22974-22985, 2022 Jun 20.
Article in English | MEDLINE | ID: mdl-36224987

ABSTRACT

In this study, we introduce a genetic algorithm (GA) into the catenary theory model to achieve automatic and inverse design for terahertz (THz) metasurface absorbers. The GA method was employed by seeking optimal dispersion distributions to achieve broadband impedance matching. A THz dual-metasurface absorber was designed using the proposed approach. The designed metasurface absorber exhibits an absorbance exceeding 88% at 0.21-5 THz. Compared to the traditional design method, the proposed method can reduce time consumption and find the optimal result to achieve high performance. The investigations provide important guidance and a promising approach for designing metasurface-based devices for practical applications.

4.
Sensors (Basel) ; 22(3)2022 Jan 19.
Article in English | MEDLINE | ID: mdl-35161485

ABSTRACT

Image registration is an important basis of image processing, which is of great significance in image mosaicking, target recognition, and change detection. Aiming at the automatic registration problem of multi-angle optical images for ground scenes, a registration method combining point features and line features to register images is proposed. Firstly, the LSD (Line Segment Detector) algorithm is used to extract line features of images. The obtained line segments whose length are less than a given threshold are eliminated by a visual significant algorithm. Then, an affine transform model obtained by estimating a Gaussian mixture model (GMM) is applied to the image to be matched. Lastly, Harris point features are utilized in fine matching to overcome shortages of methods based on line features. In experiments, the proposed algorithm is compared with popular feature-based registration algorithms. The results indicate that the proposed algorithm in this work has obvious advantages in terms of registration accuracy and reliability for optical images acquired at different angles.


Subject(s)
Algorithms , Image Processing, Computer-Assisted , Normal Distribution , Reproducibility of Results
6.
J Microencapsul ; 31(4): 317-22, 2014.
Article in English | MEDLINE | ID: mdl-24124887

ABSTRACT

In this article, the nonionic compound emulsifiers Tween80 and Span80 were used to prepare microcapsules containing phase change materials (microPCMs) with melamine-formaldehyde (MF) shells by in situ polymerization method. The effects of compound emulsifiers Tween80 and Span80 on the structure, morphologies and properties of microPCMs containing paraffin were studied. SEM morphological investigation suggests that a complex of Tween80 and Span80 as emulsifiers are optimal for the fabrication of microPCMs in this study compared to Tween60 or OP-10. The diameter distributions of microPCMs synthesized with different amounts of compound emulsifiers are uniform, whereas compound emulsifiers' amount affect the mean diameter of microPCMs decreasing from 5.34 to 3.05 µm. These microPCMs with the core/shell weight ratio 3/1 have smoother surface and a higher core content of 68.7% than other core/shell ratio. Anti-osmosis measurements indicate that microPCMs have good compactness and stable performance compared to those synthesized by one type of emulsifier.


Subject(s)
Emulsifying Agents/chemistry , Hexoses/chemistry , Polysorbates/chemistry , Triazines/chemistry , Capsules , Particle Size , Polyethylene Glycols/chemistry
7.
Mol Cell Proteomics ; 10(10): O111.008425, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21749988

ABSTRACT

Despite their importance in many biological processes, membrane proteins are underrepresented in proteomic analysis because of their poor solubility (hydrophobicity) and often low abundance. We describe a novel approach for the identification of plasma membrane proteins and intracellular microsomal proteins that combines membrane fractionation, a centrifugal proteomic reactor for streamlined protein extraction, protein digestion and fractionation by centrifugation, and high performance liquid chromatography-electrospray ionization-tandem MS. The performance of this approach was illustrated for the study of the proteome of ER and Golgi microsomal membranes in rat hepatic cells. The centrifugal proteomic reactor identified 945 plasma membrane proteins and 955 microsomal membrane proteins, of which 63 and 47% were predicted as bona fide membrane proteins, respectively. Among these proteins, >800 proteins were undetectable by the conventional in-gel digestion approach. The majority of the membrane proteins only identified by the centrifugal proteomic reactor were proteins with ≥ 2 transmembrane segments or proteins with high molecular mass (e.g. >150 kDa) and hydrophobicity. The improved proteomic reactor allowed the detection of a group of endocytic and/or signaling receptor proteins on the plasma membrane, as well as apolipoproteins and glycerolipid synthesis enzymes that play a role in the assembly and secretion of apolipoprotein B100-containing very low density lipoproteins. Thus, the centrifugal proteomic reactor offers a new analytical tool for structure and function studies of membrane proteins involved in lipid and lipoprotein metabolism.


Subject(s)
Hepatocytes/chemistry , Membrane Proteins/analysis , Proteome/analysis , Proteomics/methods , Animals , Cell Membrane/chemistry , Cell Membrane/metabolism , Centrifugation/methods , Chemical Fractionation , Chromatography, Liquid , Hepatocytes/metabolism , Lipid Metabolism , Lipoproteins/isolation & purification , Lipoproteins/metabolism , Membrane Proteins/isolation & purification , Microsomes/chemistry , Microsomes/metabolism , Proteolysis , Proteome/isolation & purification , Proteome/metabolism , Rats , Spectrometry, Mass, Electrospray Ionization
8.
IEEE/ACM Trans Comput Biol Bioinform ; 20(6): 3535-3546, 2023.
Article in English | MEDLINE | ID: mdl-37486829

ABSTRACT

Advances in single-cell biotechnologies have generated the single-cell RNA sequencing (scRNA-seq) of gene expression profiles at cell levels, providing an opportunity to study cellular distribution. Although significant efforts developed in their analysis, many problems remain in studying cell types distribution because of the heterogeneity, high dimensionality, and noise of scRNA-seq. In this study, a multi-view clustering with graph learning algorithm (MCGL) for scRNA-seq data is proposed, which consists of multi-view learning, graph learning, and cell type clustering. In order to avoid a single feature space of scRNA-seq being inadequate to comprehensively characterize the functions of cells, MCGL constructs the multiple feature spaces and utilizes multi-view learning to comprehensively characterize scRNA-seq data from different perspectives. MCGL adaptively learns the similarity graphs of cells that overcome the dependence on fixed similarity, transforming scRNA-seq analysis into the analysis of multi-view clustering. MCGL decomposes the networks of cells into view-specific and common networks in multi-view learning, which better characterizes the topological relationship of cells. MCGL simultaneously utilizes multiple types of cell-cell networks and fully exploits the connection relationship between cells through the complementarity between networks to improve clustering performance. The graph learning, graph factorization, and cell-type clustering processes are accomplished simultaneously under one optimization framework. The performance of the MCGL algorithm is validated with ten scRNA-seq datasets from different scales, and experimental results imply that the proposed algorithm significantly outperforms fourteen state-of-the-art scRNA-seq algorithms.


Subject(s)
Single-Cell Analysis , Single-Cell Gene Expression Analysis , Single-Cell Analysis/methods , Algorithms , Transcriptome , Cluster Analysis , Sequence Analysis, RNA/methods , Gene Expression Profiling/methods
9.
IEEE/ACM Trans Comput Biol Bioinform ; 20(3): 2050-2063, 2023.
Article in English | MEDLINE | ID: mdl-37015414

ABSTRACT

The accumulated DNA methylation and gene expression provide a great opportunity to exploit the epigenetic patterns of genes, which is the foundation for revealing the underlying mechanisms of biological systems. Current integrative algorithms are criticized for undesirable performance because they fail to address the heterogeneity of expression and methylation data, and the intrinsic relations among them. To solve this issue, a novel multi-view clustering with self-representation learning and low-rank tensor constraint (MCSL-LTC) is proposed for the integration of gene expression and DNA methylation data, which are treated as complementary views. Specifically, MCSL-LTC first learns the low-dimensional features for each view with the linear projection, and then these features are fused in a unified tensor space with low-rank constraints. In this case, the complementary information of various views is precisely captured, where the heterogeneity of omic data is avoided, thereby enhancing the consistency of different views. Finally, MCSL-LTC obtains a consensus cluster of genes reflecting the structure and features of various views. Experimental results demonstrate that the proposed approach outperforms state-of-the-art baselines in terms of accuracy on both the social and cancer data, which provides an effective and efficient method for the integration of heterogeneous genomic data.


Subject(s)
Algorithms , DNA Methylation , DNA Methylation/genetics , Cluster Analysis , Genomics , Gene Expression
10.
Proc Natl Acad Sci U S A ; 106(49): 20936-41, 2009 Dec 08.
Article in English | MEDLINE | ID: mdl-19926863

ABSTRACT

Perturbation of lipid second messenger networks is associated with the impairment of synaptic function in Alzheimer disease. Underlying molecular mechanisms are unclear. Here, we used an unbiased lipidomic approach to profile alkylacylglycerophosphocholine second messengers in diseased tissue. We found that specific isoforms defined by a palmitic acid (16:0) at the sn-1 position, namely 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (C16:0 PAF) and 1-O-hexadecyl-sn-glycero-3-phosphocholine (C16:0 lyso-PAF), were elevated in the temporal cortex of Alzheimer disease patients, transgenic mice expressing human familial disease-mutant amyloid precursor protein, and human neurons directly exposed to amyloid-beta(42) oligomers. Acute intraneuronal accumulation of C16:0 PAF but not C16:0 lyso-PAF initiated cyclin-dependent kinase 5-mediated hyperphosphorylation of tau on Alzheimer disease-specific epitopes. Chronic elevation caused a caspase 2 and 3/7-dependent cascade resulting in neuronal death. Pharmacological inhibition of C16:0 PAF signaling, or molecular strategies increasing hydrolysis of C16:0 PAF to C16:0 lyso-PAF, protected human neurons from amyloid-beta(42) toxicity. Together, these data provide mechanistic insight into how disruptions in lipid metabolism can determine neuronal response to accumulating oligomeric amyloid-beta(42).


Subject(s)
Amyloid beta-Peptides/metabolism , Neurons/metabolism , Neurons/pathology , Peptide Fragments/metabolism , Phosphatidylcholines/metabolism , Signal Transduction , tau Proteins/metabolism , Aged , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Amyloid beta-Peptides/chemistry , Amyloid beta-Peptides/toxicity , Animals , Calpain/metabolism , Caspases/metabolism , Cell Survival/drug effects , Cytoprotection/drug effects , Endoplasmic Reticulum/drug effects , Endoplasmic Reticulum/enzymology , Endoplasmic Reticulum/pathology , Enzyme Activation/drug effects , Epitopes/immunology , Glycogen Synthase Kinase 3/metabolism , Humans , Intracellular Space/drug effects , Intracellular Space/metabolism , Mice , Mice, Transgenic , Peptide Fragments/chemistry , Peptide Fragments/toxicity , Phospholipid Ethers/metabolism , Phosphorylation/drug effects , Protein Structure, Quaternary , Signal Transduction/drug effects , Stress, Physiological/drug effects
11.
Nanomaterials (Basel) ; 12(20)2022 Oct 13.
Article in English | MEDLINE | ID: mdl-36296781

ABSTRACT

In the past decades, metasurfaces have shown their extraordinary abilities on manipulating the wavefront of electromagnetic wave. Based on the ability, various kinds of metasurfaces are designed to realize new functional metadevices based on wavefront manipulations, such as anomalous beam steering, focus metalens, vortex beams generator, and holographic imaging. However, most of the previously proposed designs based on metasurfaces are fixed once design, which is limited for applications where light modulation needs to be tunable. In this paper, we proposed a design for THz tunable wavefront manipulation achieved by the combination of plasmonic metasurface and phase change materials (PCMs) in THz region. Here, we designed a metal-insulator-metal (MIM) metasurface with the typical C-shape split ring resonator (CSRR), whose polarization conversion efficiency is nearly 90% for circular polarized light (CPL) in the range of 0.95~1.15 THz when PCM is in the amorphous state, but the conversion efficiency turns to less than 10% in the same frequency range when PCM switches into the crystalline state. Then, benefiting from the high polarization conversion contrast of unit cell, we can achieve tunable wavefront manipulation by utilizing the Pancharatnam-Berry (PB) phase between the amorphous and crystalline states. As a proof-of-concept, the reflective tunable anomalous beam deflector and focusing metalens are designed and characterized, and the results further verify their capability for tunable wavefront manipulation in THz range. It is believed that the design in our work may pave the way toward the tunable wavefront manipulation of THz waves and is potential for dynamic tunable THz devices.

12.
Mass Spectrom Rev ; 29(6): 877-929, 2010.
Article in English | MEDLINE | ID: mdl-20931646

ABSTRACT

Lipid mediators participate in signal transduction pathways, proliferation, apoptosis, and membrane trafficking in the cell. Lipids are highly complex and diverse owing to the various combinations of polar headgroups, fatty acyl chains, and backbone structures. This structural diversity continues to pose a challenge for lipid analysis. Here we review the current state of the art in lipidomics research and discuss the challenges facing this field. The latest technological developments in mass spectrometry, the role of bioinformatics, and the applications of lipidomics in lipid metabolism and cellular physiology and pathology are also discussed.


Subject(s)
Lipid Metabolism/physiology , Lipids/chemistry , Metabolomics/methods , Cell Membrane/ultrastructure , Cell Physiological Phenomena , Computational Biology , Fats, Unsaturated/chemistry , Homeostasis , Humans , Hydrocarbons/chemistry , Lipid Metabolism/genetics , Lipids/physiology , Mass Spectrometry/instrumentation , Molecular Conformation , Signal Transduction , Tandem Mass Spectrometry
13.
Rapid Commun Mass Spectrom ; 25(1): 205-17, 2011 Jan 15.
Article in English | MEDLINE | ID: mdl-21157865

ABSTRACT

In this work we report the development of a novel methodology for the determination of stereospecificity of diacyl glycerophospholipids, including glycerophosphatidic acids (PA), glycerophosphoserines (PS), glycerophosphoglycerols (PG), glycerophosphoinositols (PI), and glycerophosphoethanolamines (PE), which can be conventionally ionized in negative ion mode. This methodology uses MS(2) recorded on a hybrid quadrupole time-of-flight mass spectrometer to determine the stereospecificity of diacyl glycerophospholipids based on the lyso-form fragment ions, attributed to the neutral loss of fatty acyl moieties. The fragmentation patterns of a variety of diacyl glycerophospholipid standards were first fully examined over a wide range of collision energy. We observed that lyso-form fragment ions corresponding to the neutral loss of fatty acyl moieties attached to the sn2 position as free fatty acids ([M-Sn2](-) ) and as ketenes ([M-(Sn2-H(2) O)](-) ) exhibited consistently higher intensity than their counterpart ions due to the neutral loss of fatty acyl moieties attached to the sn1 position ([M-Sn1](-) and [M-(Sn1-H(2) O)](-) ). Therefore, we concluded that an empirical fragmentation rule can be used to precisely determine the stereospecificity of diacyl glycerophospholipids, primarily on the basis of relative abundance of the lyso-form fragment ions. We then examined the product ion spectra of diacyl glycerophospholipids recorded from lipid extracts of rat hepatoma cells, where the stereospecific information of these lipids was conclusively determined. Combining the novel methodology reported in this work with the currently widely practiced mass spectrometric techniques such as multiple precursor ion scans (MPIS), fatty acyl scans (FAS), and multidimensional mass spectrometry based shotgun lipidomics (MDMS-SL), should enable a reliable and convenient platform for comprehensive glycerophospholipid profiling.


Subject(s)
Diglycerides/chemistry , Glycerophospholipids/chemistry , Mass Spectrometry/methods , Animals , Lipids/chemistry , Nuclear Proteins/metabolism , Rats , Stereoisomerism , Tumor Cells, Cultured
14.
J Proteome Res ; 9(3): 1279-88, 2010 Mar 05.
Article in English | MEDLINE | ID: mdl-20067319

ABSTRACT

Protein phosphorylation is an important post-translational modification involved in the regulation of many cellular processes. Mass spectrometry has been successfully used to identify protein phosphorylation in specific pathways and for global phosphoproteomic analysis. However, phosphoproteomics approaches do not evaluate the subcellular localization of the phosphorylated forms of proteins, which is an important factor for understanding the roles of protein phosphorylation on a global scale. The in-depth mapping of protein phosphorylation at the subcellular level necessitates the development of new methods capable of specifically and efficiently enriching phosphopeptides from highly complex samples. Here, we report a novel microfluidic device called the phosphoproteomic reactor that combines efficient processing of proteins followed by phosphopeptide enrichment by Ti-IMAC. To illustrate the potential of this novel technology, we mapped the phosphoproteins in subcellular organelles of liver cells. Fifteen subcellular fractions from liver cell cultures were processed on the phosphoproteomic reactor in combination with nano-LC-MS/MS analysis. We identified thousands of phosphorylation sites in over 600 phosphoproteins in different organelles using minute amounts of starting material. Overall, this approach provides a new avenue for studying the phosphoproteome of the subcellular organelles.


Subject(s)
Microfluidic Analytical Techniques/instrumentation , Nanotechnology/instrumentation , Organelles/chemistry , Phosphoproteins/chemistry , Proteomics/instrumentation , Amino Acid Sequence , Cell Line, Tumor , Chromatography, Affinity , Cluster Analysis , Hepatocytes/chemistry , Hepatocytes/metabolism , Humans , Microfluidic Analytical Techniques/methods , Models, Molecular , Molecular Sequence Data , Phosphoproteins/metabolism , Protein Interaction Mapping , Proteome/chemistry , Proteome/metabolism , Proteomics/methods , Tandem Mass Spectrometry
15.
Langmuir ; 26(14): 12165-72, 2010 Jul 20.
Article in English | MEDLINE | ID: mdl-20560559

ABSTRACT

The structural arrangement of type I collagen in vivo is critical for the normal functioning of tissues, such as bone, cornea, and blood vessels. At present, there are no low-cost techniques for fabricating aligned collagen structures for applications in regenerative medicine. Here, we report a straightforward approach to fabricate collagen films, with defined orientation of collagen fibrillar aggregates within a matrix of oriented collagen molecules. Langmuir-Blodgett (LB) technology was used to deposit thin films of oriented type I collagen onto substrates. It was found that collagen does not behave like classical LB materials, such as amphiphilic hydrocarbon acids or lipids. The thickness of the deposited collagen films and the area-pressure isotherms were found to depend on the amount of material spread. In addition, no film collapse was detected and the deposited LB films were thicker than the theoretical dimension of a collagen monolayer (1.5 nm) formed by triple helical collagen molecules. Individual LB films with thicknesses of up to 20 nm were obtained, and multiple depositions yielded overall film thicknesses of up to 100 nm. Films consisted of a matrix of collagen molecules containing thicker fibrillar aggregates of collagen (micrometers in length). These fibrillar aggregates were built up of shorter unit molecules forming "spun thread" structures, some of which exhibited a zigzag pattern. In addition to aligning collagen unidirectionally (similar for example to tendon), we performed a two-step deposition procedure, in which the substrate was turned 90 degrees between two consecutive collagen deposition steps. The resulting films showed orthogonally aligned collagen layers, mimicking the structure of cornea. Thus, this technique permits control of the thickness of individual layers, the orientation of successive layers, and the number of layers within the construct. Therefore, it may have widespread applicability for the engineering of collagen-rich tissues.


Subject(s)
Biomimetics/methods , Collagen Type I/chemistry , Adsorption , Animals , Glass/chemistry , Gold/chemistry , Hydrophobic and Hydrophilic Interactions , Protein Conformation , Rats , Silanes/chemistry , Surface Properties
16.
Anal Bioanal Chem ; 397(8): 3421-30, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20517600

ABSTRACT

The enrichment and processing of proteomic samples prior to multi-dimensional chromatography remain a challenge in 'gel-free' proteomics. We previously reported the development of a microfluidic device called the "proteomic reactor" that relied on enriching proteins by using strong cation exchange (SCX) followed by trypsin digestion in an interstitial volume as little as 50 nL. Here, we report a novel proteomic reactor that is based on polymeric strong anion exchange (SAX) material to analyse proteomic samples. We also compare the performance of the SAX proteomic reactor to our previously reported SCX proteomic reactor for analysing complex yeast proteomes. Our results indicate that the SAX protein reactor preferentially identifies more acidic peptides and proteins compared to the SCX reactor. We show that the SAX and SCX reactors are complementary and that their combination increases the number of unique peptides and proteins identified by 50%. Furthermore, we show that the number of protein identified can be increased further by up to 40% using different proteolytic enzymes on the proteomic reactor.


Subject(s)
Anion Exchange Resins/chemistry , Chromatography, Ion Exchange/instrumentation , Enzymes/chemistry , Fungal Proteins/chemistry , Proteomics/instrumentation , Yeasts/chemistry , Adsorption , Chromatography, Ion Exchange/methods , Fungal Proteins/isolation & purification , Microfluidic Analytical Techniques/instrumentation , Microfluidic Analytical Techniques/methods , Proteomics/methods
17.
Brief Funct Genomic Proteomic ; 7(5): 395-409, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18805902

ABSTRACT

Lipid analysis is a well-established field of research that focuses on one lipid or a few lipids. The recent developments in mass spectrometry technologies have enabled more comprehensive studies to be performed on lipids present in a sample. The move towards extensive lipid research has led to the coining of the term lipidomics, which is defined as the ensemble of lipids present in a sample. In this review, we will discuss the technical developments in the field of lipidomics and the current limitations of this nascent field.


Subject(s)
Lipids , Lipids/chemistry , Molecular Structure , Spectrometry, Mass, Electrospray Ionization , Tandem Mass Spectrometry
18.
BMC Neurosci ; 9: 92, 2008 Sep 22.
Article in English | MEDLINE | ID: mdl-18808659

ABSTRACT

BACKGROUND: Alpha-Synuclein (alpha-syn), a 140 amino acid protein associated with presynaptic membranes in brain, is a major constituent of Lewy bodies in Parkinson's disease (PD). Three missense mutations (A30P, A53T and E46K) in the alpha-syn gene are associated with rare autosomal dominant forms of familial PD. However, the regulation of alpha-syn's cellular localization in neurons and the effects of the PD-linked mutations are poorly understood. RESULTS: In the present study, we analysed the ability of cytosolic factors to regulate alpha-syn binding to synaptic membranes. We show that co-incubation with brain cytosol significantly increases the membrane binding of normal and PD-linked mutant alpha-syn. To characterize cytosolic factor(s) that modulate alpha-syn binding properties, we investigated the ability of proteins, lipids, ATP and calcium to modulate alpha-syn membrane interactions. We report that lipids and ATP are two of the principal cytosolic components that modulate Wt and A53T alpha-syn binding to the synaptic membrane. We further show that 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (C16:0 PAF) is one of the principal lipids found in complex with cytosolic proteins and is required to enhance alpha-syn interaction with synaptic membrane. In addition, the impaired membrane binding observed for A30P alpha-syn was significantly mitigated by the presence of protease-sensitive factors in brain cytosol. CONCLUSION: These findings suggest that endogenous brain cytosolic factors regulate Wt and mutant alpha-syn membrane binding, and could represent potential targets to influence alpha-syn solubility in brain.


Subject(s)
Cytosol/metabolism , Mutation , Synaptic Membranes/metabolism , alpha-Synuclein/genetics , alpha-Synuclein/metabolism , Adenosine Triphosphate/analysis , Adenosine Triphosphate/metabolism , Animals , Blotting, Western , Brain Chemistry , Calcium/analysis , Calcium/metabolism , Cytosol/chemistry , Genotype , Humans , Lipids/analysis , Membrane Proteins/chemistry , Membrane Proteins/genetics , Membrane Proteins/metabolism , Mice , Mice, Knockout , Mutation, Missense , Parkinson Disease/genetics , Parkinson Disease/metabolism , Platelet Activating Factor/analogs & derivatives , Platelet Activating Factor/analysis , Platelet Activating Factor/metabolism , Protein Binding , Synaptosomes/metabolism , alpha-Synuclein/analysis
19.
Circ Res ; 98(1): 111-8, 2006 Jan 06.
Article in English | MEDLINE | ID: mdl-16306447

ABSTRACT

Akt is a central regulator of cardiomyocyte survival after ischemic injury in vitro and in vivo, but the mechanisms regulating Akt activity in the postischemic cardiomyocyte are not known. Furthermore, although much is known about the detrimental role that the c-Jun N-terminal kinases (JNKs) play in promoting death of cells exposed to various stresses, little is known of the molecular mechanisms by which JNK activation can be protective. We report that JNKs are necessary for the reactivation of Akt after ischemic injury. We identified Thr450 of Akt as a residue that is phosphorylated by JNKs, and the phosphorylation status of Thr450 regulates reactivation of Akt after hypoxia, apparently by priming Akt for subsequent phosphorylation by 3-phosphoinositide-dependent protein kinase. The reduction in Akt activity that is induced by JNK inhibition may have significant biological consequences, as we find that JNKs, acting via Akt, are critical determinants of survival in posthypoxic cardiomyocytes in culture. Furthermore, in contrast to selective p38-mitogen-activated protein kinase inhibition, which was cardioprotective in vivo, concurrent inhibition of both JNKs and p38-mitogen-activated protein kinases increased ischemia/reperfusion injury in the heart of the intact rat. These studies demonstrate that reactivation of Akt after resolution of hypoxia and ischemia is regulated by JNKs and suggest that this is likely a central mechanism of the myocyte protective effect of JNKs.


Subject(s)
Hypoxia/pathology , JNK Mitogen-Activated Protein Kinases/physiology , Myocytes, Cardiac/physiology , Proto-Oncogene Proteins c-akt/metabolism , Animals , Apoptosis , Cell Survival , Enzyme Activation , Humans , Hypoxia/metabolism , Phosphorylation , Rats , Signal Transduction , p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors , p38 Mitogen-Activated Protein Kinases/physiology
20.
PLoS One ; 9(11): e111562, 2014.
Article in English | MEDLINE | ID: mdl-25365028

ABSTRACT

OBJECTIVE: We aimed at investigating prospective memory and its socio-demographic and neurocognitive correlates in non-psychotic, first-degree relatives (FDRs) of patients with schizophrenia compared to patients with first episode schizophrenia (FES), and healthy controls (HCs). METHODS: Forty-seven FES patients, 50 non-psychotic FDRs (23 offspring and 27 siblings) of patients with chronic schizophrenia (unrelated to the FES group) and 51 HCs were studied. The Chinese version of the Cambridge Prospective Memory Test (C-CAMPROMPT) was used to measure time-based prospective memory (TBPM) and event-based prospective memory (EBPM) performance. Other cognitive functions (involving respective memory and executive functions) were evaluated with standardized tests. RESULTS: After controlling for basic demographic characteristics including age, gender and educational level, there was a significant difference between FDRs, FES and HCs with respect to both TBPM (F(2,142) = 10.4, p<0.001) and EBPM (F(2,142) = 10.8, p<0.001). Multiple linear regression analyses revealed that lower scores of the Hopkins Verbal Learning Test-Revised (HVLT-R) and the STROOP Word-Color Test (SWCT) contributed to TBPM impairment, while lower educational level and higher scores of the Color Trails Test-2 (CTT-2) contributed to EBPM deficit in FDRs. CONCLUSIONS: FDRs share similar but attenuated prospective memory impairments with schizophrenia patients, suggesting that prospective memory deficits may represent an endophenotype of schizophrenia.


Subject(s)
Memory, Episodic , Nuclear Family/psychology , Schizophrenia , Adult , Female , Humans , Male , Neuropsychological Tests , Risk Factors , Young Adult
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