Early detection of neurodegeneration in brain ischemia by manganese-enhanced MRI

This study aims to employ in vivo manganese-enhanced MRI (MEMRI) to detect neurodegenerative changes in two models of brain ischemia, photothrombotic cortical injury (PCI) and transient middle cerebral artery occlusion (MCAO) in rodents. After systemic Mn 2+ injection to both ischemic models, a close pattern of Tl-weighted hyperintensity was observed throughout different brain regions in comparison to the distribution of GFAP, MnSOD and GS immunoreactivities, whereby conventional MRI could hardly detect such. In addition, the infarct volumes in the posterior parts of the brain had significantly reduced after Mn 2+ injection to the MCAO model. It is suggested that exogenous Mn 2+ injection may provide enhanced MEMRI detection of oxidative stress and gliosis early after brain ischemia. Manganese may also mediate infarctions at remote brain regions in transient focal cerebral ischemia before delayed secondary damage takes place. © 2008 IEEE.published_or_final_versionThe 30th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBS) 2008, Vancouver, BC., 20-25 August 2008. in Proceedings of the 30th EMBS, 2008, p. 3884-388

Chronic adiponectin deficiency leads to Alzheimer’s disease-like cognitive impairments and pathologies through AMPK inactivation and cerebral insulin resistance in aged mice

BACKGROUND: Insulin resistance is the major pathogenesis underlying type 2 diabetes mellitus (T2DM) and these patients have doubled risk of Alzheimer's disease (AD). Increasing evidence suggests that insulin resistance plays an important role in AD pathogenesis, possibly due to abnormal GSK3β activation, causing intra- and extracellular amyloid-beta (Aβ) accumulation. Adiponectin (APN) is an adipokine with insulin-sensitizing and anti-inflammatory effects. Reduced circulatory APN level is associated with insulin resistance and T2DM. The role of APN in AD has not been elucidated. In this study, we aim to examine if adiponectin deficiency would lead to cerebral insulin resistance, cognitive decline and Alzheimer's-like pathology in mice. METHODS: To study the role of adiponectin in cognitive functions, we employed adiponectin-knockout (APN-KO) mice and demonstrated chronic APN deficiency in their CNS. Behavioral tests were performed to study the cognitions of male APN-KO mice. Brains and tissue lysates were collected to study the pathophysiological and molecular changes in the brain of APN-KO mice. SH-SY5Y neuroblastoma cell line was used to study the molecular mechanism upon APN and insulin treatment. RESULTS: Aged APN-deficient mice displayed spatial memory and learning impairments, fear-conditioned memory deficit as well as anxiety. These mice also developed AD pathologies including increased cerebral Aβ42 level, Aβ deposition, hyperphosphorylated Tau proteins, microgliosis and astrogliosis with increased cerebral IL-1β and TNFα levels that associated with increased neuronal apoptosis and reduced synaptic proteins levels, suggesting APN deficiency may lead to neuronal and synaptic loss in the brain. AD pathologies-associated APN-KO mice displayed attenuated AMPK phosphorylation and impaired insulin signaling including decreased Akt induction and increased GSK3β activation in the hippocampus and frontal cortex. Aged APN-KO mice developed hippocampal insulin resistance with reduced pAkt induction upon intracerebral insulin injection. Consistently, APN treatment in SH-SY5Y cells with insulin resistance and overexpressing Aβ induce higher pAkt levels through AdipoR1 upon insulin treatment whereas the induction was blocked by compound C, indicating APN can enhance neuronal insulin sensitivity through AMPK activation. CONCLUSION: Our results indicated that chronic APN deficiency inactivated AMPK causing insulin desensitization and elicited AD-like pathogenesis in aged mice which also developed significant cognitive impairments and psychiatric symptoms.published_or_final_versio

Three-dimensionally Ordered Macroporous Structure Enabled Nanothermite Membrane of Mn2O3/Al

Mn2O3 has been selected to realize nanothermite membrane for the first time in the literature. Mn2O3/Al nanothermite has been synthesized by magnetron sputtering a layer of Al film onto three-dimensionally ordered macroporous (3DOM) Mn2O3 skeleton. The energy release is significantly enhanced owing to the unusual 3DOM structure, which ensures Al and Mn2O3 to integrate compactly in nanoscale and greatly increase effective contact area. The morphology and DSC curve of the nanothermite membrane have been investigated at various aluminizing times. At the optimized aluminizing time of 30 min, energy release reaches a maximum of 2.09 kJ∙g−1, where the Al layer thickness plays a decisive role in the total energy release. This method possesses advantages of high compatibility with MEMS and can be applied to other nanothermite systems easily, which will make great contribution to little-known nanothermite research

Experimental observation of topological Fermi arcs in type-II Weyl semimetal MoTe2

Weyl semimetal is a new quantum state of matter [1-12] hosting the condensed matter physics counterpart of relativisticWeyl fermion [13] originally introduced in high energy physics. The Weyl semimetal realized in the TaAs class features multiple Fermi arcs arising from topological surface states [10, 11, 14-16] and exhibits novel quantum phenomena, e.g., chiral anomaly induced negative mag-netoresistance [17-19] and possibly emergent supersymmetry [20]. Recently it was proposed theoretically that a new type (type-II) of Weyl fermion [21], which does not have counterpart in high energy physics due to the breaking of Lorentz invariance, can emerge as topologically-protected touching between electron and hole pockets. Here, we report direct spectroscopic evidence of topological Fermi arcs in the predicted type-II Weyl semimetal MoTe2 [22-24]. The topological surface states are confirmed by directly observing the surface states using bulk-and surface-sensitive angle-resolved photoemission spectroscopy (ARPES), and the quasi-particle interference (QPI) pattern between the two putative Fermi arcs in scanning tunneling microscopy (STM). Our work establishes MoTe2 as the first experimental realization of type-II Weyl semimetal, and opens up new opportunities for probing novel phenomena such as exotic magneto-transport [21] in type-II Weyl semimetals.Comment: submitted on 01/29/2016. Nature Physics, in press. Spectroscopic evidence of the Fermi arcs from two complementary surface sensitive probes - ARPES and STS. A comparison of the calculated band structure for T_d and 1T' phase to identify the topological Fermi arcs in the T_d phase is also included in the supplementary informatio

Synthesis and Thermoelectric Properties of Bi2Se3 Nanostructures

Bismuth selenide (Bi2Se3) nanostructures were synthesized via solvothermal method. The crystallinity of the as-synthesized sample has been analyzed by X-ray diffraction, which shows the formation of rhombohedral Bi2Se3. Electron microscopy examination indicates that the Bi2Se3 nanoparticles have hexagonal flake-like shape. The effect of the synthesis temperature on the morphology of the Bi2Se3 nanostructures has also been investigated. It is found that the particle size increases with the synthesis temperature. Thermoelectric properties of the Bi2Se3 nanostructures were also measured, and the maximum value of dimensionless figure of merit (ZT) of 0.096 was obtained at 523 K

Glycan Structures Contain Information for the Spatial Arrangement of Glycoproteins in the Plasma Membrane

Glycoconjugates at the cell surface are crucial for cells to communicate with each other and the extracellular microenvironment. While it is generally accepted that glycans are vectorial biopolymers, their information content is unclear. This report provides evidence that distinct N-glycan structures influence the spatial arrangement of two integral membrane glycoproteins, Kv3.1 and E-cadherin, at the adherent membrane which in turn alter cellular properties. Distinct N-glycan structures were generated by heterologous expression of these glycoproteins in parental and glycosylation mutant Chinese hamster ovary cell lines. Unlike the N-linked glycans, the O-linked glycans of the mutant cell lines are similar to those of the parental cell line. Western and lectin blots of total membranes and GFP immunopurified samples, combined with glycosidase digestion reactions, were employed to verify the glycoproteins had predominantly complex, oligomannose, and bisecting type N-glycans from Pro(-)5, Lec1, and Lec10B cell lines, respectively. Based on total internal reflection fluorescence and differential interference contrast microscopy techniques, and cellular assays of live parental and glycosylation mutant CHO cells, we propose that glycoproteins with complex, oligomannose or bisecting type N-glycans relay information for localization of glycoproteins to various regions of the plasma membrane in both a glycan-specific and protein-specific manner, and furthermore cell-cell interactions are required for deciphering much of this information. These distinct spatial arrangements also impact cell adhesion and migration. Our findings provide direct evidence that N-glycan structures of glycoproteins contribute significantly to the information content of cells

Large-Scale Streamwise Vortices in Turbulent Channel Flow Induced by Active Wall Actuations

© 2017, Springer Science+Business Media B.V., part of Springer Nature. Direct numerical simulations of turbulent flow in a plane channel using spanwise alternatively distributed strips (SADS) are performed to investigate the characteristics of large-scale streamwise vortices (LSSVs) induced by small-scale active wall actuations, and their role in suppressing flow separation. SADS control is obtained by alternatively applying out-of-phase control (OPC) and in-phase control (IPC) to the wall-normal velocity component of the lower channel wall, in the spanwise direction. Besides the non-controlled channel flow simulated as a reference, four controlled cases with 1, 2, 3 and 4 pairs of OPC/IPC strips are studied at M = 0.2 and Re = 6,000, based on the bulk velocity and the channel half height. The case with 2 pairs of strips, whose width is Δz+ = 264 based on the friction velocity of the non-controlled case, is the most effective in terms of generating large-scale motions. It is also found that the OPC (resp. IPC) strips suppress (resp. enhance) the coherent structures and that leads to the creation of a vertical shear layer, which is responsible for the LSSVs presence. They are in a statistically steady state and their cores are located between two neighbouring OPC and IPC strips. These motions contribute significantly to the momentum transport in the wall-normal and spanwise directions showing potential for flow separation suppression

Maize haplotype with a helitron-amplified cytidine deaminase gene copy

BACKGROUND: Genetic maps are based on recombination of orthologous gene sequences between different strains of the same species. Therefore, it was unexpected to find extensive non-collinearity of genes between different inbred strains of maize. Interestingly, disruption of gene collinearity can be caused among others by a rolling circle-type copy and paste mechanism facilitated by Helitrons. However, understanding the role of this type of gene amplification has been hampered by the lack of finding intact gene sequences within Helitrons. RESULTS: By aligning two haplotypes of the z1C1 locus of maize we found a Helitron that contains two genes, one encoding a putative cytidine deaminase and one a hypothetical protein with part of a 40S ribosomal protein. The cytidine deaminase gene, called ZmCDA3, has been copied from the ZmCDA1 gene on maize chromosome 7 about 4.5 million years ago (mya) after maize was formed by whole-genome duplication from two progenitors. Inbred lines contain gene copies of both progenitors, the ZmCDA1 and ZmCDA2 genes. Both genes diverged when the progenitors of maize split and are derived from the same progenitor as the rice OsCDA1 gene. The ZmCDA1 and ZmCDA2 genes are both transcribed in leaf and seed tissue, but transcripts of the paralogous ZmCDA3 gene have not been found yet. Based on their protein structure the maize CDA genes encode a nucleoside deaminase that is found in bacterial systems and is distinct from the mammalian RNA and/or DNA modifying enzymes. CONCLUSION: The conservation of a paralogous gene sequence encoding a cytidine deaminase gene over 4.5 million years suggests that Helitrons could add functional gene sequences to new chromosomal positions and thereby create new haplotypes. However, the function of such paralogous gene copies cannot be essential because they are not present in all maize strains. However, it is interesting to note that maize hybrids can outperform their inbred parents. Therefore, certain haplotypes may function only in combination with other haplotypes or under specialized environmental conditions

Identification of miRNA from Porphyra yezoensis by High-Throughput Sequencing and Bioinformatics Analysis

BACKGROUND: miRNAs are a class of non-coding, small RNAs that are approximately 22 nucleotides long and play important roles in the translational level regulation of gene expression by either directly binding or cleaving target mRNAs. The red alga, Porphyra yezoensis is one of the most important marine economic crops worldwide. To date, only a few miRNAs have been identified in green unicellar alga and there is no report about Porphyra miRNAs. METHODOLOGY/PRINCIPAL FINDINGS: To identify miRNAs in Porphyra yezoensis, a small RNA library was constructed. Solexa technology was used to perform high throughput sequencing of the library and subsequent bioinformatics analysis to identify novel miRNAs. Specifically, 180,557,942 reads produced 13,324 unique miRNAs representing 224 conserved miRNA families that have been identified in other plants species. In addition, seven novel putative miRNAs were predicted from a limited number of ESTs. The potential targets of these putative miRNAs were also predicted based on sequence homology search. CONCLUSIONS/SIGNIFICANCE: This study provides a first large scale cloning and characterization of Porphyra miRNAs and their potential targets. These miRNAs belong to 224 conserved miRNA families and 7 miRNAs are novel in Porphyra. These miRNAs add to the growing database of new miRNA and lay the foundation for further understanding of miRNA function in the regulation of Porphyra yezoensis development

The Two-Domain LysX Protein of Mycobacterium tuberculosis Is Required for Production of Lysinylated Phosphatidylglycerol and Resistance to Cationic Antimicrobial Peptides

The well-recognized phospholipids (PLs) of Mycobacterium tuberculosis (Mtb) include several acidic species such as phosphatidylglycerol (PG), cardiolipin, phosphatidylinositol and its mannoside derivatives, in addition to a single basic species, phosphatidylethanolamine. Here we demonstrate that an additional basic PL, lysinylated PG (L-PG), is a component of the PLs of Mtb H37Rv and that the lysX gene encoding the two-domain lysyl-transferase (mprF)-lysyl-tRNA synthetase (lysU) protein is responsible for L-PG production. The Mtb lysX mutant is sensitive to cationic antibiotics and peptides, shows increased association with lysosome-associated membrane protein–positive vesicles, and it exhibits altered membrane potential compared to wild type. A lysX complementing strain expressing the intact lysX gene, but not one expressing mprF alone, restored the production of L-PG and rescued the lysX mutant phenotypes, indicating that the expression of both proteins is required for LysX function. The lysX mutant also showed defective growth in mouse and guinea pig lungs and showed reduced pathology relative to wild type, indicating that LysX activity is required for full virulence. Together, our results suggest that LysX-mediated production of L-PG is necessary for the maintenance of optimal membrane integrity and for survival of the pathogen upon infection