Overexpression of serine racemase in retina and overproduction of D-serine in eyes of streptozotocin-induced diabetic retinopathy

<p>Abstract</p> <p>Background</p> <p>Recent data indicate that inflammatory mechanisms contribute to diabetic retinopathy (DR). We have determined that serine racemase (SR) expression is increased by inflammatory stimuli including liposaccharide (LPS), amyloid β-peptide (A-beta), and secreted amyloid precursor protein (sAPP); expression is decreased by the anti-inflammatory drug, dexamethasone. We tested possibility that SR and its product, D-serine, were altered in a rat model of DR.</p> <p>Methods</p> <p>Intraperitoneal injection of streptozotocin (STZ; 70 mg/kg body weight) to Sprague-Dawley rats produced type-I diabetic mellitus (fasting blood sugar higher than 300 mg/dL). At 3 and 5 months after STZ or saline injection, retinas from some rats were subjected to cryosectioning for immunofluorescent analysis of SR and TUNEL assay of apoptosis. Retinal homogenates were used to detect SR levels and Jun N-terminal kinase (JNK) activation by immunoblotting. Aqueous humor and retina were also collected to assay for neurotransmitters, including glutamate and D-serine, by reverse-phase HPLC.</p> <p>Results</p> <p>Compared to saline-injected rats, STZ-injected (diabetic) rats showed elevation of SR protein levels in retinal homogenates, attributed to the inner nuclear layer (INL) by immunofluorescence. Aqueous humor fluid from STZ-injected rats contained significantly higher levels of glutamate and D-serine compared to controls; by contrast, D-serine levels in retinas did not differ. Levels of activated JNK were elevated in diabetic retinas compared to controls.</p> <p>Conclusions</p> <p>Increased expression of SR in retina and higher levels of glutamate and D-serine in aqueous humor of STZ-treated rats may result from activation of the JNK pathway in diabetic sequelae. Our data suggest that the inflammatory conditions that prevail during DR result in elevation of D-serine, a neurotransmitter contributing to glutamate toxicity, potentially exacerbating the death of retinal ganglion cells in this condition.</p

Geochemical characteristics of rare earth elements in Late Permian coals in Western Henan and indicative meaning

With the wide application of rare earth metals in high-tech fields such as medical treatment and new materials, its strategic position has been increasing. As a major country in rare earth, China supplies rare earth products of different varieties and grades to all countries in the world, making great contributions to the development of emerging industries in the world .In order to explore the enrichment degree, occurrence state and sedimentary environment of rare earth elements in late Permian coal in western Henan, 20 stratified coal samples from No.21 coal in Huixiang mining area in western Henan were taken as the main research object. The rare earth elements and major elements in stratified coal samples were measured by ICP-MS and XRF, and the content characteristics and enrichment degree of rare earth elements in coal samples were discussed. The occurrence state and sedimentary environment of rare earth elements in samples were discussed by correlation analysis and characteristic parameters .The results show that the mass concentration of REY is 35.29-133.61 μg/g, and the average concentration is 79.14 μg/g, which is slightly higher than the average concentration of REY in the world coal, but obviously lower than the average concentration of REY in China coal. The REY content is low, and LREY is mainly enriched. There is a significant positive correlation between REY and ash content (Ad), SiO2, Al2O3 and other major oxides in the No.21 coal of Huixiang mining area, indicating that REY mainly occurs in clay minerals .The negative anomalies of Ce and Eu elements and slight positive anomalies of (Gd/Gd)N* in the samples in the study area indicate that the study area is mainly affected by terrigenous sources and the coal forming environment is a weakly acidic reducing environment

Tumor Suppressor Spred2 Interaction with LC3 Promotes Autophagosome Maturation and Induces Autophagy-Dependent Cell Death

The tumor suppressor Spred2 (Sprouty-related EVH1 domain-2) induces cell death in a variety of cancers. However, the underlying mechanism remains to be elucidated. Here we show that Spred2 induces caspase-independent but autophagy-dependent cell death in human cervical carcinoma HeLa and lung cancer A549 cells. We demonstrate that ectopic Spred2 increased both the conversion of microtubule-associated protein 1 light chain 3 (LC3), GFP-LC3 puncta formation and p62/SQSTM1 degradation in A549 and HeLa cells. Conversely, knockdown of Spred2 in tumor cells inhibited upregulation of autophagosome maturation induced by the autophagy inducer Rapamycin, which could be reversed by the rescue Spred2. These data suggest that Spred2 promotes autophagy in tumor cells. Mechanistically, Spred2 co-localized and interacted with LC3 via the LC3-interacting region (LIR) motifs in its SPR domain. Mutations in the LIR motifs or deletion of the SPR domain impaired Spred2-mediated autophagosome maturation and tumor cell death, indicating that functional LIR is required for Spred2 to trigger tumor cell death. Additionally, Spred2 interacted and co-localized with p62/SQSTM1 through its SPR domain. Furthermore, the co-localization of Spred2, p62 and LAMP2 in HeLa cells indicates that p62 may be involved in Spred2-mediated autophagosome maturation. Inhibition of autophagy using the lysosomal inhibitor chloroquine, reduced Spred2-mediated HeLa cell death. Silencing the expression of autophagy-related genes ATG5, LC3 or p62 in HeLa and A549 cells gave similar results, suggesting that autophagy is required for Spred2-induced tumor cell death. Collectively, these data indicate that Spred2 induces tumor cell death in an autophagy-dependent manner

Electronic and magnetic properties of multishell Co nanowires coated with Cu

The structural, electronic, and magnetic properties of ultrathin Cu-coated Co nanowires have been studied by using empirical genetic algorithm simulations and a tight-binding $spd$ model Hamiltonian in the unrestricted Hartree-Hock approximation. For some specific stoichiometric compositions, Cu atoms occupy the surface, while Co atoms prefer to stay in the interior, forming the perfect coated multishell structures. The outer Cu layers lead to substantial variations of the magnetic moment of interior Co atoms, depending on the structure and thickness of Cu layers. In particular, single Co atom row in the center of nanowire is found to be nonmagnetic when coated with two Cu layers. All the other Co nanowires in the coated Cu shell are still magnetic but the magnetic moments are reduced as compared with Co nanowires without Cu coating. The interaction between Cu and Co atoms induces nonzero magnetic moment for Cu atoms.Comment: 7 pages, 2 fugure

Crop Diversity for Yield Increase

Traditional farming practices suggest that cultivation of a mixture of crop species in the same field through temporal and spatial management may be advantageous in boosting yields and preventing disease, but evidence from large-scale field testing is limited. Increasing crop diversity through intercropping addresses the problem of increasing land utilization and crop productivity. In collaboration with farmers and extension personnel, we tested intercropping of tobacco, maize, sugarcane, potato, wheat and broad bean – either by relay cropping or by mixing crop species based on differences in their heights, and practiced these patterns on 15,302 hectares in ten counties in Yunnan Province, China. The results of observation plots within these areas showed that some combinations increased crop yields for the same season between 33.2 and 84.7% and reached a land equivalent ratio (LER) of between 1.31 and 1.84. This approach can be easily applied in developing countries, which is crucial in face of dwindling arable land and increasing food demand

CdSe Quantum Dot (QD)-Induced Morphological and Functional Impairments to Liver in Mice

Quantum dots (QDs), as unique nanoparticle probes, have been used in in vivo fluorescence imaging such as cancers. Due to the novel characteristics in fluorescence, QDs represent a family of promising substances to be used in experimental and clinical imaging. Thus far, the toxicity and harmful health effects from exposure (including environmental exposure) to QDs are not recognized, but are largely concerned by the public. To assess the biological effects of QDs, we established a mouse model of acute and chronic exposure to QDs. Results from the present study suggested that QD particles could readily spread into various organs, and liver was the major organ for QD accumulation in mice from both the acute and chronic exposure. QDs caused significant impairments to livers from mice with both acute and chronic QD exposure as reflected by morphological alternation to the hepatic lobules and increased oxidative stress. Moreover, QDs remarkably induced the production of intracellular reactive oxygen species (ROS) along with cytotoxicity, as characterized by a significant increase of the malondialdehyde (MDA) level within hepatocytes. However, the increase of the MDA level in response to QD treatment could be partially blunted by the pre-treatment of cells with beta-mercaptoethanol (β-ME). These data suggested ROS played a crucial role in causing oxidative stress-associated cellular damage from QD exposure; nevertheless other unidentified mediators might also be involved in QD-mediated cellular impairments. Importantly, we demonstrated that the hepatoxicity caused by QDs in vivo and in vitro was much greater than that induced by cadmium ions at a similar or even a higher dose. Taken together, the mechanism underlying QD-mediated biological influences might derive from the toxicity of QD particles themselves, and from free cadmium ions liberated from QDs as well

Phosphodiesterase-4 Inhibition Alters Gene Expression and Improves Isoniazid – Mediated Clearance of Mycobacterium tuberculosis in Rabbit Lungs

Tuberculosis (TB) treatment is hampered by the long duration of antibiotic therapy required to achieve cure. This indolent response has been partly attributed to the ability of subpopulations of less metabolically active Mycobacterium tuberculosis (Mtb) to withstand killing by current anti-TB drugs. We have used immune modulation with a phosphodiesterase-4 (PDE4) inhibitor, CC-3052, that reduces tumor necrosis factor alpha (TNF-α) production by increasing intracellular cAMP in macrophages, to examine the crosstalk between host and pathogen in rabbits with pulmonary TB during treatment with isoniazid (INH). Based on DNA microarray, changes in host gene expression during CC-3052 treatment of Mtb infected rabbits support a link between PDE4 inhibition and specific down-regulation of the innate immune response. The overall pattern of host gene expression in the lungs of infected rabbits treated with CC-3052, compared to untreated rabbits, was similar to that described in vitro in resting Mtb infected macrophages, suggesting suboptimal macrophage activation. These alterations in host immunity were associated with corresponding down-regulation of a number of Mtb genes that have been associated with a metabolic shift towards dormancy. Moreover, treatment with CC-3052 and INH resulted in reduced expression of those genes associated with the bacterial response to INH. Importantly, CC-3052 treatment of infected rabbits was associated with reduced ability of Mtb to withstand INH killing, shown by improved bacillary clearance, from the lungs of co-treated animals compared to rabbits treated with INH alone. The results of our study suggest that changes in Mtb gene expression, in response to changes in the host immune response, can alter the responsiveness of the bacteria to antimicrobial agents. These findings provide a basis for exploring the potential use of adjunctive immune modulation with PDE4 inhibitors to enhance the efficacy of existing anti-TB treatment

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead