The roles of autophagy in cerebral ischemia

Recent studies indicate the existence of autophagy in cerebral ischemia, but the functions of autophagy in this setting remain unclear. Here we discuss the role of autophagy in cerebral ischemia based on our own publication and the literature on this subject. We propose that oxidative and endoplasmic reticulum (ER) stresses n cerebral ischemia-hypoxia are potent stimuli of autophagy in neurons. We also reviewed evidence suggesting autophagosomes may have a shorter half-life in neurons and that a fraction of LC3 protein is degraded within autolysosomes, leading to a smaller detectable amount of LC3-II in the brain while there are clear indications of on-going autophagy. Finally, we suggest autophagy is an important modifier of cell death and survival, interacting with necrosis and apoptosis in determining the outcomes and final morphology of deceased neurons.     

A meta-analysis of tumor necrosis factor-alpha, interleukin-6, and interleukin-10 in preeclampsia

Inflammation may play a major role in the pathogenesis of preeclampsia (PE). In this meta-analysis, we determined whether maternal polymorphisms and serum concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) were associated with PE. All studies investigating the associations between PE and maternal polymorphisms of TNF-α-308G/A, IL-6-174G/C, and IL-10-1082A/G or serum concentrations of TNF-α, IL-6, and IL-10 were reviewed. We found that neither maternal TNF-α-308G/A (p=0.86, odds ratio [OR]=0.98, 95% confidence interval [CI], 0.76-1.25), IL-6 174G/C (p=0.14, OR=1.23, 95% CI, 0.93-1.61), nor IL-10-1082A/G (p=0.72, OR=1.07, 95% CI, 0.75-1.52) were associated with PE. On the other hand, maternal TNF-α (p<0.00001, weighted mean difference [WMD]=19.63 pg/ml, 95% CI, 18.54-20.72 pg/ml), IL-6 (p<0.00001, WMD=6.58 pg/ml, 95% CI, 5.49-7.67 pg/ml), and IL-10 (p=0.0005, WMD=19.30 pg/ml, 95% CI, 8.42-30.17 pg/ml) concentrations were significantly higher in PE patients versus controls. Our findings strengthen the clinical evidence that PE is accompanied by exaggerated inflammatory responses, but do not support TNF-α-308G/A, IL-6-174G/C, and IL-10-1082A/G as candidate susceptibility loci in PE.     

Application of Multiplexed Kinase Inhibitor Beads to Study Kinome Adaptations in Drug-Resistant Leukemia

Protein kinases play key roles in oncogenic signaling and are a major focus in the development of targeted cancer therapies. Imatinib, a BCR-Abl tyrosine kinase inhibitor, is a successful front-line treatment for chronic myelogenous leukemia (CML). However, resistance to imatinib may be acquired by BCR-Abl mutations or hyperactivation of Src family kinases such as Lyn. We have used multiplexed kinase inhibitor beads (MIBs) and quantitative mass spectrometry (MS) to compare kinase expression and activity in an imatinib-resistant (MYL-R) and -sensitive (MYL) cell model of CML. Using MIB/MS, expression and activity changes of over 150 kinases were quantitatively measured from various protein kinase families. Statistical analysis of experimental replicates assigned significance to 35 of these kinases, referred to as the MYL-R kinome profile. MIB/MS and immunoblotting confirmed the over-expression and activation of Lyn in MYL-R cells and identified additional kinases with increased (MEK, ERK, IKKα, PKCβ, NEK9) or decreased (Abl, Kit, JNK, ATM, Yes) abundance or activity. Inhibiting Lyn with dasatinib or by shRNA-mediated knockdown reduced the phosphorylation of MEK and IKKα. Because MYL-R cells showed elevated NF-κB signaling relative to MYL cells, as demonstrated by increased IκBα and IL-6 mRNA expression, we tested the effects of an IKK inhibitor (BAY 65-1942). MIB/MS and immunoblotting revealed that BAY 65-1942 increased MEK/ERK signaling and that this increase was prevented by co-treatment with a MEK inhibitor (AZD6244). Furthermore, the combined inhibition of MEK and IKKα resulted in reduced IL-6 mRNA expression, synergistic loss of cell viability and increased apoptosis. Thus, MIB/MS analysis identified MEK and IKKα as important downstream targets of Lyn, suggesting that co-targeting these kinases may provide a unique strategy to inhibit Lyn-dependent imatinib-resistant CML. These results demonstrate the utility of MIB/MS as a tool to identify dysregulated kinases and to interrogate kinome dynamics as cells respond to targeted kinase inhibition.     

Surface exploration of Amphibalanus amphitrite cyprids on microtextured surfaces

Microtopography is one of several strategies used by marine organisms to inhibit colonization by fouling organisms. While replicates of natural microtextures discourage settlement, details of larval interactions with the structured surfaces remain scarce. Close-range microscopy was used to quantify the exploration of cyprids of Amphibalanus amphitrite on cylindrical micropillars with heights of 5 and 30 μm and diameters ranging from 5 to 100 μm. While 5 μm-high structures had little impact, 30 μm-high pillars significantly influenced cyprid exploration. An observed step length decrease and step duration increase on 5 μm diameter pillars is attributed to the small dimensions of the voids excluding the cyprid's attachment disc and consequently reducing the area of adhesive contact. When exploring larger diameter pillars, cyprids preferred using the voids to form temporary attachment points. This may enhance their resistance to flow. No-choice assay settlement patterns mirrored this exploration behaviour, albeit in a pattern counter to what was predicted.     

Leaf epidermal features of Rhododendron (Ericaceae)from China and their systematic significance

Rhododendron is the largest genus within the subfamily Rhododendroideae, which has about 1000 known species in the world and more than 500 species in China. Since the genus was established by Linnaeus, its infrageneric relationships have been well studied by many taxonomists on the basis of morphological characters and molecular data. In 1996, Chamberlain et al. proposed a new system of Rhododendron with eight subgenera, i.e., Azaleastrum, Candidastrum, Hymenanthes, Mumeazalea, Pentanthera, Rhododendron, Therorhodion, and Tsutsusi. In this paper, micromorphological characters of leaf epidermis in 4 varieties, 48 species, 6 subgenera of Rhododendron from China were examined using light microscopy (LM) and scanning electron microscopy (SEM). Leaf epidermal features are described and micromorphological types are distinguished here according to morphological characters such as scale, gland, foliar trichome and stomatal apparatus of leaf epidermis. It is shown that the leaf epidermal cells are usually irregular or polygonal in shape. The patterns of anticlinal walls are straight, arched or undulate. The stomatal apparatuses are anomocytic and are usually found on abaxial, not adaxial, epidermis. The results also show that: (1) the lepidote rhododendron (i.e., subgen. Rhododendron), which has both scales and papillae on leaf epidermis, differs distinctly from the elepidote rhododendron; (2) three types of leaf epidermis are identified in subgen. Hymenanthes (i.e., R. fortunei-type, R. chihsinianum-type and R. simiarum-type), whereas four in subgen. Tsutsusi (i.e., R. mariesii-type, R. simsii-type, R. mariae-type and R. flosculum-type); (3) except for R. westlandii and R. henryi, the species of subgen. Azaleastrum show similar morphological characters, i.e., dense stomatal apparatuses surrounded by ringed or discontinuous striates; (4) R. molle of subgen. Pentanthera differs from the species of other subgenera on morphological characters such as foliar trichomes, dense stomatal apparatuses with asymmetrical outer stomatal rims surrounded by undulate-striates, and no gland; (5) only R. redowskianum is found with distinct T-pieces at the polar region of guard cells in Rhododendron. The results support the conclusion inferred from molecular systematic studies that subgen. Therorhodion is the basal clade of Rhododendron. Finally, the relationships between the closely related species are also discussed on the basis of leaf epidermal features.     

Extensive and Modular Intrinsically Disordered Segments in C. elegans TTN-1 and Implications in Filament Binding, Elasticity and Oblique Striation

TTN-1, a titin like protein in Caenorhabditis elegans, is encoded by a single gene and consists of multiple Ig and fibronectin 3 domains, a protein kinase domain and several regions containing tandem short repeat sequences. We have characterized TTN-1's sarcomere distribution, protein interaction with key myofibrillar proteins as well as the conformation malleability of representative motifs of five classes of short repeats. We report that two antibodies developed to portions of TTN-1 detect an ∼ 2-MDa polypeptide on Western blots. In addition, by immunofluorescence staining, both of these antibodies localize to the I-band and may extend into the outer edge of the A-band in the obliquely striated muscle of the nematode. Six different 300-residue segments of TTN-1 were shown to variously interact with actin and/or myosin in vitro. Conformations of synthetic peptides of representative copies of each of the five classes of repeats—39-mer PEVT, 51-mer CEEEI, 42-mer AAPLE, 32-mer BLUE and 30-mer DispRep—were investigated by circular dichroism at different temperatures, ionic strengths and solvent polarities. The PEVT, CEEEI, DispRep and AAPLE peptides display a combination of a polyproline II helix and an unordered structure in aqueous solution and convert in trifluoroethanol to α-helix (PEVT, CEEEI, DispRep) and β-turn (AAPLE) structures, respectively. The octads in BLUE motifs form unstable α-helix-like structures coils in aqueous solution and negligible heptad-based, α-helical coiled-coils. The α-helical structure, as modeled by threading and molecular dynamics simulations, tends to form helical bundles and crosses based on its 8-4-2-2 hydrophobic helical patterns and charge arrays on its surface. Our finding indicates that APPLE, PEVT, CEEEI and DispRep regions are all intrinsically disordered and highly reminiscent of the conformational malleability and elasticity of vertebrate titin PEVK segments. The proposed presence of long, modular and unstable α-helical oligomerization domains in the BLUE region of TTN-1 could bundle TTN-1 and stabilize oblique striation of the sarcomere.     

鳞翅目幼虫分科检索表

昆虫幼期分类的发展是比较晚近的;但不论在理论上或实用上都很重要。国外对於鳞翅目幼虫(通称蠋)的分类进展很快,而在国内还没有引起广泛的注意和研究。过去作者(陆近仁,1943)虽在昆明做过一些工作,但不过是一个起始。我们     

Spartina alterniflora invasion increases soil inorganic nitrogen pools through interactions with tidal subsidies in the Yangtze Estuary, China

Invasive alien plants increase both plant N and soil inorganic N pools in many terrestrial ecosystems. This is believed to be the result of altered plant-soil-microbe feedbacks that accelerate N cycling. However, it may also be due to the greater ability of invasive species to uptake lateral N subsidies that can modify ecosystem N dynamics. We conducted manipulative field experiments to determine the impact of smooth cordgrass (Spartina alterniflora) invasion on the N cycling of salt marsh ecosystems in the Yangtze Estuary, China. The results showed that the aboveground plant N and soil inorganic N pools in S. alterniflora marshes, 14.39 and 3.16 g N m(-2), were significantly higher than those in native common reed (Phragmites australis) marshes, 11.61 and 2.29 g N m(-2). These increases after invasion were explained by a significantly higher uptake of dissolved inorganic N (DIN) from tidal subsidies in S. alterniflora marshes (6.59 g N m(-2)) than from those in P. australis marshes (1.61 g N m(-2)), and not by soil organic N mineralization, which was not significantly different between S. alterniflora (6.45 g N m(-2)) and P. australis marshes (6.84 g N m(-2)) during the growing season. Our study indicated that the ecosystem engineering effects of S. alterniflora, which increases the interception of external N input, can be an alternative mechanism that increases plant N and soil inorganic N pools--especially in ecosystems with ample anthropogenic N subsidies, such as the coastal wetlands of China.