Acylation-stimulating protein/C5L2-neutralizing antibodies alter triglyceride metabolism in vitro and in vivo

Acylation-stimulating protein (ASP), a lipogenic hormone, stimulates triglyceride (TG) synthesis and glucose transport upon activation of C5L2, a G protein-coupled receptor. ASP-deficient mice have reduced adipose tissue mass due to increased energy expenditure despite increased food intake. The objective of this study was to evaluate the blocking of ASP-C5L2 interaction via neutralizing antibodies (anti-ASP and anti-C5L2-L1 against C5L2 extracellular loop 1). In vitro, anti-ASP and anti-C5L2-L1 blocked ASP binding to C5L2 and efficiently inhibited ASP stimulation of TG synthesis and glucose transport. In vivo, neither anti-ASP nor anti-C5L2-L1 altered body weight, adipose tissue mass, food intake, or hormone levels (insulin, leptin, and adiponectin), but they did induce a significant delay in TG clearance [P < 0.0001, 2-way repeated-measures (RM) ANOVA] and NEFA clearance (P < 0.0001, 2-way RM ANOVA) after a fat load. After treatment with either anti-ASP or anti-C5L2-L1 antibody there was no change in adipose tissue AMPK activity, but neutralizing antibodies decreased perirenal TG mass (-38.4% anti-ASP, -18.8% anti-C5L2, P < 0.01-0.001) and perirenal LPL activity (-75.6% anti-ASP, -72.5% anti-C5L2, P < 0.05). In liver, anti-C5L2-L1 decreased TG mass (-42.8%, P < 0.05), whereas anti-ASP increased AMPK activity (+34.6%, P < 0.001). In the muscle, anti-C5L2-L1 significantly increased TG mass (+128.0%, P < 0.05), LPL activity (+226.1%, P < 0.001), and AMPK activity (+71.1%, P < 0.01). In addition, anti-ASP increased LPL activity (+164.4, P < 0.05) and AMPK activity (+53.9%, P < 0.05) in muscle. ASP/C5L2-neutralizing antibodies effectively block ASP-C5L2 interaction, altering lipid distribution and energy utilization.     

EP300 contributes to high-altitude adaptation in Tibetans by regulating nitric oxide production

The genetic adaptation of Tibetans to high altitude hypoxia likely involves a group of genes in the hypoxic pathway,as suggested by earlier studies.To test the adaptive role of the previously reported candidate gene EP300 (histone acetyltransferase p300),we conducted resequencing of a 108.9 kb gene region of EP300 in 80 unrelated Tibetans.The allele-frequency and haplotype-based neutrality tests detected signals of positive Darwinian selection on EP300 in Tibetans,with a group of variants showing allelic divergence between Tibetans and lowland reference populations,including Han Chinese,Europeans,and Africans.Functional prediction suggested the involvement of multiple EP300 variants in gene expression regulation.More importantly,genetic association tests in 226 Tibetans indicated significant correlation of the adaptive EP300 variants with blood nitric oxide (NO) concentration.Collectively,we propose that EP300 harbors adaptive variants in Tibetans,which might contribute to high-altitude adaptation through regulating NO production.     

Single Nanostructure Electrochemical Devices for Studying Electronic Properties and Structural Changes in Lithiated Si Nanowires

Nanostructured Si is a promising anode material for the next generation of Li‐ion batteries, but few studies have focused on the electrical properties of the Li‐Si alloy phase, which are important for determining power capabilities and ensuring sufficient electrical conduction in the electrode structure. Here, we demonstrate an electrochemical device framework suitable for testing the electrical properties of single Si nanowires (NWs) at different lithiation states and correlating these properties with structural changes via transmission electron microscopy (TEM). We find that single Si NWs usually exhibit Ohmic I–V response in the lithiated state, with conductivities two to three orders of magnitude higher than in the delithiated state. After a number of sequential lithiation/delithiation cycles, the single NWs show similar conductivity after each lithiation step but show large variations in conductivity in the delithiated state. Finally, devices with groups of NWs in physical contact were fabricated, and structural changes in the NWs were observed after lithiation to investigate how the electrical resistance of NW junctions and the NWs themselves affect the lithiation behavior. The results suggest that electrical resistance of NW junctions can limit lithiation. Overall, this study shows the importance of investigating the electronic properties of individual components of a battery electrode (single nanostructures in this case) along with studying the nature of interactions within a collection of these component structures.     

Neutrophil beta2 integrin inhibition by enhanced interactions of vasodilator-stimulated phosphoprotein with S-nitrosylated actin

Production of reactive species in neutrophils exposed to hyperoxia causes S-nitrosylation of β-actin, which increases formation of short actin filaments, leading to alterations in the cytoskeletal network that inhibit β(2) integrin-dependent adherence (Thom, S. R., Bhopale, V. M., Mancini, D. J., and Milovanova, T. N. (2008) J. Biol. Chem. 283, 10822-10834). In this study, we found that vasodilator-stimulated protein (VASP) exhibits high affinity for S-nitrosylated short filamentous actin, which increases actin polymerization. VASP bundles Rac1, Rac2, cyclic AMP-dependent, and cyclic GMP-dependent protein kinases in close proximity to short actin filaments, and subsequent Rac activation increases actin free barbed end formation. Using specific chemical inhibitors or reducing cell concentrations of any of these proteins with small inhibitory RNA abrogates enhanced free barbed end formation, increased actin polymerization, and β(2) integrin inhibition by hyperoxia. Alternatively, incubating neutrophils with formylmethionylleucylphenylalanine or 8-bromo-cyclic GMP activates either cyclic AMP-dependent or cyclic GMP-dependent protein kinase, respectively, outside of the short F-actin pool and phosphorylates VASP on serine 153. Phosphorylated VASP abrogates the augmented polymerization normally observed with S-nitrosylated actin, VASP binding to actin, elevated Rac activity, and elevated formation of actin free barbed ends, thus restoring normal β(2) integrin function.     

Ferrous Iron Induces Nrf2 Expression in Mouse Brain Astrocytes to Prevent Neurotoxicity

Free radical damage caused by ferrous iron is involved in the pathogenesis of secondary brain injury after intracerebral hemorrhage (ICH). NF‐E2‐related factor 2 (Nrf2), a major phase II gene regulator that binds to antioxidant response element, represents an important cellular cytoprotective mechanism against oxidative damage. We hypothesized that Nrf2 might protect astrocytes from damage by Fe²⁺. Therefore, we examined cytotoxicity in primary astrocytes induced by iron overload and evaluated the effects of Fe²⁺ on Nrf2 expression. The results demonstrated that 24‐h Fe²⁺ exposure exerted time‐ and concentration‐dependent cytotoxicity in astrocytes. Furthermore, Fe²⁺ exposure in astrocytes resulted in time‐ and concentration‐dependent increases in Nrf2 expression, which preceded Fe²⁺ toxicity. Nrf2‐specific siRNA further knocked down Nrf2 levels, resulting in greater Fe²⁺‐induced astrocyte cytotoxicity. These data indicate that induction of Nrf2 expression could serve as an adaptive self‐defense mechanism, although it is insufficient to completely protect primary astrocytes from Fe²⁺‐induced neurotoxicity.     

土壤因子对府谷清水川流域砒砂岩区刺槐和沙棘AMF的影响

应用相关性分析和通径分析研究了府谷清水川流域砒砂岩区土壤因子对刺槐(Robinia pseudoacacia)和沙棘(Hippophae rhamnoides)根际丛枝菌根真菌(AMF)的影响.结果表明:AMF可以与刺槐和沙棘形成良好的共生关系;从两种植物根际土中共分离鉴定出AMF 13种,其中摩西囊霉(Glomus mosseae)、地球囊霉(Glomus geospo-rum)和缩球囊霉(Glomus constrictum)为优势种;AMF平均侵染率为90.6%,平均孢子密度为559.1个?100 g-1干土;AMF的孢子密度、侵染率和种类之间没有显著的相关性;刺槐和沙棘根际AMF侵染率均与pH呈显著正相关,在刺槐根际,pH和有效氮通过直接作用影响侵染率,有机质和有效磷通过间接作用影响侵染率;在沙棘根际,pH和有效磷通过直接作用影响侵染率,有机质和有效氮通过间接作用影响侵染率;在沙棘根际,有机质和pH主要是通过直接作用影响AMF种类,有效氮主要通过有效磷的间接作用影响AMF种类.     

EFFECTS OF LIGHT ON PHOTOSYNTHESIS,GRAZING, AND POPULATION DYNAMICS OF THE HETEROTROPHIC DINOFLAGELLATE PFIESTERIA PISCICIDA (DINOPHYCEAE)1

In studying how environmental factors control the population dynamics of Pfiesteria piscicida Steidinger et Burkholder, we examined the influence of light regime on kleptoplastidic photosynthesis, growth, and grazing. Prey (Rhodomonas sp.)‐saturated growth rate of P. piscicida increased (0.67 ± 0.03 d^?1 to 0.91 ± 0.11 d^?1) with light intensity varying from 0 to 200 μmol photons·m^?2·s^?1. No significant effect was observed on grazing, excluding the possibility that light enhanced P. piscicida growth through stimulating grazing. Light‐grown P. piscicida exhibited a higher gross growth efficiency (0.78 ± 0.10) than P. piscicida incubated in the dark (0.32 ± 0.16), and photosynthetic inhibitors significantly decreased growth of recently fed populations. These results demonstrate a role of kleptoplastidic photosynthesis in enhancing growth in P. piscicida. However, when the prey alga R. sp. was depleted, light's stimulating effect on P. piscicida growth diminished quickly, coinciding with rapid disappearance of Rhodomonas‐derived pigments and RUBISCO from P. piscicida cells. Furthermore, the effect of light on growth was reversed after extended starvation, and starved light‐grown P. piscicida declined at a rate significantly greater than dark‐incubated cultures. The observed difference in rates of decline appeared to be attributable to light‐dependent cannibalism. Using a 5‐chloromethylfluorescein diacetate staining technique, cannibalistic grazing was observed after 7 days of starvation, at a rate four times greater under illumination than in the dark. The results from this study suggest that kleptoplastidy enhances growth of P. piscicida only in the presence of algal prey. When prey is absent, P. piscicida populations may become vulnerable to light‐stimulated cannibalism.     

中华通草蛉成虫越冬体色变化与滞育的关系

对自然条件下中华通草蛉成虫越冬体色变化与滞育关系的系统研究表明,成虫在越冬过程中都经历了一个较明显的体色变化过程,主要表现在体躯底色从绿色到土黄色及体背面滞育斑由褐色到红褐色的改变,据此将成虫体色分成5个级别,在越冬过程中约80%个体体色经历了在生殖型体色（1级）和滞育型体色（4,5级）之间的明显变化,约有20%个体体色维持在2、3级,在越冬前,成虫滞育斑出现后其卵巢不再发育或者发育受抑而逐渐停止发育,滞育斑的出现是成虫开始滞育的重要标志;越冬后,随着成虫体色由滞育型向生殖型的转变,当大多数个体体色变为3级以下时,卵巢开始发育,这些结果说明,中华通草蛉越冬成虫体色的变化是其滞育越冬的一个重要形态指标,越冬前后体色的改变,标志着成虫滞育的开始和结束。