N-syndecan and HB-GAM in neural migration and differentiation : Modulation of growth factor activity in brain

The juvenile sea squirt wanders through the sea searching for a suitable rock or hunk of coral to cling to and make its home for life. For this task it has a rudimentary nervous system. When it finds its spot and takes root, it doesn't need its brain any more so it eats it. It's rather like getting tenure. Daniel C. Dennett (from Consciousness Explained, 1991) The little sea squirt needs its brain for a task that is very simple and short. When the task is completed, the sea squirt starts a new life in a vegetative state, after having a nourishing meal. The little brain is more tightly structured than our massive primate brains. The number of neurons is exact, no leeway in neural proliferation is tolerated. Each neuroblast migrates exactly to the correct position, and only a certain number of connections with the right companions is allowed. In comparison, growth of a mammalian brain is a merry mess. The reason is obvious: Squirt brain needs to perform only a few, predictable functions, before becoming waste. The more mobile and complex mammals engage their brains in tasks requiring quick adaptation and plasticity in a constantly changing environment. Although the regulation of nervous system development varies between species, many regulatory elements remain the same. For example, all multicellular animals possess a collection of proteoglycans (PG); proteins with attached, complex sugar chains called glycosaminoglycans (GAG). In development, PGs participate in the organization of the animal body, like in the construction of parts of the nervous system. The PGs capture water with their GAG chains, forming a biochemically active gel at the surface of the cell, and in the extracellular matrix (ECM). In the nervous system, this gel traps inside it different molecules: growth factors and ECM-associated proteins. They regulate the proliferation of neural stem cells (NSC), guide the migration of neurons, and coordinate the formation of neuronal connections. In this work I have followed the role of two molecules contributing to the complexity of mammalian brain development. N-syndecan is a transmembrane heparan sulfate proteoglycan (HSPG) with cell signaling functions. Heparin-binding growth-associated molecule (HB-GAM) is an ECM-associated protein with high expression in the perinatal nervous system, and high affinity to HS and heparin. N-syndecan is a receptor for several growth factors and for HB-GAM. HB-GAM induces specific signaling via N-syndecan, activating c-Src, calcium/calmodulin-dependent serine protein kinase (CASK) and cortactin. By studying the gene knockouts of HB-GAM and N-syndecan in mice, I have found that HB-GAM and N-syndecan are involved as a receptor-ligand-pair in neural migration and differentiation. HB-GAM competes with the growth factors fibriblast growth factor (FGF)-2 and heparin-binding epidermal growth factor (HB-EGF) in HS-binding, causing NSCs to stop proliferation and to differentiate, and affects HB-EGF-induced EGF receptor (EGFR) signaling in neural cells during migration. N-syndecan signaling affects the motility of young neurons, by boosting EGFR-mediated cell migration. In addition, these two receptors form a complex at the surface of the neurons, probably creating a motility-regulating structure.

Heparin-binding growth-associated molecule (HB-GAM) in activity-dependent neuronal plasticity in hippocampus

Cell adhesion and extracellular matrix (ECM) molecules play a significant role in neuronal plasticity both during development and in the adult. Plastic changes in which ECM components are implicated may underlie important nervous system functions, such as memory formation and learning. Heparin-binding growthassociated molecule (HB-GAM, also known as pleiotrophin), is an ECM protein involved in neurite outgrowth, axonal guidance and synaptogenesis during perinatal period. In the adult brain HB-GAM expression is restricted to the regions which display pronounced synaptic plasticity (e.g., hippocampal CA3-CA1 areas, cerebral cortex laminae II-IV, olfactory bulb). Expression of HB-GAM is regulated in an activity-dependent manner and is also induced in response to neuronal injury. In this work mutant mice were used to study the in vivo function of HB-GAM and its receptor syndecan-3 in hippocampal synaptic plasticity and in hippocampus-dependent behavioral tasks. Phenotypic analysis of HBGAM null mutants and mice overexpressing HB-GAM revealed that opposite genetic manipulations result in reverse changes in synaptic plasticity as well as behavior in the mutants. Electrophysiological recordings showed that mice lacking HB-GAM have an increased level of long-term potentiation (LTP) in the area CA1 of hippocampus and impaired spatial learning, whereas animals with enhanced level of HB-GAM expression have attenuated LTP, but outperformed their wild-type controls in spatial learning. It was also found that GABA(A) receptor-mediated synaptic transmission is altered in the transgenic mice overexpressing HB-GAM. The results suggest that these animals have accentuated hippocampal GABAergic inhibition, which may contribute to the altered glutamatergic synaptic plasticity. Structural studies of HB-GAM demonstrated that this protein belongs to the thrombospondin type I repeat (TSR) superfamily and contains two β-sheet domains connected by a flexible linker. It was found that didomain structure is necessary for biological activity of HB-GAM and electrophysiological phenotype displayed by the HB-GAM mutants. The individual domains displayed weaker binding to heparan sulfate and failed to promote neurite outgrowth as well as affect hippocampal LTP. Effects of HB-GAM on hippocampal synaptic plasticity are believed to be mediated by one of its (co-)receptor molecules, namely syndecan-3. In support of that, HB-GAM did not attenuate LTP in mice deficient in syndecan-3 as it did in wild-type controls. In addition, syndecan-3 knockout mice displayed electrophysiological and behavioral phenotype similar to that of HB-GAM knockouts (i.e. enhanced LTP and impaired learning in Morris water-maze). Thus HB-GAM and syndecan-3 are important modulators of synaptic plasticity in hippocampus and play a role in regulation of learning-related behavior.

Mass spectrometry based characterization of Hb Beckman variant in a falsely elevated HbA(1c) sample

Glycated hemoglobin (HbA(1c)) is a `gold standard' biomarker for assessing the glycemic index of an individual. HbA(1c) is formed due to nonenzymatic glycosylation at N-terminal valine residue of the P-globin chain. Cation exchange based high performance liquid chromatography (CE HPLC) is mostly used to quantify HbA(1c), in blood sample. A few genetic variants of hemoglobin and post-translationally modified variants of hemoglobin interfere with CE HPLC-based quantification,. resulting in its false positive estimation. Using mass spectrometry, we analyzed a blood sample with abnormally high HbA(1c) (52.1%) in the CE HPLC method. The observed HbA(1c) did not corroborate the blood glucose level of the patient. A mass spectrometry based bottom up proteomics approach, intact globin chain mass analysis, and chemical modification of the proteolytic peptides identified the presence of Hb Beckman, a genetic variant of hemoglobin, in the experimental sample. A similar surface area to charge ratio between HbA(1c) and Hb Beckman might have resulted in the coelution of the variant with HbA(1c) in CE HPLC. Therefore, in the screening of diabetes mellitus through the estimation of HbA(1c), it is important to look for genetic variants of hemoglobin in samples that show abnormally high glycemic index, and HbA(1c) must be estimated using an alternative method. (C) 2015 Elsevier Inc. All rights reserved.

大型瑵HB对五氯苯酚的富集与释放动力学研究

大型瑵ＨＢ对五氯苯酚的富集与释放动力学研究谭渝云，孙美娟（中国科学院水生生物研究所，武汉，４３００７２）关键词大型；动力学；富集：释放；五氯苯酚．五氯苯酚（ＰＣＰ）是一种应用十分广泛的杀虫剂和防腐剂，Ｄｅｔｒｉｃｋ报道了世界上ＰＣＰ每年施用量约为９×...

一种耐高温大型溞HB的培养和生物学的初步研究

本文介绍了夏季在武汉鱼池所采的耐高温大型溞(Daphnia magna HB),对其生长繁殖及其实验室条件下溞的种群密度、食物、温度和光照强度对生长、发育的影响,并对其培养和保种方法进行了研究。连续3年实验室的培养表明,在以新鲜藻类为食物的情况下,此种溢在15—31℃时能正常生长、繁殖。在31℃时,其最大体长为3.65mm,最高怀卵量为26个。根据国际标准法组织所介绍的(ISO 6341)对标准毒物——重铬酸钾的敏感性试验,24hEC_(50)为0.92mg/L(20%)。

HB型厌氧生物工艺净化染色废水中间试验

<正> 染色废水作为一种主要污染源对环境构成的严重危害人所共知。随着“四化”建设的发展和人民生活水平的提高,轻纺工业在全国大、中、小城市乃至乡村小镇蓬勃发展,给污染防治工作带来极为艰巨的任务。至今,国内外染色废水的净化采用了多种物理化学和生物氧化的方法,虽有一定效果,也存在不同程度的问题,如电耗大、脱色率

HB型厌气工艺处理染色废水的研究 Ⅰ、HB-1型厌气反应器运转试验

<正> 染色废水长期以来是世界公认的严重污染源之一。基于染料类型的多样性和化学结构的复杂性,给废水处理带来了一定的难度。在桥本 茂等(1981)对多种染料及其助剂的COD、BOD、TOC、磷素和氮素值的研究中,已证明了上述事实。目前,国

Toxicity of cypermethrin to Daphnia magna HB

The acute toxic effect of the pesticide cypermethrin to Daphnia magna HB was examined. D. magna HB was exposed to cypermethrin at concentrations of 0, 1, 3, 5, 7, and 9 mg/L for 24 In. Data showed that the 24 h-LC50 of cypermthrin on D. magna HB was 4.81 mg/L. In contrast, the 24 h-LC50 of K2Cr2O7 (the national standard toxicant) to Daphnia magna was 0.38 mg/L in the current study. Results indicated that the Daphnia magna was very sensitive to pesticides. In addition, the effects of the culture condition(such as hardness, temperature and DO etc.) on Daphnia magna HB was also studied.

P(HB-co-HV)/PVPh的相容性与聚集态结构

采用差热扫描分析、红外光谱、固体核磁、小角Ｘ光散射等方法研究了聚（β－羟基丁酸酯－ｃｏ－β－羟基戊酸酯（Ｐ（ＨＢ－ｃｏ－ＨＶ））／聚（对－羟基苯乙烯）（简称ＰＶＰｈ）共混物的相容性和形态．结果表明两组分间形成较强的分子间氢键，形成完全相容的共混体系．固体核磁结果表明Ｐ（ＨＢ－ｃｏ－ＨＶ）／ＰＶＰｈ（５０／５０）在３．４ｎｍ尺寸上是完全均相的．小角Ｘ光散射结果表明，在等温结晶的共混物中无定形的ＰＶＰｈ分子分散在Ｐ（ＨＢ－ｃｏ－ＨＶ）片晶之间与非晶的Ｐ（ＨＢ－ｃｏ－ＨＶ）分子形成非晶区，从而使非晶区加宽，长周