Neural modeling with dynamically adjustable threshold and refractory period.

A variant of the FitzHugh-Nagumo model is proposed in order to fully make use of the computational properties of intraneuronal dynamics. The mechanisms of threshold and refractory periods resulting from the double dynamical processes are qualitatively studied through computer simulation. The results show that the variant neuron model has the property that its threshold, refractory period and response amplitude are dynamically adjustable. This paper has also discussed some problems relating to collective property, learning and implementation of the neural network based on the neuron model proposed. It is noted that the implicit way to describe threshold and refractory period is advantageous to adaptive learning in neural networks and that molecular electronics probably provides an effective approach to implementing the above neuron model.     

墨江蜈蚣与少棘蜈蚣的比较研究──Ⅱ．药效和毒理

本文比较了墨江蜈蚣与少棘蜈蚣的药效学和毒理学作用，实验包括抗惊厥试验、对致病性真菌和细菌体外生长的影响、急性毒性试验和染色体畸变实验等。结果两种蜈蚣的３％醋酸提取液对所试的真菌有抑制作用但无杀真菌作用，而对细菌无抑制作用。两种蜈蚣的毒性很低，在给小鼠５０ｇ／ｋｇ的剂量下都无法测出ＬＤ５０。在２０５ｍｇ／ｋｇ条件下的致突变率与未给药的突变率接近，表明两者都无遗传毒性。     

人睫状神经营养因子的原核表达,纯化及其生物效应

人睫状神经营养因子（ｈＣＮＴＦ）克隆入ｐＢＶ２２０中，在ＤＨ５α菌株中表达，重组蛋白以包含体的形式存在，表达量为菌体总蛋白的５０％左右。经比较发现用２ｍｏｌ／Ｌ脲洗涤包含体可溶解大量可溶性细菌蛋白，且包含体损失较小。在高浓度变性剂条件下进行ｓｅｐｈａｒｃｙｌＳ－２００凝胶过滤，解决了纯化中ｈＣＮＴＦ易聚合的问题，在低浓度变性剂条件下进行ＤＥＡＥ离子交换，有利于蛋白活性的保持。经两步纯化后得到均一性ｈＣＮＴＦ，纯度达９５％以上。在自然状态下使ｈＣＮＴＦ复性。纯化复性后的ｈＣＮＴＦ对无血清培养的鸡胚背根节神经元和脊髓腹角运动神经元有明显的维持存活和促进生长发育的生物效应。     

Depolarization and Activation of Dihydropyridine-Sensitive Ca2+ Channels Stimulate Inositol Phosphate Accumulation in Photoreceptor-Enriched Chick Retinal Cell Cultures

Abstract: Elevated concentrations of extracellular K⁺ increased inositol phosphate accumulation in primary cultures of chick retinal photoreceptors and multipolar neurons. K⁺-evoked stimulation of inositol phosphate accumulation was greater in photoreceptor-enriched cell cultures than in cultures where multipolar neurons were the predominant cell type. Destroying multipolar neurons, but not photoreceptors, with kainic acid and N -methyl- d -aspartate did not reduce the K⁺-evoked stimulation of inositol phosphate accumulation. Both of these observations indicate that the observed effects occur in photoreceptor cells. The K⁺-evoked stimulation of inositol phosphate accumulation was blocked by omitting Ca²⁺ from the incubation medium or by adding the dihydropyridine-sensitive Ca²⁺-channel antagonists, nitrendipine and nifedipine. Bay K 8644, a dihydropyridine agonist, stimulated inositol phosphate accumulation and enhanced the effect of K⁺. ω-Conotoxin GVIA, an inhibitor of N-type Ca²⁺ channels, had no significant effect on K⁺-stimulated inositol phosphate accumulation. Pretreatment with pertussis toxin neither blocked K⁺-evoked inositol phosphate accumulation nor altered the inhibitory effect of nifedipine. K⁺-evoked inositol phosphate accumulation appears to reflect activation of phosphatidylinositol-specific phospholipase C, as it is inhibited by U-73122. These results indicate that Ca²⁺ influx through voltage-gated, dihydropyridine-sensitive channels activates phospholipase C in photoreceptor inner segments and/or synaptic terminals.     

Soil management legacy alters weed-crop competition through biotic and abiotic pathways

Plant and Soil - Agricultural practices often have persistent effects on soil physicochemical properties and soil biota, which can feedback to influence plant performance. We investigated...     

Cardiomyocyte Antihypertrophic Effect of Adipose Tissue Conditioned Medium from Rats and Its Abrogation by Obesity is Mediated by the Leptin to Adiponectin Ratio

White adipocytes are known to function as endocrine organs by secreting a plethora of bioactive adipokines which can regulate cardiac function including the development of hypertrophy. We determined whether adipose tissue conditioned medium (ATCM) generated from the epididymal regions of normal rats can affect the hypertrophic response of cultured rat ventricular myocytes to endothelin-1 (ET-1) administration. Myocytes were treated with ET-1 (10 nM) for 24 hours in the absence or presence of increasing ATCM concentrations. ATCM supressed the hypertrophic response to ET-1 in a concentration-dependent manner, an effect enhanced by the leptin receptor antagonist and attenuated by an antibody against the adiponectin AdipoR1 receptor. Antihypertrophic effects were also observed with ATCM generated from perirenal-derived adipose tissue. However, this effect was absent in ATCM from adipose tissue harvested from corpulent JCR:LA-cp rats. Detailed analyses of adipokine content in ATCM from normal and corpulent rats revealed no differences in the majority of products assayed, although a significant increase in leptin concentrations concomitant with decreased adiponectin levels was observed, resulting in a 11 fold increase in the leptin to adiponectin ratio in ATCM from JCR:LA-cp. The antihypertrophic effect of ATCM was associated with increased phosphorylation of AMP-activated protein kinase (AMPK), an effect abrogated by the AdipoR1 antibody. Moreover, the antihypertrophic effect of ATCM was mimicked by an AMPK activator. There was no effect of ET-1 on mitogen-activated protein kinase (MAPK) activities 24 hour after its addition either in the presence or absence of ATCM. Our study suggests that adipose tissue from healthy subjects exerts antihypertrophic effects via an adiponectin–dependent pathway which is impaired in obesity, most likely due to adipocyte remodelling resulting in enhanced leptin and reduced adiponectin levels.     

Preparation of cross-linked carboxymethyl chitosan for repairing sciatic nerve injury in rats

A successful nerve regeneration process was achieved with nerve repair tubes made up of 1-ethyl-3(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) cross-linked carboxymethyl chitosan (CM-chitosan) with improved biodegradability. Chitosan has a very slow degradation rate, while the EDC cross-linked CM-chitosan tubes degraded to 30% of original weight during 8 weeks of incubation in lysozyme solution. In vitro cell culture indicated that the CM-chitosan films presented no cytotoxicity to Schwann cells. From in vivo studies using a 10 mm rat sciatic nerve defect model investigated by histomorphometry analysis, the average diameter of the fibers and the average thickness of myelin sheath in the CM-chitosan tubes were 3.7 ± 0.33 and 0.33 ± 0.04 μm, respectively, which demonstrated equivalence to nerve autografts (the current “gold” standard); furthermore, the average fiber density in the CM-chitosan tubes was 20.5 × 10³/mm², which was similar to that of autografts (21 × 10³/mm²) and significantly higher than that of common chitosan tubes (15.3 × 10³/mm²).     

Aurin tricarboxylic acid, the anti-AIDS compound, prevents the binding of interferon-alpha to its receptor

Binding of HIV to its receptor, the CD4 molecule of lymphocytes, can be prevented by chemical agents. These agents could be considered as potential anti-AIDS drugs. We have shown that aurin tricarboxylic acid (ATA, 3 microM) specifically blocks the binding of gp120, the HIV coat protein, to the CD4 molecule. We have also found that ATA prevents the binding of interferon-alpha to its receptor in a dose-dependent manner (12-50 microM range). Membrane potential shift, associated with binding of interferon-alpha to its receptor, was also blocked by ATA in a dose-dependent fashion. Our results indicate that potential anti-AIDS drugs should be screened for such undesired side effects.     

Isolation of polyhydroxyalkanoate-producing bacteria from an integrated-farming pond and palm-oil mill effluent ponds

Bacterial isolates from two environments, an integrated-farming pond in the university and palm-oil mill effluent (POME) ponds at a local palm-oil-processing factory, were screened for polyhydroxyalkanoates (PHAs). Initially Sudan Black B staining was performed to detect lipid cellular inclusions. Lipid-positive isolates were then grown in a nitrogen-limiting medium containing 2% (w/v) glucose to promote accumulation of PHA before the subsequent Nile Blue A staining. The PHA extracted from positive isolates was confirmed by nuclear magnetic resonance (NMR) spectroscopy. The proportion of PHA-positive bacterial isolates was higher in the POME ponds compared to the integrated-farming pond.     

DIA-Based Proteomics Identifies IDH2 as a Targetable Regulator of Acquired Drug Resistance in Chronic Myeloid Leukemia

Drug resistance is a critical obstacle to effective treatment in patients with chronic myeloid leukemia. To understand the underlying resistance mechanisms in response to imatinib mesylate (IMA) and adriamycin (ADR), the parental K562 cells were treated with low doses of IMA or ADR for 2 months to generate derivative cells with mild, intermediate, and severe resistance to the drugs as defined by their increasing resistance index. PulseDIA-based (DIA [data-independent acquisition]) quantitative proteomics was then employed to reveal the proteome changes in these resistant cells. In total, 7082 proteins from 98,232 peptides were identified and quantified from the dataset using four DIA software tools including OpenSWATH, Spectronaut, DIA-NN, and EncyclopeDIA. Sirtuin signaling pathway was found to be significantly enriched in both ADR-resistant and IMA-resistant K562 cells. In particular, isocitrate dehydrogenase (NADP(+)) 2 was identified as a potential drug target correlated with the drug resistance phenotype, and its inhibition by the antagonist AGI-6780 reversed the acquired resistance in K562 cells to either ADR or IMA. Together, our study has implicated isocitrate dehydrogenase (NADP(+)) 2 as a potential target that can be therapeutically leveraged to alleviate the drug resistance in K562 cells when treated with IMA and ADR.