Presynaptic α2 Adrenoceptors Inhibit Glutamate Release from Rat Spinal Cord Synaptosomes

Abstract: The presynaptic regulation of amino acid release from nerve terminals was investigated using synaptosomes prepared from the rat spinal cord. The basal releases of endogenous glutamate (Glu), aspartate (Asp), and γ-amino-butyric acid (GABA) were 34.6, 21.5, and 10.0 pmol/min/mg of protein, respectively. Exposure to a depolarizing concentration of KCl (30 m M ) evoked 2.7-, 1.5-, and 2.9-fold increases in Glu, Asp, and GABA release, respectively. Clonidine reduced the K⁺-evoked overflow of Glu to 56% of the control overflow with a potency (IC₅₀) of 17 n M , but it did not affect K⁺-evoked overflow of Asp, GABA, and their basal releases. Similarly, noradrenaline inhibited the K⁺-evoked overflow of Glu, although phenylephrine and isoproterenol showed no effect. The inhibitory effect of clonidine was counteracted by α₂-adrenoceptor antagonists, rauwolscine, yohimbine, and idazoxan, regardless of the imidazoline structures. Because Glu is considered a neurotransmitter of primary afferents that transmit both nociceptive and nonnociceptive stimuli in the spinal cord, these data suggest that part of Glu release may be regulated by the noradrenergic system through α₂ adrenoceptors localized on the primary afferent terminals.     

Quantitative Detection of 15 Serum Bile Acid Metabolic Products by LC/MS/MS in the Diagnosis of Primary Biliary Cholangitis

To determine 15 bile acid metabolic products in human serum by liquid chromatography-tandem mass spectrometry (LC/MS/MS) and value their diagnostic outcome in primary biliary cholangitis (PBC). Serum from 20 healthy controls and 26 patients with PBC were collected and went LC/MS/MS analysis of 15 bile acid metabolic products. The test results were analyzed by bile acid metabolomics, and the potential biomarkers were screened and their diagnostic performance was judged by statistical methods such as principal component and partial least squares discriminant analysis and area under curve (AUC). 8 differential metabolites can be screened out: Deoxycholic acid (DCA), Glycine deoxycholic acid (GDCA), Lithocholic acid (LCA), Glycine ursodeoxycholic acid (GUDCA), Taurolithocholic acid (TLCA), Tauroursodeoxycholic acid (TUDCA), Taurodeoxycholic acid (TDCA), Glycine chenodeoxycholic acid (GCDCA). The performance of the biomarkers was evaluated by the AUC, specificity and sensitivity. In conclusion, DCA, GDCA, LCA, GUDCA, TLCA, TUDCA, TDCA and GCDCA were identified as eight potential biomarkers to distinguish between healthy people and PBC patients by multivariate statistical analysis, which provided reliable experimental basis for clinical practice.     

肝硬化原发性肝癌直径<1 cm超声造影表现及其与血清AFU、AFP-L3、GPC3、TSGF、GP73水平相关性研究

摘要 目的：探讨肝硬化原发性肝癌（PHC）直径<1cm超声造影（CEUS）表现及其与血清α-L-岩藻糖苷酶（AFU）、甲胎蛋白异质体-L3（AFP-L3）、磷脂酰肌醇蛋白聚糖-3（GPC3）、肿瘤特异生长因子（TSGF）、高尔基体糖蛋白（GP73）水平相关性。方法：选取2018年1月-2022年8月于湖北省襄阳市中医院收治的肝硬化PHC直径<1 cm患者44例,根据术后病理结果分为高分化组、中分化组和低分化组。所有患者术前均完善CEUS和血清AFU、AFP-L3、GPC3、TSGF、GP73水平检查。比较三组CEUS表现、定量时间-强度曲线（TIC）分析、血清AFU、AFP-L3、GPC3、TSGF、GP73水平。采用Spearman相关性分析肝硬化PHC直径<1 cm患者的CEUS表现与血清AFU、AFP-L3、GPC3、TSGF、GP73水平的相关性。结果：44例肝硬化PHC直径<1 cm患者的CEUS表现均为肝内单发病灶,呈圆形或类圆形,病灶边界清晰,周围可见声晕。不同分化程度肝硬化PHC直径<1 cm患者在动脉期、门脉期和延迟期的CEUS表现上差异均无统计学意义（P＞0.05）。高分化组、中分化组和低分化组的达峰时间、廓清时间和峰值加速时间逐渐减少,差异有统计学意义（P＜0.05）。而高分化组、中分化组和低分化组的峰值强度增加率逐渐增加,差异有统计学意义（P＜0.05）。高分化组、中分化组和低分化组的增强时间对比差异无统计学意义（P＞0.05）。高分化组、中分化组和低分化组血清AFU、AFP-L3、GPC3、TSGF、GP73水平逐渐升高,差异有统计学意义（P＜0.05）。Spearman相关性分析显示,达峰时间、廓清时间和峰值加速时间与血清AFU、AFP-L3、GPC3、TSGF、GP73水平呈负相关（P＜0.05）;峰值强度增加率与血清AFU、AFP-L3、GPC3、TSGF、GP73水平呈正相关（P＜0.05）。结论：肝硬化PHC直径<1 cm患者的CEUS表现均为肝内单发病灶,呈圆形或类圆形,病灶边界清晰,周围可见声晕。CEUS表现和血清AFU、AFP-L3、GPC3、TSGF、GP73水平具有相关性,两者可辅助鉴别肝硬化PHC直径<1 cm的不同分化程度。     

Coding of odor intensity in a steady-state deterministic model of an olfactory receptor neuron

The coding of odor intensity by an olfactory receptor neuron model was studied under steady-state stimulation. Our model neuron is an elongated cylinder consisting of the following three components: a sensory dendritic region bearing odorant receptors, a passive region consisting of proximal dendrite and cell body, and an axon. First, analytical solutions are given for the three main physiological responses: (1) odorant-dependent conductance change at the sensory dendrite based on the Michaelis-Menten model, (2) generation and spreading of the receptor potential based on a new solution of the cable equation, and (3) firing frequency based on a Lapicque model. Second, the magnitudes of these responses are analyzed as a function of odorant concentration. Their dependence on chemical, electrical, and geometrical parameters is examined. The only evident gain in magnitude results from the activation-to-conductance conversion. An optimal encoder neuron is presented that suggests that increasing the length of the sensory dendrite beyond about 0.3 space constant does not increase the magnitude of the receptor potential. Third, the sensivities of the responses are examined as functions of (1) the concentration at half-maximum response, (2) the lower and upper concentrations actually discriminated, and (3) the width of the dynamic range. The overall gain in sensitivity results entirely from the conductance-to-voltage conversion. The maximum conductance at the sensory dendrite appears to be the main tuning constant of the neuron because it determines the shift toward low concentrations and the increase in dynamic range. The dynamic range of the model cannot exceed 5.7 log units, for a sensitivity increase at low odor concentration is compensated by a sensitivity decrease at high odor concentration.     

Investigating hypothetical products from noncoding frames (HyPNoFs)

Hypothetical Products from Noncoding Frames (i.e., HyPNoFs) are hypothetical, not-coded proteins, translated from alternate reading frames (i.e., coding+1 and coding+2) of cDNAs. HyPNoFs of CD4, PKC, oncostatin, bcl-2 proto-oncogene, tumor suppressor p53, cystic fibrosis transmembrane regulator (CFTR), and tumor necrosis factors a and were searched as query sequences vs the SWISS-PROT data bank. Homology searches carried out revealed that hypothetical products (i.e., HyPNoFs) may share high similarity with real protein products actually coded. Sequence similarity of hypothetical products to real proteins is sometimes very high, suggesting common conformational features, according to the Sander and Schneider cutoff value. This finding supports the hypothesis that eukaryotic DNA, currently considered to be monocistronic, might occasionally have polycistronic regions, carrying different protein messages on overlapping frames. As yet, polycistronic genes have been observed in viral genomes only. The presence of polycistronic regions in eukaryotic genes is likely reminiscent of an ancient strategy, rather than a present feature of the genome in eukaryotes.These data suggest that thorough investigation of HyPNoFs is likely to improve our ability to trace genes' evolution and to investigate structure-function relationships of protein and DNA sequences.     

Ultrastructure of sensory receptors on the labium of the cassava mealybug,Phenacoccus manihoti Matile Ferrero

The ultrastructure of the sensory receptors located on the labium of the cassava mealybugPhenacoccus manihoti Matile-Ferrero (Homoptera, Pseudococcidae) was studied with scanning and transmission electron microscopes. Trichoid hairs of probable mechanoreceptive function are distributed over the labium. Uniporous chemosensilla which possess a mechanoreceptive dendrite, multiporous chemosensilla and mechanoreceptive pegs are present on the tip of the labium. The presence of contact and olfactory chemoreceptors on the labial tip ofP. manihoti suggests that tapping it on the cassava leaf provides the pest with information about the chemical nature of the leaf surface. ORSTOM     

Stereospecific assignment of the NH2 resonances from the primary amides of asparagine and glutamine side chains in isotopically labeled proteins

An HMQC-based pulse scheme is presented for the stereospecific assignment of asparagineand glutamine side-chain amide protons. The approach makes use of the recently developedquantitative-J correlation spectroscopy [Bax, A. et al. (1994) Methods Enzymol., 239,79–105] to distinguish the E and Z primary amide protons and, as such, eliminates theneed for assignments derived from more time-consuming and potentially ambiguous NOEmethods. An application of this method to a uniformly 15N,13C-labeled cellulose-bindingdomain is presented. When used in combination with a NOESY-HSQC experiment, thepredominant 2 dihedral angles of two asparagine side chains in this protein can also bedefined.     

兔感觉神经特异蛋白的纯化及稳定性观察

以兔脊神经节及背根纤维为材料,通过制备匀浆,DEAE-Sephacel阴离子交换层析,高压液相凝胶过滤层析分离纯化了感觉神经特异蛋白29 ku,并进行了该蛋白的稳定性观察.     

Resolution of sensory and mucoid glycoconjugates with terminal α-galactose residues in the mucomicrovillar complex of the vomeronasal sensory epithelium by dual confocal laser scanning microscopy

The organization of the mucomicrovillar complex of the vomeronasal sensory epithelium of adult rats was examined using confocal laser scanning microscopy. In specimens labeled with the FITC-conjugated isolectin B₄ of Bandeiraea simplicifolia, which recognizes terminal -galactose sugar residues of glycoconjugates, we demonstrated that the mucomicrovillar complex was composed of islet-like structures with a high-density -galactose core. The mucomicrovillar complex was further resolved into sensory and mucoid components in double-labeling and dual scanning experiments. The sensory component, which consists of the dendritic terminals of olfactory marker protein-immunoreactive vomeronasal receptor neurons, contained cytosolic glycoconjugates with terminal -galactose sugar residues. The extracellular mucoid component consisted of glycoconjugates containing terminal -galactose derived from the glands associated with the vomeronasal organ. These results demonstrated the complex microchemical organization of the sensory and mucoid components of the mucomicrovillar complex.     

Functional organization of the macroglomerular complex related to behaviourally expressed olfactory redundancy in male cabbage looper moths

Abstract. The neurophysiological bases for behaviourally expressed olfactory redundancy in the sex pheromone communication system of the cabbage looper moth, Trichoplusia ni (Hübner) (Lepidoptera: Noctuidae), were examined by coupling the cut-sensillum extracellular recording technique with a highly specific neuronal marking method for moth peripheral receptors. In seventy-two antennal sensilla, axonal pathways of cobalt-stained neurones could be traced into the male-specific macroglomerular complex in the antennal lobe. In T. ni males this comprises five glomeruli, two of which are subdivided into morphologically, and in some instances functionally identifiable, regions. Axonal arborizations of forty-eight neurones (single stainings) showed high fidelity (98%) for containment within a specific glomerulus or glomerular subdivision, and the neuropil targeted seemed to be related to the specificity of a neurone to a particular female-emitted sex pheromone component (27-12:Ac, Z7-14:Ac, Z9-14:Ac, 12:Ac, 11–12:Ac, Z5-12:Ac), or to a behavioural antagonist (Z7-12:OH). Double (twenty-one) and multiple stainings (three) showed axons projecting into two or more glomeruli, respectively, with 100% fidelity for the component-specific glomerulus or glomerular subdivision to be targeted. We suggest that the potential for a single minor component to cross-stimulate two or more neurones within a sensillum may enable partial blends to continue to provide sensory input into all of the pheromone-processing glomeruli of the complex. Our interpretation is that redundancy occurs at the receptor level on neighbouring dendrites, and thus allows various four-component partial blends to evoke full pheromone-mediated behaviour.