Potentiation of ethanol narcosis by dopamine- and l-DOPA-based isoquinolines.

The isoquinolines, salsolinol and 3-carboxysalsolinol, prolong ethanol-induced narcosis in mice. Pretreatment with carbidopa increases the effect of 3-carboxysalsolinol but not of salsolinol. These results suggest that ethanol sleeping-time potentiation by l-LOPA may involve a partial conversion to the isoquinoline in vivo. A central depressant action of salsolinol or the 3-carboxy analogue is suggested.     

Displacement activity of some natural cularine alkaloids at striatal3H-SCH 23 390 and3H-raclopride binding sites

Five natural cularines isolated from the aerial parts ofSarcocapnos crassifolia (Fumariaceae) and a cularioid isolated from the bark ofGuatteria ouregou (Annonaceae) were tested for their ability to displace³H-SCH 23 390 and³H-raclopride from their striatal binding sites. Celtisine, breoganine and cularidine were able to inhibit the binding at D-1 and D-2 dopaminergic sites at nanomolar concentrations. Other alkaloids were active at micromolar concentrations. These data suggest that the presence of an oxepine system in the isoquinoline skeleton could lead to compounds which would be very active and possibly selective at dopaminergic receptor sites.     

PAP/REG3A favors perineural invasion in pancreatic adenocarcinoma and serves as a prognostic marker

Pancreatic ductal adenocarcinoma (PDA) is a fatal and insidious malignant disease for which clinicians’ tools are restricted by the current limits in knowledge of how tumor and stromal cells act during the disease. Among PDA hallmarks, neural remodeling (NR) and perineural invasion (PNI) drastically influence quality of life and patient survival. Indeed, NR and PNI are associated with neuropathic pain and metastasis, respectively, both of which impact clinicians’ decisions and therapeutic options. The aim of this study was to determine the impact and clinical relevance of the peritumoral microenvironment, through pancreatitis-associated protein (PAP/REG3A) expression, on PNI in pancreatic cancer. First, we demonstrated that, in PDA, PAP/REG3A is produced by inflamed acinar cells from the peritumoral microenvironment and then enhances the migratory and invasive abilities of cancer cells. More specifically, using perineural ex vivo assays we revealed that PAP/REG3A favors PNI through activation of the JAK/STAT signaling pathway in cancer cells. Finally, we analyzed the level of PAP/REG3A in blood from healthy donors or patients with PDA from three independent cohorts. Patients with high levels of PAP/REG3A had overall shorter survival as well as poor surgical outcomes with reduced disease-free survival. Our study provides a rationale for using the PAP/REG3A level as a biomarker to improve pancreatic cancer prognosis. It also suggests that therapeutic targeting of PAP/REG3A activity in PDA could limit tumor cell aggressiveness and PNI.     

Comparison of soluble antigens of 2 cultured clones, of different age, from the same strain of a flagellate parasite: Trichomonas vaginalis Donné, 1837]

Antigenic analysis released indications that there seemed to be a qualitative difference between two clones (A2, A3) as well as between a young clone A2 and an old one (the latter having been in culture for 12 months) both of them originating from the same initial clone. Such differences are reduced to quantitative level by the results of cross absorptions. Antigenic variations mentioned by the previous authors are to be questioned.     

Hormonal control of mammalian oocyte meiosis at diplotene stage

Mammalian oocytes grow and undergo meiosis within ovarian follicles. Fully grown oocytes are arrested at the first meiotic prophase by a mural granulosa origin “arrester” until a surge of luteinizing hormone (LH) from the pituitary at the mid-cycle stimulates the immature oocyte to resume meiosis. Recent evidence indicates that natriuretic peptide precursor type C (NPPC) produced by mural granulosa cells stimulates the generation of cyclic guanosine 3′,5′-monophosphate (cGMP) by cumulus cell natriuretic peptide receptor 2 (NPR2), which diffuses into oocyte via gap junctions and inhibits oocyte phosphodiesterase 3A (PDE3A) activity and cyclic adenosine 3′,5′-monophosphate (cAMP) hydrolysis and maintains meiotic arrest with a high intraoocyte cAMP level. This cAMP is generated through the activity of the Gs G-protein by the G-protein-coupled receptor, GPR3 and GPR12, and adenylyl cyclases (ADCY) endogenous to the oocyte. Further studies suggest that endocrine hormones, such as follicle-stimulating hormone (FSH), LH, 17β-estradiol (E2) and oocyte-derived paracrine factors (ODPFs), participate in oocyte meiosis possibly by the regulation of NPPC and/or NPR2. A detailed investigation of NPPC and NPR2 expression in follicle cells will elucidate the precise molecular mechanisms of gonadotropins, and control the arrest as well as resumption of meiosis.     

Mechanism of inhibition of IgE-dependent histamine release from rat mast cells by xestobergsterol A from the Okinawan marine spongeXestospongia bergquistia

Histamine release from rat peritoneal mast cells induced by anti-IgE was essentially complete within 4–5 min. Xestobergsterol A and B, which are constituents of the Okinawan marine spongeXestospongia bergquistia Fromont, dose-dependently inhibited anti-IgE-induced histamine release from rat mast cells. The IC₅₀ values of xestobergsterol A and B for histamine release in mast cells activated by anti-IgE were 0.07 and 0.11 M, respectively. Anti-IgE stimulated PI-PLC activity in a mast cell membrane preparation. Xestobergsterol A dose-dependently inhibited the generation of IP3 and membrane-bound PI-PLC activity. Moreover, xestobergsterol A inhibited Ca²⁺-mobilization from intracellular Ca²⁺-stores as well as histamine release in mast cells activated by anti-IgE. On the other hand, xestobergsterol B did not inhibit the membrane-bound and cytosolic PI-PLC activity, IP3 generation or the initial rise in [Ca²⁺]_i in mast cells activated by anti-IgE. These results suggest that the mechanism of inhibition by xestobergsterol A of the initial rise in [Ca²⁺]_i, of the generation of IP3, and of histamine release induced by anti-IgE, was through the inhibition of PI-PLC activity.     

Catalase in sulfide- and methane-dependent macrofauna from petroleum seeps

Vesicomyid and lucinid clams and tubeworms from Gulf of Mexico petroleum seeps, all of which bear symbiotic sulfide-oxidizing bacteria, have much lower catalase activities than shallow-water species lacking symbionts. A petroleum seep mussel bearing methane-oxidizing bacteria is unusual in having catalase activities as high as shallow-water bivalves. Unlike sulfide-dependent meiofauna from shallow-water marine sands, catalase from all petroleum seep species was inhibited by 3-amino-1,2,4-triazole.Acknowledgments. We thank S. McDonald and the crew of R/V Gyre for assistance in animal collection. This research was funded by NSF grant OCE-8219792 to EP and NSF grant OCE-83-01538 and funds from the Offshore Operators Committee to J. Brooks. We appreciate this support.     

Model systems demonstrating the volatile mutagenicity and carcinogenicity of sodium nitrite in rats

Summary Volatile mutagens derived from sodium nitrite buffered at various pH values or in the presence of human feces were detected using AmesSalmonella tester strain TA 1535 on petrie plates inverted over samples. Volatile mutagenicity increased as the pH decreased and was primarily a function of the nitrous acid produced from sodium nitrite and hydrogen ions. Sodium nitrite administered intracecally to 3 Wistar rats through surgically implanted cannula caused tumors (fibrosarcoma: 1/3 and squamous cell, 2/3). The possible role of nitrite-derived mutagens in GI cancer is discussed.The authors are grateful to Dr A. Carl MacDonald of the Dept. of Surgery, Dalhousie University for his advice and encouragement in this project.This work was supported by the National Cancer Institute of Canada.     

基于语义约束与Graph Cuts的稠密三维场景重建

本文提出一种新颖、有效的稠密三维场景重建算法.在城市建筑场景的重建中,为了快速恢复稠密、准确的深度信息,本文算法首先在视图中对建筑区域进行了语义分割以降低非重建区域(如天空、地面等)的干扰,在提高整体重建速度的同时也增强了采用平面模型对其进行重建的可靠性;然后,在通过基于DAISY特征的空间点扩散方法获取的初始深度图的基础上,针对传统算法难以重建的弱纹理、倾斜表面等区域,本文算法依据场景分段平滑的假设,在超像素级MRF能量优化框架中对其相应的空间平面进行了推断.由于能量函数融合了初始深度图的约束、空间平面先验及空间平面间的几何关系等信息,而且候选平面集通过平面拟合和已知平面约束下的多方向平面扫描两种方法构造,使得相应的两阶段迭代Graph Cuts对能量函数的求解更快速和精确.在标准数据集和真实数据上的实验表明,本文算法能有效克服光照变化、透视畸变、弱纹理区域等因素的影响,快速恢复建筑区域完整的深度图.     

Synthesis of juvenile hormones in vitro by the corpora allata of 5th stage larva of Locusta migratoria migratorioides (R and F) (Insecta, Orthopteroida)]

Corpora allata of Locusta migratoria 5th stage larvae synthesize J.H.1, J.H.2 and J.H.3 in vitro. The C.A. of insects of different ages exbit different rates of J.H. synthesis. J.H.1 and J.H.2 synthesis is less than 1 ng/48 h/gland. During the same time the J.H.3 production may be as much as 25.6 ng/gland. J.H. synthetic activity is the same between right and left C.A. The release of J.H. from the C.A. occurs immediately following synthesis. These results are compared with in vivo haemolymphatic J.H. levels.     

Release of platelet activating factor (P.A.F.-acether) by isolated perfused rat kidney

Platelet-activating factor (a 1-0-alkyl-2-acetyl glyceryl-3-phosphorylcholine, P.A.F.-acether) causes the aggregation of platelets from various Mammalian species and the release of their granule content. P.A.F.-acether activity has been recovered in vitro from perfused isolated Rat kidneys, stimulated by the ionophore A 23187. The maximum release was reached 10 min. after addition of the ionophore. P.A.F.-acether from kidney exhibited the same physico-chemical and biological characteristics as P.A.F.-acether from leucocytes. These data demonstrate that the kidney secretes a mediator of immediate hypersensitivity (P.A.F.-acether) in the veinous vasculature. Therefore the kidney itself has the ability of inducing intravascular platelet aggregation with subsequent local increase in vasopermeability.     

Profiling of the secreted proteins during 3T3-L1 adipocyte differentiation leads to the identification of novel adipokines

Adipose tissue is an endocrine organ capable of secreting a number of adipokines with a role in the regulation of adipose tissue and whole-body metabolism. We used two-dimensional gel electrophoresis combined with mass spectrometry to profile the secreted proteins from (pre)adipocytes. The culture medium of 3T3-L1 cells during adipocyte differentiation was screened, and 41 proteins that responded to blocking of secretion by 20°C treatment and/or brefeldin A treatment were identified. Prohibitin, stress-70 protein, and adhesion-regulating molecule 1 are reported for the first time as secreted proteins. In addition, procollagen C-proteinase enhancer protein, galectin-1, cyclophilin A and C, and SF20/IL-25 are newly identified as adipocyte secreted factors. Secretion profiles indicated a dynamic environment including an actively remodeling extracellular matrix and several factors involved in growth regulation.Received 15 June 2004; received after revision 26 July 2004; accepted 2 August 2004     

Experimental studies on the symmetry reaction of axolotl oocytes and eggs: factors affecting the early appearance of the grey crescent following heat shock]

A heat-shock (36.8 degrees C for 10 min.) can induce the immediate appearance of the grey crescent in a high proportion of freshly laid fertilised or artificially activated Axolotl eggs, but only if that shock occurs within 1 h 30 min. following deposit of eggs (at 18 degrees C) and if eggs are not dejellied. On non-activated virgin eggs, the heat-shock is efficient during at least 3 hrs. This symmetry reaction can be induced on in vitro artificially matured oocytes, still protected by follicular cells. It is uncommon in oocytes taken from coelomic cavity or from the anterior part of the oviduct, but occurs with a high frequency as soon as the occytes are coated with the innermost and medium jelly layers.     

Chromosomal and morphological diversity in 2 populations of Asian mountain vole, Alticola lemminus Miller (Rodentia, Cricetidae).

Voles from Yakutia and Chukotka were found to differ in the morphology of 3 pairs of autosomes and sex chromosomes, as well as in M3-structure and skull dimensions. This makes their conspecificity doubtful. A variation in short arm lengths of the X- and Y-chromosomes has been discovered.     

Antimutagenic unusual amino acids from plants

Five unusual amino acids were identified as antimutagens against spontaneous mutation of Salmonella typhimurium TA100: L-azetidine-2-carboxylic acid (1) from Liliaceae plants, alpha-(methylenecyclopropyl)glycine (2) from Litchi chinensis seeds, and 2-amino-4-methylhex-5-ynoic acid (3), hypoglycin A (4), and (2S,4R)-2-amino-4-hydroxyhept-6-ynoic acid (5) from Euphoria longana seeds. The absolute stereochemistry of 5 was determined by its chiral synthesis from L-allylglycine, proving that 5 is the C-4 epimer of the amino acid previously isolated from dried longan seeds.     

Synphilin-1 isoforms in Parkinson’s disease: regulation by phosphorylation and ubiquitylation

Parkinson’s disease (PD) is characterized by the death of dopaminergic neurons and the presence of Lewy bodies in the substantia nigra pars compacta. The mechanisms involved in the death of neurons as well as the role of Lewy bodies in the pathogenesis of the disease are still unclear. Lewy bodies are made of aggregated proteins, in which α-synuclein represents their major component. α-Synuclein interacts with synphilin-1, a protein that is also present in Lewy bodies. When expressed in cells, synphilin-1 forms inclusions together with α-synuclein that resemble Lewy bodies. Synphilin-1 is ubiquitylated by various E3 ubiquitin-ligases, such as SIAH, parkin and dorfin. Ubiquitylation of synphilin-1 by SIAH is essential for its aggregation into inclusions. We recently identified a new synphilin-1 isoform, synphilin-1A, that is toxic to neurons, aggregation-prone and accumulates in detergent-insoluble fractions of brains from α-synucleinopathy patients. Synphilin-1A inclusions recruit both α-synuclein and synphilin-1. Aggregation of synphilin-1 and synphilin-1A seems to be protective to cells. We now discuss several aspects of the neurobiology and pathology of synphilin-1 isoforms, focusing on possible implications for PD. Received 26 July 2007; received after revision 19 September 2007; accepted 15 October 2007