Activation of macrophage adenylate cyclase by stimulants of the oxidative burst and by arachidonic acid--two distinct mechanisms

The effect of agents stimulating the oxidative burst (OB) in oil-elicited guinea pig peritoneal macrophages (MPs) on cyclic adenosine 3′,5′-monophosphate (cAMP) levels was examined. We found that: (i) Phorbol myristate acetate (PMA), the Ca²⁺ ionophore A23187, concanavalin A (Con A), wheat germ agglutinin (WGA), N-formyl-l-methionyl-l-leucyl-l-phenylalanine (FMLP) and opsonized zymosan, elevated cAMP levels two- to fivefold; (ii) the biologically inactive PMA analog, 4-O-methyl-PMA, was proportionally less effective than PMA in stimulating cAMP accumulation; (iii) increased levels of cAMP were evident after 10 min of incubation with the stimulants, in the presence of the phosphodiesterase inhibitor 3-isobutyl methylxanthine (IBX); (iv) basal cAMP levels in MPs increased proportionally with the extracellular Ca²⁺ concentration; (v) the cAMP-elevating effect of all stimulants (with the exception of A23187) was more pronounced in low Ca²⁺ media, associated with lower basal cAMP levels. A23187 did not elevate cAMP levels in the absence of extracellular Ca²⁺; (vi) short-term incubation of MPs with arachidonic acid and with the arachidonic acid precursor, linoleic acid, induced an increase in the level of cAMP; (vii) the elevations in cAMP levels induced by OB stimulants were enhanced, not blocked, by mepacrine, 5,8,11,14-eicosatetraynoic acid (ETYA), indomethacin or aspirin, demonstrating that prostaglandin (PG) synthesis was not involved; (viii) the cAMP-elevating effect of arachidonic and linoleic acids was blocked by ETYA and indomethacin, indicating that it was mediated by PGs. The mechanism by which OB stimulants elevate cAMP levels could not be determined but changes in the cellular level of Ca²⁺ seem to play a pivotal role.     

The schulterkofel section in the Carnic Alps,Austria: Implications for the carboniferous-permian boundary

Summary The upper part of the LowerPseudoschwagerina Limestone (Rattendorf Group), outcropping on the northwestern flank of Schulterkofel Mountain, Carnic Alps (Austria) is described with special emphasis on fusulinid microfossils and facies. This fusulinid-rich section offers an ideal opportunity for biostratigraphy in defining the Permo-Carboniferous boundary in this region. The LowerPseudoschwagerina Limestone is composed of shallow-marine limestones with intercalated thin siltstone and sandstone beds. Fusulinid limestones are represented by two types of wackestones, both containing large quantities of smaller foraminifers. Fusulinid grainstones are rare. Limestones rich in fusulinids were found only within the bedded limestone facies in beds both below and especially above siliciclastic intercalations. This may indicate that the best living conditions for fusulinids existed immediately before and especially after the climax of a regressive phase (sea-level lowstand). The fusulinid limestones were deposited within a protected, shallow-marine shelf environment with normal salinity. Pseudoschwagerinid fusulinids appear in the upper part of the LowerPseudoschwagerina Limestone, in samples SK 107d (undeterminable species) and SK 108, i.e. between 92 m and 93 m above the base of the section within a bedded limestone immediately above the uppermost clastic intercalation. The fusulinid fauna is represented by about 30 species belonging to only a few genera. Species ofTriticites andRugosofusulina dominate, whereas those ofDaixina, Rugosochusenella andPseudofusulina are rare. A characteristic feature of the fauna is the strong similarity with fusulinid faunas described from Russia as well as from Middle and East Asia. Some of the described fusulinids are new for the Carnic Alps. The first appearance ofPseudoschwagerina andOccidentoschwagerina (Occidentoschwagerina alpina Zone) in the upper part of the LowerPseudoschwagerina Limestone in the Schulterkofel section defines the position of the Carboniferous-Permian boundary.     

Reduced biliverdin reductase-A levels are associated with early alterations of insulin signaling in obesity

Biliverdin reductase-A (BVR-A) is a serine/threonine/tyrosine kinase involved in the regulation of insulin signaling. In vitro studies have demonstrated that BVR-A is a substrate of the insulin receptor and regulates IRS1 by avoiding its aberrant activation, and in animal model of obesity the loss of hepatic BVR-A has been associated with glucose/insulin alterations and fatty liver disease. However, no studies exist in humans. Here, we evaluated BVR-A expression levels and activation in peripheral blood mononuclear cells (PBMC) from obese subjects and matched lean controls and we investigated the related molecular alterations of the insulin along with clinical correlates. We showed that BVR-A levels are significantly reduced in obese subjects and associated with a hyper-activation of the IR/IRS1/Akt/GSK-3β/AS160/GLUT4 pathway. Low BVR-A levels also associate with the presence of obesity, metabolic syndrome, NASH and visceral adipose tissue inflammation. These data suggest that the reduction of BVR-A may be responsible for early alterations of the insulin signaling pathway in obesity and in this context may represent a novel molecular target to be investigated for the comprehension of the process of insulin resistance development in obesity.     

中国葱属根茎组植物15种25居群的核型研究

采用常规压片法,对15种25居群葱属根茎组植物进行核型研究,首次报道荒漠韭Allium tekesicola、蓝花韭A.beesianum的染色体数目和核型,并增补了一些根茎组植物的细胞学资料。结果表明：供试类群为二倍体或四倍体,核型类型为1A、2A或2B;高山韭A.sikkimense壤塘居群和荒漠韭具短臂随体,宽苞韭A.platyspathum的和布克赛尔居群、奇台居群具居间随体;野黄韭A.rude雅江居群和荒漠韭中各存在1条B染色体。结合前人研究结果,我们讨论了中国根茎组植物的染色体基数、随体染色体的多型性、B染色体的进化意义和该组植物的进化方式,探讨了天蓝韭A.cyaneum、齿丝山韭A.nutans的地理分布成因,得到了如下推论：（1）中国根茎组植物的染色体基数x=8;（2）中国根茎组植物的核型进化趋势为：1A→2A→2B→2C;（3）中国根茎组植物的随体染色体具多型性;（4）多倍化和结构变异是中国根茎组植物进化的两种重要方式;（5）天蓝韭和齿丝山韭以多倍化和无性生殖来克服扩大新的生存空间遇到的困难。     

21株马特组镰刀菌遗传多样性的ISSR分析

为明确马特组镰刀菌种间和种内的遗传差异与亲缘关系,本文利用ISSR分子标记技术对21个马特组菌株进行了遗传多样性分析.结果表明:利用筛选出的15条引物对3种供试菌株进行扩增,共扩增出239条条带,其中多态性条带230条,多态性位点比例为96.2％,平均每条引物产生条带数为15.3条.21个菌株间的遗传相似系数范围为0.494～0.933,平均为0.640.在遗传相似系数为0.593时,供试的21株马特组镰刀菌可明显分成2个ISSR类群(IG),IG-Ⅰ包括1～17号菌株,为Fusarium solani和F solani var.coeruleum;IG-Ⅱ包括18 ～21号菌株,全部为F.ventricosum.在遗传相似系数为0.933时,供试的21个菌株可被全部区分开.供试的镰刀菌基因组在SSR区域具有丰富的多态性;ISSR类群划分与菌种分类之间存在一定相关性,但与菌株的地理来源没有相关性;而同一类群中,不同菌株之间的遗传相似性与菌株的地理来源存在一定的相关性.同一地区同种寄主的相同菌种,其菌株间也存在一定的遗传差异.     

Synthesis and biological evaluation of [18F]fluorovinpocetine,a potential PET radioligand for TSPO imaging

Despite of various PET radioligands targeting the translocator protein TSPO 18-KDa are used for the investigations of neuroinflammatory conditions associated with neurological disorders, development of new TSPO radiotracers is still an active area of the researches with a major focus on the ¹⁸F-labelled radiotracers. Here, we report the radiochemical synthesis of [¹⁸F]vinpocetine, fluorinated analogue of previously reported TSPO radioligand, [¹¹C]vinpocetine. Radiolabeling was achieved by [¹⁸F]fluoroethylation of apovincaminic acid with [¹⁸F]fluoroethyl bromide. [¹⁸F]vinpocetine was obtained in quantities >2.7 GBq in RCY of 13% (non–decay corrected), and molar activity >60 GBq/µmol within 95 min synthesis time. Preliminary PET studies in a cynomolgus monkey and metabolite studies by HPLC demonstrated similar results by [¹⁸F]vinpocetine as for [¹¹C]vinpocetine, including high blood-brain barrier permeability, regional uptake pattern and fast washout from the NHP brain. These results demonstrate that [¹⁸F]fluorovinpocetine warrants further evaluation as an easier accessible alternative to [¹¹C]vinpocetine.