降脂蛋白(a)研究

脂蛋白(a)[Lp(a)]是由载脂蛋白(a)(apo(a))与载脂蛋白B100(apoB100)通过共价键连接的脂蛋白。高血浆水平Lp(a)是心血管疾病的独立风险因子,Lp(a)的血浆水平主要受遗传因素调控,主要有LPA[lipoprotein,Lp(a)]基因的三环结构域kringle IV/2拷贝数和单核苷酸多态性(SNP)。欧洲动脉粥样硬化协会(EAS)和美国心脏病协会(AHA)建议对于高Lp(a)的人群应当考虑降高Lp(a)的治疗。目前已有多种降高Lp(a)的药物和方法,如血浆分离置换法、雌激素治疗、反义核苷酸治疗、类法尼醇X核内受体(farnesoid X receptor,FXR)激动治疗等,但应用于临床的降高Lp(a)的药物和方法依然缺乏。本文拟就降Lp(a)的药物和方法进展情况进行综述。     

脂蛋白(a)合成的调节

脂蛋白(a) ［ LP(a)］是一种与低密度脂蛋白(LDL)结构极其相似的脂蛋白,它由LDL脂质核心、载脂蛋白B100(apoB100)及特异性的成分载脂蛋白(a)［ apo(a)］组成. 大量的研究表明,高LP(a)是动脉粥样硬化独立的危险因素.而LP(a)在血浆中的水平及致病能力取决于其合成的速率及其颗粒的大小. 因此, 如何抑制LP(a)合成,进而从源头减少LP(a) 的血浆水平,对动脉粥样硬化的防治具有重要的意义.本文就当前关于影响LP(a)合成的环节及相关机制进行综述, 从而为降LP(a)药物的研究提供新的视角.     

What Is (Not) a Baboon?

The term “baboon” is the common name used for a subset of terrestrial Cercopithecines with large bodies and protruding snouts. Although the application of the term has changed considerably over the years, we argue that common names, such as “baboon,” should reflect the current state of phylogenetic knowledge. This practice promotes a broader understanding of taxonomic diversity that can impact decisions related to ecotourism, wildlife management, and conservation. Thus, we argue that “baboon” should be used only for members of the genus Papio.     

Molecular Dynamics Simulations of Adrenocorticotropin (1–24) Peptide in a Solvated Dodecylphosphocholine (DPC) Micelle and in a Dimyistoylphosphatidylcholine (DMPC) Bilayer

Abstract

The structure and interactions of the 1–24 fragment of the adrenocorticotropin hormone, ACTH (1–24), with membrane have been studied by molecular dynamics (MD) simulation in an NPT ensembles in two explicit membrane mimics, a dodecylphosphocholine (DPC) micelle and a dimyristoylphosphatidylcholine (DMPC) bilayer. The starting configuration of the peptide/lipid systems had the 1–10 segment of the peptide lying on the surface of the model membrane, the same as the equilibrated structure (by MD) of ACTH (1–10) in a DPC micelle. The simulations showed that the peptide adopts the surface-binding mode and essentially the same structure in both systems. Thus the results of this work lend support to the assumption that micelles are reasonable mimics for biological membranes for the study of peptide binding. The 1–10 segment is slightly tilted from the parallel orientation to the interface and interacts strongly with the membrane surface while the more polar 11–24 segment shows little tendency to interact with the membrane surface, preferring to reside primarily in the aqueous phase. Furthermore, the 1–10 segment of the peptide binds to the DPC micelle in essentially the same way as ACTH (1–10). Thus the MD results are in excellent agreement with the model of interaction of ACTH (1–24) with membrane derived from NMR experiments. The secondary structure and the hydration of the peptide and the interactions of specific residues with the lipid head groups have also been analyzed.     

Ecological requirements of Ostracoda (Crustacea) in a heavily polluted shallow lake,Lake Yeniçağa (Bolu,Turkey)

Although the area of Lake Yeniça?a is a potential candidate for RAMSAR convention, several anthropogenic factors compromise its biological diversity. This is mostly due to nutrient-rich water released from both point and nonpoint sources. Thirteen ostracod taxa (Candona neglecta, C. candida, Ilyocypris bradyi, Darwinula stevensoni, Cypridopsis vidua, Physocypria kraepelini, Cypria ophtalmica, Prionocypris zenkeri, Eucypris virens, Herpetocypris reptans, Pseudocandona compressa, Fabaeformiscandona fabaeformis Potamocypris cf. fulva) were found during this study. Potamocypris cf. fulva is a new record for the Turkish freshwater ostracod fauna. The first nine of these species have broad geographic ranges, implying high tolerance levels to different environmental variables. Based on the estimated species optima and tolerance levels, two species exhibited higher effective number of occurrences (C. neglecta, and D. stevensoni, respectively) than the other species. Three species (C. neglecta, D. stevensoni, I. bradyi) did not show significant correlation with any environmental variable we used. Both Canonical correspondence (CCA) and Pearson correlation analyses showed that temperature was the most effective predictor of species occurrence, followed by electrical conductivity and redox potential. In contrast, pH and dissolved oxygen of water were the least effective predictors. Approximately 71% of the correlation between community composition and environmental variables was explained by the first axis of the CCA diagram, which had a relatively low (7.7%) cumulative variance of species. The lower (560 μg/l) and the upper (2030 μg/l) levels of ammonia (NH₃) exceeded the limits during winter season. The concentrations of total coliform and Escherichia coli bacteria were measured up to 10 × 10⁷ cfu/ml and 10 × 10³ cfu/ml, respectively. Results of physicochemical measurements, microbiological counts, and species data indicate that water quality of Lake Yeniça?a has been rapidly deteriorated by anthropogenic factors that are the main threat for not only the lake’s aquatic diversity but also human health around the lake.     

IsBombus inexspectatus (Tkalcu) a workerless obligate parasite? (Hym. Apidae)

Summary Bombus inexspectatus (Tkalc) is now known from 50 males, 36 females and two individuals which have been described as workers; the species has been found in the mountains of Austria, France, Italy, Spain and Switzerland at altitudes between 1,181 m. (N.W. Spain) and 2,100 m. (N.E. Italy). More than 10,000 bumblebees have been captured in localities whereB.inexspectatus is known to occur yet no further worker individuals have been discovered. The capture of some very undersized females in spring long before workers of any other species were flying puts the status of the two so-called workers in considerable doubt and examination of these two specimens points very strongly to their being females and not workers. The possibility that the femaleB. inexspectatus behaves like aPsithyrus and lives in the nest of another bee seems a not improbable explanation of the situation though proof may come only by chance discovery. Certain peculiarities of the female, notably absence of any indication, in pinned specimens, of either wax secretion or pollen collecting and at least the suggestion that the pollen collecting equipment may be degenerate if not entirely non-functional are added pointers to the necessity of a parasitic mode of living.Bombus ruderarius Müller is suggested as a likely host.

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Zusammenfassung Bombus inexspectatus (Tkalc), ist jetzt nach 50 Männchen, 36 Weibchen und 2 als Arbeiter beschriebenen Exemplaren bekannt; die Art ist in den Gebirgen Österreichs, Frankreichs, Italiens, Spaniens und der Schweiz in Höhen zwischen 1181 m. (N.W. Spanien) und 2100 m. (N.O. Italien) gefunden worden. Mehr als 10000 Hummeln sind an den Fundorten gefangen worden, wo das Vorkommen vonB. inexspectatus bekannt ist, doch hat man keine weiteren Arbeiter entdeckt. Das Sammeln einiger sehr kleinen Weibchen am Anfang des Frühlings — lange vor der Flugzeit der Arbeiter anderer Arten — lässt den Status der zwei Arbeiter bezweifeln, und eine Untersuchung zeigt, dass sie wahrscheinlich Weibchen und keine Arbeiter sind. Es ist durchaus möglich, dass das Weibchen vonB. inexspectatus sich wie einPsithyrus verhält und im Nest einer anderen Hummel lebt, doch vielleicht könnte eine zufällige Entdeckung diese Hypothese bestätigen. Gewisse Eigentümlichkeiten des Weibchens sind weitere Anzeiger der Notwendigkeit einer parasitischen Lebensweise: besonders die Abwesenheit jeder Andeutung entweder von Waschsabscheidung oder von Pollensammeln und die Möglichkeit, dass der Pollensammelapparat wenigstens degeneriert, wenn nicht ganz funktionlos geworden, ist.Bombus ruderarius Müller wird als wahrscheinlicher Wirt vorgeschlagen.

     

Lipoprotein(a): still an enigma?

PURPOSE OF REVIEW: Lipoprotein(a) belongs to the class of the most atherogenic lipoproteins. Despite intensive research - in the last year more than 80 papers have been published on this topic - information is still lacking on the physiological function of lipoprotein(a) and the site of its catabolism. Important advances have been made in the knowledge of these points, which may have some therapeutic implications. RECENT FINDINGS: The association of high lipoprotein(a) values with an increase in risk for coronary events has been documented in further prospective studies. This increased risk may relate to recent findings that apolipoprotein(a) is produced in situ within the vessel wall. In addition, lipoprotein(a) binds and inactivates the tissue factor pathway inhibitor and induces plasminogen activator inhibitor type 2 expression in monocytes. A new antisense oligonucleotide strategy has been proposed which efficiently inhibits apolipoprotein(a) expression in vitro and in vivo. Apolipoprotein(a), however, suppresses angiogenesis and thus may interfere with the infiltration of tumor cells. Finally, the enzymatic activity leading to the formation of apolipoprotein(a) fragments in plasma and their catabolism have been further elucidated. SUMMARY: We are still far away from understanding the pathways involved in lipoprotein(a) catabolism, and the physiological function of this lipoprotein. Recent findings, however, provide new insight into pathomechanisms in patients with increased lipoprotein(a) related to hemostasis, which may serve as a basis for designing new treatment strategies.     

利用[~(14)C]—B(a)P 研究微生物对水稻植株吸收苯并(a)芘的影响

众所周知,苯并(a)芘(BaP)是一种强致癌性多环芳烃,它的生成是多源的,且在环境中有广泛分布。近年来,国内外对苯并(a)芘污染环境及其生物氧化已有越来越多的报导。对它进入植物体及在植物体内进行再分配     

Congenital absence of a tail in a Reeves‘ muntjac (Muntiacus reevesi)

Two abnormalities of the tail have been observed in Reeves muntjac. A male was born acaudate and an adult doe had a tail less than a third of the normal length. The range and mean of lengths of body and tail are given for animals over 2 years old.     

Wide-range protein photo-crosslinking achieved by a genetically encoded N(ε)-(benzyloxycarbonyl)lysine derivative with a diazirinyl moiety

A derivative of N(ε)-benzyloxycarbonyl-L-lysine with a photo-reactive diazirinyl group, N(ε)-[((4-(3-(trifluoromethyl)-3H-diazirin-3-yl)benzyl)oxy)carbonyl]-L-lysine, was site-specifically incorporated into target proteins in mammalian cells. The incorporated photo-crosslinker is able to react not only with residues as distant as about 15 ? but also with those in closer proximity, thus enabling "wide-range" photo-crosslinking of proteins.     

Mir-26a调控子宫肌瘤中孕激素受体a(PRa)、雌激素受体α(ERα)的表达

目的:雌激素和孕激素在子宫肌瘤发病中起重要作用。但miRNA在子宫肌瘤发病中的作用还知之甚少,我们前期已证实mir-26a在子宫肌瘤中低表达,本实验进一步探讨mir-26a在体外对子宫肌瘤中孕激素受体a(PRa)、雌激素受体α(ERα)表达的调控。方法:利用TargetScan软件预测mir-26a的潜在靶基因,找出靶基因3'UTR区片段,插入PmirGLO绿色荧光蛋白编码区下游,构建报告基因载体,同时原代培养子宫肌瘤平滑肌细胞。将报告基因载体与mir-26a共转染入原代培养的子宫肌瘤平滑肌细胞,引入双荧光素酶报告基因系统对mir-26a的靶基因进行验证。转染mir-26amimics于子宫肌瘤平滑肌细胞,westernblotting检测子宫肌瘤平滑肌细胞中mir-26a靶蛋白表达水平。结果:用TargetScan软件和双荧光素酶报告基因系统证实ERα、PRa为mir-26a的靶基因。蛋白水平进一步验证,mir-26amimics的转染量不同,ERα、PRa的蛋白表达水平下调不同。结论:Mir-26a通过结合靶基因的3'-UTR区调控靶基因的mRNA水平。Mir-26a抑制雌激素受体α(ERα)、孕激素受体a(PRa)在子宫肌瘤中的表达。Mir-26a可能通过调控雌激素受体α(ERα)、孕激素受体a(PRa)影响子宫肌瘤的发展。本实验通过确定mir-26a对子宫肌瘤的作用机制,有望进一步提高子宫肌瘤的治疗技术,减少手术治疗的创伤。     

Plasma anti-α-galactoside antibody binds to serine- and threonine-rich peptide sequence of apo(a) subunit in Lp(a)

Lipoprotein(a) immune complexes [Lp(a) IC] of varying particle density obtained by ultracentrifugation of plasma from normal healthy donors were markedly dominated by IgG. Lp(a) and immunoglobulins were liberated from plasma Lp(a) IC by treatment with melibiose, a sugar specific for circulating anti-α-galactoside antibody (anti-Gal). Upon incubation with plasma lipoprotein fraction anti-Gal but not the α-glucoside-specific antibody from human plasma formed de novo IC with Lp(a). Binding of Lp(a) sugar-reversibly enhanced the fluorescence of FITC-labeled anti-Gal as did binding of α-galactoside-containing glycoproteins. This effect apparently due to conformational shift in the Fc region of the antibody was also produced by apo(a) subunit separated from Lp(a) and de-O–glycosylated apo(a) but not by any other plasma lipoproteins or by Lp(a) pre-incubated with the O–glycan-specific lectin jacalin. O–Glycans and their terminal sialic acid moieties in apo(a) of circulating Lp(a)-anti-Gal IC, in contrast to those in pure Lp(a), were inaccessible to jacalin and anion exchange resin, respectively. Unlike other plasma lipoproteins, Lp(a) inhibited Griffonia simplicifolia isolectin B4 which also accommodates serine- and threonine-rich peptide sequence (STPS) as surrogate ligand to α-galactosides at its binding site. Results suggest that anti-Gal recognizes STPS in the O-glycan-rich regions of apo(a) subunit in Lp(a) which contains no α-linked galactose.     

X-ray photochemistry in iron complexes from Fe(0) to Fe(IV) - Can a bug become a feature?

Under intense soft X-ray irradiation, we have observed time-dependent changes in the soft X-ray spectra of virtually all the Fe coordination complexes that we have examined, indicating chemical transformation of the compound under study. Each compound, with oxidation states ranging from Fe(IV) to Fe(0), has been studied with either Fe L-edge spectroscopy or N K-edge spectroscopy. We find that very often a well-defined spectroscopic change occurs, at least initially, which is apparently capable of straightforward interpretation in terms of X-ray induced photoreduction, photooxidation or ligand photolysis. We briefly discuss the probable chemical nature of the changes and then estimate the rate of chemical change, thereby establishing the necessary radiation dose. We also demonstrate that the photochemistry not only depends on the Fe oxidation state but also the coordination chemistry of the complex. It seems that a proper understanding of such X-ray photochemical effects could well greatly assist the assignment of soft X-ray spectra of uncharacterized metal sites.     

Pyrenomycetes sensu lato from Almería (Spain)

Forty-seven taxa of Pyrenomycetes sensu lato from Almería, southern Spain, have been studied. The following are new records for the Spanish mycobiota: Capronia inconspicua, Comoclathris planispora, Diaporthopsis trinucleata, Eutypa consobrina, Eutypella kochiana, Montagnula longipes, Montagnula infernalis, Mycosphaerella nicotianae, Nectriella jucunda, Phaeosphaeria phragmitis, Pleospora dichromatricha, Pleospora rudis, Pleospora subalpina, Teichospora opuntiae and Trematosphaeria endoxyloides. Two new species are also described: Diademosa sabulosa and Phaeosphaeria rubescens.     

(—)-Massoniresinol,a lignan from Pinus massoniana

A new lignan, named (—)-massoniresinol, has been isolated from Pinus massoniana needles. Its structure has been proved to be (2R,3S,4R)-3,4-dihydroxy-2-(4-hydroxy-3-methoxyphenyl)-4-(4-hydroxy-3-methoxybenzyl)-3-tetrahydrofuranmethanol by ¹H NMR, ¹³C NMR, mass and CD spectroscopy.