Lipid mimetics: A versatile toolbox for lipid biology and beyond

Being the principal component of biological membranes lipids are essential building blocks of life. Given their huge biological importance, the investigation of lipids, their properties, interactions and metabolic pathways is of prime importance for the fundamental understanding of living cells and organisms as well as the emergence of diseases. Different strategies have been applied to investigate lipid-mediated biological processes, one of them being the use of lipid mimetics. They structurally resemble their natural counterparts but are equipped with functionality that can be used to probe or manipulate lipid-mediated biological processes and biomembranes. Lipid mimetics therefore constitute an indispensable toolbox for lipid biology and membrane research but also beyond for potential applications in medicine or synthetic biology. Herein, we highlight recent advances in the development and application of lipid-mimicking compounds.     

可视化多镜联合治疗复杂鹿角结石的对比研究

摘要 目的：研究不同组合方式治疗复杂鹿角样结石的疗效对比。方法：选取 80例我院治疗的复杂鹿角样结石患者,将患者随机分成两组,A组以经皮肾镜 +针状肾镜 （needle-perc） 的方式清理结石,B组以经皮肾镜 +输尿管软镜（flexibleureteroscope,F-URS）的方式清理结石,术后收集患者相关数据包括穿刺时间,单次穿刺成功率,单位结石量手术时间,清石效率,术中出血量,术后并发症,完全清石率等参数评估手术效果。结果：80例患者一期完成,主通道穿刺时间 A组（6± 1.62）min小于 B组（10±3.25）min（P<0.001）。单次穿刺成功率 A组（38/40）优于 B组（32/40）（P<0.05）。主通道清石时间 A组（40.94± 8.09）min和 B组（37.29± 4.19）min相比较无统计学意义（P>0.05）。残石处理时间 A组（34.37± 6.68）min小于 B组（49.55± 11.62）min（P<0.05）,主通道结石清石效率 A组（0.27± 0.05）cm3/min和 B组（0.26± 0.06）cm3/min相比较无统计学意义（P>0.05）,残石清石效率 A组（0.05± 0.01）cm3/min高于 B组（0.03± 0.01）cm3/min（P<0.05）。术后并发症及完全清石率两组无统计学意义（P>0.05）。结论：作为标准通道的辅助手段,needle-perc和输尿管软镜能很好的完成残石的处理,同超声定位穿刺相比较,可视穿刺花费时间更短,穿刺单次穿刺成功率更高,相对于软镜处理残石,needle-perc有更高的清石效率。两种方法的术中及术后并发症发生率,完全清石率无差别。     

输尿管软镜结合输尿管硬镜治疗复杂上尿路结石的效果评价及对预后的影响

目的 探讨输尿管软镜协同输尿管硬镜治疗复杂上尿路结石的临床效果.方法 选择我院收治的复杂上尿路结石患者96例,按入院顺序分为对照组和观察组,每组48例.对照组采取输尿管硬镜钬激光碎石术治疗,观察组采取输尿管软镜协同输尿管硬镜钬激光碎石术治疗.比较两组患者1次性碎石成功率、结石彻底清除率、炎症反应情况以及生活质量、住院时...     

基因外显子连接序列与相应内含子序列的相互作用

剪接后的内含子与相应mRNA序列的相互作用在基因表达调控过程中起着非常重要的作用。基于27个物种的核糖核蛋白基因序列,采用Smith—Waterman局域比对方法得到外显子连接序列与相应内含子序列的最佳匹配片段,分析了外显子连接序列上的匹配频率分布和匹配片段的序列特征。发现一些低等真核生物EJC结合区域的匹配频率明显低于其它区域,所有物种EJC结合区域的序列构成呈现出相对低的结构序。最佳匹配片段的平均长度和配对率分布与siRNA和miRNA的结合特征相同。推测EJC和内含子在与外显子序列结合的过程中存在相互竞争和相互协作的关系,内含子中部序列在基因表达调控过程中起着重要的作用。     

\vec H^ + /2\bar e Stoichiometry of the NADH:Ubiquinone Reductase Reaction Catalyzed by Submitochondrial Particles

Mitochondrial NADH:ubiquinone-reductase (Complex I) catalyzes proton translocation into inside-out submitochondrial particles. Here we describe a method for determining the stoichiometric ratio (n) for the coupled reaction of NADH oxidation by the quinone acceptors. Comparison of the initial rates of NADH oxidation and alkalinization of the surrounding medium after addition of small amounts of NADH to coupled particles in the presence of Q₁ gives the value of n = 4. Thermally induced deactivation of Complex I [1,2] results in complete inhibition of the NADH oxidase reaction but only partial inhibition of the NADH:Q₁-reductase reaction. N-Ethylmaleimide (NEM) prevents reactivation and thus completely blocks the thermally deactivated enzyme. The residual NADH:Q₁-reductase activity of the deactivated, NEM-treated enzyme is shown to be coupled with the transmembraneous proton translocation (n = 4). Thus, thermally induced deactivation of Complex I as well as specific inhibitors of the endogenous ubiquinone reduction (rotenone, piericidin A) do not inhibit the proton translocating activity of the enzyme.     

Bile and bile salts and exsheathment of the intestinal nematodes Trichostrongylus colubriformis and Nematodirus battus

1972. Bile and bile salts and exsheathment of the intestinal nematodes Trichostrongylus colubriformis and Nematodirus battus. International Journal for Parasitology, 2: 433–438. Exsheathment of T. colubriformis was potentiated at physiological levels of CO₂ by bile and bile salts. Lamb bile and crude sodium taurocholate preparations produced the greatest increase in exsheathment while rabbit bile, sodium glycocholate and deoxycholate had less pronounced effects. Exsheathment in bile and taurocholate occurred at a pH above 4 and it is therefore suggested that infective larvae which fail to exsheath in the abomasum could well do so in the proximal part of the small intestine. Pure sodium taurocholate was found to greatly potentiate exsheathment of N. battus in vitro but this occurred at a pH below 3 and thus the action of this bile salt could not affect exsheathment in the host.     

Inversion of selectivity of N-substituted propargylamine monoamine oxidase inhibitors following structural modifications to quaternary salts

A number of N-substituted-propargylamines are well known mechanism-based MAO inhibitors. Clorgyline and deprenyl in fact represent archetypal MAO-A and MAO-B inhibitors respectively. In the present study several ring-substituted deprenyl structural analogues were synthesized and alterations of selectivity and potency towards MAO-A and MAO-B activities were found. When deprenyl and its structural analogues were further modified to their corresponding quaternary ammonium salts, i.e. by attaching either an extra propargyl or a methyl group to the nitrogen atom, the potency of inhibition of MAO-B activity was drastically reduced and inhibition of MAO-A activity substantially increased. Such a complete inversion of selectivity may be related to a hydrophilic and electrophilic region seemingly present only in the MAO-A but not in the MAO-B molecule. The results also suggest that at least three sites are required for the selectivity and mechanism-based action of an inhibitor towards MAO.     

AFM imaging of surface adsorbed polymeric 3-alkylpyridinium salts from the marine sponge Reniera sarai

Bioactive 3-alkylpyridinium polymers (poly-APS) have recently been isolated from the marine sponge Reniera sarai. Previous results have shown that these molecules in aqueous solutions form supramolecular aggregates with an average hydrodynamic radius of 23±2 nm. To obtain additional evidences about the shape and the dimensions of poly-APS aggregates, we used atomic force microscopy (AFM) operating in tapping mode. The images clearly showed adsorbed aggregates with a lateral dimension of ≈40 nm and a thickness of the order of ≈1 nm. The distribution of volumes of the adsorbed aggregates is very similar to the distribution of hydrodynamic radii as obtained from the dynamic light scattering experiments. The volume distribution of these aggregates shows a maximum at 1750 nm³, which corresponds to a sphere with a radius of 7.5 nm.     

Respiratory Chains from Aerobic Thermophilic Prokaryotes

Thermophiles are organisms that grow optimally above 50 degrees C and up to approximately 120 degrees C. These extreme conditions must have led to specific characteristics of the cellular components. In this paper we extensively analyze the types of respiratory complexes from thermophilic aerobic prokaryotes. The different membrane-bound complexes so far characterized are described, and the genomic data available for thermophilic archaea and bacteria are analyzed. It is observed that no specific characteristics can be associated to thermophilicity as the different types of complexes I-IV are present randomly in thermophilic aerobic organisms, as well as in mesophiles. Rather, the extensive genomic analyses indicate that the differences concerning the several complexes are related to the organism phylogeny, i.e., to evolution and lateral gene transfer events.     

Gamma carbonic anhydrase like complex interact with plant mitochondrial complex I

We report the identification by two hybrid screens of two novel similar proteins, called Arabidopsis thaliana gamma carbonic anhydrase like1 and 2 (AtCAL1 and AtCAL2), that interact specifically with putative Arabidopsis thaliana gamma Carbonic Anhydrase (AtCA) proteins in plant mitochondria. The interaction region that was located in the N-terminal 150 amino acids of mature AtCA and AtCA like proteins represents a new interaction domain. In vitro experiments indicate that these proteins are imported into mitochondria and are associated with mitochondrial complex I as AtCAs. All plant species analyzed contain both AtCA and AtCAL sequences indicating that these genes were conserved throughout plant evolution. Structural modeling of AtCAL sequences show a deviation of functionally important active site residues with respect to CAs but could form active interfaces in the interaction with AtCAs. We postulate a CA complex tightly associated to plant mitochondrial complex.