Assessing heterogeneity in oligomeric AAA+ machines

ATPases Associated with various cellular Activities (AAA+ ATPases) are molecular motors that use the energy of ATP binding and hydrolysis to remodel their target macromolecules. The majority of these ATPases form ring-shaped hexamers in which the active sites are located at the interfaces between neighboring subunits. Structural changes initiate in an active site and propagate to distant motor parts that interface and reshape the target macromolecules, thereby performing mechanical work. During the functioning cycle, the AAA+ motor transits through multiple distinct states. Ring architecture and placement of the catalytic sites at the intersubunit interfaces allow for a unique level of coordination among subunits of the motor. This in turn results in conformational differences among subunits and overall asymmetry of the motor ring as it functions. To date, a large amount of structural information has been gathered for different AAA+ motors, but even for the most characterized of them only a few structural states are known and the full mechanistic cycle cannot be yet reconstructed. Therefore, the first part of this work will provide a broad overview of what arrangements of AAA+ subunits have been structurally observed focusing on diversity of ATPase oligomeric ensembles and heterogeneity within the ensembles. The second part of this review will concentrate on methods that assess structural and functional heterogeneity among subunits of AAA+ motors, thus bringing us closer to understanding the mechanism of these fascinating molecular motors.     

Proliferation status defines functional properties of endothelial cells

Homeostasis of solid tissue is characterized by a low proliferative activity of differentiated cells while special conditions like tissue damage induce regeneration and proliferation. For some cell types it has been shown that various tissue-specific functions are missing in the proliferating state, raising the possibility that their proliferation is not compatible with a fully differentiated state. While endothelial cells are important players in regenerating tissue as well as in the vascularization of tumors, the impact of proliferation on their features remains elusive. To examine cell features in dependence of proliferation, we established human endothelial cell lines in which proliferation is tightly controlled by a doxycycline-dependent, synthetic regulatory unit. We observed that uptake of macromolecules and establishment of cell–cell contacts was more pronounced in the growth-arrested state. Tube-like structures were formed in vitro in both proliferating and non-proliferating conditions. However, functional vessel formation upon transplantation into immune-compromised mice was restricted to the proliferative state. Kaposi’s sarcoma-associated herpes virus (KSHV) infection resulted in reduced expression of endothelial markers. Upon transplantation of infected cells, drastic differences were observed: proliferation arrested cells acquired a high migratory activity while the proliferating counterparts established a tumor-like phenotype, similar to Kaposi Sarcoma lesions. The study gives evidence that proliferation governs endothelial functions. This suggests that several endothelial functions are differentially expressed during angiogenesis. Moreover, since proliferation defines the functional properties of cells upon infection with KSHV, this process crucially affects the fate of virus-infected cells.     

Genome sequence and analysis of the tuber crop potato

Potato (Solanum tuberosum L.) is the world's most important non-grain food crop and is central to global food security. It is clonally propagated, highly heterozygous, autotetraploid, and suffers acute inbreeding depression. Here we use a homozygous doubled-monoploid potato clone to sequence and assemble 86% of the 844-megabase genome. We predict 39,031 protein-coding genes and present evidence for at least two genome duplication events indicative of a palaeopolyploid origin. As the first genome sequence of an asterid, the potato genome reveals 2,642 genes specific to this large angiosperm clade. We also sequenced a heterozygous diploid clone and show that gene presence/absence variants and other potentially deleterious mutations occur frequently and are a likely cause of inbreeding depression. Gene family expansion, tissue-specific expression and recruitment of genes to new pathways contributed to the evolution of tuber development. The potato genome sequence provides a platform for genetic improvement of this vital crop.     

碳酸盐建造天然储层及其在地质历史中的演化

流体分布特征及其在储层中的运移取决于岩石的储集性和层序内部结构。块状储层一般是礁或浮游生物建造,部分属地台底栖生物建造,其中流体可进行垂向和横向运移;层状储层是典型的底栖生物建造,具不同渗透性的岩层成互层状,以横向运移为主;岩性圈闭储层产于未补偿拗陷的沥青质-硅质、粘土-碳酸盐建造。层状储层遍及整个显生宙,但其相型、孔隙空间的组成及特征均有所改变。礁块储层的意义在地质历史中随其厚度及非均质性的增加均有所增长。在中生代末的浮游生物建造中常有块状储层。岩性圈闭储层自泥盆纪以来零星出现于较年轻的沉积中。     

Development of the new Pacinian corpuscles. Studies on the foreign innervation of mesentery

Zusammenfassung Nach Implantation des proximalen Stumpfes eines afferenten, somatosensiblen Nerven in das Mesenterium einer Katze bilden sich um die auswachsenden Nervenfasern nach 3–5 Monaten neue, aber dem Ort entsprechende Rezeptoren aus, im Fall des Katzenmesenteriums also Pacinische Körperchen, Rezeptoren, die normalerweise nicht im Gebiet des implantierten Nerven vorkommen.     

白藜芦醇对酒精性肝损伤大鼠保护作用的研究

研究白藜芦醇对大鼠血清指标及肝指数的影响,探讨白藜芦醇对肝损伤大鼠的保护作用.将72只雄性大鼠随机分为6组,空白对照组、模型对照组、低、中、高剂量组和阳性药物对照组.连续给药30 d后称取大鼠重量,取血清分别检测血清谷草转氨酶(AST)、谷丙转氨酶(ALT)和超氧化物歧化酶(SOD)、丙二醛(MDA)含量,并测定肝指数、肾指数、脾指数.结果表明,白藜芦醇能降低大鼠血清中ALT、AST、TG的水平(P0.05),提高了SOD的含量、降低了MDA的含量(P0.05).说明白藜芦醇具有降低大鼠ALT、AST的作用,对肝损伤大鼠具有肝保护作用.     

Polymorphism for a 1.6-Mb deletion of the human Y chromosome persists through balance between recurrent mutation and haploid selection

Many human Y-chromosomal deletions are thought to severely impair reproductive fitness, which precludes their transmission to the next generation and thus ensures their rarity in the population. Here we report a 1.6-Mb deletion that persists over generations and is sufficiently common to be considered a polymorphism. We hypothesized that this deletion might affect spermatogenesis because it removes almost half of the Y chromosome's AZFc region, a gene-rich segment that is critical for sperm production. An association study established that this deletion, called gr/gr, is a significant risk factor for spermatogenic failure. The gr/gr deletion has far lower penetrance with respect to spermatogenic failure than previously characterized Y-chromosomal deletions; it is often transmitted from father to son. By studying the distribution of gr/gr-deleted chromosomes across the branches of the Y chromosome's genealogical tree, we determined that this deletion arose independently at least 14 times in human history. We suggest that the existence of this deletion as a polymorphism reflects a balance between haploid selection, which culls gr/gr-deleted Y chromosomes from the population, and homologous recombination, which continues to generate new gr/gr deletions.     

Specific structural features of LnZrOx (Ln: La, Sm) mixed oxides prepared by different methods

LnZrOx(Ln: La, Sm) mixed oxides of Ln: Zr = 1 were prepared by different methods(complex polymerized method, sorption of cations on starch from aqueous salt solution and conventional co-precipitation with additional redispersion of precipitate by ultra sound) and calcined at 700–1300 °C. Their specific structural features and changes were studied and discussed. Various characterization methods were used such as X-ray diffraction,Electron microscopy, Fourier-transform infrared and Raman spectroscopy, UV–Vis spectroscopy, X-Ray absorption fine structure and X-ray photoelectron spectroscopy.The formation of pyrochlore structure occurred at 1100–1300 °C from fluorite-like pseudocubic phase ZrO_2 regardless the method of preparation. This phase had a block-like structure consisting of ZrO_2 nanocrystals stabilized by Ln cations and residual anions such as hydroxyls and carbonates. The desorption of such anions with heating already started at 900 °C and lead to local changes of Zr cations coordination to octahedral and to the formation of pyrochlore nanodomains inclusions within fluorite-like phase. The increased cation mobility and further elimination of anions caused by further heating was accompanied by the formation of bulk pyrochlore phase at 1100–1300 °C. Even after calcination at 1300 °C the local microheterogeneity as well as defects were identified at domains boundaries or sintered microstructure. These specific features of the formed pyrochlores depend on the method of preparation.