Pinocytose und Bewegung von Amöben

Zusammenfassung Die Mucoidschicht von Amoeba proteus enthält saure Mucopolysaccharide und ist funktionell einem Kationenaustauscher vergleichbar. Schwermetallpartikel und Proteine werden in Abhängigkeit vom pH-Wert des Kulturmediums in unterschiedlich starken Mengen an die Mucoidfilamente gebunden. Die dem Plasmalemm unmittelbar aufliegende globuläre Grundschicht besitzt dagegen für die untersuchten Substanzen keine Adsorptionsfunktion und unterscheidet sich demnach sowohl physiologisch als auch chemisch von der filamentartigen Zone.Quantitative Messungen über die pH-abhängige Anlagerung von Ferritin haben ergeben, daß die Mucoidfilamente in der Lage sind, Kationen aus dem Kulturmedium bis zu einer um das 17fache höheren Konzentration anzureichern.Die Ergebnisse der vorliegenden Untersuchung sprechen dafür, daß die Anreicherung derartiger Substanzen an der Zelloberfläche eine notwendige und physiologisch sinnvolle Voraussetzung für die Auslösung einer induzierten Endocytose darstellt.

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Pinocytosis and locomotion of amoebaeX. The significance of the mucous layer for the initial phase of the induced endocytosis in Amoeba proteus

Summary The mucoid layer of Amoeba proteus contains acid mucopolysaccharides, which are involved in the exchange of cations. Depending on the pH of the external medium, different amounts of heavy metal particles and proteins are bound to the mucoid filaments. The globular ground layer, which is directly apposed to the plasma membrane does not bind any of the substances studied and, therefore, differs from the mucoid filaments in function as well as chemical nature. Measurements of the pH-dependent adsorption of ferritin demonstrate that the mucoid filaments are able to accumulate cations in concentrations 17 times that of the external medium. These results suggest that the accumulation of substances at the cell surface is a prerequisite for the initiation of induced endocytosis.

     

Estimation of Variances at Different Significance Levels

Variance components and their ratios broad-sense heritability and constancy were estimated for some quantitative traits in northwestern Spain populations of maize. Estimations were carried out at the significance levels of 5% and 25% and without significance limits. It can be concluded that estimation without significance limits is more efficient than the estimations at the usual levels in the method of analysis of experimental data from fields experiments.     

Interactome Analysis of Human Phospholipase D and Phosphatidic Acid-Associated Protein Network

Mammalian phospholipase D (PLD) enzyme family consists of six members. Among them, PLD1/2/6 catalyzes phosphatidic acid (PA) production, while PLD3/4/5 has no catalytic activities. Deregulation of the PLD-PA lipid signaling has been associated with various human diseases including cancer. However, a comprehensive analysis of the regulators and effectors for this crucial lipid metabolic pathway has not been fully achieved. Using a proteomic approach, we defined the protein interaction network for the human PLD family of enzymes and PA and revealed diverse cellular signaling events involving them. Through it, we identified PJA2 as a novel E3 ubiquitin ligase for PLD1 involved in control of the PLD1-mediated mammalian target of rapamycin signaling. Additionally, we showed that PA interacted with and positively regulated sphingosine kinase 1. Taken together, our study not only generates a rich interactome resource for further characterizing the human PLD-PA lipid signaling but also connects this important metabolic pathway with numerous biological processes.     

Alport 综合征1 例报道及文献复习

目的:探讨Alport综合征的临床表现,病理学特征及研究进展。方法:分析1例此病患者的临床资料。结果:本例患者临床表现为慢性视力下降。尿常规检查提示蛋白尿,血尿。肾肾穿刺活检的光镜、电镜检查均支持诊断。结论:Alport综合征患者中眼部异常的表现有独特性;了解眼部病变特征并结合全身病史,病理学检查有助于疾病的诊断和随诊。     

Second-generation aryl isonitrile compounds targeting multidrug-resistant Staphylococcus aureus

Antibiotic resistance remains a major global public health threat that requires sustained discovery of novel antibacterial agents with unexploited scaffolds. Structure-activity relationship of the first-generation aryl isonitrile compounds we synthesized led to an initial lead molecule that informed the synthesis of a second-generation of aryl isonitriles. From this new series of 20 compounds, three analogues inhibited growth of methicillin-resistant Staphylococcus aureus (MRSA) (from 1 to 4?µM) and were safe to human keratinocytes. Compound 19, with an additional isonitrile group exhibited improved activity against MRSA compared to the first-generation lead compound. This compound emerged as a candidate worthy of further investigation and further reinforced the importance of the isonitrile functionality in the compounds’ anti-MRSA activity. In a murine skin wound model, 19 significantly reduced the burden of MRSA, similar to the antibiotic fusidic acid. In summary, 19 was identified as a new lead aryl isonitrile compound effective against MRSA.     

Measurement of plasma α-ketoisocaproate concentrations and specific radioactivity by high-performance liquid chromatography

An isocratic high-performance liquid chromatographic technique for the measurement of the specific radioactivity and concentration of α-ketoisocaproate in plasma is described. Plasma proteins are precipitated by additions of acetone, the supernatant is applied to a cation-exchange column, and the resulting eluate is injected into a C₁₈ reverse-phase column. Analysis time is approximately 10 min. Quantitative recovery, specificity, and sensitivity of this method are described and make this system attractive for in vivo α-ketoisocaproate kinetic studies. Using this procedure, the apparent flux of α-ketoisocaproate in postabsorptive dogs was determined during an infusion of α-[U-¹⁴C]ketoisocaproate and averaged 2.8 + 0.41 μmol/kg-min.     

Concurrent inhibition of the low-affinity Ca2+-stimulated ATPase and MgATP-dependent endocytosis in erythrocyte ghosts by N-naphthylmaleimide and carbonylcyanide-m-chlorophenylhydrazone.

Energy-dependent endocytosis and the low Ca²⁺ affinity Ca²⁺-stimulated ATPase activity of erythrocyte ghosts were inhibited concurrently by two inhibitors, carbonylcyanide-m-chlorophenylhydrazone (CCCP) and N-naphthylmaleimide. The conditions required to observe 50% inhibition of this Ca²⁺-stimulated ATPase activity with either inhibitor were the same conditions required to observe this level of inhibition of endocytosis. Under these conditions, none of the other ATPase activities measured were inhibited more than 20% by either of these reagents. This concurrence of inhibition of endocytosis and the low-affinity Ca²⁺-stimulated ATPase and the possible involvement of this ATPase in the mechanism by which endocytosis occurs is discussed.     

Recognition of phylogenetic relationships from polypeptide chain fold similarities

Summary Structural similarities between proteins with no amino acid sequence homology either indicate a phylogenetic relationship, or they are merely the expression of a physically preferred way of folding a polypeptide chain. It is shown that one can distinguish between these alternatives by evaluating the significance of the similarity. Such significances have been derived for comparison between chain folds containing-pleated sheets (Schulz and Schirmer, 1974; Richardson et al., 1976; Sternberg and Thornton, 1976). An extension of this method to comparisons between any two chain folds is outlined here.     

Epithelial–mesenchymal transition in cancer metastasis: Mechanisms,markers and strategies to overcome drug resistance in the clinic

Epithelial–mesenchymal transition (EMT) is a key step during embryogenesis. Accumulating evidence suggests a critical role in cancer progression, through which tissue epithelial cancers invade and metastasise. Cell characteristics are highly affected during EMT, resulting in altered cell–cell and cell–matrix interactions, cell motility and invasiveness. Nevertheless, the demonstration of this process in human cancer has been proven difficult and controversial. Besides the fact that the acquisition of mesenchymal characteristics is not a prerequisite for cell migration/invasion, it is a transient event that concerns only few cells in a tumour mass. The induction of EMT depends on the tumour type and its genetic alterations as well as on its interaction with the extracellular matrix. In parallel, trials for EMT identification in clinical samples lack of a widely accepted methodology, nomenclature and reliable markers. This review summarizes the main EMT characteristics and proposes methodologies for better analysis in vitro. It also highlights recent studies identifying cells with EMT characteristics in human cancer and proposes certain markers to identify them in tumour samples. Finally, it cites the recent literature concerning the mechanisms of drug resistance related to EMT in the context of anti-tumour therapies and proposes related new targets for therapy.