Sulfatide-tenascin interaction mediates binding to the extracellular matrix and endocytic uptake of liposomes in glioma cells

Tenascin-C is an extracellular matrix glycoprotein, whose expression is highly restricted in normal adult tissues, but markedly up-regulated in a range of tumors, and therefore serves as a potential receptor for targeted anticancer drug or gene delivery. We describe here a liposomal carrier system in which the targeting ligand is sulfatide. Experiments with tenascin-C-expressing glioma cells demonstrated that binding of liposomes to the extracellular matrix relied essentially on the sulfatide-tenascin-C interaction. Following binding to the extracellular matrix, the sulfatide-containing liposomes were internalized via both caveolae/lipid raft- and clathrin-dependent pathways, which would ensure direct cytoplasmic release of the cargoes carried in the liposomes. Such natural lipid-guided intracellular delivery targeting at the extracellular matrix glycoproteins of tumor cells thus opens a new direction for development of more effective anticancer chemotherapeutics in future. K. Shao & Q. Hou: These authors contributed equally to this work. Received 22 September 2006; received after revision 5 December 2006; accepted 9 January 2007     

Process optimization of reaction of acid leaching residue of asbestos tailing and sodium hydroxide aqueous solution

Silica is the major component of the acid leaching residue of asbestos tailing.The waterglass solution can be prepared by the reaction of the residue with sodium hydroxide aqueous solution.Compared to the high temperature reaction method,this process is environmental friendly and low cost.In this paper,the reaction process of the residue and the sodium hydroxide aqueous solution is optimized.The optimum reaction process parameters are as follows:the usage of sodium hydroxide is 26.4 g/100 g acid leaching residue,the reaction temperature is 90℃,the reaction time is 1 h,and the ratio of the liquid/solid is 2.0.The significance sequence of the process parameters to the alkali leaching reaction effect is the usage of sodium hydroxidethe ratio of the liquid/solidthe reaction timethe reaction temperature.The significance sequence to the leaching ratio of SiO2 is the ratio of the liquid/solidthe usage of sodium hydroxidethe reaction timethe reaction temperature.The significance sequence to the modulus of the sodium silicate is the ratio of the liquid/solidthe usage of sodium hydroxidethe reaction timethe reaction temperature.Under the optimum conditions,the leaching ratio of the SiO2 is 77.5%,and the modulus of the sodium silicate is 3.15.The XRD analysis result indicates that the major components of the alkali leaching residue are serpentine,talc,quartz and some albite.     

Molecular mechanisms in therapy of acid-related diseases

Inhibition of gastric acid secretion is the mainstay of the treatment of gastroesophageal reflux disease and peptic ulceration; therapies to inhibit acid are among the best-selling drugs worldwide. Highly effective agents targeting the histamine H2 receptor were first identified in the 1970s. These were followed by the development of irreversible inhibitors of the parietal cell hydrogen-potassium ATPase (the proton pump inhibitors) that inhibit acid secretion much more effectively. Reviewed here are the chemistry, biological targets and pharmacology of these drugs, with reference to their current and evolving clinical utilities. Future directions in the development of acid inhibitory drugs include modifications of current agents and the emergence of a novel class of agents, the acid pump antagonists. Received 30 May 2007; received after revision 15 August 2007; accepted 13 September 2007     

The short-term effects of ingested chrysotile asbestos DNA synthesis in the pancreas and other organs of a primate

Summary Single oral administration of chrysotile asbestos to monkeys resulted 9 days later in the stimulation of DNA synthesis in the pancreas as evidenced by increased incorporation of tritiated thymidine.Environmental Health Programs, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106. This work was supported by grants from the Cleveland and Rockefeller Foundations.     

The use of the information-theoretic entropy in thermodynamics

When considering controversial thermodynamic scenarios such as Maxwell's demon, it is often necessary to consider probabilistic mixtures of macrostates. This raises the question of how, if at all, to assign entropy to them. The information-theoretic entropy is often used in such cases; however, no general proof of the soundness of doing so has been given, and indeed some arguments against doing so have been presented. We offer a general proof of the applicability of the information-theoretic entropy to probabilistic mixtures of macrostates that is based upon a probabilistic generalisation of the Kelvin statement of the second law. We defend the latter and make clear the other assumptions on which our main result depends. We also briefly discuss the interpretation of our result.     

The role of orientation experiments in discovering mechanisms

Many types of experiments have been recognized in the literature. One important type we discuss in this article is the orientation experiment. While orientation experiments are like other types of experiments in that they are tests for causal relevance, they also have other qualities. One important (but not the only) goal of these experiments is to offer a rough, qualitative characterization of the mechanism responsible for a capacity of interest, effectively constraining future research. This makes them particularly useful during the early stages of investigation, when an explanandum-phenomenon has just been identified and several (often competing) hypotheses as to the qualitative character of the mechanism responsible for it are proposed. We illustrate our claims, and explicate a number of additional aims that orientation experiments can sometimes serve, by considering three case studies from different era's, namely the discovery of the mechanisms responsible for i) the capacity of eels to produce numbing sensations (17th and 18th century), ii) puerperal fever in Semmelweis' Vienna Maternity Hospital (19th century), and iii) the capacity of pigeons to home (20th century).     

Protecting DNA from errors and damage: an overview of DNA repair mechanisms in plants compared to mammals

The genome integrity of all organisms is constantly threatened by replication errors and DNA damage arising from endogenous and exogenous sources. Such base pair anomalies must be accurately repaired to prevent mutagenesis and/or lethality. Thus, it is not surprising that cells have evolved multiple and partially overlapping DNA repair pathways to correct specific types of DNA errors and lesions. Great progress in unraveling these repair mechanisms at the molecular level has been made by several talented researchers, among them Tomas Lindahl, Aziz Sancar, and Paul Modrich, all three Nobel laureates in Chemistry for 2015. Much of this knowledge comes from studies performed in bacteria, yeast, and mammals and has impacted research in plant systems. Two plant features should be mentioned. Plants differ from higher eukaryotes in that they lack a reserve germline and cannot avoid environmental stresses. Therefore, plants have evolved different strategies to sustain genome fidelity through generations and continuous exposure to genotoxic stresses. These strategies include the presence of unique or multiple paralogous genes with partially overlapping DNA repair activities. Yet, in spite (or because) of these differences, plants, especially Arabidopsis thaliana, can be used as a model organism for functional studies. Some advantages of this model system are worth mentioning: short life cycle, availability of both homozygous and heterozygous lines for many genes, plant transformation techniques, tissue culture methods and reporter systems for gene expression and function studies. Here, I provide a current understanding of DNA repair genes in plants, with a special focus on A. thaliana. It is expected that this review will be a valuable resource for future functional studies in the DNA repair field, both in plants and animals.     

The information in the term structure: A non-parametric investigation

This paper proposes a non-linear term structure model that nests the discrete and continuous time models as special cases. I estimate the model non-parametrically using nearest-neighbours regression. In sample, the non-linear model matches the standard theories, but out of sample, it offers substantial improvement. Linear models fail to track future interest rates: a random walk dominates the forward rate as a predictor for 3-month Treasury bills. A non-linear forecast based on the spread is shown statistically to be the best forecast.     

The molecular mechanisms of congenital hypofibrinogenaemia

Congenital hypofibrinogenaemia is characterized by abnormally low levels of fibrinogen and is usually caused by heterozygous mutations in the fibrinogen chain genes (, and ). However, it does not usually result in a clinically significant condition unless inherited in a homozygous or compound heterozygous state, where it results in a severe bleeding disorder, afibrinogenaemia. Various protein and expression studies have improved our understanding of how mutations causing hypo- and afibrinogenaemia affect secretion of the mature fibrinogen molecule from the hepatocyte. Some mutations can perturb chain assembly as in the 153 Cys Arg case, while others such as the B Leu Arg and the B414 Gly Ser mutations allow intracellular hexamer assembly but inhibit protein secretion. An interesting group of mutations, such as 284 Gly Arg and 375 Arg Trp, not only cause hypofibrinogenaemia but are also associated with liver disease. The nonexpression of these variant chains in plasma fibrinogen is due to retention in the endoplasmic reticulum, which in turn leads to hypofibrinogenaemia.Received 17 December 2003; received after revision 19 January 2004; accepted 21 January 2004     

The experimental induction of ultrastructural damage in cardiac muscle

Experimentally-induced rises in intracellular calcium ([Ca2+]i) promote rapid myofilament degradation in amphibian and mammalian cardiac muscle strips. The relevance of these studies to the subcellular injury produced by ischaemia, the possible involvement of lysosomal enzymes and similarities with skeletal muscle are discussed.     

Retention of topical liposomal formulations on the cornea

Summary The ability of liposomes composed of different kinds of phospholipid materials to adhere to the surface of the cornea was studied in the rabbit. The liposomes were labelled with tracer amounts of an I¹²⁵-labelled phosphatidylethanolamine derivative and were instilled in 10 l drops onto the cornea. The retention of radioactivity was monitored. The results show that liposomes containing positively charged phospholipids are better retained than an albumin control. Thus, it may be possible to develop a drug delivery, liposome system which would permit long-term sustained release of ophthalmic drugs onto the cornea.     

The use of fungal protoplasts in the study of aflatoxin biosynthesis

Summary Protoplasts derived fromAspergillus flavus are shown to be capable of synthesizing aflatoxins when incubated in a chemically defined medium.¹⁴C-Acetate and¹⁴C-Versicolorin A, added to protoplasts from 3-day-old mycelium, are incorporated into aflatoxin B₁.