The syntaxin Tlg1p mediates trafficking of chitin synthase III to polarized growth sites in yeast

Tlg1p and Tlg2p, members of the syntaxin family of SNAREs in yeast, have been implicated in both endocytosis and the retention of late Golgi markers. We have investigated the functions of these and the other endocytic syntaxins Pep12p and Vam3p. Remarkably, growth is possible in the absence of all four proteins. In the absence of the others, Pep12p and Tlg1p can each create endosomes accessible to the endocytic tracer dye FM4-64. However, although Pep12p is required for the ligand-induced internalization of the alpha factor receptor and its passage via Pep12p-containing membranes to the vacuole, Tlg1p is not. In contrast, Tlg1p is required for the efficient localization of the catalytic subunit of chitin synthase III (Chs3p) to the bud neck, a process that involves endocytosis and polarized delivery of Chs3p. In wild-type cells, internalized Chs3p cofractionates with Tlg1p and Tlg2p, and in a strain lacking the other endocytic syntaxins, either Tlg1p or Tlg2p is sufficient for correct localization of the enzyme. Pep12p is neither necessary nor sufficient for this process. We conclude that there are two endocytic routes in yeast that can operate independently and that Tlg1p is located at the junction of one of these with the polarized exocytic pathway.     

Concentration-dependent changes in the latency and amplitude of somatosensory-evoked potentials by desflurane, isoflurane and sevoflurane

Despite improvement in early diagnosis, surgical techniques, and general patient care, most deaths of cancer patients result from metastases. Recent studies have revealed that cytokines produced by cancer cells or by stromal cells play an important role into development the cancer metastasis. The formation of a cancer metastasis involves several major steps: 1) extensive vascularization; 2) local invasion; 3) adherence either to capillary endothelial cells or to subendothelial basement membrane; 4) extravasation; and 5) proliferation. In colon cancer, several cytokines such as growth factors, inflammatory cytokines, and angiogenic factors have been confirmed to be involved in each step of metastasis. This paper summarizes the involvement of cytokines in the development of invasion and metastasis in colon cancer.     

Perthes' disease treated by prolonged recumbency and femoral head containment: a long-term appraisal

The results of a long-term review of 102 hips in eighty-seven patients with Perthes' disease are described, the mean follow-up interval being seventeen years. All had been treated by an extremely rigorous conservative regime in which the patients were kept in hospital for an average period of twenty-six months, during which time they were confined to bed with the legs in wide abduction, first in traction and later in "broomstick" plasters to ensure "containment" of the femoral head. The patients were assessed by the joint clincial and radiological method described by Ratliff (1956). The results were very satisfactory, with only 2 per cent poor results and 10 per cent fair. The remaining 88 per cent were good. The radiological results at the end of treatment have also been compared with control series described by Catterall (1972) and with the osteotomy series of Lloyd-Roberts, Catterall and Salamon (1976). From this it appears that the described regime offers no benefit compared with the natural history in Catterall's Groups I and II, and in Group III the results were only marginally better than those following osteotomy. In Group IV cases, however, where the femoral head was totally involved, the benefit was important, and since these are the cases which carry the worst natural prognosis it is suggested that the use of the method described in such instances must be seriously considered in spite of its social disadvantages. The theoretical implications of the findings are considered, and it is concluded that the benefits of the method cannot be ascribed wholly to the application of the "containment" principle.     

The effect of compatibilization on the behavior of a polycarbonate/polymer liquid crystal blend

Polymer liquid crystalline materials (PLC) blended with engineering plastics (EP) have the potential to reduce viscosity and increase the modulus of the EP, particularly if the PLC is in a favorable fibrillar morphology. A major deficiency in these blends—as with many other immiscible polymeric systems—is poor failure properties. In this paper, polycarbonate (PC) and a rigid, all-aromatic commercial PLC are blended and a third resin, a copolymer of methyl methacrylate and N-methyl-dimethyl-glutarimide is included as a compatibilizing agent. Characterization of the binary and ternary blends is carried out using rheological, mechanical, morphological, and dynamic mechanical characterization techniques. Binary blends of PLC in a PC matrix result in an immiscible, nodular morphology with low failure stresses. The addition of the copolymeric compatibilizer—particularly one with reactive functionalities—is found to improve tensile strength and yield a fibrillar blend morphology. It is proposed that this may be due to the compatibilizer reducing interfacial tension and adhering to the blend phases, rather than by causing a major change in blend viscosity.     

O6-alkylguanine-DNA alkyltransferase inactivation by ester prodrugs of O6-benzylguanine derivatives and their rate of hydrolysis by cellular esterases

To modulate the bioavailability and perhaps improve the tumor cell selectivity of O6-alkylguanine-DNA alkyltransferase (AGT) inactivators, pivaloyloxymethyl ester derivatives of O6-benzylguanine (BG) were synthesized and tested as AGT inactivators and as substrates for cellular esterases. The potential prodrugs examined were the 7- and 9-pivaloyloxymethyl derivatives of O6-benzylguanine (7- and 9-esterBG), and of 8-aza-O6-benzylguanine (8-aza-7-esterBG and 8-aza-9-esterBG) and the 9-pivaloyloxymethyl derivative of 8-bromo-O6-benzylguanine (8-bromo-9-esterBG). The benzylated purines were all potent inactivators of the pure AGT and of the AGT activity in HT29 cells and cell extracts. Each ester was at least 75 times less potent than the corresponding benzylated purine against the pure human AGT. In contrast, the activities of esters and their respective benzylated purine were similar in crude cell extracts and in intact cells. The increase in potency of esters in cellular extracts could be explained by a conversion of the respective prodrug to the more potent benzylated purine in the presence of cellular esterases. The apparent catalytic activity (Vmax/Km) of liver microsomal esterase for 8-azaBG ester prodrugs was 70-130 times greater than for BG prodrugs and 10-20 times greater than for 8-bromo-9-esterBG. Tumor cell hydrolysis of the esters varied considerably as a function of cell type and prodrug structure. These data suggest that these or related prodrugs may be advantageous for selective AGT inactivation in certain tumor types.     

Reaction and total cross sections for low energy pi + and pi - on isospin zero nuclei

We calculated the electrostatic force between a planar interface, such as a planar-supported lipid bilayer membrane, and the tip of a stylus on which another lipid bilayer or some other biomacromolecular system might be deposited. We considered styli with rounded tips as well as conical tips. To take into account the effect of dynamical hydrogen-bonded structures in the aqueous phase, we used a theory of nonlocal electrostatics. We used the Derjaguin approximation and identified the systems for which its use is valid. We pointed out where our approach differs from previous calculations and to what extent the latter are inadequate. We found that 1) the nonlocal interactions have significant effects over distances of 10-15 A from the polar zone and that, at the surface of this zone, the effect on the calculated force can be some orders of magnitude; 2) the lipid dipoles and charges are located a distance L from the hydrophobic layer in the aqueous medium and this can have consequences that may not be appreciated if it is ignored; 3) dipoles, located in the aqueous region, can give rise to forces even though the polar layer is unchanged, and if this is ignored the interpretation of force data can be erroneous if an attempt is made to rationalize an observed force with a knowledge of an uncharged surface; 4) the shape of the stylus tip can be very important, and a failure to take this into account can result in incorrect conclusions, a point made by other workers; and 5) when L is nonzero, the presence of charges and dipoles can yield a force that can be nonmonotonic as a function of ionic concentration.     

In vivo electrochemical studies of dopamine clearance in subregions of rat nucleus accumbens: differential properties of the core and shell

The effects of the rodent hepatocarcinogens clofibric acid and diprofibrate on the activity of the peroxisomal fatty acyl-CoA oxidase, DNA synthesis, and apoptosis were compared in cultured rat and human hepatocytes. Rat hepatocytes expressed a 10-fold greater level of the peroxisomal fatty acyl-CoA oxidase compared to human hepatocytes. At the highest concentration (1.0 mM), both drugs induced a two- to threefold increase in this enzyme activity in both rat and human hepatocytes. Ciprofibrate (0.1 and 0.2 mM) caused a twofold increase in DNA synthesis in rat hepatocytes, whereas clofibric acid had no effect on DNA synthesis in these cells. In contrast, increasing concentrations of both clofibric acid and ciprofibrate produced inhibition of DNA synthesis in human hepatocytes. By using the terminal transferase dUTP-biotin nick end labeling technique, it was observed that 0.1 and 0.2 mM clofibric acid and ciprofibrate suppressed transforming growth factor-beta (TGF beta)-induced apoptosis by 50% in rat hepatocytes, but they had no effect on TGF beta-induced apoptosis in human hepatocytes. Although clofibric acid and ciprofibrate diminished TGF beta-induced apoptosis, they had no effect on the basal apoptotic levels in the rat hepatocyte cultures. However, both drugs significantly increased the percent of apoptotic cells in the human hepatocyte cultures. It is concluded that primary rat and human hepatocyte cultures respond differently to peroxisome proliferators. The differences in effects on DNA synthesis and apoptosis support the hypothesis that human liver cells are refractory to peroxisome proliferator-induced hepatocarcinogenesis.     

6 Top Tools for Taming Big Data

The industry now has a buzzword, "big data," for how we’re going to do something with the huge amount of information piling up. "Big data" is replacing "business     

Subtle variations in the structure of crosslinked epoxy networks and the impact upon mechanical and thermal properties

Presented here is an investigation of the structure–property relationships of crosslinked networks using three bi-functional glycidyl ether aromatic epoxy resins, two bi-aryl and one tri-aryl, cured with bi- and tri-aryl amines. Subtle changes to the monomer chemistry including changing aromatic substitution patterns from meta to para, methylene to isopropyl and isopropyl to ether were explored. Changing an epoxy resin backbone from methylene to isopropyl enhances backbone rigidity thus increasing glass transition temperature (T_g), yield strength, and strain despite reducing modulus. Changing meta-substitution to para increases T_g and yield strain while leaving strength unaffected and reducing modulus. Changing isopropyl linkages to ether reduces modulus, strength, T_g, and yield strain reflecting increased molecular flexibility. Using three instead of two aromatic rings increases the molecular weight between crosslinks thereby decreasing T_g and yield strain while increasing modulus and strength. Despite the complexities of multiple systems for varying epoxy resins and amine hardeners, the effect upon network properties is explained in terms of short- and long-range molecular and segmental mobility, crosslink density, and equilibrium packing density. © 2020 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48874.