Regulation of secretory activity in the albumen gland of the pulmonate snail Lymnaea stagnalis (L.)

The secretory activity of the albumen gland of the freshwater snail Lymnaea stagnalis was studied morphometrically (both at the light- and at the electron-microscope level) and biochemically under the following experimental conditions: (1) glandular tissue was implanted into acceptor snails and the glandular activity of the implants was compared to that of the glands of the donors and acceptors; (2) glandular activity was measured at various periods after oviposition; and (3) the activity was measured during a 24 h cycle (diurnal activity). The results indicate that cellular release of secretion material is regulated by a nervous mechanism, whereas synthetic activity is under hormonal control.     

Fused thiazolyl alkynes as potent mGlu5 receptor positive allosteric modulators

A new series of potent fused thiazole mGlu₅ receptor positive allosteric modulators (PAMs) (10, 11 and 27–31) are disclosed and details of the SAR and optimization are described. Optimization of alkynyl thiazole 9 (Lu AF11205) led to the identification of potent fused thiazole analogs 10b, 27a, 28j and 31d. In general, substituted cycloalkyl, aryl and heteroaryl carboxamides, and carbamate analogs are mGlu₅ PAMs, whereas smaller alkyl carboxamide, sulfonamide and sulfamide analogs tend to be mGlu₅ negative allosteric modulators (NAMs).     

The effect of pH on the lability of lead and cadmium sorbed on humic acid particles

Abstract

Sorption of lead(II) or cadmium(II) ions on humic acid particles (at pH 3.5) yields surface complexes which are sparingly soluble in the pH 3.55 region. Interaction of these species with acetic acid or dilute nitric acid released ASV labile metal species (mainly hydrated metal ion). When the pH was adjusted between 4 and 7, increasing amounts of the metal humate species (and humic acid substrate) dissolved and low levels of ASV labile species were detected. Overnight interaction with an excess of acetate ions (0.01 M) led to higher lability values (attributed to acetate/humate ligand exchange). The percentage of labile metal ion detected in acetate solutions varied with the amount of metal ion initially sorbed (range 100 to 500 mmol g^?1). With the lower loadings, the ASV labile levels peaked in the pH 6–7 region (at around 12% of total sorbed cadmium, and 4% of total lead). In alkaline solutions, the percentage of labile Cd fell to about half of the peak value, but with Pb, lability values increased at pH > 8, due possibly to the formation of hydroxy complex species. The ASV lability of the Cd and Pb humates, and their 24 hour lability values (determined using a transfer to cation exchanger technique) has been compared with the behaviour of Cu and Zn humates (using similar conditions).     

Determination of nitrite in lake sediments

Abstract

An evaluation of nitrite determination in marine lake sediments has shown that spectrophotometric measurements can be in error due to light scattering by colloidal (<0.2 μm) matter in extract solutions and incomplete nitrite recovery. The scatter error can be minimised by using uncoloured extract in the reference beam but precision at low levels remains poor (RSD 25 to 100%). Recovery tests on ‘spiked’ sediment indicated that optimum retrieval (～85%) occurred with 30 minute mixing with 0.2 M NH₄Cl, using a sediment to extractant ratio of 1:30. To counter this variable, calibration based on standard addition to sample suspensions is recommended. Modified procedure proposed is suitable for measuring up to 10 μg g^?1 of nitrite N; the lake sediments tested contained <100 ng g^?1     

Interactions between cadherin-11 and platelet-derived growth factor receptor-alpha signaling link cell adhesion and proliferation

Cadherins are homophilic cell-to-cell adhesion molecules that help cells respond to environmental changes. Newly formed cadherin junctions are associated with increased cell phosphorylation, but the pathways driving this signaling response are largely unknown. Since cadherins have no intrinsic signaling activity, this phosphorylation must occur through interactions with other signaling molecules. We previously reported that cadherin-11 engagement activates joint synovial fibroblasts, promoting inflammatory and degradative pathways important in rheumatoid arthritis (RA) pathogenesis. Our objective in this study was to discover interacting partners that mediate cadherin-11 signaling. Protein array screening showed that cadherin-11 extracellular binding domains linked to an Fc domain (cad11Fc) induced platelet-derived growth factor (PDGFR)-α phosphorylation in synovial fibroblasts and glioblastoma cells. PDGFRs are growth factor receptor tyrosine kinases that promote cell proliferation, survival, and migration in mesodermally derived cells. Increased PDGFR activity is implicated in RA pathology and associates with poor prognosis in several cancers, including sarcoma and glioblastoma. PDGFRα activation by cadherin-11 signaling promoted fibroblast proliferation, a signaling pathway independent from cadherin-11-stimulated IL-6 or matrix metalloproteinase (MMP)-3 release. PDGFRα phosphorylation mediated most of the cad11Fc-induced phosphatidyl-3-kinase (PI3K)/Akt activation, but only part of the mitogen-activated protein kinase (MAPK) response. PDGFRα-dependent signaling did not require cell cadherin-11 expression. Rather, cad11Fc immunoprecipitated PDGFRα, indicating a direct interaction between cadherin-11 and PDGFRα extracellular domains. This study is the first to report an interaction between cadherin-11 and PDGFRα and adds to our growing understanding that cadherin-growth factor receptor interactions help balance the interplay between tissue growth and adhesion.     

Inhibitors of polyamine metabolism: Review article

Summary. The identification of increased polyamine concentrations in a variety of diseases from cancer and psoriasis to parasitic infections has led to the hypothesis that manipulation of polyamine metabolism is a realistic target for therapeutic or preventative intervention in the treatment of certain diseases.The early development of polyamine biosynthetic single enzyme inhibitors such as -difluoromethylornithine (DFMO) and methylglyoxal bis(guanylhydrazone) showed some interesting early promise as anticancer drugs, but ultimately failed in vivo. Despite this, DFMO is currently in use as an effective anti-parasitic agent and has recently also been shown to have further potential as a chemopreventative agent in colorectal cancer.The initial promise in vitro led to the development and testing of other potential inhibitors of the pathway namely the polyamine analogues. The analogues have met with greater success than the single enzyme inhibitors possibly due to their multiple targets. These include down regulation of polyamine biosynthesis through inhibition of ornithine decarboxylase and S-adenosylmethionine decarboxylase and decreased polyamine uptake. This coupled with increased activity of the catabolic enzymes, polyamine oxidase and spermidine/spermine N¹-acetyltransferase, and increased polyamine export has made the analogues more effective in depleting polyamine pools. Recently, the identification of a new oxidase (PAO-h1/SMO) in polyamine catabolism and evidence of induction of both PAO and PAO-h1/SMO in response to polyamine analogue treatment, suggests the analogues may become an important part of future chemotherapeutic and/or chemopreventative regimens.     

Signal transduction pathways linking polyamines to apoptosis

Summary. Polyamines are important multifunctional cellular components and are classically considered as mediators of cell growth and division. Recently polyamines have been also implicated in cell death. Now it appears that polyamines are bivalent regulators of cellular functions, promoting proliferation or cell death depending on the cell type and on environmental signals. This review draws a picture about the role of polyamines in signalling pathways related to apoptotic cell death and the proposed molecular targets of these polycations at the level of the apoptotic cascade. Solid evidence indicates that polyamines may affect the mitochondrial and postmitochondrial phases of apoptosis, by modulating cytochrome c release from mitochondria and activation of caspases. Recently, polyamines have been also implicated in the regulation of the premitochondrial phase of apoptosis, during which upstream apoptotic signal transduction pathways are activated. The studies reviewed here suggest that polyamines may participate in loops involving interaction with signal transduction pathways and activation/expression of proteins that may control cell death or cell growth.     

A distinctive class of spermidine synthase is involved in chilling response in rice

A cDNA for a putative 42 kD spermidine synthase (OsSPDS2) was cloned from rice. The deduced OsSPDS2 sequence showed highest similarity with Arabidopsis AtSPDS3. Phylogenetic analysis revealed that OsSPDS2 and AtSPDS3 form a distinctive subclass in the spermidine synthase family in plants. OsSPDS2 mRNA accumulated in roots during long term exposure to chilling temperature (12 degrees C). In contrast, no such induction of the paralogous OsSPDS1 was observed during the chilling treatment. ABA treatment up-regulated OsSPDS2, whereas salt stress did not change OsSPDS2 levels significantly. Data suggested a distinct function of OsSPDS2 in chilling response in rice.     

Biosynthesis, oxidation and conjugation of aliphatic polyamines in higher plants

Summary. This chapter will focus on polyamine biosynthesis, oxidation, conjugation processes, mainly to hydroxycinnamic acids, and compartmentation of enzymes, substrates and products, giving an overview about recent results especially in higher plants. New research advances regarding the cloning of the main cDNA encoding for polyamine biosynthetic and oxidative enzymes, will be taken into consideration. Received January 4, 2000 Accepted March 7, 2000     

Analysis of Cre-loxP interaction by surface plasmon resonance: influence of spermidine on cooperativity

To study target site selectivity of one important class of DNA-binding proteins, site-specific DNA recombinases, we developed an automated real-time kinetic assay based on surface plasmon resonance (BIACORE) and formulated a curve-fitting model that takes into account cooperative interactions. Monitoring the interaction between the Cre DNA recombinase and its specific target site loxP by BIACORE, we found that Cre associates with loxP tightly and highly cooperatively. We observed that the cooperative moment of the Cre-loxP interaction is strongly dependent on the concentration of spermidine, a small polyamine influencing DNA conformation. Thus, DNA conformation can have a profound impact on substrate recognition and subsequent recombination.