Pharmacological versus binding analysis of receptor systems: How do they interplay? Myometrial cell receptors for oxytocin as a paradigm

Summary Binding studies in various biological systems frequently indicate the presence of several binding sites for a biologically active ligand. They differ in their affinity for the ligand in question, binding capacity, and Hill coefficient, which suggests differences in the mechanisms of the binding site-ligand interactions. Identification of the true receptors (sites initiating a cellular response) appears to be difficult. Three clusters of binding sites for oxytocin were found on rat myometrial cells. The oxytocin receptor seems to be linked to the medium-affinity site; the cooperation between the high-and medium-affinity sites in eliciting the uterotonic response seems likely, but lacks experimental proof. Dose-response analysis in partially irreversibly inhibited uterus preparations, the method of equipotent doses (Furchgott-Bursztyn method), and structure-activity analysis of oxytocin-like peptides acting as competitive inhibitors of oxytocin, turned out to be suitable for pharmacological analysis of this receptor system.     

Potentiating action of hexoprenaline on14C-aminopyrine uptake by isolated rat parietal cells

Summary Hexoprenaline potentiated the¹⁴C-aminopyrine uptake (a reliable index of H⁺ generation) of isolated rat gastric cells stimulated by 10^–6–10^–4 mol/l carbachol, and inhibited that in response to 10^–4 mol/l histamine without and in the presence of propranolol. It is concluded that hexoprenaline acts as a partial agonist on parietal cell H₂-receptors and that -adrenoceptor activation may functionally modualte gastric acid secretion.Acknowledgments. S. Maliski, Institute of Rheumatology, Warszawa, held a fellowship of the Alexander v. Humboldt-Foundation. The study was supported by the Deutsche Forschungsgemeinschaft. The skilful technical assistance of Mrs R. Maier and Mr R. Beer is gratefully acknowledged.     

Nuclear lamellae in the germ-line cells of gall midges (Cecidomyiidae,Diptera)

Summary Lamellar structures in oogonial and spermatogonial cells of gall midges were found to form a complicated system of intranuclear compartments inside which all heteropycnotic chromosomes present in the germ-line cells of these insects are located. In this way, the heteropycnotic S-chromosomes are separated by the nuclear lamellae from the remaining, decondensed chromosomes (E-chromosomes) of the interphase germ-line nucleus.This investigation was supported in part under Contract DPKBN/52/76-II.1.3.10. with the Polish Academy of Sciences.     

Presence of natural killer cells in Peyer's patches of the mouse

Summary Natural cell-mediated cytotoxicity of normal murine Peyer's patch cells against Ehrlich ascites carcinoma was found in a short-term⁵¹Cr release assay. Peyer's patch and lymph node cells showed natural cytotoxicity at approximately the same level.Acknowledgments. This work was supported by grant No. 10.5 from the Polish Academy of Sciences.     

Down's syndrome: changes in protein fractions of blood plasma

Summary A statistically significant decrease of prealbumin and statistically significant increases of alpha₂-macroglobulin and IgA were found in blood plasma of patients with Down's syndrome using quantitative crossed immunoelectrophoresis.We are indebted to Prof. T.C. Bøg-Hansen, University of Copenhagen, for the helpful discussion of our results.     

Influence of ethanol on thyroxine accumulation in the hypothalamus,pituitary gland and cerebrospinal fluid in the newborn rabbit

Summary The effect of ethanol on thyroxine (T₄) accumulation in the hypothalamus (H), pituitary gland (P) and cerebrospinal fluid (CSF) has been investigated in 1–15-day-old rabbits. It has been found that H or CSF serum ratios decreased with age by about 2 in the course of 13 postnatal days. Stable T₄ resulted in an increase of¹²⁵I-T₄ in H, P and CSF. Ethanol per se caused an increase in transfer and accumulation of radiothyroxine or made the changes after loading animals with carrier T₄ more pronounced.     

Telomerase and drug resistance in cancer

It is well known that a decreased expression or inhibited activity of telomerase in cancer cells is accompanied by an increased sensitivity to some drugs (e.g., doxorubicin, cisplatin, or 5-fluorouracil). However, the mechanism of the resistance resulting from telomerase alteration remains elusive. There are theories claiming that it might be associated with telomere shortening, genome instability, hTERT translocation, mitochondria functioning modulation, or even alterations in ABC family gene expression. However, association of those mechanisms, i.e., drug resistance and telomerase alterations, is not fully understood yet. We review the current theories on the aspect of the role of telomerase in cancer cells resistance to therapy. We believe that revealing/unravelling this correlation might significantly contribute to an increased efficiency of cancer cells elimination, especially the most difficult ones, i.e., drug resistant.     

Spin-based logic in semiconductors for reconfigurable large-scale circuits

Research in semiconductor spintronics aims to extend the scope of conventional electronics by using the spin degree of freedom of an electron in addition to its charge. Significant scientific advances in this area have been reported, such as the development of diluted ferromagnetic semiconductors, spin injection into semiconductors from ferromagnetic metals and discoveries of new physical phenomena involving electron spin. Yet no viable means of developing spintronics in semiconductors has been presented. Here we report a theoretical design that is a conceptual step forward-spin accumulation is used as the basis of a semiconductor computer circuit. Although the giant magnetoresistance effect in metals has already been commercially exploited, it does not extend to semiconductor/ferromagnet systems, because the effect is too weak for logic operations. We overcome this obstacle by using spin accumulation rather than spin flow. The basic element in our design is a logic gate that consists of a semiconductor structure with multiple magnetic contacts; this serves to perform fast and reprogrammable logic operations in a noisy, room-temperature environment. We then introduce a method to interconnect a large number of these gates to form a 'spin computer'. As the shrinking of conventional complementary metal-oxide-semiconductor (CMOS) transistors reaches its intrinsic limit, greater computational capability will mean an increase in both circuit area and power dissipation. Our spin-based approach may provide wide margins for further scaling and also greater computational capability per gate.     

Ciliary proteins Fap43 and Fap44 interact with each other and are essential for proper cilia and flagella beating

Cilia beating is powered by the inner and outer dynein arms (IDAs and ODAs). These multi-subunit macrocomplexes are arranged in two rows on each outer doublet along the entire cilium length, except its distal end. To generate cilia beating, the activity of ODAs and IDAs must be strictly regulated locally by interactions with the dynein arm-associated structures within each ciliary unit and coordinated globally in time and space between doublets and along the axoneme. Here, we provide evidence of a novel ciliary complex composed of two conserved WD-repeat proteins, Fap43p and Fap44p. This complex is adjacent to another WD-repeat protein, Fap57p, and most likely the two-headed inner dynein arm, IDA I1. Loss of either protein results in altered waveform, beat stroke and reduced swimming speed. The ciliary localization of Fap43p and Fap44p is interdependent in the ciliate Tetrahymena thermophila.