The effects of parabiotic union with a normal partner on the blood tissue of the b/b rat suffering from an inheritable anemia

Summary The parabiotic union of a b/b rat, suffering from a red blood cell anemia, with a normal partner will restore to normal the functioning of this type of blood cell. The effect of parabiotic union is evident for several weeks following the separation of the parabiotic partners. It would be logical to conclude that the normal partner supplies a factor absent in the anemic animal needed for normal functioning of the red cell.     

Oxytalan fibres in human dental pulp

Summary Scarce and randomly oriented oxytalan fibres are present in the connective tissue of dental pulp in both deciduous and permanent teeth.This investigation was supported by grant No.V-10/78 from the SIZ-V of S. R. Croatia.     

Diabetogenic action of alloxan-like derivatives of uric acid

Summary Two new potent diabetogenic substances 4,5-dihydro-4,5-dihydroxyuric acid (1) and 5-hydroxy-pseudouric acid (2) have been found.     

The Heuristic Function of Mathematics in Physics and Astronomy

This paper considers the role of mathematics in the process of acquiring new knowledge in physics and astronomy. The defining of the notions of continuum and discreteness in mathematics and the natural sciences is examined. The basic forms of representing the heuristic function of mathematics at theoretical and empirical levels of knowledge are studied: deducing consequences from the axiomatic system of theory, the method of generating mathematical hypotheses, “pure” proofs for the existence of objects and processes, mathematical modelling, the formation of mathematics on the basis of internal mathematical principles and the mathematical theory of experiment.     

Isolation of peptides blocking the function of anti-apoptotic Livin protein

Livin (ML-IAP) is a cancer-associated member of the inhibitor of apoptosis protein (IAP) family. By yeast two-hybrid screening of a randomized peptide expression library, we isolated short linear peptides that specifically bind to Livin, but not to other IAPs. Intracellular expression of the peptides sensitized livin-expressing cancer cells toward different pro-apoptotic stimuli. The bioactive peptides neither showed sequence homologies to Smac-derived IAP inhibitors, nor did they interfere with the binding of Livin to Smac. Intracellular expression of the peptides did not affect the levels or the subcellular distribution of Livin. Growth of livin-expressing tumor cells was inhibited in colony formation assays by the Livin-targeting peptides. These findings provide evidence that the targeted inhibition of Livin by peptides represents a viable approach for the apoptotic sensitization and growth inhibition of tumor cells. The inhibitory peptides isolated here could form a novel basis for the development of therapeutically useful Livin inhibitors.     

Empirical Evidence in the Structure of Physical Theories

The author considers the empirical component of physical theories. He studies the origin and development of the theory of physical experiment, the structure and gnoseological hypotheses of the measuring process, as well as the relativity principle concerning the measuring equipment. Examples of modern physical theories are used in order to demonstrate the influence of experimental facts on the formation and development, verification and accepting of these theories in the structure of scientific systems. The role of accidental experimental facts in this process is also the subject.     

Early blastomere determines embryo proliferation and caste fate in a polyembryonic wasp

Polyembryonic development is a unique mode of metazoan development in which a single zygote generates multiple embryos by clonal proliferation. The polyembryonic parasitic insect Copidosoma floridanum shows one of the most extreme cases of polyembryony, producing up to 2,000 embryos from a single egg. In addition, this wasp exhibits an unusual polyphenism, producing two morphologically distinct larval castes, termed precocious and reproductive, that develop clonally from the same zygote. This form of development seems incompatible with a model of insect development in which maternal pre-patterning of the egg specifies embryonic axial polarity. Here we show that maternal pre-patterning in the form of germ plasm creates cellular asymmetry at the four-cell stage embryo of Copidosoma that is perpetuated throughout development. Laser ablations of cells show that the cell inheriting the germ plasm regulates both the fate and proliferation of the reproductive caste. Thus, we have uncovered a new mechanism of caste specification, mediated by the regulatory capacity of a single cell. This study shows that the evolution of mammalian-like regulative development of an insect embryo relies on a novel cellular context that might ultimately enhance developmental plasticity.     

Crystal structure of human cytochrome P450 2C9 with bound warfarin

Cytochrome P450 proteins (CYP450s) are membrane-associated haem proteins that metabolize physiologically important compounds in many species of microorganisms, plants and animals. Mammalian CYP450s recognize and metabolize diverse xenobiotics such as drug molecules, environmental compounds and pollutants. Human CYP450 proteins CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 are the major drug-metabolizing isoforms, and contribute to the oxidative metabolism of more than 90% of the drugs in current clinical use. Polymorphic variants have also been reported for some CYP450 isoforms, which has implications for the efficacy of drugs in individuals, and for the co-administration of drugs. The molecular basis of drug recognition by human CYP450s, however, has remained elusive. Here we describe the crystal structure of a human CYP450, CYP2C9, both unliganded and in complex with the anti-coagulant drug warfarin. The structure defines unanticipated interactions between CYP2C9 and warfarin, and reveals a new binding pocket. The binding mode of warfarin suggests that CYP2C9 may undergo an allosteric mechanism during its function. The newly discovered binding pocket also suggests that CYP2C9 may simultaneously accommodate multiple ligands during its biological function, and provides a possible molecular basis for understanding complex drug-drug interactions.     

Effects of ovarian steroids on superoxide dismutase activity in the rat brain

The levels of manganese superoxide dismutase (MnSOD) and copper-zinc superoxide dismutase (CuZnSOD) were determined in appropriate subcellular fractions prepared from whole brain homogenates of cycling and long-term (3 week) ovariectomized (OVX) Wistar rats, and were compared to the levels found in corresponding samples prepared from OVX rats treated with progesterone (P) or estradiol 17B-benzoate (EB). The activity of both SODs was steady during the estrous cycle, except at proestrus, when MnSOD activity was elevated significantly. Bilateral ovariectomy resulted three weeks later in an increase of the MnSOD activity even higher than that recorded at proestrus. High post-castration MnSOD activity was lowered profoundly by exogenous P (2 mg) or EB (0.5 g), given s.c. to OVX animals 2 h or 24 h before sacrifice. Neither removal of the ovaries nor the hormone treatments affected the activity of CuZnSOD. These results suggest suppressive effects of ovarian steroids on MnSOD activity in the rat brain.