Factors which may influence the effectiveness of L-asparaginases as tumor inhibitors.

A NUMBER of tumors of experimental animals and of man are strongly inhibite

STUDIES ON THE MECHANISM OF TUMOR INHIBITION BY L-ASPARAGINASE : EFFECTS OF THE ENZYME ON ASPARAGINE LEVELS IN THE BLOOD, NORMAL TISSUES, AND 6C3HED LYMPHOMAS OF MICE: DIFFERENCES IN ASPARAGINE FORMATION AND UTILIZATION IN ASPARAGINASE-SENSITIVE AND -RESISTANT LYMPHOMA CELLS

L-asparaginases of agouti serum and Escherichia coli cause a profound lowering in the level of free asparagine in the blood of treated mice and also in the tissues. During treatment, normal tissues and resistant 6C3HED lymphomas survive unharmed with intracellular asparagine levels which are critically low for sensitive lymphomas. An explanation for this contrast between the two types of lymphoma is provided by the finding that resistant cells have not only a higher asparagine synthetic capacity than sensitive cells but appear able to utilize endogenous asparagine preferentially for protein synthesis. Cell-free extracts of resistant cells contain an asparaginase synthetase, but this is not found in preparations from sensitive cells

Observation of Entanglement-Dependent Two-Particle Holonomic Phase

Holonomic phases---geometric and topological---have long been an intriguing aspect of physics. They are ubiquitous, ranging from observations in particle physics to applications in fault tolerant quantum computing. However, their exploration in particles sharing genuine quantum correlations lack in observations. Here we experimentally demonstrate the holonomic phase of two entangled-photons evolving locally, which nevertheless gives rise to an entanglement-dependent phase. We observe its transition from geometric to topological as the entanglement between the particles is tuned from zero to maximal, and find this phase to behave more resilient to evolution changes with increasing entanglement. Furthermore, we theoretically show that holonomic phases can directly quantify the amount of quantum correlations between the two particles. Our results open up a new avenue for observations of holonomic phenomena in multi-particle entangled quantum systems.Comment: 8 pages, 6 figure

In Vitro RNase and Nucleic Acid Binding Activities Implicate Coilin in U snRNA Processing

Coilin is known as the marker protein for Cajal bodies (CBs), subnuclear domains important for the biogenesis of small nuclear ribonucleoproteins (snRNPs) which function in pre-mRNA splicing. CBs associate non-randomly with U1 and U2 gene loci, which produce the small nuclear RNA (snRNA) component of the respective snRNP. Despite recognition as the CB marker protein, coilin is primarily nucleoplasmic, and the function of this fraction is not fully characterized. Here we show that coilin binds double stranded DNA and has RNase activity in vitro. U1 and U2 snRNAs undergo a processing event of the primary transcript prior to incorporation in the snRNP. We find that coilin displays RNase activity within the CU region of the U2 snRNA primary transcript in vitro, and that coilin knockdown results in accumulation of the 3′ pre-processed U1 and U2 snRNA. These findings present new characteristics of coilin in vitro, and suggest additional functions of the protein in vivo

THE ANTICOAGULANT AND ANTILYMPHOMA PROPERTIES OF ARSENIC AZOPROTEINS : I. ANTICOAGULANT EFFECTS OF ARSENIC AZOPROTEINS IN VIVO AND IN VITRO: COMPARISON OF ARSENICALS AS ANTICOAGULANTS AND AS ANTILYMPHOMA AGENTS: MOLECULAR STRUCTURE IN RELATION TO ANTICOAGULANT AND ANTILYMPHOMA PROPERTIES

Experiments given in this paper have shown that 4-arsonophenylazoproteins possess marked anticoagulant activity both in vivo and in vitro. Mice and rabbits given moderate amounts of the arsenic azoprotein, for example, often bled to death from injuries that proved trivial in control animals, and their blood remained liquid during many hours' postmortem even when left in contact with transected tissues, fibrinolysis having no part in the outcome. So, too, the addition of minute amounts of 4-arsonophenylazoprotein to plasma procured from citrated rabbit or human blood greatly prolonged the time required for clotting after recalcification. Other arsenic-containing compounds,—for example, those in which arsenic See PDF for Structure was joined to amino acids or peptides through the azo linkage, or to proteins through couplings other than the azo linkage,—were largely devoid of anticoagulant and antilymphoma effects. The findings as a whole show clearly that the structural requirements for anticoagulant and antilymphoma effects are: (a) possession of negatively charged arsonic or arsinoso groups, (b) large molecular size (protein), and (c) linkage of arsenic-containing groups to protein through the azo bond. Two acidic azoproteins that were devoid of arsenic,—namely 4-carboxyphenylazoprotein and 4-sulfonophenylazoprotein,—were also found to have marked anticoagulant effects in vitro, but they had no inhibitory action against cells of Lymphoma 6C3HED in vivo, even when they were given to mice in maximum tolerated amounts. The essential part played by arsenic in the antilymphoma activity of arsenic azoproteins was further emphasized by the action of dimercaprol (BAL) in preventing the antilymphoma effects of 4-arsonophenylazoprotein on Lymphoma 6C3HED cells in vivo. In an associated paper the anticoagulant and antilymphoma effects of 4-arsonophenylazoproteins are studied further, and consideration is given to the ways in which these effects may be brought about

PROMOTION OF REPLICATION IN LYMPHOID CELLS BY SPECIFIC THIOLS AND DISULFIDES IN VITRO : EFFECTS ON MOUSE LYMPHOMA CELLS IN COMPARISON WITH SPLENIC LYMPHOCYTES

Numerous lines of mouse lymphoid tumors (13 of 22 tested) showed, with increased sensitivity, a property of normal mouse splenic lymphocytes, the potential for growth promotion in vitro by specific thiols added to standard culture media. For lymphoma L1210 (V), structure activity relationships were examined; 9 of 30 thiols promoted growth; the most active was α-thioglycerol, effective at 0.2 µM. Thiols became oxidized under conditions of tissue culture and had half-lives of less than 8 h. Disulfides of active thiols promoted growth of lymphoma cells. The mitogenic response of splenic lymphocytes to lectins was increased by thiols-disulfides which promoted the growth of lymphoma cells, but the response varied with the mitogen preparation used and under some conditions thiols-disulfides were inhibitory