Current status of space gravitational wave antenna DECIGO and B-DECIGO

Deci-hertz Interferometer Gravitational Wave Observatory (DECIGO) is the future Japanese space mission with a frequency band of 0.1 Hz to 10 Hz. DECIGO aims at the detection of primordial gravitational waves, which could be produced during the inflationary period right after the birth of the universe. There are many other scientific objectives of DECIGO, including the direct measurement of the acceleration of the expansion of the universe, and reliable and accurate predictions of the timing and locations of neutron star/black hole binary coalescences. DECIGO consists of four clusters of observatories placed in the heliocentric orbit. Each cluster consists of three spacecraft, which form three Fabry-Perot Michelson interferometers with an arm length of 1,000 km. Three clusters of DECIGO will be placed far from each other, and the fourth cluster will be placed in the same position as one of the three clusters to obtain the correlation signals for the detection of the primordial gravitational waves. We plan to launch B-DECIGO, which is a scientific pathfinder of DECIGO, before DECIGO in the 2030s to demonstrate the technologies required for DECIGO, as well as to obtain fruitful scientific results to further expand the multi-messenger astronomy

Inhibition of the Nicotinic Acetylcholine Receptors by Cobra Venom α-Neurotoxins: Is There a Perspective in Lung Cancer Treatment?

Nicotine exerts its oncogenic effects through the binding to nicotinic acetylcholine receptors (nAChRs) and the activation of downstream pathways that block apoptosis and promote neo-angiogenesis. The nAChRs of the α7 subtype are present on a wide variety of cancer cells and their inhibition by cobra venom neurotoxins has been proposed in several articles and reviews as a potential innovative lung cancer therapy. However, since part of the published results was recently retracted, we believe that the antitumoral activity of cobra venom neurotoxins needs to be independently re-evaluated

Current status of space gravitational wave antenna DECIGO and B-DECIGO

The Deci-hertz Interferometer Gravitational Wave Observatory (DECIGO) is a future Japanese space mission with a frequency band of 0.1 Hz to 10 Hz. DECIGO aims at the detection of primordial gravitational waves, which could have been produced during the inflationary period right after the birth of the Universe. There are many other scientific objectives of DECIGO, including the direct measurement of the acceleration of the expansion of the Universe, and reliable and accurate predictions of the timing and locations of neutron star/black hole binary coalescences. DECIGO consists of four clusters of observatories placed in heliocentric orbit. Each cluster consists of three spacecraft, which form three Fabry-Pérot Michelson interferometers with an arm length of 1000 km. Three DECIGO clusters will be placed far from each other, and the fourth will be placed in the same position as one of the other three to obtain correlation signals for the detection of primordial gravitational waves. We plan to launch B-DECIGO, which is a scientific pathfinder for DECIGO, before DECIGO in the 2030s to demonstrate the technologies required for DECIGO, as well as to obtain fruitful scientific results to further expand multi-messenger astronomy

Genomic Plasticity of the Human Fungal Pathogen Candida albicans▿

The genomic plasticity of Candida albicans, a commensal and common opportunistic fungal pathogen, continues to reveal unexpected surprises. Once thought to be asexual, we now know that the organism can generate genetic diversity through several mechanisms, including mating between cells of the opposite or of the same mating type and by a parasexual reduction in chromosome number that can be accompanied by recombination events (2, 12, 14, 53, 77, 115). In addition, dramatic genome changes can appear quite rapidly in mitotic cells propagated in vitro as well as in vivo. The detection of aneuploidy in other fungal pathogens isolated directly from patients (145) and from environmental samples (71) suggests that variations in chromosome organization and copy number are a common mechanism used by pathogenic fungi to rapidly generate diversity in response to stressful growth conditions, including, but not limited to, antifungal drug exposure. Since cancer cells often become polyploid and/or aneuploid, some of the lessons learned from studies of genome plasticity in C. albicans may provide important insights into how these processes occur in higher-eukaryotic cells exposed to stresses such as anticancer drugs

Cancer cell injury by cytotoxins from cobra venom is mediated through lysosomal damage

Cytotoxins from cobra venom are known to manifest cytotoxicity in various cell types. It is widely accepted that the plasma membrane is a target of cytotoxins, but the mechanism of their action remains obscure. Using the confocal spectral imaging technique, we show for the first time that cytotoxins from cobra venom penetrate readily into living cancer cells and accumulate markedly in lysosomes. Cytotoxins CT1 and CT2 from Naja oxiana, CT3 from Naja kaouthia and CT1 from Naja haje are demonstrated to possess this property with respect to human lung adenocarcinoma A549 and promyelocytic leukaemia HL60 cells. Immobilized plasma membrane binding accompanies the internalization of CT3 from Naja kaouthia in the HL60 cells, but it is very weak for other cytotoxins. Detectable membrane binding is not a property of any of the cytotoxins tested in A549 cells. The kinetics and concentration-dependence of cytotoxin accumulation in lysosomes correlate well with their cytotoxic effects. On the basis of the results obtained, we propose that lysosomes are a primary target of the lytic action of cytotoxins. Plasma membrane permeabilization seems to be a downstream event relative to lysosome rupture. Direct damage to the plasma membrane may be a complementary mechanism, but its relative contribution to the cytotoxic action depends on the cytotoxin structure and cell type

Delineation of the functional site of a snake venom cardiotoxin : preparation, structure, and function of monoacetylated derivatives

Toxin gamma, a cardiotoxin from the venom of the cobra Naja nigricollis, was modified with acetic anhydride, and the derivatives were separated by cation-exchange and reverse-phase chromatography. Nine monoacetylated derivatives were obtained, and those modified at positions 1, 2, 12, 23, and 35 were readily identified by automated sequencing. The overall structure of toxin gamma, composed of three adjacent loops (I, II, and III) rich in beta-sheet, was not affected by monoacetylation as revealed by circular dichroic analysis. Trp-11, Tyr-22, and Tyr-51 fluorescence intensities were not affected by modifications at Lys-12 and Lys-35, whereas Trp-11 fluorescence intensity slightly increased when Lys-1 and Lys-23 were modified. The cytotoxic activity of toxin gamma to FL cells in culture was unchanged after modification at positions 1 and 2, whereas it was 3-fold lower after modification at Lys-23 and Lys-35. The derivative modified at Lys-12 was 10-fold less active than native toxin. Using two isotoxins, we found that substitutions at positions 28, 30, 31, and 57 did not change the cytotoxic potency of toxin gamma. A good correlation between cytotoxicity, lethality, and, to some extent, depolarizing activity on cultured skeletal muscle cells was found. In particular, the derivative modified at Lys-12 always had the lowest potency. Our data show that the site responsible for cytotoxicity, lethality, and depolarizing activity is not diffuse but is well localized on loop I and perhaps at the base of loop II. This site is topographically different from the AcChoR binding site of the structurally similar snake neurotoxins