Overexpression of the human MNB/DYRK1A gene induces formation of multinucleate cells through overduplication of the centrosome

BACKGROUND: Previously we cloned the human MNB/DYRK1A gene from the "Down syndrome critical region" on chromosome 21. This gene encodes a dual specificity protein kinase that catalyzes its autophosphorylation on serine/threonine and tyrosine residues. But, the functions of the MNB/DYRK1A gene in cellular processes are unknown. RESULTS: In this study, we examined HeLa cells transfected with cDNA encoding a green fluorescent protein (GFP)-MNB/DYRK1A fusion protein and found 2 patterns of expression: In one group of transfected cells, GFP-MNB/DYRK1A was localized as dots within the nucleus; and in the other group, it was overexpressed and had accumulated all over the nucleus. In the cells overexpressing GFP-MNB/DYRK1A, multinucleation was clearly observed; whereas in those with the nuclear dots, such aberrant nuclei were not found. Furthermore, in the latter cells, essential processes such as mitosis and cytokinesis occurred normally. Multinucleation was dependent on the kinase activity of MNB/DYRK1A, because it was not observed in cells overexpressing kinase activity-negative mutants, GFP-MNB/DYRK1A (K179R) and GFP-MNB/DYRK1A (Y310F/Y312F). Immunostaining of GFP-MNB/DYRK1A-overexpressing cells with specific antibodies against α- and γ-tubulin revealed that multiple copies of centrosomes and aberrant multipolar spindles were generated in these cells. CONCLUSIONS: These results indicate that overexpression of MNB/DYRK1A induces multinucleation in HeLa cells through overduplication of the centrosome during interphase and production of aberrant spindles and missegregation of chromosomes during mitosis

Formation of unipolar outflow and protostellar rocket effect\textit{protostellar rocket effect} in magnetized turbulent molecular cloud cores

Observed protostellar outflows exhibit a variety of asymmetrical features, including remarkable unipolar outflows and bending outflows. Revealing the formation and early evolution of such asymmetrical protostellar outflows, especially the unipolar outflows, is essential for a better understanding of the star and planet formation because they can dramatically change the mass accretion and angular momentum transport to the protostars and protoplanetary disks. Here, we perform the three-dimensional non-ideal magnetohydrodynamics simulations to investigate the formation and early evolution of the asymmetrical protostellar outflows in magnetized turbulent isolated molecular cloud cores. We find, for the first time to our knowledge, that the unipolar outflow forms even in the single low-mass protostellar system. The results show that the unipolar outflow is driven in the weakly magnetized cloud cores with the dimensionless mass-to-flux ratios of $\mu=8$ and $16$. Furthermore, we find the $\textit{protostellar rocket effect}$ of the unipolar outflow, which is similar to the launch and propulsion of a rocket. The unipolar outflow ejects the protostellar system from the central dense region to the outer region of the parent cloud core, and the ram pressure caused by its ejection suppresses the driving of additional new outflows. In contrast, the bending bipolar outflow is driven in the moderately magnetized cloud core with $\mu=4$. The ratio of the magnetic to turbulent energies of a parent cloud core may play a key role in the formation of asymmetrical protostellar outflows.Comment: 24 pages, 6 figures, accepted for publication in Ap

The Japanese space gravitational wave antenna; DECIGO

DECi-hertz Interferometer Gravitational wave Observatory (DECIGO) is the future Japanese space gravitational wave antenna. DECIGO is expected to open a new window of observation for gravitational wave astronomy especially between 0.1 Hz and 10 Hz, revealing various mysteries of the universe such as dark energy, formation mechanism of supermassive black holes, and inflation of the universe. The pre-conceptual design of DECIGO consists of three drag-free spacecraft, whose relative displacements are measured by a differential Fabry– Perot Michelson interferometer. We plan to launch two missions, DECIGO pathfinder and pre- DECIGO first and finally DECIGO in 2024

DECIGO pathfinder

DECIGO pathfinder (DPF) is a milestone satellite mission for DECIGO (DECi-hertz Interferometer Gravitational wave Observatory) which is a future space gravitational wave antenna. DECIGO is expected to provide us fruitful insights into the universe, in particular about dark energy, a formation mechanism of supermassive black holes, and the inflation of the universe. Since DECIGO will be an extremely large mission which will formed by three drag-free spacecraft with 1000m separation, it is significant to gain the technical feasibility of DECIGO before its planned launch in 2024. Thus, we are planning to launch two milestone missions: DPF and pre-DECIGO. The conceptual design and current status of the first milestone mission, DPF, are reviewed in this article

The status of DECIGO

DECIGO (DECi-hertz Interferometer Gravitational wave Observatory) is the planned Japanese space gravitational wave antenna, aiming to detect gravitational waves from astrophysically and cosmologically significant sources mainly between 0.1 Hz and 10 Hz and thus to open a new window for gravitational wave astronomy and for the universe. DECIGO will consists of three drag-free spacecraft arranged in an equilateral triangle with 1000 km arm lengths whose relative displacements are measured by a differential Fabry-Perot interferometer, and four units of triangular Fabry-Perot interferometers are arranged on heliocentric orbit around the sun. DECIGO is vary ambitious mission, we plan to launch DECIGO in era of 2030s after precursor satellite mission, B-DECIGO. B-DECIGO is essentially smaller version of DECIGO: B-DECIGO consists of three spacecraft arranged in an triangle with 100 km arm lengths orbiting 2000 km above the surface of the earth. It is hoped that the launch date will be late 2020s for the present

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Reactive Casting of Ni-Al-Fe Ternary Intermetallic Alloys

NiAl-base intermetallic alloys containing iron up to 25 at% are produced by reactive casting, which involves an exothermic reaction between elemental liquids and enables one to cast high-melting-point intermetallic alloys without the need of external heating. In this study, aluminum liquid at 1023 K and a moltennickeliron alloy at 1773 K are mixed to produce a molten Ni–Al–Fe ternary intermetallic alloy with a temperature of over 2300 K, which is approximately 400 K higher than the melting point of the alloy produced. The concentrations of the constituent elements are approximately homogeneous in the ingot of 30 mm in diameter and 130 mm in height. The grain size of the ingot decreases, as the iron content increases. The increase in iron content improves the hardness, bending strength and wear resistance of the alloy. Young's modulus of the alloy decreases with the increase in temperature and iron content

Effect of bile acids on the uptake of irinotecan and its active metabolite, SN-38, by intestinal cells

The intestinal transport of irinotecan (CPT-11) and its active metabolite, SN-38, has been previously reported (K. Kobayashi et al., Int. J. Cancer, 83 (1999) 491-496). In the present study, the effect of the two major primary bile acids, cholic acid (CA) and taurocholic acid (TCA), on the uptake of CPT-11 and SN-38 by hamster intestinal epithelial cells was investigated. These two bile acids at concentrations up to 200 μM did not directly alter the cellular uptake of CPT-11 and SN-38. However, under physiologically acidic intestinal pH conditions, micelle formation induced by 20 mM TCA significantly reduced the cellular uptake of CPT-11 and SN-38 by 60% and 80%, respectively. © 2001 Elsevier Science B.V