1,858 research outputs found
Osteoclast differentiation independent of the TRANCE–RANK–TRAF6 axis
Osteoclasts are derived from myeloid lineage cells, and their differentiation is supported by various osteotropic factors, including the tumor necrosis factor (TNF) family member TNF-related activation-induced cytokine (TRANCE). Genetic deletion of TRANCE or its receptor, receptor activator of nuclear factor κB (RANK), results in severely osteopetrotic mice with no osteoclasts in their bones. TNF receptor-associated factor (TRAF) 6 is a key signaling adaptor for RANK, and its deficiency leads to similar osteopetrosis. Hence, the current paradigm holds that TRANCE–RANK interaction and subsequent signaling via TRAF6 are essential for the generation of functional osteoclasts. Surprisingly, we show that hematopoietic precursors from TRANCE-, RANK-, or TRAF6-null mice can become osteoclasts in vitro when they are stimulated with TNF-α in the presence of cofactors such as TGF-β. We provide direct evidence against the current paradigm that the TRANCE–RANK–TRAF6 pathway is essential for osteoclast differentiation and suggest the potential existence of alternative routes for osteoclast differentiation
Improved direct diabatization and coupled potential energy surfaces for the photodissociation of ammonia
Biogenesis of the inner membrane complex is dependent on vesicular transport by the alveolate specific GTPase Rab11B
Apicomplexan parasites belong to a recently recognised group of protozoa referred to as Alveolata. These protists contain membranous sacs (alveoli) beneath the plasma membrane, termed the Inner Membrane Complex (IMC) in the case of Apicomplexa. During parasite replication the IMC is formed de novo within the mother cell in a process described as internal budding. We hypothesized that an alveolate specific factor is involved in the specific transport of vesicles from the Golgi to the IMC and identified the small GTPase Rab11B as an alveolate specific Rab-GTPase that localises to the growing end of the IMC during replication of Toxoplasma gondii. Conditional interference with Rab11B function leads to a profound defect in IMC biogenesis, indicating that Rab11B is required for the transport of Golgi derived vesicles to the nascent IMC of the daughter cell. Curiously, a block in IMC biogenesis did not affect formation of sub-pellicular microtubules, indicating that IMC biogenesis and formation of sub-pellicular microtubules is not mechanistically linked. We propose a model where Rab11B specifically transports vesicles derived from the Golgi to the immature IMC of the growing daughter parasites
The pseudogap: friend or foe of high Tc?
Although nineteen years have passed since the discovery of high temperature
superconductivity, there is still no consensus on its physical origin. This is
in large part because of a lack of understanding of the state of matter out of
which the superconductivity arises. In optimally and underdoped materials, this
state exhibits a pseudogap at temperatures large compared to the
superconducting transition temperature. Although discovered only three years
after the pioneering work of Bednorz and Muller, the physical origin of this
pseudogap behavior and whether it constitutes a distinct phase of matter is
still shrouded in mystery. In the summer of 2004, a band of physicists gathered
for five weeks at the Aspen Center for Physics to discuss the pseudogap. In
this perspective, we would like to summarize some of the results presented
there and discuss its importance in the context of strongly correlated electron
systems.Comment: expanded version, 20 pages, 11 figures, to be published, Advances in
Physic
Search for lepton-flavor-violating decays at Belle
We have searched for neutrinoless lepton decays into and ,
where stands for an electron or muon, and for a vector meson
(, , , or ), using 543 fb
of data collected with the Belle detector at the KEKB asymmetric-energy
collider. No excess of signal events over the expected background has
been observed, and we set upper limits on the branching fractions in the range
at the 90% confidence level. These upper limits
include the first results for the mode as well as new limits that
are significantly more restrictive than our previous results for the , , and modes.Comment: 7 pages, 16 figure
Measurement of CP asymmetry in Cabibbo suppressed D0 decays
We measure the CP-violating asymmetries in decays to the D0 -> K+K- and D0 ->
pi+pi- CP eigenstates using 540 fb^{-1} of data collected with the Belle
detector at or near the Upsilon(4S) resonance. Cabibbo-favored D0 -> K-pi+
decays are used to correct for systematic detector effects. The results,
A_{CP}^{KK} = (-0.43 +- 0.30 +- 0.11)% and A_{CP}^{pipi} = (+0.43 +- 0.52 +-
0.12)%, are consistent with no CP violation.Comment: Submitted to Phys. Lett.
Common Variants in CDKN2B-AS1 Associated with Optic-Nerve Vulnerability of Glaucoma Identified by Genome-Wide Association Studies in Japanese
BACKGROUND: To date, only a small portion of the genetic variation for primary open-angle glaucoma (POAG), the major type of glaucoma, has been elucidated. METHODS AND PRINCIPAL FINDINGS: We examined our two data sets of the genome-wide association studies (GWAS) derived from a total of 2,219 Japanese subjects. First, we performed a GWAS by analyzing 653,519 autosomal common single-nucleotide polymorphisms (SNPs) in 833 POAG patients and 686 controls. As a result, five variants that passed the Bonferroni correction were identified in CDKN2B-AS1 on chromosome 9p21.3, which was already reported to be a significant locus in the Caucasian population. Moreover, we combined the data set with our previous GWAS data set derived from 411 POAG patients and 289 controls by the Mantel-Haenszel test, and all of the combined variants showed stronger association with POAG (P<5.8 × 10(-10)). We then subdivided the case groups into two subtypes based on the value of intraocular pressure (IOP)--POAG with high IOP (high pressure glaucoma, HPG) and that with normal IOP (normal pressure glaucoma, NPG)--and performed the GWAS using the two data sets, as the prevalence of NPG in Japanese is much higher than in Caucasians. The results suggested that the variants from the same CDKN2B-AS1 locus were likely to be significant for NPG patients. CONCLUSIONS AND SIGNIFICANCE: In this study, we successfully identified POAG-associated variants in the CDKN2B-AS1 locus using a Japanese population, i.e., variants originally reported as being associated with the Caucasian population. Although we cannot rule out that the significance could be due to the differences in sample size between HPG and NPG, the variants could be associated specifically with the vulnerability of the optic nerve to IOP, which is useful for investigating the etiology of glaucoma
Anticancer Gene Transfer for Cancer Gene Therapy
Gene therapy vectors are among the treatments currently used to treat malignant tumors. Gene therapy vectors use a specific therapeutic transgene that causes death in cancer cells. In early attempts at gene therapy, therapeutic transgenes were driven by non-specific vectors which induced toxicity to normal cells in addition to the cancer cells. Recently, novel cancer specific viral vectors have been developed that target cancer cells leaving normal cells unharmed. Here we review such cancer specific gene therapy systems currently used in the treatment of cancer and discuss the major challenges and future directions in this field
Search for the X(1812) in
We report on a search for the X(1812) state in the decay with a data sample of pairs collected
with the Belle detector at the KEKB collider. No significant signal is
observed. An upper limit (90% C.L.) is determined. We also constrain the
three-body decay branching fraction to be 1.9 (90% C.L.).Comment: 5pages,2 figures(3 figure files). submitted to PRD(RC
Search for CP violation in tau -> K^0_S pi nu_tau decays at Belle
We report on a search for CP violation in tau -> K^0_S pi nu_tau decays using
a data sample of 699 fb^{-1} collected in the Belle experiment at the KEKB
electron-positron asymmetric-energy collider. The CP asymmetry is measured in
four bins of the invariant mass of the K^0_S pi system and found to be
compatible with zero with a precision of O(10^{-3}) in each mass bin. Limits
for the CP violation parameter Im(eta_S) are given at a 90 % confidence level.
These limits are |Im(eta_S)|<0.026 or better, depending on the parameterization
used to describe the hadronic form factors and improve upon previous limits by
one order of magnitude
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