Reciprocal Roles for CCAAT/Enhancer Binding Protein (C/EBP) and PU.1 Transcription Factors in Langerhans Cell Commitment

Myeloid progenitor cells give rise to a variety of progenies including dendritic cells. However, the mechanism controlling the diversification of myeloid progenitors into each progeny is largely unknown. PU.1 and CCAAT/enhancing binding protein (C/EBP) family transcription factors have been characterized as key regulators for the development and function of the myeloid system. However, the roles of C/EBP transcription factors have not been fully identified because of functional redundancy among family members. Using high titer–retroviral infection, we demonstrate that a dominant-negative C/EBP completely blocked the granulocyte–macrophage commitment of human myeloid progenitors. Alternatively, Langerhans cell (LC) commitment was markedly facilitated in the absence of tumor necrosis factor (TNF)α, a strong inducer of LC development, whereas expression of wild-type C/EBP in myeloid progenitors promoted granulocytic differentiation, and completely inhibited TNFα-dependent LC development. On the other hand, expression of wild-type PU.1 in myeloid progenitors triggered LC development in the absence of TNFα, and its instructive effect was canceled by coexpressed C/EBP. Our findings establish reciprocal roles for C/EBP and PU.1 in LC development, and provide new insight into the molecular mechanism of LC development, which has not yet been well characterized

Improvement of Ic degradation of HTS Conductor (FAIR Conductor) and FAIR Coil Structure for Fusion Device

As a high-temperature superconducting (HTS) conductor with a large current capacity applicable to a nuclear fusion experimental device, REBCO (REBa 2 CuO y ) tapes and high-purity aluminum sheets are alternately laminated, placed in a groove of an aluminum alloy jacket having a circular cross section, and the lid is friction-stir welded. To make the current distribution and mechanical characteristics uniform, the conductor is twisted at the end of the manufacturing process. In the early prototype conductor, when the I c was measured in liquid nitrogen under self-magnetic field conditions, I c degradations were observed from the beginning, and the characteristic difference between the two prototype samples under the same manufacturing conditions were large. Furthermore, I c degradation was progressed by repeating the thermal cycle from room temperature to liquid nitrogen temperature. This I c degradation did not occur uniformly in the longitudinal direction of the conductor but was caused by local I c degradation occurring at multiple locations. If the conductor was not manufactured uniformly in the longitudinal direction, the difference in thermal shrinkage between the REBCO tape and the aluminum alloy jacket caused local stress concentration in the REBCO tape and buckling occurred. Element experiments to explain this mechanism were conducted to clarify the conditions under which I c degradation due to buckling occurs. Then prototype conductors were tested with improved manufacturing methods, and as a result, I c degradation could be suppressed to 20% or less. We have achieved the prospect of producing a conductor with uniform characteristics in the longitudinal direction

A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a devastating progressive motor neuron disease that affects people of all ethnicities. Approximately 90% of ALS cases are sporadic and thought to have multifactorial pathogenesis. To understand the genetics of sporadic ALS, we conducted a genome-wide association study using 1,173 sporadic ALS cases and 8,925 controls in a Japanese population. A combined meta-analysis of our Japanese cohort with individuals of European ancestry revealed a significant association at the ACSL5 locus (top SNP p = 2.97 × 10−8). We validated the association with ACSL5 in a replication study with a Chinese population and an independent Japanese population (1941 ALS cases, 3821 controls; top SNP p = 1.82 × 10−4). In the combined meta-analysis, the intronic ACSL5 SNP rs3736947 showed the strongest association (p = 7.81 × 10−11). Using a gene-based analysis of the full multi-ethnic dataset, we uncovered additional genes significantly associated with ALS: ERGIC1, RAPGEF5, FNBP1, and ATXN3. These results advance our understanding of the genetic basis of sporadic ALS

Relationship Between Diseased Lung Tissues on Computed Tomography and Motion of Fiducial Marker Near Lung Cancer

BACKGROUND: For lung cancer patients with poor pulmonary function due to emphysema or fibrosis, it is important to predict the amplitude of internal tumor motion to minimize the irradiation of the functioning lung tissue before receiving stereotactic body radiotherapy. MATERIALS AND METHODS: Two board-certified diagnostic radiologists independently assessed the degree of pulmonary emphysema and fibrosis on computed tomography (CT) in 71 patients with peripheral lung tumors before real-time tumor-tracking radiotherapy (RTRT). The relationships between CT findings of the lung parenchyma and the motion of the fiducial marker near the lung tumor were investigated. Thirty patients had normal pulmonary function. Twenty-nine patients had obstructive pulmonary dysfunction (FEV1/FVC < 70%), 6 patients had constrictive dysfunction (%VC < 80%), and 16 had mixed dysfunction. RESULTS: The upper region was associated with smaller tumor motion, as expected (p=0.0004), and presence of fibrosis (p=0.088) and pleural contact of the tumor (p=0.086) were weakly associated with the tumor motion. The presence of fibrotic change in lung tissue was associated with smaller tumor motion in the upper region (p<0.05) but not in the lower region. The findings of emphysema and pulmonary function tests were not associated with tumor motion. CONCLUSIONS: Tumors in the upper region of lungs with fibrotic changes have smaller motion than those in the upper region of lungs without fibrotic changes. Tumor motion in the lower lung region was not significantly different between patients with and those without lung fibrosis. Emphysema was not associated with the amplitude of tumor motion