Aberrant High Expression of B Lymphocyte Chemokine (Blc/Cxcl13) by C11b+Cd11c+ Dendritic Cells in Murine Lupus and Preferential Chemotaxis of B1 Cells towards Blc

We observed here that the expression of B lymphocyte chemokine (BLC/CXCL13) was markedly enhanced in the thymus and kidney in aged (NZB × NZW)F1 (BWF1) mice developing lupus nephritis, but not in similarly aged NZB and NZW mice. BLC-positive cells were present in the cellular infiltrates in the target organs with a reticular pattern of staining. CD11b+CD11c+ dendritic cells were increased in the thymus and spleen in aged BWF1 mice and identified as the major cell source for BLC. CD4+ T cells as well as B cells were dramatically increased in the thymus in aged BWF1 mice, whereas no increase was observed in aged NZB and NZW mice. B1/B2 ratio in the thymus was significantly higher than those in the spleen and peripheral blood in aged BWF1 mice. Interestingly, BLC showed preferential chemotactic activity for B1 cells derived from several mouse strains, including nonautoimmune mice. Cell surface CXCR5 expression on B1 cells was significantly higher than that on B2 cells. Thus, aberrant high expression of BLC by myeloid dendritic cells in the target organs in aged BWF1 mice may play a pivotal role in breaking immune tolerance in the thymus and in recruiting autoantibody-producing B cells in the development of murine lupus

Genome Sequence of Striga asiatica Provides Insight into the Evolution of Plant Parasitism

Parasitic plants in the genus Striga, commonly known as witchweeds, cause major crop losses in sub-Saharan Africa and pose a threat to agriculture worldwide. An understanding of Striga parasite biology, which could lead to agricultural solutions, has been hampered by the lack of genome information. Here, we report the draft genome sequence of Striga asiatica with 34,577 predicted protein-coding genes, which reflects gene family contractions and expansions that are consistent with a three-phase model of parasitic plant genome evolution. Striga seeds germinate in response to host-derived strigolactones (SLs) and then develop a specialized penetration structure, the haustorium, to invade the host root. A family of SL receptors has undergone a striking expansion, suggesting a molecular basis for the evolution of broad host range among Striga spp. We found that genes involved in lateral root development in non-parasitic model species are coordinately induced during haustorium development in Striga, suggesting a pathway that was partly co-opted during the evolution of the haustorium. In addition, we found evidence for horizontal transfer of host genes as well as retrotransposons, indicating gene flow to S. asiatica from hosts. Our results provide valuable insights into the evolution of parasitism and a key resource for the future development of Striga control strategies.Peer reviewe

Genomewide-Linkage and Haplotype-Association Studies Map Intracranial Aneurysm to Chromosome 7q11

Rupture of intracranial aneurysms (IAs) causes subarachnoid hemorrhage, a devastating condition with high morbidity and mortality. Angiographic and autopsy studies show that IA is a common disorder, with a prevalence of 3%–6%. Although IA has a substantial genetic component, little attention has been given to the genetic determinants. We report here a genomewide linkage study of IA in 104 Japanese affected sib pairs in which positive evidence of linkage on chromosomes 5q22-31 (maximum LOD score [MLS] 2.24), 7q11 (MLS 3.22), and 14q22 (MLS 2.31) were found. The best evidence of linkage is detected at D7S2472, in the vicinity of the elastin gene (ELN), a candidate gene for IA. Fourteen distinct single-nucleotide polymorphisms (SNPs) were identified in ELN, and no obvious allelic association between IA and each SNP was observed. The haplotype between the intron-20/intron-23 polymorphism of ELN is strongly associated with IA (P=3.81×10(-6)), and homozygous patients are at high risk (P=.002), with an odds ratio of 4.39. These findings suggest that a genetic locus for IA lies within or close to the ELN locus on chromosome 7

High-precision Compton imaging of 4.4 MeV prompt gamma-ray toward an on-line monitor for proton therapy

Proton therapy is a widely used and effective treatment for cancer. A high-dose concentration of proton beamreduces damage to normal tissues. However, it also requires a high accuracy of irradiation. PET is generallyused to verify the proton range after irradiation, but, the distributions of positrons and the energy deposited byprotons are not similar to each other. Recently, prompt gamma-ray imaging has attracted attention as a new,online imaging technique. In particular, 4.4 MeV gamma rays emitted from 12C* is one of the best probes tomonitor the proton dose, however imaging techniques are far from established. We have developed a novel,3-D position sensitive Compton camera based on Ce:GAGG scintillators coupled with multi-pixel photon counter(MPPC) arrays, thus making it optimized for imaging in the 1–10 MeV range. The angular resolution is 5 degrees(FWHM) at 4.4 MeV. We have established various methods to discriminate multiple-Compton and escape events,both of which can be critical backgrounds for precise imaging of prompt gamma rays. By irradiating a 70 MeVproton beam on the PMMA phantom, we demonstrated that 4.4 MeV gamma ray image is sharply concentratedon the Bragg peak, as was expected from the PHITS simulation