Quantitative Trait Loci and Maternal Effects Affecting the Strong Grain Dormancy of Wild Barley (Hordeum vulgare ssp. spontaneum)

Wild barley (Hordeum vulgare ssp. spontaneum) has strong grain dormancy, a trait that may enhance its survival in non-cultivated environments; by contrast, cultivated barley (Hordeum vulgare ssp. vulgare) has weaker dormancy, allowing uniform germination in cultivation. Malting barley cultivars have been bred for especially weak dormancy to optimize their use in malt production. Here, we analyzed the genetic mechanism of this difference in seed dormancy, using recombinant inbred lines (RILs) derived from a cross between the wild barley accession ‘H602’ and the malting barley cultivar ‘Kanto Nakate Gold (KNG)’. Grains of H602 and KNG harvested at physiological maturity and dried at 30°C for 7 days had germination of approximately 0 and 100%, respectively. Analysis of quantitative trait loci (QTL) affecting grain dormancy identified the well-known major dormancy QTL SD1 and SD2 (located near the centromeric region and at the distal end of the long arm of chromosome 5H, respectively), and QTL at the end of the long arm of chromosome 4H and in the middle of the long arm of chromosome 5H. We designated these four QTL Qsd1-OK, Qsd2-OK, Qsdw-4H, and Qsdw-5H, and they explained approximately 6, 38, 3, and 13% of the total phenotypic variation, respectively. RILs carrying H602 alleles showed increased dormancy levels for all QTL. The QTL acted additively and did not show epistasis or QTL–environment interactions. Comparison of QTL locations indicated that all QTL except Qsdw-5H are likely the same as the QTL previously detected in the doubled haploid population from a cross between the malting cultivar ‘Haruna Nijo’ and ‘H602.’ We further examined Qsd2-OK and Qsdw-5H by analyzing the segregation of phenotypes and genotypes of F2 progenies derived from crosses between RILs carrying specific segments of chromosome 5H from H602 in the KNG background. This analysis confirmed that the two genomic regions corresponding to these QTL are involved in the regulation of grain dormancy. Germination tests of F1 grains derived from reciprocal crosses between H602 and KNG revealed that the H602 strong dormancy phenotype shows maternal inheritance with incomplete dominance. These results provide new insight into the mechanisms regulating grain dormancy in barley

Clinical and cytopathological characteristics of HTLV‐1 +

Abstract Background Human T‐lymphotropic virus‐1 (HTLV‐1)+ Hodgkin lymphoma (HL) is difficult to differentiate from adult T‐cell leukemia/lymphoma (ATLL) with HL‐like histology (HL‐like ATLL). Methods Cytological and immunohistological features, HTLV‐1 proviral DNA integration, and rearrangements of the T‐cell receptor (TCR) Cβ1 gene were examined in 11 HTLV‐1+ patients with HL‐like disease. Results Six patients were classified as HTLV‐1+ HL and five as HL‐like ATLL in accordance with genetic findings of HTLV‐1 proviral DNA integration and rearrangements of the TCR Cβ1 gene. Small ordinary looking lymphocytes with round nuclei were detected in the background of six patients with HTLV‐1+ HL, which were immunohistochemically negative for CD25 and CC chemokine receptor (CCR)4 and had a low MIB1 labeling index (mean: 28.3%). In the HL‐like ATLL specimens, small‐ and medium‐sized atypical lymphocytes with indented and irregular‐shaped nuclei were found, and were diffusely positive for CD25 and CCR4, with high MIB1 labeling (mean: 76%). Both groups had scattered CD30+ and CD15+ Hodgkin and Reed Sternberg (RS) giant cells, with or without CD20 expression and Epstein‐Barr virus infection. The 50% overall survival period was significantly longer for the HTLV‐1+ HL group (180 months) than for the HL‐like ATLL group (7.8 months; P = .004). Conclusions HTLV‐1+ HL showed typical small lymphoid cells with a low MIB1 labeling index in a background of Hodgkin and RS cells, with some scattered CD25+ and CCR4+ lymphocytes. In HTLV‐1 endemic areas, distinguishing HTLV‐1+ HL from HL‐like ATLL is important because of their differing treatment strategies and prognoses

Expression of AMAP1, an ArfGAP, provides novel targets to inhibit breast cancer invasive activities

Identification of the molecular machinery employed in cancer invasion, but not in normal adult cells, will greatly contribute to cancer therapeutics. Here we found that an ArfGAP, AMAP1/PAG2, is expressed at high levels in highly invasive breast cancer cells, but at very low levels in noninvasive breast cancer cells and normal mammary epithelial cells. siRNA-mediated silencing of AMAP1 effectively blocked the invasive activities. AMAP1 expression in human breast primary tumors also indicated its potential correlation with malignancy. Paxillin and cortactin have been shown to colocalize at invadopodia and play a pivotal role in breast cancer invasion. We found that AMAP1 is also localized at invadopodia, and acts to bridge paxillin and cortactin. This AMAP1-mediated trimeric protein complex was detected only in invasive cancer cells, and blocking this complex formation effectively inhibited their invasive activities in vitro and metastasis in mice. Our results indicate that AMAP1 is a component involved in invasive activities of different breast cancers, and provide new information regarding the possible therapeutic targets for prevention of breast cancer invasion and metastasis

Phase II study of dose‐adjusted gemcitabine, dexamethasone, cisplatin, and rituximab in elderly relapsed diffuse large B‐cell lymphoma patients

Abstract High‐dose chemotherapy and autologous stem cell transplantation (ASCT) are too toxic for elderly patients with relapsed or refractory diffuse large B‐cell lymphoma (DLBCL). Therefore, effective and tolerable regimens for elderly patients are urgently needed. The present phase II study assessed the efficacy and safety of dose‐adjusted therapy with gemcitabine, dexamethasone, cisplatin, and rituximab (GDP‐R) in this population. ASCT‐ineligible elderly patients with relapsed or refractory DLBCL received dose‐adjusted GDP‐R in each 28‐day cycle for up to six cycles. The primary endpoint was overall response rate (ORR), and secondary endpoints were complete response (CR) rate, progression‐free survival (PFS), and safety. Thirty‐three patients were enrolled and received dose‐adjusted GDP‐R. The median age was 75 years (range: 68‐87 years). The ORR was 82.8% (90% confidence interval [CI], 67.1‐93.0%), with a CR rate of 58.6% (90% CI, 41.7‐74.1%). At a median follow‐up of 20.9 months, the 2‐year PFS rate was 46.8% (90% CI, 30.7‐61.5%) and the 2‐year overall survival rate was 63.2% (90% CI, 45.8‐76.3%). The most frequently observed grade 4 adverse events were neutropenia (63.6%), thrombocytopenia (57.6%), and lymphocytopenia (39.4%). Dose‐adjusted GDP‐R is a promising salvage regimen for ASCT‐ineligible elderly patients with relapsed DLBCL after rituximab‐containing chemotherapy and warrants further investigation