Background: SDF-1/CXCR4 signaling plays key roles in directed cell migration under physiological and pathological conditions. To develop agonist-based CXCR4 probes for detection of CXCR4 expression on cell lines and metastatic tumors, SAR analyses of fluorescent SDF-1 derivatives were carried out. Results: Several SDF-1 derivatives with a single fluorescent label were designed and synthesized. Modification of the SDF-1 C-terminus with AlexaFluor(®) 488 or tetramethylrhodamine provided potent CXCR4 probes. Using a potent probe, a novel binding inhibition assay was established for biological evaluation of potential CXCR4 ligands. Conclusion: SDF-1 derivatives with C-terminal modification exhibit equipotent binding with CXCR4 and an alternative SDF-1 receptor CXCR7 to unlabeled SDF-1. The SDF-1 derivatives are applicable to flow cytometry to detect the receptor expression and identify binding compounds for CXCR4.

We examined the effects of cadmium chloride (CdCl(2)) exposure on the phosphorylation and functionality of extracellular signal-regulated kinase 5 (ERK5), a recently identified member of the mitogen-activated protein kinase (MAPK) family, in HK-2 human renal proximal tubular cells. Following exposure to CdCl(2), ERK5 phosphorylation increased markedly, but the level of total ERK5 was unchanged. ERK5 phosphorylation following CdCl(2) exposure was rapid and transient, similar to the time course of ERK1/2 phosphorylation. Treatment of HK-2 cells with the MAPK/ERK kinase 5 inhibitor, BIX02189, suppressed CdCl(2)-induced ERK5 but not ERK1/2 phosphorylation. The CdCl(2)-induced increase of phosphorylated cAMP response element-binding protein (CREB) and activating transcription factor-1 (ATF-1), as well as the accumulation of mobility-shifted c-Fos protein, were suppressed by BIX02189 treatment. Furthermore, BIX02189 treatment enhanced cleavage of poly(ADP-ribose) polymerase and increased the level of cytoplasmic nucleosomes in HK-2 cells exposed to CdCl(2). These findings suggest that ERK5 pathway activation by CdCl(2) exposure might induce the phosphorylation of cell survival-transcription factors, such as CREB, ATF-1, and c-Fos, and may exert a partial anti-apoptotic role in HK-2 cells.

Skin biopsy samples from 145 relapse leprosy cases and from five different regions in Brazil, were submitted to sequence analysis of part of the genes associated with Mycobacterium leprae drug resistance. Single nucleotide polymorphisms in these genes were observed in M. leprae from four out of 92 cases with positive amplification (4.3%) and included a case with a mutation in rpoB only, another sample with SNPs in both folP1 and rpoB and two cases showing mutations in folP1, rpoB and gyrA, suggesting the existence of multi-drug resistance (MDR). The nature of the mutations were as reported in earlier studies, being CCC to CGC in codon 55 in folP (Pro to Arg), while in the case of rpoB, all mutations occurred at codon 531, two being a transition of TCG to ATG (Ser to Met), one TCG to TTC (Ser to Phe) and one TCG to TTG (Ser to Leu). The two cases with mutations in gyrA changed from GCA to GTA (Ala to Val) in codon 91. The median time from cure to relapse diagnosis was 9.45 years but was significantly shorter in patients with mutations (3.26 yrs; p = 0.0038). Over 70% of the relapses were multibacillary, including three of the mutation carrying cases; one MDR relapse patient was paucibacillary.

Seedling vigor is among the major determinants of stable stand establishment in direct-seeded rice (Oryza sativa L.) in temperate regions. Quantitative trait loci (QTL) for seedling vigor were identified using 250 recombinant inbred lines (RILs) derived from a cross between two japonica rice cultivars Kakehashi and Dunghan Shali. Seedling heights measured at 14 days after sowing were 20.3 and 29.4 cm for Kakehashi and Dunghan Shali, respectively. For the RILs, the height ranged from 14.1 to 31.7 cm. Four putative QTLs associated with seedling height were detected. qPHS3-2, the major QTL that was located on the long arm of chromosome 3, accounted for 26.2 % of the phenotypic variance. Using progeny of the near isogenic lines (NILs) produced by the backcross introduction of a chromosome segment carrying this major QTL into an elite cultivar Iwatekko, we fine-mapped qPHS3-2 to a 81-kb interval between two markers, ID_CAPS_01 and RM16227. Within this mapped region, we identified the gene OsGA20ox1, which is related to gibberellin (GA) biosynthesis. The relative expression levels of GA20ox1 in seedlings of Dunghan Shali and NILs were higher than that of Iwatekko. Concomitantly, the amount of endogenous active GA was higher in Dunghan Shali and the NILs compared to the level detected in Iwatekko. These results indicate that OsGA20ox1 is a strong candidate gene for major QTL controlling seedling vigor in rice.

A strong association between inactive aldehyde dehydrogenase-2 (ALDH2) and risk of esophageal cancer has been demonstrated in East Asian drinkers. An alcohol flushing questionnaire asking about past and current tendency for facial flushing to occur after drinking a glass (≈180 mL) of beer predicts the presence of inactive ALDH2 among Japanese aged 40 years or older with a sensitivity and specificity of approximately 90%. We invented a health-risk appraisal (HRA) model that makes it possible to identify Japanese men who are at high risk for esophageal cancer based on their past and current alcohol flushing tendency, drinking, smoking, and intake of vegetables and fruits. Between 2008 and 2009, 2221 Japanese men aged 50 years or older filled out the HRA questionnaire before undergoing a screening examination by upper gastrointestinal endoscopy at five medical facilities. The endoscopic examination resulted in a diagnosis of esophageal cancer in 19 subjects, and 117 (5.27%) subjects had an HRA score ≥11. The proportion of subjects with an HRA score ≥11 was higher in the 50-69 age group (6.11-6.88%) than in 70-89 age group (2.84-2.86%). The esophageal cancer detection rate was 4.27% among the subjects with an HRA score ≥11 and only 0.67% among the other subjects. Based on a receiver operating characteristic curve analysis, when an HRA score of ≥9 was used for subjects aged 50-69 years and of ≥8 for those aged 70-89 years as the cutoff value to select individuals with a high risk for esophageal cancer, its sensitivity and false-positive rate was 52.6% and 15.2%, respectively, and the cancer detection rate was 2.91% in the high-risk group, as opposed to 0.48% in the other group. In conclusion, the high detection rates for esophageal cancer in the high-risk groups encouraged screening based on our HRA model in larger Japanese populations.

When the gibberellin (GA) receptor GIBBERELLIN INSENSITIVE DWARF 1 (GID1) binds to GA, GID1 interacts with DELLA, a repressor of GA signaling. This interaction inhibits the suppressive function of DELLA and thereby activates the GA response. However, how suppressive function of DELLA is exhibited and how GID1 inhibits this suppressive function of DELLA are unclear. Through yeast one hybrid experiment and transiently expressing the N-terminal region of rice DELLA (SLR1) in rice callus, we established that the N-terminal DELLA/TVHYNP motif of SLR1 possesses transactivation activity. When various deletion series of SLR1 were overproduced in rice, severity of dwarfism correlated with transactivation activity observed in yeast, indicating that SLR1 suppresses plant growth through its transactivation activity. This activity was suppressed by the GA-dependent GID1-SLR1 interaction, which could explain why GA responses are induced in the presence of GA. The C-terminal GRAS domain of SLR1 also exhibits a suppressive function on plant growth, possibly through directly or indirectly interacting with the promoter region of the target genes. Our results indicate that the N-terminal region of SLR1 has two different roles in GA signaling; to interact with GID1 and to exhibit transactivation activity. © 2012 The Authors. The Plant Journal © 2012 Blackwell Publishing Ltd.

Seedling vigor, which is controlled by many quantitative trait loci (QTLs), is one of several important agronomic traits for direct-seedling rice systems. However, isolating these QTL genes is laborious and expensive. Here, we combined QTL mapping and microarray profiling to identify QTL genes for seedling vigor. By performing QTL mapping using 82 backcross inbred lines (BILs) of the Koshihikari (japonica) and Habataki (indica) cultivars for the rice initial growth, we identified two QTLs, early-stage plant development1/2 (qEPD1 and qEPD2), whose Koshihikari alleles promote plant height and/or leaf sheath length. Phenotypic analysis of the two substituted lines carrying the Habataki qEPD1 or qEPD2 allele revealed that qEPD2 functioned more dominantly for the initial growth of rice. From the microarray experiment, 55 and 45 candidate genes were found in the qEPD1 and qEPD2 genomic regions, which are expressed differentially between each SL and Koshihikari. Gibberellin 20 oxidase-2 (OsGA20ox2), which is identical to Semi Dwarf1 (SD1), was included among the 55 candidate genes of the qEPD1, whereas its paralog, OsGA20ox1, was included among the 45 candidate genes of qEPD2. Consistently, introduction of the Koshihikari OsGA20ox1 allele into SL(qEPD2) heightened its plant height and leaf sheath length significantly relative to the introduction of the Habataki OsGA20ox1 allele. Therefore, microarray profiling could be useful for rapidly screening QTL candidate genes. We concluded that OsGA20ox1 and OsGA20ox2 (SD1) function during the initial growth of rice, but OsGA20ox1 plays a dominant role in increasing plant height and leaf sheath length at the initial growth stage.

Abstract Background: Parents of children with incurable cancer face difficulties in making end-of-life decisions, and thus far, little research has been conducted on the thoughts and perceptions of these parents. Purpose: The study aims to describe parental thoughts and perceptions when they hear that their child has incurable cancer. Methods: Semi-structured, open-ended interviews were conducted with 23 parents who had lost children to cancer. A constant comparative content analysis was also conducted. Results: Regarding parental thoughts, five categories emerged:"not allowing my child to die,""being compelled to continue cancer-directed/life-sustaining treatment,""wanting to put an end to my child's suffering and wanting him/her to be comfortable,""valuing my child's wish and dignity," and "wanting to be there for my child." However, some parents did not mention all five categories. Regarding parental perceptions of their children's condition, six categories emerged:"understanding change/deterioration of my child's condition,""recognition of my child's sufferings,""awareness of the possible death of my child,""no recognition of my child's impending death as reality,""avoiding facing my child's death," and "realizing the truth and coming to terms with the reality of death." Conclusion: When parents were told that their child had incurable cancer, their first thought was to protect their child. Because thoughts and perceptions in such a situation vary across parents, health care professionals should support parents in realizing their thoughts and perceptions and in making decision as parents.

BTBD10, an Akt interactor, activates Akt by decreasing the protein phosphatase 2A-mediated dephosphorylation and inactivation of Akt. Overexpression of BTBD10 suppresses motor neuron death that is induced by a familial amyotrophic lateral sclerosis (ALS)-linked superoxide dismutase 1 (SOD1) mutant, G93A-SOD1 in vitro. In this study, we further investigated the BTBD10-mediated suppression of motor neuron death. We found that the small interfering RNA-mediated inhibition of BTBD10 expression led to the death of cultured motor neurons. In Caenorhabditis elegans (C. elegans), disruption of the btbd-10 gene caused not only loss of neurons, including both motor and touch-receptor neurons, but also a locomotion defect. In addition, we found that the expression of BTBD10 was generally decreased in the motor neurons from patients of sporadic ALS and transgenic mice overexpressing G93A-SOD1 (G93A-SOD1-transgenic mice). Collectively, these results suggest that the reduced expression of BTBD10 leads to motor neuron death both in vitro and in vivo.Cell Death and Differentiation advance online publication, 2 March 2012; doi:10.1038/cdd.2012.19.

A taxonomic study of strain M-07(T) isolated from nitrifying-denitrifying activated sludge treating piggery wastewater was performed. Phylogenetic analysis based on the 16S rRNA gene sequence demonstrated that strain M-07(T) belonged to the genus Advenella. The 16S rRNA gene sequence similarity between M-07(T) and Advenella incenata LMG 22250(T), Advenella mimigardefordensis LMG 22922(T), and Advenella kashmirensis LMG 22695(T) was 96.5, 97.3, and 96.9%, respectively. The DNA G + C content of strain M-07(T) was 49.5 mol%, which was approximately 5% lower than that of other Advenella species (53.5-58.0 mol%). The predominant cellular fatty acids of strain M-07(T) were C(16:0)(33.3%), summed feature 3 (comprising C(16:1)ω7c and/or iso-C(15:0) 2-OH; 20.5%), C(17:0) cyclo (16.8%), summed feature 2 (comprising C(14:0) 3-OH and/or iso-C(16:1) I; 9.3%), and C(18:1)ω7c (8.1%). The isoprenoid quinone of the strain was Q-8. On the basis of phenotypic characteristics, phylogenetic analysis, and DNA-DNA relatedness data, a novel species of Advenella, for which the name Advenella faeciporci sp. nov. is proposed. The type strain is M-07(T)(= JCM 17746(T)= KCTC 23732(T)).