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An acute promyelocytic leukemia (APL) patient not demonstrating the retinoic acid receptor α (RARA) translocation is rare. A 76-year-old man was diagnosed with myelodysplastic syndrome (MDS). After a year, abnormal promyelocytes were detected with pancytopenia and disseminated intravascular coagulopathy. Morphologically, the patient was diagnosed with APL; however, a genetic examination failed to detect RARA translocation. Thereafter, whole-genome sequencing revealed an NRAS missense mutation [c.38 GA (p.G13D)]. This mutation was not detected in posttreatment bone marrow aspirate, despite residual MDS. Few reports are available on similar cases. Furthermore, the NRAS c.38 GA mutation may be a novel pathogenic variant exacerbating RARA translocation-negative acute promyelocytic-like leukemia.

The arrangement of centromeres within the nucleus differs among species and cell types. However, neither the mechanisms determining centromere distribution nor its biological significance are currently well understood. In this study, we demonstrate the importance of centromere distribution for the maintenance of genome integrity through the cytogenic and molecular analysis of mutants defective in centromere distribution. We propose a two-step regulatory mechanism that shapes the non-Rabl-like centromere distribution in Arabidopsis thaliana through condensin II and the linker of the nucleoskeleton and cytoskeleton (LINC) complex. Condensin II is enriched at centromeres and, in cooperation with the LINC complex, induces the scattering of centromeres around the nuclear periphery during late anaphase/telophase. Then, after entering interphase, the positions of the scattered centromeres are stabilized by nuclear lamina proteins of the CROWDED NUCLEI (CRWN) family. We also found that, despite their strong impact on centromere distribution, condensin II and CRWNs have little effect on chromatin organization involved in the control of gene expression, indicating the robustness of chromatin organization regardless of the type of centromere distribution.

The t(12;17)(p13;q11∼21) translocation is a very rare but recurrent cytogenetic aberration observed predominantly in early pre-B acute lymphoblastic leukemia (ALL) with CD19+CD10-CD33+ phenotype. This translocation was shown to form a fusion gene between TAF15 at 17q12 and ZNF384 at 12p13. On the other hand, der(1;18)(q10;q10) has been detected as a rare unbalanced whole-arm translocation leading to trisomy 1q in myeloid malignancies. We describe here the first case of mixed phenotype acute leukemia (MPAL) with a t(12;17)(p13;q21)/TAF15-ZNF384, which also had der(1;18)(q10;q10) as an additional abnormality. A 74-year-old woman was diagnosed with MPAL, B/myeloid, because bone marrow blasts were positive for myeloperoxidase, CD19, and CD22. Chromosome analysis showed 46,XX, +1,der(1;18)(q10;q10),t(2;16)(q13;q13),t(12;17)(p13;q21). Expression of the TAF15-ZNF384 fusion transcript was confirmed: TAF15 exon 6 was fused in-frame to ZNF384 exon 3. This type of fusion gene has been reported in 1 acute myeloid leukemia case and 3 ALL cases. Thus, at present, it is difficult to find a specific association between the structure of the TAF15-ZNF384 fusion gene and the leukemia phenotype. The TAF15-ZNF384 fusion may occur in early common progenitor cells that could differentiate into both the myeloid and lymphoid lineages. Furthermore, der(1;18)(q10;q10) might play some role in the appearance of an additional myeloid phenotype.

Chromatin accessibility is closely associated with chromatin functions such as gene expression, DNA replication, and maintenance of DNA integrity. However, the relationship between chromatin accessibility and plant hormone signaling has remained elusive. Here, based on the correlation between chromatin accessibility and DNA damage, we used the sensitivity to DNA double strand breaks (DSBs) as an indicator of chromatin accessibility and demonstrated that auxin regulates chromatin accessibility through the TIR1/AFBs signaling pathway in proliferative cells. Treatment of proliferating plant cells with an inhibitor of the TIR1/AFBs auxin signaling pathway, PEO-IAA, caused chromatin loosening, indicating that auxin signaling functions to decrease chromatin accessibility. In addition, a transcriptome analysis revealed that several histone H4 genes and a histone chaperone gene, FAS1, are positively regulated through the TIR1/AFBs signaling pathway, suggesting that auxin plays a role in promoting nucleosome assembly. Analysis of the fas1 mutant of Arabidopsis thaliana confirmed that FAS1 is required for the auxin-dependent decrease in chromatin accessibility. These results suggest that the positive regulation of chromatin-related genes mediated by the TIR1/AFBs auxin signaling pathway enhances nucleosome assembly, resulting in decreased chromatin accessibility in proliferative cells.

The t(12;17)(p13;q11∼21) translocation is a very rare but recurrent cytogenetic aberration observed predominantly in early pre-B acute lymphoblastic leukemia (ALL) with CD19+CD10-CD33+ phenotype. This translocation was shown to form a fusion gene between TAF15 at 17q12 and ZNF384 at 12p13. On the other hand, der(1;18)(q10;q10) has been detected as a rare unbalanced whole-arm translocation leading to trisomy 1q in myeloid malignancies. We describe here the first case of mixed phenotype acute leukemia (MPAL) with a t(12;17)(p13;q21)/TAF15-ZNF384, which also had der(1;18)(q10;q10) as an additional abnormality. A 74-year-old woman was diagnosed with MPAL, B/myeloid, because bone marrow blasts were positive for myeloperoxidase, CD19, and CD22. Chromosome analysis showed 46,XX, +1,der(1;18)(q10;q10),t(2;16)(q13;q13),t(12;17)(p13;q21). Expression of the TAF15-ZNF384 fusion transcript was confirmed: TAF15 exon 6 was fused in-frame to ZNF384 exon 3. This type of fusion gene has been reported in 1 acute myeloid leukemia case and 3 ALL cases. Thus, at present, it is difficult to find a specific association between the structure of the TAF15-ZNF384 fusion gene and the leukemia phenotype. The TAF15-ZNF384 fusion may occur in early common progenitor cells that could differentiate into both the myeloid and lymphoid lineages. Furthermore, der(1;18)(q10;q10) might play some role in the appearance of an additional myeloid phenotype.

Prophet of Pit-1 (Prop1) is a transcription factor that regulates Pit-1 gene expression. Because Pit-1 regulates the differentiation of pituitary cells and the expressions of GH, prolactin and TSHβ genes, Prop1 mutation results in combined pituitary hormone deficiency in humans. However, Prop1-binding sites in human Pit-1 gene and the mechanism leading to combined pituitary hormone deficiency have remained unclear. In this study, we identified and analyzed Prop1-binding elements of the human Pit-1 gene. Prop1 stimulated the expression of the reporter plasmid containing Pit-1 gene from translation start site to −1340 dose dependently in GH3 cells. The activation by Prop1 was observed in GH3 and TtT/GF cells but not COS7, HeLa, JEG3, and HuH7 cells. Deletion analysis of Pit-1 gene showed that the Prop1-responsive elements were present within the −257-bp region. Within the −257-bp region, there are four elements similar to consensus sequence of paired-like transcription factors. Because Prop1 is a member of paired-like transcription factors, we assessed the elements. EMSA and transient transfection assay using the mutation of the elements revealed that the element from −63 to −53 (the proximal Prop1 binding element) was essential to Prop1-binding and Prop1-induced activation of Pit-1 reporter plasmid. A region at −8kb of human Pit-1 gene is similar to the distal region containing Prop1-binding elements in mouse Pit-1 gene. We showed the region functioned as an enhancer. Furthermore, chromatin immunoprecipitation assay showed that the proximal element could bind Prop1 in vivo cultured cells. Taken together, these findings indicated the novel functioning binding elements of Prop1 in human Pit-1 gene.

Nakanishi, T., Ohgushi, A., Yamashita, T., Sashihara, K., Takagi, T., Dobashi, E., Kamegai, T., Kasai, M., Yoshimatsu, T. and Furuse, M. 2001. Effect of orally administered conjugated linoleic acids on behaviors and tissue fatty acid compositions in mice. J. Appl. Anim. Res., 20: 157–170. To compare the influences of the oral administration of conjugated linoleic acids (CLA) on behaviors and fatty acid composition of some tissues with those of linoleic acid, (LA) and docosahexaenoic acid (DHA), mice (8-week old) were orally administered with oils containing high levels of CLA DHA or LA for 4 weeks (6 days per week, 0.2 ml per day). Control, group was administered with saline. Behavioral tests such as locomotor activity swim test elevated plus maze lest and biting test, were done on the commencement of the study (0 week) and 2 and 4 weeks after treatments. No significant changes were observed in, all the parameters. Oral. CLA increased the liver weight and reduced the epididymal, white adipose tis...

Yamashita, T., Tobisa, M., Ohgushi, A. and Furuse, M. 2001. Enhancement of plasma calcium concentration by dietary calcium sources and oligosaccharides in neonatal chicks. J. Appl. Anim. Res., 19: 25–32. The effects of dietary calcium (Ca) sources and several oligosaccharides on plasma Ca concentration were examined in the neonatal cluck. In the first experiment, the efficiency of Ca carbonate and eggshell Ca teas compared by determining plasma Ca concentration at 15, 30, 60 and 120 min post oral administration. It was significantly higher in the eggshell Ca treatment than in the Ca carbonate treatment and the peak for plasma Ca concentration was obtained at 30 min. The effect of dietary oligosaccharides on plasma Ca concentration was investigated by nsmg isomaito-oligosaccharides, gentiooligosaccharides and nigerooligosaccharides with Ca carbonate. In the second experiment Nigerooligosaccharides enhanced plasma Ca concentration when compared with other treatments. The efficacy of lactose and nig...

We investigated the central effect of the estrogenic pollutant, bisphenol A (BPA), on behaviors, growth and several organ weights in chicks.Four-day-old male chicks were injected into the brain with BPA at doses of 0, 100, 200μg. Food intake and body weight gain were determined, but no significant effects of BPA were detected. Secondly, behaviors of these chicks were tested under an isolated situation. The behaviors such as frequency of jumping, distress vocalization and duration of crouching were monitored. Central injection of BPA increased distress vocalizations in a dose-dependent manner, though no significant changes were observed in other indices. Thereafter, four organ (testis, kidney, liver and brain) weights were measured. No significant differences in all the organs were detected among all treatments.These results suggest that the accumulation of BPA in the central nervous system may somewhat induce the behavioral change in a stressful situation.

The effect of intrayolk administration of docosahexaenoic acid (DHA) on distress behavior after hatching was investigated using two types (with or without phospholipid) of DHA. Hatchability was decreased by both types of DHA, but there was no difference between sources of DHA. At two-days-of-age, birds from each treatment were individually isolated and distress vocalizations (DVs) were counted for 10min. DVs tended to decrease faster in DHA-treated birds compared with the control, but the effect was not significant. Thereafter, food intake following the intracerebroventricular injection of corticotropin- releasing factor (CRF) was monitored in three-day-old birds from each treatment. Birds hatched from eggs injected with DHA without phospholipid rapidly overcame the food intake suppression caused by CRF when compared with other treatments. In conclusion, birds hatched eggs rich in DHA may be better adapted to stressful circumstances.

It has been demonstrated that l -pipecolic acid ( l -PA), a major metabolic intermediate of l -Lysine ( l -Lys) in the brain, is involved in the functioning of Γ-aminobutyric acid. In the present work the effect of intracerebroventricular (i.c.v.) administration of l -PA, and its relatives, on food intake and behavior in neonatal chicks was investigated. The i.c.v. injection of 1 mg of l -PA and d -PA significantly inhibited food intake during the 2 h following injection, whereas greater than 2 mg of l -Lys was required to inhibit food intake. In behavioral tests, the i.c.v. injection of l -PA reduced active wakefulness and feeding behavior while inducing sleeping-like behavior in chicks. These results suggest that l -PA has an important role for the regulation of behaviors in the neonatal chick after conversion from l -Lys in the brain.