Paraburkholderia sabiae administration alters zebrafish anxiety-like behavior via gut microbial taurine metabolism.

Interventions to the gut microbiome manipulate the gut-brain axis and could be useful in the treatment of anxiety and depression. In this study, we demonstrated that administration of the bacterium Paraburkholderia sabiae reduces anxiety-like behavior in adult zebrafish. P. sabiae administration increased the diversity of the zebrafish gut microbiome. Linear discriminant analysis Effect Size (LEfSe) analysis revealed that the populations of Actinomycetales including Nocardiaceae, Nocardia, Gordoniaceae, Gordonia, Nakamurellaceae, and Aeromonadaceae were reduced, whereas those of Rhizobiales including Xanthobacteraceae, Bradyrhizobiaceae, Rhodospirillaceae, and Pirellulaceae were increased in the gut microbiome. Functional analysis using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt2) predicted that P. sabiae administration altered taurine metabolism in the zebrafish gut, and we demonstrated that P. sabiae administration increased the taurine concentration in the brain. Since taurine functions as an antidepressant neurotransmitter in vertebrates, our results suggest that P. sabiae could improve anxiety-like behavior in zebrafish via the gut-brain axis.

[Surgical Treatment for Primary Pulmonary Artery Sarcoma;Report of a Case].

Primary pulmonary artery sarcoma is a very rare tumor. The prognosis of primary pulmonary artery sarcoma is extremely poor and it is reported as 1.5 months without treatment. Here we report our experience of surgical treatment of primary pulmonary artery sarcoma. A 66-year-old woman with a diagnosis of pulmonary sarcoma by chest computed tomography( CT) scan was referred to our hospital because of a loss of consciousness. An emergecy surgery was planned to eliminate the risk of sudden death. To avoid circulatory collapse, we placed her on extracorporeal bypass before anesthesia induction. The tumor extending from right ventricle outflow tract to bilateral pulmonary artery was removed and resected without leaving residual mass, but the surgical margin was positive, and adjuvant chemoradiotherapy was performed after discharge. In conclusion, surgical resection was succesfully conducted to avoid sudden death.

Sorghum DW1 positively regulates brassinosteroid signaling by inhibiting the nuclear localization of BRASSINOSTEROID INSENSITIVE 2.

Semi-dwarf traits have been widely introgressed into cereal crops to improve lodging resistance. In sorghum (Sorghum bicolor L. Moench), four major unlinked dwarfing genes, Dw1-Dw4, have been introduced to reduce plant height, and among them, Dw3 and Dw1 have been cloned. Dw3 encodes a gene involved in auxin transport, whereas, Dw1 was recently isolated and identified as a gene encoding a protein of unknown function. In this study, we show that DW1 is a novel component of brassinosteroid (BR) signaling. Sorghum possessing the mutated allele of Dw1 (dw1), showed similar phenotypes to rice BR-deficient mutants, such as reduced lamina joint bending, attenuated skotomorphogenesis, and insensitivity against feedback regulation of BR-related genes. Furthermore, DW1 interacted with a negative regulator of BR signaling, BRASSINOSTEROID INSENSITIVE 2 (BIN2), and inhibited its nuclear localization, indicating that DW1 positively regulates BR signaling by inhibiting the function of BIN2. In contrast to rice and wheat breeding which used gibberellin (GA) deficiency to reduce plant height, sorghum breeding modified auxin and BR signaling. This difference may result from GA deficiency in rice and wheat does not cause deleterious side effects on plant morphology, whereas in sorghum it leads to abnormal culm bending.

Sorghum Dw1, an agronomically important gene for lodging resistance, encodes a novel protein involved in cell proliferation.

Semi-dwarfing genes have contributed to enhanced lodging resistance, resulting in increased crop productivity. In the history of grain sorghum breeding, the spontaneous mutation, dw1 found in Memphis in 1905, was the first widely used semi-dwarfing gene. Here, we report the identification and characterization of Dw1. We performed quantitative trait locus (QTL) analysis and cloning, and revealed that Dw1 encodes a novel uncharacterized protein. Knockdown or T-DNA insertion lines of orthologous genes in rice and Arabidopsis also showed semi-dwarfism similar to that of a nearly isogenic line (NIL) carrying dw1 (NIL-dw1) of sorghum. A histological analysis of the NIL-dw1 revealed that the longitudinal parenchymal cell lengths of the internode were almost the same between NIL-dw1 and wildtype, while the number of cells per internode was significantly reduced in NIL-dw1. NIL-dw1dw3, carrying both dw1 and dw3 (involved in auxin transport), showed a synergistic phenotype. These observations demonstrate that the dw1 reduced the cell proliferation activity in the internodes, and the synergistic effect of dw1 and dw3 contributes to improved lodging resistance and mechanical harvesting.

Identification of binding proteins of fusarielin A as actin and tubulin.

Fusarielin A (FSA), isolated from culture of Fusarium sp. K432, has anti-fungal/anti-angiogenic activity. Based on our previous structure-activity relationship studies, we prepared FSA-immobilized affinity gel. The results of affinity chromatography with this gel indicated that tubulin and actin are FSA-binding proteins. The binding affinities of tubulin and actin for FSA were estimated by the use of surface plasmon resonance spectroscopy.

Fusarielin A as an anti-angiogenic and anti-proliferative agent: basic biological characterization.

Fusarielin A shows anti-angiogenic activity in the human umbilical vein endothelial cell (HUVEC) tube formation assay. Structural development studies indicated the importance of the hydroxyl groups in this molecule. A 3H-labeled derivative and a fluorescent affinity-labeling agent were prepared and used to examine the cellular distribution and biological behavior of fusarielin A.

Effects of immunomodulatory derivatives of thalidomide (IMiDs) and their analogs on cell-differentiation, cyclooxygenase activity and angiogenesis.

Various analogs of known immunomodulatory derivatives of thalidomide (1) (IMiDs: 3, 5) were synthesized, focusing on cell-differentiation-inducing, cyclooxygenase-inhibitory and anti-angiogenesis activities. Among the prepared compounds, NIDO-33 (14) showed cell differentiation-inducing activity on HL-60 cells and anti-angiogenic activity on human umbilical vein endothelial cells (HUVEC). AIDO-00 (7) also showed anti-angiogenic activity. NIDO-11 (8) showed an enhancing effect on all-trans retinoic acid (ATRA)-induced HL-60 cell differentiation, and AIDO-30 (13) exhibited cyclooxygenase (COX)-inhibitory activity.

Angiogenesis inhibitors derived from thalidomide.

5-Hydroxy-2-(2,6-diisopropylphenyl)-1H-isoindole-1,3-dione (5HPP-33: 10), which was obtained during our previous structural development studies on thalidomide, was revealed to possess potent anti-angiogenic activity in a human umbilical vein endothelial cell (HUVEC) assay. Thalidomide (1) and its metabolite, 5-hydroxythalidomide (5-HT: 2), which possesses a hydroxyl group at the position corresponding to that of 5HPP-33, as well as IMiDs (immunomodulatory derivatives of thalidomide: 3 and 5), also showed weak or moderate activity in the same assay.