221 research outputs found

    Ebf3⁺ niche-derived CXCL12 is required for the localization and maintenance of hematopoietic stem cells

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    Lympho-hematopoiesis is regulated by cytokines; however, it remains unclear how cytokines regulate hematopoietic stem cells (HSCs) to induce production of lymphoid progenitors. Here, we show that in mice whose CXC chemokine ligand 12 (CXCL12) is deleted from half HSC niche cells, termed CXC chemokine ligand 12 (CXCL12)-abundant reticular (CAR) cells, HSCs migrate from CXCL12-deficient niches to CXCL12-intact niches. In mice whose CXCL12 is deleted from all Ebf3+/leptin receptor (LepR)+ CAR cells, HSCs are markedly reduced and their ability to generate B cell progenitors is reduced compared with that to generate myeloid progenitors even when transplanted into wild-type mice. Additionally, CXCL12 enables the maintenance of B lineage repopulating ability of HSCs in vitro. These results demonstrate that CAR cell-derived CXCL12 attracts HSCs to CAR cells within bone marrow and plays a critical role in the maintenance of HSCs, especially lymphoid-biased or balanced HSCs. This study suggests an additional mechanism by which cytokines act on HSCs to produce B cells.Nakatani T., Sugiyama T., Omatsu Y., et al. Ebf3+ niche-derived CXCL12 is required for the localization and maintenance of hematopoietic stem cells. Nature Communications 14, 6402 (2023); https://doi.org/10.1038/s41467-023-42047-2

    Genomes of Neutrophilic Sulfur-Oxidizing Chemolithoautotrophs Representing 9 Proteobacterial Species From 8 Genera

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    Even in the current era of metagenomics, the interpretation of nucleotide sequence data is primarily dependent on knowledge obtained from a limited number of microbes isolated in pure culture. Thus, it is of fundamental importance to expand the variety of strains available in pure culture, to make reliable connections between physiological characteristics and genomic information. In this study, two sulfur oxidizers that potentially represent two novel species were isolated and characterized. They were subjected to whole-genome sequencing together with 7 neutrophilic and chemolithoautotrophic sulfur-oxidizing bacteria. The genes for sulfur oxidation in the obtained genomes were identified and compared with those of isolated sulfur oxidizers in the classes Betaproteobacteria and Gammaproteobacteria. Although the combinations of these genes in the respective genomes are diverse, typical combinations corresponding to three types of core sulfur oxidation pathways were identified. Each pathway involves one of three specific sets of proteins, SoxCD, DsrABEFHCMKJOP, and HdrCBAHypHdrCB. All three core pathways contain the SoxXYZAB proteins, and a cytoplasmic sulfite oxidase encoded by soeABC is a conserved component in the core pathways lacking SoxCD. Phylogenetically close organisms share same core sulfur oxidation pathway, but a notable exception was observed in the family ‘Sulfuricellaceae’. In this family, some strains have either core pathway involving DsrABEFHCMKJOP or HdrCBAHypHdrCB, while others have both pathways. A proteomics analysis showed that proteins constituting the core pathways were produced at high levels. While hypothesized function of HdrCBAHypHdrCB is similar to that of Dsr system, both sets of proteins were detected with high relative abundances in the proteome of a strain possessing genes for these proteins. In addition to the genes for sulfur oxidation, those for arsenic metabolism were searched for in the sequenced genomes. As a result, two strains belonging to the families Thiobacillaceae and Sterolibacteriaceae were observed to harbor genes encoding ArxAB, a type of arsenite oxidase that has been identified in a limited number of bacteria. These findings were made with the newly obtained genomes, including those from 6 genera from which no genome sequence of an isolated organism was previously available. These genomes will serve as valuable references to interpret nucleotide sequences

    Long-term Survival of a Case of Rectal Neuroendocrine Carcinoma with Liver Metastasis

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    Colorectal neuroendocrine carcinoma(NEC)is extremely rare and has a dismal prognosis. However, no standardized treatment strategy has been established for this lesion. For patients with NEC and distant metastasis, disease stabilization is difficult even after treatment with multidisciplinary strategies including chemotherapy. Here we describe a case of rectal NEC that presented as multiple liver metastases; a favorable prognosis was obtained after treatment with a multidisciplinary strategy that included surgery, irradiation, and chemotherapy. A 66-year-old male presented with diarrhea and constipation. Colonoscopy and a computed tomography(CT)scan revealed a rectal mass involving all of the luminal circumference, after which a diagnosis of NEC was confirmed by pathological examination. A CT scan also revealed several liver metastases in S5, S6, and S8. Abdominoperineal resection with total mesenteric excision and lymphadenectomy, including the lateral area, was performed. After resection, we administered radiation for local disease control in the lateral area. We also administered chemotherapy consisting of cisplatin and irinotecan for the liver metastases because only the endocrine cell component constituted this tumor. After chemotherapy, a CT scan was performed to confirm that the liver metastasis in S5 and S6 had disappeared, and it was shown that the other lesion in S8 had shrunk substantially(it eventually disappeared). Then, 48 months after resection, all metastatic liver tumors were under good control, and no other recurrent lesion was recognized. In conclusion, a multidisciplinary strategy including optimal chemotherapy seems to be important to achieve a favorable prognosis of NEC of the colorectum with distant metastasis

    In vivo imaging of zebrafish retinal cells using fluorescent coumarin derivatives

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    <p>Abstract</p> <p>Background</p> <p>The zebrafish visual system is a good research model because the zebrafish retina is very similar to that of humans in terms of the morphologies and functions. Studies of the retina have been facilitated by improvements in imaging techniques. <it>In vitro </it>techniques such as immunohistochemistry and <it>in vivo </it>imaging using transgenic zebrafish have been proven useful for visualizing specific subtypes of retinal cells. In contrast, <it>in vivo </it>imaging using organic fluorescent molecules such as fluorescent sphingolipids allows non-invasive staining and visualization of retinal cells <it>en masse</it>. However, these fluorescent molecules also localize to the interstitial fluid and stain whole larvae.</p> <p>Results</p> <p>We screened fluorescent coumarin derivatives that might preferentially stain neuronal cells including retinal cells. We identified four coumarin derivatives that could be used for <it>in vivo </it>imaging of zebrafish retinal cells. The retinas of living zebrafish could be stained by simply immersing larvae in water containing 1 μg/ml of a coumarin derivative for 30 min. By using confocal laser scanning microscopy, the lamination of the zebrafish retina was clearly visualized. Using these coumarin derivatives, we were able to assess the development of the zebrafish retina and the morphological abnormalities induced by genetic or chemical interventions. The coumarin derivatives were also suitable for counter-staining of transgenic zebrafish expressing fluorescent proteins in specific subtypes of retinal cells.</p> <p>Conclusions</p> <p>The coumarin derivatives identified in this study can stain zebrafish retinal cells in a relatively short time and at low concentrations, making them suitable for <it>in vivo </it>imaging of the zebrafish retina. Therefore, they will be useful tools in genetic and chemical screenings using zebrafish to identify genes and chemicals that may have crucial functions in the retina.</p

    Subaru/HiCIAO HKsHK_{\rm s} imaging of LkHα\alpha 330 - multi-band detection of the gap and spiral-like structures

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    We present HH- and KsK_{\rm s}-bands observations of the LkHα\alpha 330 disk with a multi-band detection of the large gap and spiral-like structures. The morphology of the outer disk (rr\sim0\farcs3) at PA=0--45^\circ and PA=180--290^\circ are likely density wave-induced spirals and comparison between our observational results and simulations suggests a planet formation. We have also investigated the azimuthal profiles at the ring and the outer-disk regions as well as radial profiles in the directions of the spiral-like structures and semi-major axis. Azimuthal analysis shows a large variety in wavelength and implies that the disk has non-axisymmetric dust distributions. The radial profiles in the major-axis direction (PA=271271^\circ) suggest that the outer region (r\geq0\farcs25) may be influenced by shadows of the inner region of the disk. The spiral-like directions (PA=10^\circ and 230^\circ) show different radial profiles, which suggests that the surfaces of the spiral-like structures are highly flared and/or have different dust properties. Finally, a color-map of the disk shows a lack of an outer eastern region in the HH-band disk, which may hint the presence of an inner object that casts a directional shadow onto the disk.Comment: 12pages, 16 figures, 2 tables, accepted for publication in A
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