Let
c
≥
2
be any fixed real number. Matomäki 4 inverstigated the set of
A
>
1
such that the integer part of
A
c
k
is a prime number for every
k
∈
N
. She proved that the set is uncountable, nowhere ...dense, and has Lebesgue measure 0. In this article, we show that the set has Hausdorff dimension 1.
Children with Down syndrome (DS) are susceptible to two blood disorders, transient abnormal myelopoiesis (TAM) and Down syndrome-associated acute megakaryocytic leukemia (DS-AMKL). Mutations in GATA ...binding protein 1 (GATA1) have been identified as the cause of these diseases, and the expression levels of the resulting protein, short-form GATA1 (GATA1s), are known to correlate with the severity of TAM. On the other hand, despite the presence of GATA1 mutations in almost all cases of DS-AMKL, the incidence of DS-AMKL in TAM patients is inversely correlated with the expression of GATA1s. This discovery has required the need to clarify the role of GATA1s in generating the cells of origin linked to the risk of both diseases. Focusing on this point, we examined the characteristics of GATA1 mutant trisomy-21 pluripotent stem cells transfected with a doxycycline (Dox)-inducible GATA1s expression cassette in a stepwise hematopoietic differentiation protocol. We found that higher GATA1s expression significantly reduced commitment into the megakaryocytic lineage at the early hematopoietic progenitor cell (HPC) stage, but once committed, the effect was reversed in progenitor cells and acted to maintain the progenitors. These differentiation stage-dependent reversal effects were in contrast to the results of myeloid lineage, where GATA1s simply sustained and increased the number of immature myeloid cells. These results suggest that although GATA1 mutant cells cause the increase in myeloid and megakaryocytic progenitors regardless of the intensity of GATA1s expression, the pathways vary with the expression level. This study provides experimental support for the paradoxical clinical features of GATA1 mutations in the two diseases.
Osteopontin (OPN) is a highly phosphorylated glycoprotein that is a prominent component of the mineralized extracellular matrix of bone. The secretion of OPN by immunocompetent cells plays a role in ...the differentiation of odontoblast-like cells during pulpal healing following tooth transplantation. This study aimed to clarify the role of OPN during reparative dentinogenesis. A groove-shaped cavity was prepared on the mesial surface of the upper first molars of wild-type (WT) and Opn knockout (KO) mice, and the samples were collected at intervals of 1 to 14 d. The demineralized sections were processed for immunohistochemistry for Ki67, nestin, OPN, dentin sialoprotein (DSP), integrin αvβ3, and type I collagen; in situ hybridization for Opn, col1a1, and dentin sialophosphoprotein (Dspp); and apoptosis assay. For the loss and gain of function experiments, an in vitro culture assay for evaluating dentin-pulp complex regeneration was performed. On day 1 in WT mice, odontoblasts beneath the affected dentin lost nestin immunoreactivity. On day 3, the expression of Opn was recognized at the mesial dental pulp, and OPN was deposited along the predentin-dentin border. Nestin-positive newly differentiated odontoblast-like cells expressed both Dspp and col1a1 and showed positive immunoreactivity for integrin αvβ3, DSP, and type I collagen. Until day 14, reparative dentin formation continued next to the preexisting dentin at the mesial coronal pulp. In contrast, there was no reparative dentin in the Opn KO mice where nestin- and DSP-positive newly differentiated odontoblast-like cells lacked immunoreaction for type I collagen. The in vitro organ culture demonstrated that the administration of recombinant OPN rescued the type I collagen secretion by odontoblast-like cells in the Opn KO mice. The results suggested that the deposition of OPN at the calcification front is essential for the type I collagen secretion by newly differentiated odontoblast-like cells to form reparative dentin during pulpal healing following cavity preparation.
MicroRNAs (miRNAs) are involved in essential biological activities, and have been reported to exhibit differential expression profiles in various cancers. Our previous study demonstrated that ...intercellular adhesion molecule-2 (ICAM2) inhibition induces radiosensitisation in oral squamous cell carcinoma (OSCC) cells. Thus, we hypothesised that certain miRNAs play crucial roles in radioresistance in OSCC by regulating ICAM2 expression.
Because predicted target gene analyses revealed that microRNA-125b (miR-125b) potentially regulates ICAM2 mRNA expression, we examined the association between miR-125b and radioresistance. The expression of miR-125b was investigated by real-time quantitative reverse transcriptase-PCR. For a functional analysis, miR-125b was transfected to OSCC-derived cells.
A downregulated expression of miR-125b was found in OSCC-derived cell lines and OSCC samples. The miR-125b-transfected cells showed a decreased proliferation rate, enhanced radiosensitivity to X-ray irradiation and diminished ICAM2 mRNA expression. Moreover, miR-125b expression correlated with OSCC tumour staging and survival.
These findings suggested that the downregulated miR-125b expression was associated with proliferation and radioresistance mechanisms, probably through ICAM2 signalling. Thus, controlling the expression or activity of miR-125b might contribute to suppressing proliferation and overcoming radioresistance in OSCC.
The use of pluripotent stem cells (PSCs) as a source of natural killer cells (NK cells) can improve reproducibility in the analysis of the pathogenesis of NK cell-associated diseases and in the ...production of off-the-shelf cellular medicines. We have developed a method for the differentiation of NK cells from human PSCs under serum-free and two-dimensional condition. Our method enables the seamless transition from maintenance of PSCs to differentiation of NK cells, without the use of any techniques other than medium exchange and whole culture passage.
Abstract
It is likely that a number of Galactic globular clusters remain to be discovered, especially toward the Galactic bulge. High stellar density combined with high and differential interstellar ...reddening are the two major problems for finding globular clusters located toward the bulge. We use the deep near-IR photometry of the VISTA Variables in the Vía Láctea (VVV) Survey to search for globular clusters projected toward the Galactic bulge, and hereby report the discovery of 22 new candidate globular clusters. These objects, detected as high density regions in our maps of bulge red giants, are confirmed as globular cluster candidates by their color–magnitude diagrams. We provide their coordinates as well as their near-IR color–magnitude diagrams, from which some basic parameters are derived, such as reddenings and heliocentric distances. The color–magnitude diagrams reveal well defined red giant branches in all cases, often including a prominent red clump. The new globular cluster candidates exhibit a variety of extinctions (0.06 <
A
Ks
< 2.77) and distances (5.3 <
D
< 9.5 kpc). We also classify the globular cluster candidates into 10 metal-poor and 12 metal-rich clusters, based on the comparison of their color–magnitude diagrams with those of known globular clusters also observed by the VVV Survey. Finally, we argue that the census for Galactic globular clusters still remains incomplete, and that many more candidate globular clusters (particularly the low luminosity ones) await to be found and studied in detail in the central regions of the Milky Way.
Monocytic lineage cells (monocytes, macrophages and dendritic cells) play important roles in immune responses and are involved in various pathological conditions. The development of monocytic cells ...from human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) is of particular interest because it provides an unlimited cell source for clinical application and basic research on disease pathology. Although the methods for monocytic cell differentiation from ESCs/iPSCs using embryonic body or feeder co-culture systems have already been established, these methods depend on the use of xenogeneic materials and, therefore, have a relatively poor-reproducibility. Here, we established a robust and highly-efficient method to differentiate functional monocytic cells from ESCs/iPSCs under serum- and feeder cell-free conditions. This method produced 1.3 × 10(6) ± 0.3 × 10(6) floating monocytes from approximately 30 clusters of ESCs/iPSCs 5-6 times per course of differentiation. Such monocytes could be differentiated into functional macrophages and dendritic cells. This method should be useful for regenerative medicine, disease-specific iPSC studies and drug discovery.
Interstellar extinction toward the Galactic Center (GC) is large and significantly differential. Its reddening and dimming effects in red clump (RC) stars in the Galactic Bulge can be exploited to ...better constrain the extinction law toward the innermost Galaxy. By virtue of a deep and complete catalog of more than 30 million objects at and obtained from VVV survey observations, we apply the RC method to infer the selective-to-total extinction ratios in the Z, Y, J, H, and Ks broadband near-infrared filters. The measured values are smaller than previously reported, and are not constant, with mean values of, e.g., and . We also obtain a ratio AZ:AY:AJ:AH: of 7.74:5.38:3.30:1.88:1.0, implying extinction toward the GC to follow a distribution as a function of wavelength steeper than previously reported, consistent with a power law in the near-infrared.
We investigate interstellar extinction curve variations towards ∼4 deg2 of the inner Milky Way in VIJKs
photometry from the OGLE-III (third phase of the Optical Gravitational Lensing Experiment) and ...VVV (VISTA Variables in the Via Lactea) surveys, with supporting evidence from diffuse interstellar bands and F435W, F625W photometry. We obtain independent measurements towards ∼2000 sightlines of AI, E(V − I), E(I − J) and E(J − Ks
), with median precision and accuracy of 2 per cent. We find that the variations in the extinction ratios AI
/E(V − I), E(I − J)/E(V − I) and E(J − Ks
)/E(V − I) are large (exceeding 20 per cent), significant and positively correlated, as expected. However, both the mean values and the trends in these extinction ratios are drastically shifted from the predictions of Cardelli and Fitzpatrick, regardless of how RV
is varied. Furthermore, we demonstrate that variations in the shape of the extinction curve have at least two degrees of freedom, and not one (e.g. RV
), which we confirm with a principal component analysis. We derive a median value of 〈AV
/AKs
〉 = 13.44, which is ∼60 per cent higher than the ‘standard’ value. We show that the Wesenheit magnitude WI
= I − 1.61(I − J) is relatively impervious to extinction curve variations. Given that these extinction curves are linchpins of observational cosmology, and that it is generally assumed that RV
variations correctly capture variations in the extinction curve, we argue that systematic errors in the distance ladder from studies of Type Ia supernovae and Cepheids may have been underestimated. Moreover, the reddening maps from the Planck experiment are shown to systematically overestimate dust extinction by ∼100 per cent and lack sensitivity to extinction curve variations.
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