Hematopoietic stem cells (HSCs) reside and self-renew in the bone marrow (BM) niche. Overall, the signaling that regulates stem cell dormancy in the HSC niche remains controversial. Here, we ...demonstrate that TGF-β type II receptor-deficient HSCs show low-level Smad activation and impaired long-term repopulating activity, underlining the critical role of TGF-β/Smad signaling in HSC maintenance. TGF-β is produced as a latent form by a variety of cells, so we searched for those that express activator molecules for latent TGF-β. Nonmyelinating Schwann cells in BM proved responsible for activation. These glial cells ensheathed autonomic nerves, expressed HSC niche factor genes, and were in contact with a substantial proportion of HSCs. Autonomic nerve denervation reduced the number of these active TGF-β-producing cells and led to rapid loss of HSCs from BM. We propose that glial cells are components of a BM niche and maintain HSC hibernation by regulating activation of latent TGF-β.
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► The TGF-β/Smad signaling pathway is active in dormant hematopoietic stem cells (HSCs) ► Loss of the TGF-β type II receptor reduces long-term repopulating activity in HSCs ► Nonmyelinating Schwann (glial) cells maintain HSC dormancy by activating latent TGF-β ► Autonomic nerve denervation causes glial cell death and rapid loss of HSCs
Glial cells ensheathing sympathetic nerves in the bone marrow enable the maintenance of hematopoietic stem cells by activating TGF-β signaling
This paper proposes an experimental approximation formula for battery lifetime considering real Sigfox node behavior for smart agriculture as an internet of things (IoT) use case outdoors. To achieve ...this, a Sigfox-based sensor node is first developed using only general-purpose devices for measuring the current consumption of the sensor node by the user self. Here, the consumed current in the sleep state could be reduced significantly by improving of embedded software and leakage current countermeasures of electronic circuits. Using the node, the outdoor transmission performances such as coverage area and the best position to communicate in a farm house were demonstrated. Next, we analyze energy consumption mechanisms associated with wireless communication of Sigfox nodes and derive an experimental approximation formula of the battery lifetime of the Sigfox node using input parameters from the user and measured values in field experiments, as well as transmission performance results described above. For deriving the experimental approximation formula, we focus on the Sigfox specification, which allows users to arbitrarily set the number of communications (uplinks and downlinks) per day. Finally, we present the impcat of the number of uplink transactions in one day and payload size for battery lifetime using the proposed model numerically. Moreover, we point out that the time- and frequency- and spatial diversity effects, which are important features of Sigfox, which can be degraded because of multiple frame collisions.
Hematopoietic stem cells (HSCs) are somatic stem cells that continuously generate lifelong supply of blood cells through a balance of symmetric and asymmetric divisions. It is well established that ...the HSC pool increases with age. However, not much is known about the underlying cause for these observed changes. Here, using a novel method combining single-cell ex vivo HSC expansion with mathematical modeling, we quantify HSC division types (stem cell-stem cell (S-S) division, stem cell-progenitor cell (S-P) division, and progenitor cell-progenitor cell (P-P) division) as a function of the aging process. Our time-series experiments reveal how changes in these three modes of division can explain the increase in HSC numbers with age. Contrary to the popular notion that HSCs divide predominantly through S-P divisions, we show that S-S divisions are predominant throughout the lifespan of the animal, thereby expanding the HSC pool. We, therefore, provide a novel mathematical model-based experimental validation for reflecting HSC dynamics in vivo.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Hematopoietic stem cells (HSCs) exhibit functional alterations, such as reduced regenerative capacity and myeloid-biased differentiation, with age. The HSC niche, which is essential for the ...maintenance of HSCs, also undergoes marked changes with aging. However, it has been technically challenging to directly evaluate the contribution of niche aging to age-associated HSC alterations without niche-damaging myeloablation in HSC transplantation assays. We herein transplanted an excess of aged HSCs into young mice without preconditioning. Although aged HSCs successfully engrafted in the intact young bone marrow niche, they poorly regenerated downstream progenitors and exhibited persistent myeloid-biased differentiation, resulting in no significant functional rejuvenation. Transcriptome and methylome analyses revealed that the young niche largely restored the transcriptional profile of aged HSCs, but not their DNA methylation profiles. Therefore, the restoration of the young niche is insufficient for rejuvenating HSC functions, highlighting a key role for age-associated cell-intrinsic defects in HSC aging.
Multi-walled carbon nanotube networks were confirmed to exhibit a linear decrease in resistivity with increasing temperature from 100 to above 400 K. The linearity was explained using a defect ...scattering model that involved Friedel oscillations (that is, electron-electron interactions). The applicability of this model, which was originally proposed for graphene, to carbon nanotubes was assessed based on a comparison of various experimental data. Increases in the slopes of the resistivity-temperature plots following the introduction of defects, as well as an effect of charge concentration on the slope were key predictions of this model. The results obtained from few-walled carbon nanotube networks are also shown. In the literature, linear resistivity-temperature plots were obtained from other graphene derivatives, indicating that the linearity originates from the hexagonal symmetry of these materials. The present work also indicated a relationship between the appearance of linearity and negative magnetoresistance above 100 K. Based on a mechanism incorporating scattering in association with Friedel oscillations and conventional electron conduction models, the universality of resistivity-temperature plots obtained from carbon nanotube networks is introduced.
Origins of DNA replication on eukaryotic genomes have been observed to fire during S phase in a coordinated manner. Studies in yeast indicate that origin firing is affected by several factors, ...including checkpoint regulators and chromatin modifiers. However, it is unclear what the mechanisms orchestrating this coordinated process are. Recent studies have identified factors that regulate the timing of origin activation, including Rif1 which plays crucial roles in the regulation of the replication timing program in yeast as well as in higher eukaryotes. In mammalian cells, Rif1 appears to regulate the structures of replication timing domains through its ability to organize chromatin loop structures. Regulation of chromatin architecture by Rif1 may be linked to other chromosome transactions including recombination, repair, or transcription. This review summarizes recent progress in the effort to elucidate the regulatory mechanisms of replication timing of eukaryotic replicons.
Understanding behavioral responses of resource users to environmental changes and incentives created by management systems is imperative to implement effective resource management and development ...policies. A small-scale mixed fishery in the Maizuru Bay, Japan, provides a natural experiment to evaluate changes in small-scale fishers’ harvesting and targeting behavior over the years that one of the key species in the fishery experienced a collapse of the stock. Using data on individual fishers across the pre- and postcollapse periods, we find that inefficient fishers were forced to shut down or stay idle along with the collapse of the stock, and this behavior led to an increase in the overall efficiency in the production of clams (Venerupis philippinarum). The depletion of the stock, however, imposed a natural constraint on the operation, resulting in a substantial decline in the maximum production achievable by the remaining fishers. We further show that the collapse of the stock not only affected the harvesting behavior against the declining species but also led to the expansion of the fishing capacity and effort to catch other species and the development of aquaculture as an alternative form of fish production in the region.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The negative regulator of p53, MDM2, is frequently overexpressed in acute myeloid leukemia (AML) that retains wild-type TP53 alleles. Targeting of p53-MDM2 interaction to reactivate p53 function is ...therefore an attractive therapeutic approach for AML. Here we show that an orally active inhibitor of p53-MDM2 interaction, DS-5272, causes dramatic tumor regressions of MLL-AF9-driven AML in vivo with a tolerable toxicity. However, the antileukemia effect of DS-5272 is markedly attenuated in immunodeficient mice, indicating the critical impact of systemic immune responses that drive p53-mediated leukemia suppression. In relation to this, DS-5272 triggers immune-inflammatory responses in MLL-AF9 cells including upregulation of Hif1α and PD-L1, and inhibition of the Hif1α-PD-L1 axis sensitizes AML cells to p53 activation. We also found that NK cells are important mediators of antileukemia immunity. Our study showed the potent activity of a p53-activating drug against AML, which is further augmented by antitumor immunity.
In many wireless networks, such as ad hoc, sensor, and delay-tolerant networks, the destination node is determined from the source node by the flooding process. Flooding efficiency is important for ...nodes, because they are driven by limited batteries. In this paper, we propose a simple flooding scheme to transmit a route request (RREQ) message based on the remaining power of its own node without using control packets and complex calculations. We applied the proposed scheme to ad hoc on-demand distance vector (AODV) routing protocol as an example and carried out computer simulations (ns3). The results showed that the proposed scheme was superior to conventional schemes in static and mobile scenarios. First, we showed the limit of node density that causes the decrease of throughput in the proposed scheme and that the proposed scheme was superior in terms of energy efficiency (bits/J), including throughput and energy consumption. Next, as the number of flooding times is made uniform in the proposed scheme, all nodes will have almost the same battery replacement time. As a result, when the nodes are static, the lifetime in the proposed scheme is longer than that in the conventional scheme.
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