The quiescent state is thought to be an indispensable property for the maintenance of hematopoietic stem cells (HSCs). Interaction of HSCs with their particular microenvironments, known as the stem ...cell niches, is critical for adult hematopoiesis in the bone marrow (BM). Here, we demonstrate that HSCs expressing the receptor tyrosine kinase Tie2 are quiescent and antiapoptotic, and comprise a side-population (SP) of HSCs, which adhere to osteoblasts (OBs) in the BM niche. The interaction of Tie2 with its ligand Angiopoietin-1 (Ang-1) induced cobblestone formation of HSCs in vitro and maintained in vivo long-term repopulating activity of HSCs. Furthermore, Ang-1 enhanced the ability of HSCs to become quiescent and induced adhesion to bone, resulting in protection of the HSC compartment from myelosuppressive stress. These data suggest that the Tie2/Ang-1 signaling pathway plays a critical role in the maintenance of HSCs in a quiescent state in the BM niche.
Hox genes in vertebrates are clustered, and the organization of the clusters has been highly conserved during evolution. The conservation of Hox clusters has been attributed to enhancers located ...within and outside the Hox clusters that are essential for the coordinated "temporal" and "spatial" expression patterns of Hox genes in developing embryos. To identify evolutionarily conserved regulatory elements within and outside the Hox clusters, we obtained contiguous sequences for the conserved syntenic blocks from the seven Hox loci in fugu and carried out a systematic search for conserved noncoding sequences (CNS) in the human, mouse, and fugu Hox loci. Our analysis has uncovered unusually large conserved syntenic blocks at the HoxA and HoxD loci. The conserved syntenic blocks at the human and mouse HoxA and HoxD loci span 5.4 Mb and 4 Mb and contain 21 and 19 genes, respectively. The corresponding regions in fugu are 16-and 12-fold smaller. A large number of CNS was identified within the Hox clusters and outside the Hox clusters spread over large regions. The CNS include previously characterized enhancers and overlap with the 5' global control regions of HoxA and HoxD clusters. Most of the CNS are likely to be control regions involved in the regulation of Hox and other genes in these loci. We propose that the regulatory elements spread across large regions on either side of Hox clusters are a major evolutionary constraint that has maintained the exceptionally long syntenic blocks at the HoxA and HoxD loci.
Purpose
Parents find it challenging to follow recommendations to brush young children after feeds at night despite the increase caries risk. This study compared three clinical recommendations ...(dilution, rinsing and wiping) on plaque pH after formula consumption.
Methods
Eighteen subjects were recruited. The five interventions with 2-week washout between visits included: Rinse with undiluted formula for 30 s (UF); rinse with 50% diluted formula for 30 s (DF); rinse with undiluted formula for 30 s, followed by rinsing with water for 1 minute (UF/R); rinse with undiluted formula for 30 s, followed by wiping (UF/W); rinse with 10% sucrose for 30 s as control (C). Plaque samples were collected at baseline, 2, 5, 10, 20 and 30 min after the intervention and pH measured using the plaque sampling method.
Results
UF/R resulted in significantly smaller pH drops at 5, 10 and 20 min compared to UF. It also resulted in higher minimum pH (UF/R: 6.34 ± 0.36 Vs UF: 6.06 ± 0.40,
p
= 0.02), smaller maximum pH drop (UF/R: 0.63 ± 0.35 Vs UF: 0.90 ± 0.49,
p
= 0.03), smaller sum of change of hydrogen ion concentration (UF/R: 9.22 × 10
−7
± 7.8 × 10
−7
Vs UF: 2.30 × 10
−6
± 2.6 × 10
−6
,
p
= 0.04), and smaller area under the curve (UF/R: 7.70 ± 5.44 Vs UF: 13.44 ± 9.44,
p
= 0.02). DF and UF/W did not result in any significant pH change compared to UF.
Conclusions
Of the three clinical recommendations, only rinsing with water for 1 min after undiluted formula reduced plaque acidogenicity. Teeth wiping with a moist cloth and 50% dilution of infant formula did not have an effect on plaque acidity.
Summary
Background
The plasma protease factor VII‐activating protease (FSAP) can release nucleosomes from late apoptotic cells. Nucleosomes are markers of cell death, and extracellular cell‐free DNA ...has been suggested to play an important role in inflammation and has been demonstrated to correlate with severity and outcome in sepsis patients.
Objective
To investigate FSAP activation in patients suffering from Burkholderia pseudomallei infection (melioidosis), an important cause of Gram‐negative sepsis in Southeast Asia. As diabetes mellitus (DM) is the most important risk factor for both melioidosis and sepsis, we were also able to examine the role of DM in FSAP activation in this cohort of patients.
Methods
In a prospective observational study, complexes of FSAP with α2‐antiplasmin (AP) were assayed in 44 patients with melioidosis, 34 of whom were classified as diabetic. Eighty‐two healthy subjects served as controls (52 with DM and 30 without).
Results
FSAP–AP complex levels were markedly elevated in patients as compared with controls. The FSAP level increased by 16.82 AU mL−1 in patients with melioidosis after adjustment for the effect of DM in the regression model. As expected, FSAP activation was correlated with nucleosome release (slope = 0.74). No difference in FSAP activation on admission was seen between survivors and non‐survivors, but the extent of FSAP activation correlated with stage of the disease; repeated testing during convalescence showed a return towards normal values (day 0 vs. day 28, 4.16 AU mL−1, 95% confidence interval CI 1.42–12.22).
Conclusion
Patients with Gram‐negative sepsis caused by B. pseudomallei have abundant FSAP activation, which significantly correlates with stage of disease. The presence of DM, however, does not influence the extent of FSAP activation.
In order to identify the origin of saline groundwater in the eastern part of Jeju volcanic island, Korea, a hydrogeochemical and isotopic study has been carried out for 18 observation wells located ...in east and southeast coastal regions. The total dissolved solid contents of groundwaters are highly variable (77–21,782
mg/l). Oxygen, hydrogen, sulfur, and strontium isotopic data clearly show that the saline water results from mixing of groundwater with seawater. Strontium isotopic compositions and Br/Cl and I/Cl ratios strongly suggest that the source of salinity is modern seawater intrusion. Hydrogeochemical characteristics based on bivariate diagrams of major and minor ions show that changes in the chemical composition of groundwater are mainly controlled by the salinization process followed by cation-exchange reactions. The highly permeable aquifers at the east coastal region are characterized by low hydraulic gradient and discharge rate and high hydraulic conductivity as compared with other regions. These properties enhance the salinization of groundwater observed in the study area. Based on the Cl, Br, and
δ
18O data, seawater was determined to have intruded inland some 2.5
km from the coastline. Considering the poor correlation of sampling depth and Cl concentrations observed, the position of seawater-freshwater interface is not uniformly distributed in the study area, due to heterogeneities of the basaltic aquifers.
Patient-specific (PS) implantation surgical technology has been introduced in recent years and a gradual increase in the associated number of surgical cases has been observed. PS technology uses a ...patient's own geometry in designing a medical device to provide minimal bone resection with improvement in the prosthetic bone coverage. However, whether PS unicompartmental knee arthroplasty (UKA) provides a better biomechanical effect than standard off-the-shelf prostheses for UKA has not yet been determined, and still remains controversial in both biomechanical and clinical fields. Therefore, the aim of this study was to compare the biomechanical effect between PS and standard off-the-shelf prostheses for UKA.
The contact stresses on the polyethylene (PE) insert, articular cartilage and lateral meniscus were evaluated in PS and standard off-the-shelf prostheses for UKA using a validated finite element model. Gait cycle loading was applied to evaluate the biomechanical effect in the PS and standard UKAs.
The contact stresses on the PE insert were similar for both the PS and standard UKAs. Compared with the standard UKA, the PS UKA did not show any biomechanical effect on the medial PE insert. However, the contact stresses on the articular cartilage and the meniscus in the lateral compartment following the PS UKA exhibited closer values to the healthy knee joint compared with the standard UKA.
The PS UKA provided mechanics closer to those of the normal knee joint. The decreased contact stress on the opposite compartment may reduce the overall risk of progressive osteoarthritis.
: K-T. Kang, J. Son, D-S. Suh, S. K. Kwon, O-R. Kwon, Y-G. Koh. Patient-specific medial unicompartmental knee arthroplasty has a greater protective effect on articular cartilage in the lateral compartment: A Finite Element Analysis.
2018;7:20-27. DOI: 10.1302/2046-3758.71.BJR-2017-0115.R2.
The rise of blockchain technology could radically disrupt the global economy. As an emergent technology, blockchain is of broad and current interest in the tourism industry. Small island economies ...are at the forefront of adopting this digital asset and technology. For instance, the Caribbean economies are launching their first digital legal tender, and Aruba is developing a blockchain platform to boost tourism revenue. Given the velocity of adoption, blockchain technology holds significant implications for tourism development. This research letter provides a discourse on the adoption of blockchain technology among small island economies concerning the opportunities and potential challenges faced and offers practical implications for tourism stakeholders.
The advent of deepfake videos, a new form of media manipulation, took the world by storm. Malicious use of this technology for fraud, misrepresentation, and abuse created more perils than ...opportunities for various stakeholders. However, little is known about Generative Adversarial Networks utilized by deepfake to manipulate videos. Viewing from the social construction of technology theory, we explore the redress of the adversarial purposes of deepfake. At the moment, there are more misgivings than credence about the possible application of this technology. Our research note provides a discourse on the rapid advances of deepfake and its potential impact on tourism and raises the call for research on the beneficial uses of deepfake.
The strategy of clinically targeting cancerous cells at their most vulnerable state during mitosis has instigated numerous studies into the mitotic cell death (MCD) pathway. As the hallmark of cancer ...revolves around cell-cycle deregulation, it is not surprising that antimitotic therapies are effective against the abnormal proliferation of transformed cells. Moreover, these antimitotic drugs are also highly selective and sensitive. Despite the robust rate of discovery and the development of mitosis-selective inhibitors, the unpredictable complexities of the human body's response to these drugs still herald the biggest challenge towards clinical success. Undoubtedly, the need to bridge the gap between promising preclinical trials and effective translational bedside treatment prompts further investigations towards mapping out the mechanistic pathways of MCD, understanding how these drugs work as medicine in the body and more comprehensive target validations. In this review, current antimitotic agents are summarized with particular emphasis on the evaluation of their clinical efficacy as well as their limitations. In addition, we discuss the basis behind the lack of activity of these inhibitors in human trials and the potential and future directions of mitotic anticancer strategies.
The fabrication of hydrogel microstructures based upon poly(ethylene glycol) diacrylates, dimethacrylates, and tetraacrylates patterned photolithographically on silicon or glass substrates is ...described. A silicon/silicon dioxide surface was treated with 3-(trichlorosilyl)propyl methacrylate to form a self-assembled monolayer (SAM) with pendant acrylate groups. The SAM presence on the surface was verified using ellipsometry and time-of-flight secondary ion mass spectrometry. A solution containing an acrylated or methacrylated poly(ethylene glycol) derivative and a photoinitiator (2,2-dimethoxy-2-phenylacetophenone) was spin-coated onto the treated substrate, exposed to 365 nm ultraviolet light through a photomask, and developed with either toluene, water, or supercritical CO2. As a result of this process, three-dimensional, cross-linked PEG hydrogel microstructures were immobilized on the surface. Diameters of cylindrical array members were varied from 600 to 7 micrometers by the use of different photomasks, while height varied from 3 to 12 micrometers, depending on the molecular weight of the PEG macromer. In the case of 7 micrometers diameter elements, as many as 400 elements were reproducibly generated in a 1 mm2 square pattern. The resultant hydrogel patterns were hydrated for as long as 3 weeks without delamination from the substrate. In addition, micropatterning of different molecular weights of PEG was demonstrated. Arrays of hydrogel disks containing an immobilized protein conjugated to a pH sensitive fluorophore were also prepared. The pH sensitivity of the gel-immobilized dye was similar to that in an aqueous buffer, and no leaching of the dye-labeled protein from the hydrogel microstructure was observed over a 1 week period. Changes in fluorescence were also observed for immobilized fluorophore labeled acetylcholine esterase upon the addition of acetyl acholine.
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