Recently, nanocarriers that transport bioactive substances to a target site in the body have attracted considerable attention and undergone rapid progression in terms of the state of the art. ...However, few nanocarriers can enter the brain via a systemic route through the blood-brain barrier (BBB) to efficiently reach neurons. Here we prepare a self-assembled supramolecular nanocarrier with a surface featuring properly configured glucose. The BBB crossing and brain accumulation of this nanocarrier are boosted by the rapid glycaemic increase after fasting and by the putative phenomenon of the highly expressed glucose transporter-1 (GLUT1) in brain capillary endothelial cells migrating from the luminal to the abluminal plasma membrane. The precisely controlled glucose density on the surface of the nanocarrier enables the regulation of its distribution within the brain, and thus is successfully optimized to increase the number of nanocarriers accumulating in neurons.There are only a few examples of nanocarriers that can transport bioactive substances across the blood-brain barrier. Here the authors show that by rapid glycaemic increase the accumulation of a glucosylated nanocarrier in the brain can be controlled.
Objectives: MicroRNAs (miRNAs) are small functional RNAs that regulate mRNAs for degradation or translational suppression. In the present study, we aimed to reveal functional importance of miRNA‐494 ...(miR‐494) in A549 human lung cancer cells.
Materials and methods: We established A549 cells that constitutively expressed miR‐494. Next, we sought to investigate insulin‐like growth factor 2 mRNA‐binding protein 1 (IGF2BP1) mRNA as an miR‐494 target. For this, we constructed a reporter plasmid bearing potential miR‐494 binding sequences derived from the 3′‐untranslated region (3′‐UTR) of IGF2BP1 mRNA in the 3′‐UTR of the luciferase gene.
Results: Through comparison between miR‐494 expressing cells and control cells, we revealed that miR‐494 suppressed cell proliferation and colony forming activity, and induced senescence. Reporter activity was inhibited by miR‐494. In addition, IGF2BP1 mRNA levels were down‐regulated in A549 cells that constitutively expressed miR‐494. IGF2BP1 has been shown to bind and suppress IGF2 mRNA, and this could be a reason why IGF2BP1 can regulate cell function. Therefore, we analysed IGF2 mRNA levels and revealed that IGF2 was up‐regulated in A549 cells that constitutively expressed miR‐494. Finally, elevated IGF2 mRNA levels in A549 cells that constitutively expressed miR‐494 were suppressed to basal level by an miR‐494 inhibitor.
Conclusions: Taken together, IGF2BP1 and its downstream target IGF2 could be a crucial axis for miR‐494 in regulation of the destiny of A549 cells.
A model to rate color combinations that considers human aesthetic preferences is proposed. The proposed method does not assume that a color palette has a specific number of colors, i.e., input is not ...restricted to a two‐, three‐, or five‐color palettes. We extract features from a color palette whose size does not depend on the number of colors in the palette. The proposed rating prediction model is trained using a human color preference dataset. The model allows a user to extend a color palette, e.g., from three colors to five or seven colors, while retaining color harmony. In addition, we present a color search scheme for a given palette and a customized version of the proposed model for a specific color tone. We demonstrate that the proposed model can also be applied to various palette‐based applications.
The surface detector array of the Telescope Array experiment Abu-Zayyad, T.; Aida, R.; Anderson, R. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
10/2012, Letnik:
689
Journal Article
Recenzirano
Odprti dostop
The Telescope Array (TA) experiment, located in the western desert of Utah, USA, is designed for the observation of extensive air showers from extremely high energy cosmic rays. The experiment has a ...surface detector array surrounded by three fluorescence detectors to enable simultaneous detection of shower particles at ground level and fluorescence photons along the shower track. The TA surface detectors and fluorescence detectors started full hybrid observation in March, 2008. In this article we describe the design and technical features of the TA surface detector.
Since 2007, the Telescope Array (TA) experiment, based in Utah, USA, has been observing ultra high energy cosmic rays to understand their origins. The experiment includes a surface detector (SD) ...array and three fluorescence detector (FD) stations. The FD stations, installed surrounding the SD array, measure the air fluorescence light emitted from extensive air showers (EASs) for precise determination of their energies and species. The detectors employed at one of the three FD stations were relocated from the High Resolution Fly's Eye (HiRes) experiment. At the other two stations, newly designed detectors were constructed for the TA experiment. An FD consists of a primary mirror and a camera equipped with photomultiplier tube pixels. To obtain the EAS parameters with high accuracy, understanding the FD optical characteristics is important. In this paper, we report the characteristics and installation of the new FDs and the performances of the FD components. The results of the monitored mirror reflectance during the observation time are also described in this report.
Abstract Current technology of siRNA delivery relies on pharmaceutical dosage forms to route maximal doses of siRNA to the tumor. However, this rationale does not address intracellular bottlenecks ...governing silencing activity. Here, we tested the impact of hydroxychloroquine conjugation on the intracellular fate and silencing activity of siRNA conjugated PEGylated gold nanoparticles. Addition of hydroxychloroquine improved endosomal escape and increased siRNA guide strand distribution to the RNA induced silencing complex (RISC), both crucial obstacles to the potency of siRNA. This modification significantly improved gene downregulation in cellulo . Altogether, our data suggest the benefit of this modification for the design of improved siRNA delivery systems.
Lubricant transfer or pickup from a disk to a head slider is a crucial issue in designing the head-disk interfaces of hard disk drives (HDDs). A method based on ellipsometric microscopy is presented ...for observing thin lubricant film on a head slider in real time. The use of rotating-compensator ellipsometry (RCE) results in one order of magnitude higher temporal resolution (0.6 frames/s) and several times higher thickness resolution (0.2 nm) compared to null-ellipsometry-based microscopy, which was recently proposed. RCE-based ellipsometric microscopy will be useful in clarifying the mechanism of lubricant pickup for higher density HDDs.
Among some local side effects of prostaglandin-associated periorbitopathy (PAP), deepening of the upper eyelid sulcus (DUES) is the most prominent clinical feature, and is one of the most significant ...adverse cosmetic events. Here, we prospectively investigated the incidence of DUES in Japanese open-angle glaucoma patients initially treated with latanoprost (Xalatan 0.005%) ophthalmic solution.
This was an open-label prospective study. Facial photographs and subjective reports of the recognition of DUES were obtained at the beginning of latanoprost treatment and at 2, 4, and 6 months thereafter. Intraocular pressure (IOP) was measured at three consecutive visits before and after treatment with latanoprost. The incidence of DUES was evaluated objectively by three blinded investigators who compared the series of photographs.
A total of 52 eyes of 52 newly diagnosed open-angle glaucoma Japanese patients (28 males, 24 females) were evaluated. The objective rate of DUES was 1/52 (2%; 95% CI 0.05 to 10.7%) at 2 months, 2/52 (4%; 95% CI 0.5 to 13.9%) at 4 months, and 3/52 (6%; 95% CI 1.2 to 16.9%) at 6 months. During this period, no patient self-reported an occurrence of DUES. Mean IOPs before and after treatment were 16.5±2.9 and 13.8±3.0 mm Hg, respectively. Latanoprost reduced the IOP significantly (P<0.0001, paired t-test).
Latanoprost caused DUES rarely and had a robust IOP-lowering effect in Japanese glaucoma patients.
Summary
To elucidate mutation spectrum and genotype-phenotype correlations in Japanese patients with OI, we conducted comprehensive genetic analyses using NGS, as this had not been analyzed ...comprehensively in this patient population. Most mutations were located on
COL1A1
and
COL1A2
. Glycine substitutions in
COL1A1
resulted in the severe phenotype.
Introduction
Most cases of osteogenesis imperfecta (OI) are caused by mutations in
COL1A1
or
COL1A2
, which encode α chains of type I collagen. However, mutations in at least 16 other genes also cause OI. The mutation spectrum in Japanese patients with OI has not been comprehensively analyzed, as it is difficult to identify using classical Sanger sequencing. In this study, we aimed to reveal the mutation spectrum and genotype-phenotype correlations in Japanese patients with OI using next-generation sequencing (NGS).
Methods
We designed a capture panel for sequencing 15 candidate OI genes and 19 candidate genes that are associated with bone fragility or Wnt signaling. Using NGS, we examined 53 Japanese patients with OI from unrelated families.
Results
Pathogenic mutations were detected in 43 out of 53 individuals. All mutations were heterozygous. Among the 43 individuals, 40 variants were identified including 15 novel mutations. We found these mutations in
COL1A1
(
n
= 30, 69.8%),
COL1A2
(
n
= 12, 27.9%), and
IFITM5
(
n
= 1, 2.3%). Patients with glycine substitution on
COL1A1
had a higher frequency of fractures and were more severely short-statured. Although no significant genotype-phenotype correlation was observed for bone mineral density, the trabecular bone score was significantly lower in patients with glycine substitutions.
Conclusion
We identified pathogenic mutations in 81% of our Japanese patients with OI. Most mutations were located on
COL1A1
and
COL1A2
. This study revealed that glycine substitutions on
COL1A1
resulted in the severe phenotype among Japanese patients with OI.
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