Characteristics and outcome of suspected cerebrovascular disease in dogs: 66 cases (2009-2016).

OBJECTIVES: To characterise the clinical signs of suspected cerebrovascular disease in dogs. MATERIALS AND METHODS: Medical records of one hospital were searched from November 2009 to December 2016 for dogs that suffered of cerebrovascular disease. We diagnosed cerebrovascular disease based on acute onset, clinical signs and magnetic resonance imaging findings. The medical history, clinical signs, concurrent disease, area of infarction, cerebrospinal fluid results, month at onset and outcome were investigated in the cerebrovascular disease group and in a control group (dogs with brain disorders other than cerebrovascular disease). RESULTS: A total of 122 CVD cases were extracted from the 5312 patients that visited during the study period. Of these 122 cases, 66 (1.2%) matched the subject selection criteria of our study and were included in the analysis. Forebrain infarction was observed in 51 of 66 cases, of which 24 (47.1%) suffered from seizures. The number of dogs diagnosed with cerebrovascular disease was disproportionately high in August (nine of 59 cases) and December (13 of 59 cases). In the outcome survey, deterioration was observed in 11 of 55 cases. CLINICAL SIGNIFICANCE: Seizure is an important clinical sign of cerebrovascular disease in dogs. There was a significant seasonal variation in the number of dogs diagnosed with cerebrovascular disease in Japan. Clinical features observed in this report differ from those of previous reports and highlight the need for additional research in this area.

Semi-Dirac Transport and Anisotropic Localization in Polariton Honeycomb Lattices.

Compression dramatically changes the transport and localization properties of graphene. This is intimately related to the change of symmetry of the Dirac cone when the particle hopping is different along different directions of the lattice. In particular, for a critical compression, a semi-Dirac cone is formed with massless and massive dispersions along perpendicular directions. Here we show direct evidence of the highly anisotropic transport of polaritons in a honeycomb lattice of coupled micropillars implementing a semi-Dirac cone. If we optically induce a vacancylike defect in the lattice, we observe an anisotropically localized polariton distribution in a single sublattice, a consequence of the semi-Dirac dispersion. Our work opens up new horizons for the study of transport and localization in lattices with chiral symmetry and exotic Dirac dispersions.

Analysis of Arch Widths in Patients With Isolated Pierre Robin Sequence.

OBJECTIVE: To compare arch widths of patients with isolated Robin sequence (IRS) operated using modified von Langenbeck technique and modified Furlow double-opposing z-plasty. DESIGN: Retrospective, transversal study. SETTING: Hospital of Rehabilitation of Craniofacial Anomalies, University of São Paulo, Bauru, Brazil. PATIENTS: Three groups of patients were analyzed. Group VL comprised 30 patients with IRS operated by von Langenbeck technique (mean age of 8.1 years); group FL included 30 patients with IRS operated by Furlow technique (7.6 years); and the control group included 30 noncleft patients with class I occlusion (7.4 years). The palate repair was performed between 1.0 and 1.7 years of age in both study groups. Transversal measurements of maxillary and mandibular arches were performed digitally on 3D digital models. STATISTIC: The intergroup comparison was performed using analysis of variance and Tukey test. An independent t test was used to compare the complete and incomplete types of cleft in both study groups. The level of significance was 5%. RESULTS: No statistically significant difference was found between the VL and FL groups for maxillary and mandibular arches. However, both groups showed decreased transversal dimensions compared with the control group (P < .01) for both dental arches. No differences for arch widths were observed for complete or incomplete palatal clefts. CONCLUSIONS: No influence of palate repair techniques was observed in the transversal arch widths in patients with IRS. Children with IRS operated for palate repair showed constriction of the maxillary and mandibular dental arches compared with noncleft children regardless the palatal cleft extension.

CCAT1 and CCAT2 long noncoding RNAs, located within the 8q.24.21 'gene desert', serve as important prognostic biomarkers in colorectal cancer.

BACKGROUND: 8q24.21 is a frequently amplified genomic region in colorectal cancer (CRC). This region is often referred to as a 'gene desert' due to lack of any important protein-coding genes, highlighting the potential role of noncoding RNAs, including long noncoding RNAs (lncRNAs) located around the proto-oncogene MYC. In this study, we have firstly evaluated the clinical significance of altered expression of lncRNAs mapped to this genomic locus in CRC. PATIENTS AND METHODS: A total of 300 tissues, including 280 CRC and 20 adjacent normal mucosa specimens were evaluated for the expression of 12 lncRNAs using qRT-PCR assays. We analyzed the associations between lncRNA expression and various clinicopathological features, as well as with recurrence free survival (RFS) and overall survival (OS) in two independent cohorts. RESULTS: The expression of CCAT1, CCAT1-L, CCAT2, PVT1, and CASC19 were elevated in cancer tissues (P = 0.039, <0.001, 0.018, <0.001, 0.002, respectively). Among these, high expression of CCAT1 and CCAT2 was significantly associated with poor RFS (P = 0.049 and 0.022, respectively) and OS (P = 0.028 and 0.015, respectively). These results were validated in an independent patient cohort, in which combined expression of CCAT1 and CCAT2 expression was significantly associated with a poor RFS (HR:2.60, 95% confidence interval [CI]: 1.04-6.06, P = 0.042) and a poor OS (HR:8.38, 95%CI: 2.68-37.0, P < 0.001). We established a RFS prediction model which revealed that combined expression of CCAT1, CCAT2, and carcinoembryonic antigen was a significant determinant for efficiently predicting RFS in stage II (P = 0.034) and stage III (P = 0.001) CRC patients. CONCLUSIONS: Several lncRNAs located in 8q24.21 locus are highly over-expressed in CRC. High expression of CCAT1 and CCAT2 significantly associates with poor RFS and OS. The expression of these two lncRNAs independently, or in combination, serves as important prognostic biomarkers in CRC.

Relationships Between Gum Chewing and Stroop Test: A Pilot Study.

Cognitive function tends to decrease with aging, therefore maintenance of this function in an aging society is an important issue. The role of chewing in nutrition is important. Although several studies indicate that gum chewing is thought to improve cognitive function, it remains debatable whether gum-chewing does in fact improve cognitive function. The Stroop test is a psychological tool used to measure cognition. A shorter reaction time indicates a mean higher behavioral performance and higher levels of oxy-Hb concentration. fNIRS is a powerful, non-invasive imaging technique offering many advantages, including compact size, no need for specially equipped facilities, and the potential for real-time measurement. The left dorsolateral prefrontal cortex (DLPFC) seems to be mainly involved in the Stroop task.The aim of the present study was to investigate the hypothesis that gum-chewing changes cerebral blood flow in the left DLPFC during the Stroop test, and also changes the reaction time. Fourteen healthy volunteers (mean age 26.9 years) participated in this study after providing written informed consent. A piece of tasteless gum weighing 1.0 g was used. Each session was designed in a block manner, i.e. 4 rests (30 s) and 3 blocks of task (30 s). A computerized Stroop test was used (including both congruent and incongruent Stroop tasks) which calculates a response time automatically. The Binominal test was used for comparisons (p < 0.05). The results show activation of the left DLPFC during the Stroop task and that gum chewing significantly increases responses/oxy-Hb concentration and significantly shortens the reaction time.

Orbital Edge States in a Photonic Honeycomb Lattice.

We experimentally reveal the emergence of edge states in a photonic lattice with orbital bands. We use a two-dimensional honeycomb lattice of coupled micropillars whose bulk spectrum shows four gapless bands arising from the coupling of p-like photonic orbitals. We observe zero-energy edge states whose topological origin is similar to that of conventional edge states in graphene. Additionally, we report novel dispersive edge states in zigzag and armchair edges. The observations are reproduced by tight-binding and analytical calculations, which we extend to bearded edges. Our work shows the potentiality of coupled micropillars in elucidating some of the electronic properties of emergent two-dimensional materials with orbital bands.

Label-free versus conventional cellular assays: Functional investigations on the human histamine H1 receptor.

A set of histamine H1 receptor (H1R) agonists and antagonists was characterized in functional assays, using dynamic mass redistribution (DMR), electric cell-substrate impedance sensing (ECIS) and various signaling pathway specific readouts (Fura-2 and aequorin calcium assays, arrestin recruitment (luciferase fragment complementation) assay, luciferase gene reporter assay). Data were gained from genetically engineered HEK293T cells and compared with reference data from GTPase assays and radioligand binding. Histamine and the other H1R agonists gave different assay-related pEC50 values, however, the order of potency was maintained. In the luciferase fragment complementation assay, the H1R preferred ß-arrestin2 over ß-arrestin1. The calcium and the impedimetric assay depended on Gq coupling of the H1R, as demonstrated by complete inhibition of the histamine-induced signals in the presence of the Gq inhibitor FR900359 (UBO-QIC). Whereas partial inhibition by FR900359 was observed in DMR and the gene reporter assay, pertussis toxin substantially decreased the response in DMR, but increased the luciferase signal, reflecting the contribution of both, Gq and Gi, to signaling in these assays. For antagonists, the results from DMR were essentially compatible with those from conventional readouts, whereas the impedance-based data revealed a trend towards higher pKb values. ECIS and calcium assays apparently only reflect Gq signaling, whereas DMR and gene reporter assays appear to integrate both, Gq and Gi mediated signaling. The results confirm the value of the label-free methods, DMR and ECIS, for the characterization of H1R ligands. Both noninvasive techniques are complementary to each other, but cannot fully replace reductionist signaling pathway focused assays.

Monitoring of RNA Dynamics in Living Cells Using PUM-HD and Fluorescent Protein Reconstitution Technique.

Fluorescence live-cell RNA imaging to monitor the intracellular localization and dynamics of the target RNA is a challenging subject. One of the difficulties to achieve this is to establish a precise method to enable a fluorescent labeling to the target RNA in living cells. Technologies to reduce the background fluorescence and to detect the RNA with high sensitivity are also necessary to visualize and analyze the intracellular localization and dynamic of the target RNA precisely. Especially in monitoring single-molecule motion, a special setup of a microscope system is required. Such technical problems make the live-cell RNA imaging to be a difficult subject. We recently developed a methodology to label and to visualize a target RNA in living cells with low background fluorescence by using a probe that is based on an RNA-binding protein domain PUM-HD (pumilio homology domain) and a fluorescent protein reconstitution method. A noteworthy property of PUM-HD to apply RNA probes is that this protein domain can be modified to recognize a particular 8-base RNA sequence by inducing tailor-made designed mutagenesis. The fluorescent protein reconstitution method allows us to detect the target RNA with high signal-to-noise ratio. Using the probe based on PUM-HD, a fluorescent protein reconstitution method, and a homebuilt fluorescent microscope system, we succeeded in single-molecule observation of a target RNA in living cells. In this chapter, the techniques to establish the probe and to observe the motion of single-molecule RNA are described.

Optogenetic activation of axon guidance receptors controls direction of neurite outgrowth.

Growth cones of extending axons navigate to correct targets by sensing a guidance cue gradient via membrane protein receptors. Although most signaling mechanisms have been clarified using an in vitro approach, it is still difficult to investigate the growth cone behavior in complicated extracellular environment of living animals due to the lack of tools. We develop a system for the light-dependent activation of a guidance receptor, Deleted in Colorectal Cancer (DCC), using Arabidopsis thaliana Cryptochrome 2, which oligomerizes upon blue-light absorption. Blue-light illumination transiently activates DCC via its oligomerization, which initiates downstream signaling in the illuminated subcellular region. The extending axons are attracted by illumination in cultured chick dorsal root ganglion neurons. Moreover, light-mediated navigation of the growth cones is achieved in living Caenorhabditis elegans. The photo-manipulation system is applicable to investigate the relationship between the growth cone behavior and its surrounding environment in living tissue.

The Americleft Project: A Proposed Expanded Nasolabial Appearance Yardstick for 5- to 7-Year-Old Patients With Complete Unilateral Cleft Lip and Palate (CUCLP).

OBJECTIVE: To develop a yardstick of reference photographs for nasolabial appearance assessments of 5- to 7-year-old patients with complete unilateral cleft lip and palate (CUCLP). DESIGN: Blind retrospective analysis of clinical records and comparison to historical controls. PATIENTS: Subjects were two groups of 6- to 12-year-olds (n = 124 and n = 135) and one group of 5- to 7-year-olds (n = 149) with nonsyndromic CUCLP from three previous Americleft studies, including cohorts from seven different cleft/craniofacial centers. INTERVENTIONS: All patients received the infant management protocols of their respective centers. Eleven trained and calibrated judges (five participated in all three studies) did blind ratings of nasolabial appearance using the Asher-McDade method. MAIN OUTCOME MEASURES: Patients receiving the most consistent ratings between judges, selected first from the groups of 6- to 12-year-olds, were used to create a pilot yardstick for eventual use in the third study of 5- to 7-year-olds. For each of the Asher-McDade categories, 8 of the 5- to 7-year-old patients receiving the most consistent scores between raters were ranked by 10 judges for a final elimination to leave three per category. RESULTS: Using this method of successive changes in rating methods, a new reference yardstick for nasolabial appearance rating was established and linked to the original Asher-McDade method as well as the single examples in a previously published yardstick for patients with CUCLP. Pilot testing using the yardstick improved reliabilities. CONCLUSIONS: Use of an expanded nasolabial yardstick of reference photographs representative of the range of possibilities of each of the five Asher-McDade categories is now available to see if reliability of these ratings can be improved.

Four-Dimensional Quantum Hall Effect with Ultracold Atoms.

We propose a realistic scheme to detect the 4D quantum Hall effect using ultracold atoms. Based on contemporary technology, motion along a synthetic fourth dimension can be accomplished through controlled transitions between internal states of atoms arranged in a 3D optical lattice. From a semiclassical analysis, we identify the linear and nonlinear quantized current responses of our 4D model, relating these to the topology of the Bloch bands. We then propose experimental protocols, based on current or center-of-mass-drift measurements, to extract the topological second Chern number. Our proposal sets the stage for the exploration of novel topological phases in higher dimensions.

Development of an aerodynamic measurement system for hypersonic rarefied flows.

A hypersonic rarefied wind tunnel (HRWT) has lately been developed at Japan Aerospace Exploration Agency in order to improve the prediction of rarefied aerodynamics. Flow characteristics of hypersonic rarefied flows have been investigated experimentally and numerically. By conducting dynamic pressure measurements with pendulous models and pitot pressure measurements, we have probed flow characteristics in the test section. We have also improved understandings of hypersonic rarefied flows by integrating a numerical approach with the HRWT measurement. The development of the integration scheme between HRWT and numerical approach enables us to estimate the hypersonic rarefied flow characteristics as well as the direct measurement of rarefied aerodynamics. Consequently, this wind tunnel is capable of generating 25 mm-core flows with the free stream Mach number greater than 10 and Knudsen number greater than 0.1.

Growth of In x Ga1-x Sb alloy semiconductor at the International Space Station (ISS) and comparison with terrestrial experiments.

BACKGROUND: In x Ga1-x Sb is an important material that has tunable properties in the infrared (IR) region and is suitable for IR-device applications. Since the quality of crystals relies on growth conditions, the growth process of alloy semiconductors can be examined better under microgravity (µG) conditions where convection is suppressed. AIMS: To investigate the dissolution and growth process of In x Ga1-x Sb alloy semiconductors via a sandwiched structure of GaSb(seed)/InSb/GaSb(feed) under normal and µG conditions. METHODS: In x Ga1-x Sb crystals were grown at the International Space Station (ISS) under µG conditions, and a similar experiment was conducted under terrestrial conditions (1G) using the vertical gradient freezing (VGF) method. The grown crystals were cut along the growth direction and its growth properties were studied. The indium composition and growth rate of grown crystals were calculated. RESULTS: The shape of the growth interface was nearly flat under µG, whereas under 1G, it was highly concave with the initial seed interface being nearly flat and having facets at the peripheries. The quality of the µG crystals was better than that of the 1G samples, as the etch pit density was low in the µG sample. The growth rate was higher under µG compared with 1G. Moreover, the growth started at the peripheries under 1G, whereas it started throughout the seed interface under µG. CONCLUSIONS: Kinetics played a dominant role under 1G. The suppressed convection under µG affected the dissolution and growth process of the In x Ga1-x Sb alloy semiconductor.

Developing a potentially immunologically inert tetracycline-regulatable viral vector for gene therapy in the peripheral nerve.

Viral vector-mediated gene transfer of neurotrophic factors is an emerging and promising strategy to promote the regeneration of injured peripheral nerves. Unfortunately, the chronic exposure to neurotrophic factors results in local trapping of regenerating axons or other unwanted side effects. Therefore, tight control of therapeutic gene expression is required. The tetracycline/doxycycline-inducible system is considered to be one of the most promising systems for regulating heterologous gene expression. However, an immune response directed against the transactivator protein rtTA hampers further translational studies. Immunogenic proteins fused with the Gly-Ala repeat of the Epstein-Barr virus Nuclear Antigen-1 protein have been shown to successfully evade the immune system. In this article, we used this strategy to demonstrate that a chimeric transactivator, created by fusing the Gly-Ala repeat with rtTA and embedded in a lentiviral vector (i) retained its transactivator function in vitro, in muscle explants, and in vivo following injection into the rat peripheral nerve, (ii) exhibited a reduced leaky expression, and (iii) had an immune-evasive advantage over rtTA as shown in a novel bioassay for human antigen presentation. The current findings are an important step toward creating a clinically applicable potentially immune-evasive tetracycline-regulatable viral vector system.

TRIM3, a tumor suppressor linked to regulation of p21(Waf1/Cip1.).

The TRIM family of genes is largely studied because of their roles in development, differentiation and host cell antiviral defenses; however, roles in cancer biology are emerging. Loss of heterozygosity of the TRIM3 locus in ∼20% of human glioblastomas raised the possibility that this NHL-domain containing member of the TRIM gene family might be a mammalian tumor suppressor. Consistent with this, reducing TRIM3 expression increased the incidence of and accelerated the development of platelet-derived growth factor -induced glioma in mice. Furthermore, TRIM3 can bind to the cdk inhibitor p21(WAF1/CIP1). Thus, we conclude that TRIM3 is a tumor suppressor mapping to chromosome 11p15.5 and that it might block tumor growth by sequestering p21 and preventing it from facilitating the accumulation of cyclin D1-cdk4.

Blue LED light exposure develops intracellular reactive oxygen species, lipid peroxidation, and subsequent cellular injuries in cultured bovine retinal pigment epithelial cells.

The effects of blue light emitter diode (LED) light exposure on retinal pigment epithelial cells (RPE cells) were examined to detect cellular damage or change and to clarify its mechanisms. The RPE cells were cultured and exposed by blue (470 nm) LED at 4.8 mW/cm(2). The cellular viability was determined by XTT assay and cellular injury was determined by the lactate dehydrogenase activity in medium. Intracellular reactive oxygen species (ROS) generation was determined by confocal laser microscope image analysis using dihydrorhodamine 123 and lipid peroxidation was determined by 4-hydroxy-2-nonenal protein-adducts immunofluorescent staining (HNE). At 24 h after 50 J/cm(2) exposures, cellular viability was significantly decreased to 74% and cellular injury was significantly increased to 365% of control. Immediately after the light exposure, ROS generation was significantly increased to 154%, 177%, and 395% of control and HNE intensity was increased to 211%, 359%, and 746% of control by 1, 10, and 50 J/cm(2), respectively. These results suggest, at least in part, that oxidative stress is an early step leading to cellular damage by blue LED exposure and cellular oxidative damage would be caused by the blue light exposure at even lower dose (1, 10 J/cm(2)).

Decontamination of outdoor school swimming pools in Fukushima after the nuclear accident in March 2011.

Because of radioactive fallout resulting from the Fukushima Daiichi Nuclear Power Plant (NPP) accident, water discharge from many outdoor swimming pools in Fukushima was suspended out of concern that radiocesium in the pool water would flow into farmlands. The Japan Atomic Energy Agency has reviewed the existing flocculation method for decontaminating pool water and established a practical decontamination method by demonstrating the process at eight pools in Fukushima. In this method, zeolite powder and a flocculant are used for capturing radiocesium present in pool water. The supernatant is discharged if the radiocesium concentration is less than the targeted level. The radioactive residue is collected and stored in a temporary storage space. Radioactivity concentration in water is measured with a NaI(Tl) or Ge detector installed near the pool. The demonstration results showed that the pool water in which the radiocesium concentration was more than a few hundred Bq L was readily purified by the method, and the radiocesium concentration was reduced to less than 100 Bq L. The ambient dose rates around the temporary storage space were slightly elevated; however, the total increase was up to 30% of the background dose rates when the residue was shielded with sandbags.