Changes in the composition of molecular species of covalently bound and free ceramides [EOS], and their correlation with disease severity in atopic dermatitis.

Ceramides are major constituents of stratum corneum (SC) intercellular lipids involved in skin barrier function. The ratio of molecular species of ceramides and their correlation with disease severity was examined in patients with atopic dermatitis (AD). Thirty-eight patients with AD and 32 healthy controls (HCs) were assessed for transepidermal water loss, SC collection and clinical assessment. The ceramide content of different molecular species in the samples was quantified using high-performance liquid chromatography coupled with tandem mass spectrometry. Unsaturated acyl chains of both covalently bound and free ceramides [EOS] were higher in AD lesional skin than those in AD non-lesional or normal HC skin. The proportion of unsaturated acyl chains (C30:1, C32:1 and C34:1) was higher than other ceramide molecular species among covalently bound and free ceramides [EOS] in patients with AD. The proportion of unsaturated acyl chains in covalently bound ceramides was positively correlated with transepidermal water loss (r = 0.600) when considering the total number of non-lesional and lesional skin. Additionally, thymus and activation-regulated chemokine (TARC) showed a positive correlation with unsaturated acyl chains proportion in AD non-lesional (r = 0.676) and lesional (r = 0.503) skin. Our study is the first to show the increase in unsaturated acyl chains of both covalently bound and free ceramides [EOS] in lesional and non-lesional skin in AD for each molecular species. This increase is associated with dryness and impaired barrier function, which correlates with TARC levels, a marker for the degree of type 2 inflammation. We speculate that type 2 inflammation exacerbation leads to abnormal epidermal lipid metabolism in the skin of patients with AD.

Redox-labelled electrochemical aptasensors with nanosupported cancer cells.

The transfer of redox-labelled bioelectrochemical sensors from proteins to cells is not straightforward because of the cell downward force issue on the surface of the sensors. In this paper, 20-nm-thick nanopillars are introduced to overcome this issue, in a well-controlled manner. We show on both molecular dynamics simulations and experiments that suspending cells a few nanometers above an electrode surface enables redox-labelled tethered DNA aptamer probes to move freely, while remaining at an interaction distance from a target membrane protein, i. e. epithelial cell adhesion molecule (EpCAM), which is typically overexpressed in cancer cells. By this nanopillar configuration, the interaction of aptamer with cancer cells is clearly observable, with 13 cells as the lower limit of detection. Nanoconfinement induced by the gap between the electrode surface and the cell membrane appears to improve the limit of detection and to lower the melting temperature of DNA aptamer hairpins, offering an additional degree of freedom to optimize molecular recognition mechanisms. This novel nanosupported electrochemical DNA cell sensor scheme including Brownian-fluctuating redox species opens new opportunities for the design of all-electrical sensors using redox-labelled probes.

Alleviative effects of glutamate against chemotherapeutic agent-induced intestinal mucositis.

5-Fluorouracil (5-FU) is one of the most widely used chemotherapeutic agents; however, it often causes intestinal mucositis with severe diarrhea. An efficient treatment strategy to reduce this side effect is lacking. Glutamate (Glu), a nonessential amino acid, is the most important energy source in the small intestine and has been shown to maintain intestinal morphology, barrier function, and antioxidative capacity. However, the effects of Glu on intestinal mucositis induced by chemotherapeutic agents have not been explored. This study aimed to demonstrate the alleviative effects of Glu on 5-FU-induced intestinal mucositis. Mucositis was induced in C57B/6N mice by intraperitoneal injection of 5-FU (50 mg/kg) for 6 days and assessed by histological and physiological analyses. Glu (500 or 1000 mg/kg) was orally administered as a pretreatment twice daily for 7 days before the initial treatment of 5-FU. Cellular proliferation and apoptosis were assessed using Ki-67 immunostaining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, respectively. Furthermore, fluorescein isothiocyanate-dextran infiltration was assessed to measure intestinal permeability. In vitro experiments using rat intestinal epithelial cells (IEC-6 cells) were performed to clarify the effect of Glu on 5-FU-induced barrier dysfunction. Glu alleviated 5-FU-induced intestinal mucositis by reducing villi shortening, enhancing cell proliferation, and suppressing apoptosis. It also alleviated the 5-FU-induced increased intestinal permeability. In vitro studies revealed significantly increased trans-epithelial electrical resistance (TEER) in Glu-pretreated IEC-6 cells compared to that in 5-FU-treated and control cells. In conclusion, the findings of this study provide evidence for the potential of Glu to protect against 5-FU-induced intestinal mucositis in patients with cancer.

An outbreak of food poisoning due to Escherichia coli serotype O7:H4 carrying astA for enteroaggregative E. coli heat-stable enterotoxin1 (EAST1).

In June 2020, a large-scale food poisoning outbreak involving about 3000 elementary and junior high school students occurred in Yashio, Saitama, Japan. A school lunch was the only food stuff ingested by all of the patients. Escherichia coli serotype O7:H4 carrying the astA gene for enteroaggregative E. coli (EAggEC) heat-stable enterotoxin 1 (EAST1) was detected in faecal specimens from the patients, and sample inspection revealed its presence in a seaweed salad and red seaweed (Gigartina tenella) as one of the raw materials. Analysis of the antibiotic sensitivity of the isolates revealed resistance to ampicillin and cefotaxime. All isolates were confirmed to be of the same origin by pulsed-field gel electrophoresis after digestion with the restriction enzyme XbaI, and single nucleotide polymorphism analysis using whole genome sequencing. To our knowledge, this is the first report of a large-scale food poisoning caused by E. coli O7:H4, which lacks well-characterized virulence genes other than astA.

Selective layer-free blood serum ionogram based on ion-specific interactions with a nanotransistor.

Despite being ubiquitous in the fields of chemistry and biology, the ion-specific effects of electrolytes pose major challenges for researchers. A lack of understanding about ion-specific surface interactions has hampered the development and application of materials for (bio-)chemical sensor applications. Here, we show that scaling a silicon nanotransistor sensor down to ~25 nm provides a unique opportunity to understand and exploit ion-specific surface interactions, yielding a surface that is highly sensitive to cations and inert to pH. The unprecedented sensitivity of these devices to Na+ and divalent ions can be attributed to an overscreening effect via molecular dynamics. The surface potential of multi-ion solutions is well described by the sum of the electrochemical potentials of each cation, enabling selective measurements of a target ion concentration without requiring a selective organic layer. We use these features to construct a blood serum ionogram for Na+, K+, Ca2+ and Mg2+, in an important step towards the development of a versatile, durable and mobile chemical or blood diagnostic tool.

Plasma natriuretic peptide levels in fetuses with congenital heart defect and/or arrhythmia.

OBJECTIVE: Diagnosing fetal heart failure remains challenging because it is difficult to know how well the fetal myocardium will perform as loading conditions change. In adult cardiology, natriuretic peptides (NPs) are established markers of heart failure. However, the number of studies investigating NP levels in fetuses is quite limited. The aim of this study was to evaluate the significance of plasma NP levels in the assessment of heart failure in fetuses with a congenital heart defect (CHD) and/or arrhythmia. METHODS: This was a prospective observational study conducted at a tertiary pediatric cardiac center. A total of 129 singletons with CHD and/or arrhythmia and 127 controls were analyzed between 2012 and 2015. Umbilical cord plasma atrial NP, brain NP and N-terminal pro-brain NP levels at birth were compared with ultrasonography findings indicating fetal heart failure, such as cardiovascular profile (CVP) score and morphological characteristics. RESULTS: Fetuses with CHD and/or arrhythmia had higher NP levels than did controls (P < 0.01). NP levels of fetuses with CHD and/or arrhythmia were correlated inversely with CVP score (P for trend < 0.01). No differences in NP levels were found in fetuses with CHD and/or arrhythmia and a CVP score of ≥ 8 in comparison to controls. Multivariate analysis showed that a CVP score of ≤ 5, tachy- or bradyarrhythmia at birth, preterm birth and umbilical artery pH < 7.15 were associated independently with high NP levels (P < 0.01). Among fetuses with a CVP score of ≤ 7, abnormal venous Doppler sonography findings were significantly more common and more severe in fetuses with tachy- or bradyarrhythmia than in those with CHD, and those with tachy- or bradyarrhythmia had higher NP levels than did those with CHD (P = 0.01). Fetuses with right-heart defect and moderate or severe tricuspid valve regurgitation had significantly higher NP levels than did fetuses with other types of CHD (P < 0.01). CONCLUSIONS: Plasma NP levels in fetuses with CHD and/or arrhythmia are correlated with the severity of fetal heart failure. Elevated NP levels are attributed mainly to an increase in central venous pressure secondary to arrhythmia or atrioventricular valve regurgitation due to CHD, rather than to the morphological abnormality itself. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

The muscular dystrophic chicken is hypernatremic.

1. The E3 ubiquitin protein ligase 1 (WWP1) gene, the mutation of which causes muscular dystrophy in chickens, is expressed not only in the pectoral muscle, but also in a number of tissues such as the kidney. Therefore, this study examined some parameters related to kidney function in muscular dystrophic (MD) chickens. 2. Plasma osmolality, Na+ and K+ concentrations, aldosterone levels, and the expression of aquaporin (AQP) 2, AQP3, and α subunits of the amiloride-sensitive epithelial sodium channel (αENaC) were analysed in the kidneys of 5-week-old MD chickens and White Leghorn (WL) chickens under physiological conditions or after one day of water deprivation. 3. Plasma osmolality, Na+ concentrations, and plasma aldosterone levels were significantly higher in MD chickens than in WL chickens. αENaC mRNA expression levels were lower in MD chickens than in WL chickens. AQP2 and AQP3 mRNA expression levels were similar in the two strains of chickens. 4. Plasma osmolality correlated with aldosterone levels and AQP2 and αENaC mRNA levels in WL chickens. In MD chickens, plasma osmolality correlated with AQP2 mRNA levels, but not with plasma aldosterone or αENaC mRNA levels. 5. These results suggest that neither water reabsorption nor the expression of AQP2 and AQP3 is impaired in MD chickens and that a WWP1 gene mutation may or may not directly induce an abnormality in Na+-reabsorption in the kidneys of MD chickens, potentially through αENaC.

Estimation of π-π Electronic Couplings from Current Measurements.

The π-π interactions between organic molecules are among the most important parameters for optimizing the transport and optical properties of organic transistors, light-emitting diodes, and (bio-) molecular devices. Despite substantial theoretical progress, direct experimental measurement of the π-π electronic coupling energy parameter t has remained an old challenge due to molecular structural variability and the large number of parameters that affect the charge transport. Here, we propose a study of π-π interactions from electrochemical and current measurements on a large array of ferrocene-thiolated gold nanocrystals. We confirm the theoretical prediction that t can be assessed from a statistical analysis of current histograms. The extracted value of t ≈35 meV is in the expected range based on our density functional theory analysis. Furthermore, the t distribution is not necessarily Gaussian and could be used as an ultrasensitive technique to assess intermolecular distance fluctuation at the subangström level. The present work establishes a direct bridge between quantum chemistry, electrochemistry, organic electronics, and mesoscopic physics, all of which were used to discuss results and perspectives in a quantitative manner.

Multidirectional lip-closing force in adult females after short-term lip training.

The purpose of this study was to investigate the multidirectional lip-closing force in adult females before and after short-term lip training. Sixty-six Japanese females participated in this study. The subjects performed lip training that involved maintaining 200 or 400 g of bottled water in the oral vestibule. The signals of directional lip-closing force were investigated in eight directions before training and 5 and 7 days after the lip training. The differences in the closing force between pre- and post-training were then analysed statistically. The lip-closing force increased in the following order: pre-training, 5 days post-training and 7 days post-training in every direction (P < 0·05). The patterns of the increase in the lip-closing force in the upper, lower, right and left directions as a result of the repetitions were similar. No significant differences were noted between the training effects with loads of 200 and 400 g. Our findings demonstrated that the lip-closing force was influenced by the short-term lip training.

Valley polarization assisted spin polarization in two dimensions.

Valleytronics is rapidly emerging as an exciting area of basic and applied research. In two-dimensional systems, valley polarization can dramatically modify physical properties through electron-electron interactions as demonstrated by such phenomena as the fractional quantum Hall effect and the metal-insulator transition. Here, we address the electrons' spin alignment in a magnetic field in silicon-on-insulator quantum wells under valley polarization. In stark contrast to expectations from a non-interacting model, we show experimentally that less magnetic field can be required to fully spin polarize a valley-polarized system than a valley-degenerate one. Furthermore, we show that these observations are quantitatively described by parameter-free ab initio quantum Monte Carlo simulations. We interpret the results as a manifestation of the greater stability of the spin- and valley-degenerate system against ferromagnetic instability and Wigner crystalization, which in turn suggests the existence of a new strongly correlated electron liquid at low electron densities.

Dispersive and dissipative coupling in a micromechanical resonator embedded with a nanomechanical resonator.

A micromechanical resonator embedded with a nanomechanical resonator is developed whose dynamics can be captured by the coupled-Van der Pol-Duffing equations. Activating the nanomechanical resonator can dispersively shift the micromechanical resonance by more than 100 times its bandwidth and concurrently increase its energy dissipation rate to the point where it can even be deactivated. The coupled-Van der Pol-Duffing equations also suggest the possibility of self-oscillations. In the limit of strong excitation for the nanomechanical resonator, the dissipation in the micromechanical resonator can not only be reduced, resulting in a quality factor of >3× 10(6), it can even be eliminated entirely resulting in the micromechanical resonator spontaneously vibrating.

Electric tuning of direct-indirect optical transitions in silicon.

Electronic band structures in semiconductors are uniquely determined by the constituent elements of the lattice. For example, bulk silicon has an indirect bandgap and it prohibits efficient light emission. Here we report the electrical tuning of the direct/indirect band optical transition in an ultrathin silicon-on-insulator (SOI) gated metal-oxide-semiconductor (MOS) light-emitting diode. A special Si/SiO2 interface formed by high-temperature annealing that shows stronger valley coupling enables us to observe phononless direct optical transition. Furthermore, by controlling the gate field, its strength can be electrically tuned to 16 times that of the indirect transition, which is nearly 800 times larger than the weak direct transition in bulk silicon. These results will therefore assist the development of both complementary MOS (CMOS)-compatible silicon photonics and the emerging "valleytronics" based on the control of the valley degree of freedom.

Cost-effective development of highly polymorphic microsatellite in Japanese quail facilitated by next-generation sequencing.

Next-generation sequencing technologies permit rapid and cost-effective identification of numerous putative microsatellite loci. Here, from the genome sequences of Japanese quail, we developed microsatellite markers containing dinucleotide repeats and employed these for characterisation of genetic diversity and population structure. A total of 385 individuals from 12 experimental and one wild-derived Japanese quail lines were genotyped with newly developed autosomal markers. The maximum number of alleles, expected heterozygosity and polymorphic information content (PIC) per locus were 10, 0.80 and 0.77 respectively. Approximately half of the markers were highly informative (PIC ≥ 0.50). The mean number of alleles per locus and observed heterozygosity within a line were in the range of 1.3-4.1 and 0.11-0.53 respectively. Compared with the wild-derived line, genetic diversity levels were low in the experimental lines. Genetic differentiation (FST ) between all pairs of the lines ranged from 0.13 to 0.83. Genetic clustering analyses based on multilocus genotypes of individuals showed that most individuals formed clearly defined clusters corresponding to the origins of the lines. These results suggest that Japanese quail experimental lines are highly structured. Microsatellite markers developed in this study may be effective for future genetic studies of Japanese quail.

A multimode electromechanical parametric resonator array.

Electromechanical resonators have emerged as a versatile platform in which detectors with unprecedented sensitivities and quantum mechanics in a macroscopic context can be developed. These schemes invariably utilise a single resonator but increasingly the concept of an array of electromechanical resonators is promising a wealth of new possibilities. In spite of this, experimental realisations of such arrays have remained scarce due to the formidable challenges involved in their fabrication. In a variation to this approach, we identify 75 harmonic vibration modes in a single electromechanical resonator of which 7 can also be parametrically excited. The parametrically resonating modes exhibit vibrations with only 2 oscillation phases which are used to build a binary information array. We exploit this array to execute a mechanical byte memory, a shift-register and a controlled-NOT gate thus vividly illustrating the availability and functionality of an electromechanical resonator array by simply utilising higher order vibration modes.

Clinical characteristics classified by the serum KL-6 level in patients with organizing pneumonia.

BACKGROUND: The serum Krebs von der Lungen-6 (KL-6) level is a useful marker correlated with the severity of various interstitial lung diseases. There have been few reports about the clinical characteristics of organizing pneumonia (OP) associated with the serum KL-6 levels. OBJECTIVE: This study was performed to determine whether the serum KL-6 levels can help determine the optimal treatment for OP. DESIGNS: Patients diagnosed with OP by clinical, radiological and histopathological findings were retrospectively reviewed. The OP patients were classified into two groups based on their serum KL-6 levels: normal KL-6 and high KL-6 groups. The two groups were compared with regard to their clinical and radiological data and therapeutic response one month after the start of treatment. RESULTS: The clinical records of twenty-two patients diagnosed with OP were reviewed. The serum KL-6 level was elevated in 11 of the 22 patients. There were no obvious differences in the clinical data between the two groups, although patients in the normal KL-6 group tended to have a fever. There were no significant differences in the chest X-ray (CXR) score or computed tomography (CT) score between the two groups. The CXR scores were correlated with the serum KL-6 levels. At 1 month after the diagnosis, 11 patients who needed treatment with prednisolone were included in the high KL-6 group. CONCLUSIONS: Patients with normal KL-6 levels showed lower CXR and CT scores. The serum KL-6 level on admission is a useful marker to judge the need for corticosteroid treatment in OP patients.

Water electrolysis and energy harvesting with zero-dimensional ion-sensitive field-effect transistors.

The relationship of the gas bubble size to the size distribution critically influences the effectiveness of electrochemical processes. Several optical and acoustical techniques have been used to characterize the size and emission frequency of bubbles. Here, we used zero-dimensional (0D) ion-sensitive field-effect transistors (ISFETs) buried under a microbath to detect the emission of individual bubbles electrically and to generate statistics on the bubble emission time. The bubble size was evaluated via a simple model of the electrolytic current. We suggest that energy lost during water electrolysis could be used to generate electric pulses at an optimal efficiency with an array of 0D ISFETs.

Metallic behaviour in SOI quantum wells with strong intervalley scattering.

The fundamental properties of valleys are recently attracting growing attention due to electrons in new and topical materials possessing this degree-of-freedom and recent proposals for valleytronics devices. In silicon MOSFETs, the interest has a longer history since the valley degree of freedom had been identified as a key parameter in the observation of the controversial "metallic behaviour" in two dimensions. However, while it has been recently demonstrated that lifting valley degeneracy can destroy the metallic behaviour, little is known about the role of intervalley scattering. Here, we show that the metallic behaviour can be observed in the presence of strong intervalley scattering in silicon on insulator (SOI) quantum wells. Analysis of the conductivity in terms of quantum corrections reveals that interactions are much stronger in SOI than in conventional MOSFETs, leading to the metallic behaviour despite the strong intervalley scattering.

Anomalous pressure effect in heteroacene organic field-effect transistors.

Anomalous pressure dependent conductivity is revealed for heteroacene organic field-effect transistors of dinaphtho[2, 3-b:2', 3'-f]thieno[3, 2-b]thiophene single crystals in the direction of a and b crystallographic axes. In contrast to the normal characteristics of a monotonic increase in mobility µ with the application of external hydrostatic pressure P in conductors, we found that the present organic semiconductor devices exhibit nonmonotonic and gigantic pressure dependence including an even negative pressure coefficient dµ/dP. In combination with a structural analysis based on x-ray diffraction experiments under pressure, it is suggested that on-site molecular orientation and displacement peculiar in heteroacene molecules are responsible for the anomalous pressure effect.

Efficacy of hypofractionated radiotherapy for nasal tumours in 38 dogs (2005-2008).

OBJECTIVES: To evaluate the efficacy of hypofractionated radiotherapy for canine nasal tumours, including the improvement in clinical signs, rate of complications and assessment of prognostic factors. METHODS: Medical records of 38 dogs with malignant nasal tumours were reviewed, and those treated with a weekly schedule of hypofractionated radiotherapy were included in the study. Acute and late side effects were defined as complications noted either within 1 month or after 6 months of irradiation, respectively. Progression-free interval and overall survival were calculated using the Kaplan-Meier method. Log-rank test and Cox proportional hazard model were also performed. RESULTS: Clinical signs improved in 30 of 36 dogs. Acute complications were seen in 28 of 36 dogs and were considered manageable. Late complications were observed in 17 of 30 dogs that survived 6 months or longer, but severe side effects were not observed. The median progression-free interval and overall survival was 245 days (95% CI: 127-512 days) and 512 days (95% CI: 203-820 days), respectively. Age, breed and presence of dyspnoea were negatively correlated with overall survival. CLINICAL SIGNIFICANCE: These results suggest that hypofractionated radiotherapy could be a viable option for the treatment of nasal tumours in dogs that are not candidates for conventional multi-fractionated radiotherapy.