bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic and clinical characteristics in Japanese hereditary breast and ovarian cancer: first report after establishment of HBOC registration system in Japan
Authors: Arai Masami , Yokoyama Shiro , Watanabe Chie , Yoshida Reiko , Kita Mizuho , Okawa Megumi , Sakurai Akihiro , Sekine Masayuki , Yotsumoto Junko , Nomura Hiroyuki , Akama Yoshinori , Inuzuka Mayuko , Nomizu Tadashi , Enomoto Takayuki , Nakamura Seigo
Published: November 2017

The hereditary breast and ovarian cancer (HBOC) registration system of Japan was established by the Japanese HBOC Consortium. The first trial was registered in 2015 in four institutions to which some registration committee members belonged. We analyzed the information of 830 Japanese pedigrees, who underwent BRCA1/2 genetic testing, including mutation carriers with BRCA1 (N = 127) and BRCA2 (N = 115), and their families. The mutation-positive rate was 19.7%. Variants of uncertain significance were found in 6.5% of all individuals subjected to genetic testing for BRCA1/2. Compared to the United States, Japan had a higher mutation-positive rate in most categories, except for the groups with male breast cancer. Among the intrinsic subtypes of BRCA1-associated breast cancers, 75.8% were triple-negative. The incidence rate of contralateral breast cancer in BRCA1/2 mutation carriers was 0.99%/year. Among 240 mutation carriers, 26 and 62 patients underwent risk-reducing mastectomy (RRM) and risk-reducing salpingo-oophorectomy (RRSO), respectively; the respective frequencies of occult cancer were 7.1 and 3.2%. Metachronous breast cancer after RRM or peritoneal cancer after RRSO was not observed during the follow-up period. The nationwide registration system began last year and the system enables follow-up analysis in Japan.
Both Nodal signalling and stochasticity select for prospective distal visceral endoderm in mouse embryos
Authors: Takaoka Katsuyoshi , Nishimura Hiromi , Hamada Hiroshi
Published: November 2017

Anterior–posterior (A–P) polarity of mouse embryos is established by distal visceral endoderm (DVE) at embryonic day (E) 5.5. Lefty1 is expressed first at E3.5 in a subset of epiblast progenitor cells (L1epi cells) and then in a subset of primitive endoderm cells (L1dve cells) fated to become DVE. Here we studied how prospective DVE cells are selected. Lefty1 expression in L1epi and L1dve cells depends on Nodal signaling. A cell that experiences the highest level of Nodal signaling begins to express Lefty1 and becomes an L1epi cell. Deletion of Lefty1 alone or together with Lefty2 increased the number of prospective DVE cells. Ablation of L1epi or L1dve cells triggered Lefty1 expression in a subset of remaining cells. Our results suggest that selection of prospective DVE cells is both random and regulated, and that a fixed prepattern for the A–P axis does not exist before the blastocyst stage.
Myokine mediated muscle-kidney crosstalk suppresses metabolic reprogramming and fibrosis in damaged kidneys
Authors: Peng Hui , Wang Qianqian , Lou Tanqi , Qin Jun , Jung Sungyun , Shetty Vivekananda , Li Feng , Wang Yanlin , Feng Xin-hua , Mitch William E. , Graham Brett H. , Hu Zhaoyong
Published: November 2017

Kidney injury initiates metabolic reprogramming in tubule cells that contributes to the development of chronic kidney disease (CKD). Exercise has been associated with beneficial effects in patients with CKD. Here we show that the induction of a myokine, irisin, improves kidney energy metabolism and prevents kidney damage. In response to kidney injury, mice with muscle-specific PGC-1α overexpression (mPGC-1α) exhibit reduced kidney damage and fibrosis. Metabolomics analysis reveals increased ATP production and improved energy metabolism in injured kidneys from mPGC-1α mice. We identify irisin as a serum factor that mediates these metabolic effects during progressive kidney injury by inhibiting TGF-β type 1 receptor. Irisin depletion from serum blunts the induction of oxygen consumption rate observed in tubule cells treated with mPGC-1α serum. In mice, recombinant irisin administration attenuates kidney damage and fibrosis and improves kidney functions. We suggest that myokine-mediated muscle-kidney crosstalk can suppress metabolic reprograming and fibrogenesis during kidney disease.
O-GlcNAcylation of SIRT1 enhances its deacetylase activity and promotes cytoprotection under stress
Authors: Han Cuifang , Gu Yuchao , Shan Hui , Mi Wenyi , Sun Jiahui , Shi Minghui , Zhang Xinling , Lu Xinzhi , Han Feng , Gong Qianhong , Yu Wengong
Published: November 2017

SIRT1 is the most evolutionarily conserved mammalian sirtuin, and it plays a vital role in the regulation of metabolism, stress responses, genome stability, and ageing. As a stress sensor, SIRT1 deacetylase activity is significantly increased during stresses, but the molecular mechanisms are not yet fully clear. Here, we show that SIRT1 is dynamically modified with O-GlcNAc at Ser 549 in its carboxy-terminal region, which directly increases its deacetylase activity both in vitro and in vivo. The O-GlcNAcylation of SIRT1 is elevated during genotoxic, oxidative, and metabolic stress stimuli in cellular and mouse models, thereby increasing SIRT1 deacetylase activity and protecting cells from stress-induced apoptosis. Our findings demonstrate a new mechanism for the activation of SIRT1 under stress conditions and suggest a novel potential therapeutic target for preventing age-related diseases and extending healthspan.
The deep conservation of the Lepidoptera Z chromosome suggests a non-canonical origin of the W
Authors: Fraïsse Christelle , Picard Marion A. L. , Vicoso Beatriz
Published: November 2017

Moths and butterflies (Lepidoptera) usually have a pair of differentiated WZ sex chromosomes. However, in most lineages outside of the division Ditrysia, as well as in the sister order Trichoptera, females lack a W chromosome. The W is therefore thought to have been acquired secondarily. Here we compare the genomes of three Lepidoptera species (one Dytrisia and two non-Dytrisia) to test three models accounting for the origin of the W: (1) a Z-autosome fusion; (2) a sex chromosome turnover; and (3) a non-canonical mechanism (e.g., through the recruitment of a B chromosome). We show that the gene content of the Z is highly conserved across Lepidoptera (rejecting a sex chromosome turnover) and that very few genes moved onto the Z in the common ancestor of the Ditrysia (arguing against a Z-autosome fusion). Our comparative genomics analysis therefore supports the secondary acquisition of the Lepidoptera W by a non-canonical mechanism, and it confirms the extreme stability of well-differentiated sex chromosomes.
A rapid cosmic-ray increase in BC 3372–3371 from ancient buried tree rings in China
Authors: Wang F. Y. , Yu H. , Zou Y. C. , Dai Z. G. , Cheng K. S.
Published: November 2017

Cosmic rays interact with the Earth’s atmosphere to produce 14C, which can be absorbed by trees. Therefore, rapid increases of 14C in tree rings can be used to probe previous cosmic-ray events. By this method, three 14C rapidly increasing events have been found. Plausible causes of these events include large solar proton events, supernovae, or short gamma-ray bursts. However, due to the lack of measurements of 14C by year, the occurrence frequency of such 14C rapidly increasing events is poorly known. In addition, rapid increases may be hidden in the IntCal13 data with five-year resolution. Here we report the result of 14C measurements using an ancient buried tree during the period between bc 3388 and 3358. We found a rapid increase of about 9‰ in the 14C content from bc 3372 to bc 3371. We suggest that this event could originate from a large solar proton event.
Rethinking phonons: The issue of disorder
Authors: Seyf Hamid Reza , Yates Luke , Bougher Thomas L. , Graham Samuel , Cola Baratunde A. , Detchprohm Theeradetch , Ji Mi-Hee , Kim Jeomoh , Dupuis Russell , Lv Wei , Henry Asegun
Published: November 2017

Current understanding of phonons treats them as plane waves/quasi-particles of atomic vibration that propagate and scatter. The problem is that conceptually, when any level of disorder is introduced, whether compositional or structural, the character of vibrational modes in solids changes, yet nearly all theoretical treatments continue to assume phonons are still waves. For example, the phonon contributions to alloy thermal conductivity (TC) rely on this assumption and are most often computed from the virtual crystal approximation (VCA). Good agreement is obtained in some cases, but there are many instances where it fails—both quantitatively and qualitatively. Here, we show that the conventional theory and understanding of phonons requires revision, because the critical assumption that all phonons/normal modes resemble plane waves with well-defined velocities is no longer valid when disorder is introduced. Here we show, surprisingly, that the character of phonons changes dramatically within the first few percent of impurity concentration, beyond which phonons more closely resemble the modes found in amorphous materials. We then utilize a different theory that can treat modes with any character and experimentally confirm its new insights.
Estimation of Ground PM2.5 Concentrations using a DEM-assisted Information Diffusion Algorithm: A Case Study in China
Authors: Ma Lei , Gao Yu , Fu Tengyu , Cheng Liang , Chen Zhenjie , Li Manchun
Published: November 2017

When estimating national PM2.5 concentrations, the results of traditional interpolation algorithms are unreliable due to a lack of monitoring sites and heterogeneous spatial distributions. PM2.5 spatial distribution is strongly correlated to elevation, and the information diffusion algorithm has been shown to be highly reliable when dealing with sparse data interpolation issues. Therefore, to overcome the disadvantages of traditional algorithms, we proposed a method combining elevation data with the information diffusion algorithm. Firstly, a digital elevation model (DEM) was used to segment the study area into multiple scales. Then, the information diffusion algorithm was applied in each region to estimate the ground PM2.5 concentration, which was compared with estimation results using the Ordinary Kriging and Inverse Distance Weighted algorithms. The results showed that: (1) reliable estimate at local area was obtained using the DEM-assisted information diffusion algorithm; (2) the information diffusion algorithm was more applicable for estimating daily average PM2.5 concentrations due to the advantage in noise data; (3) the information diffusion algorithm required less supplementary data and was suitable for simulating the diffusion of air pollutants. We still expect a new comprehensive model integrating more factors would be developed in the future to optimize the interpretation accuracy of short time observation data.
Maternal impulse control disability and developmental disorder traits are risk factors for child maltreatment
Authors: Tachibana Yoshiyuki , Takehara Kenji , Kakee Naoko , Mikami Masashi , Inoue Eisuke , Mori Rintaro , Ota Erika , Koizumi Tomoe , Okuyama Makiko , Kubo Takahiko
Published: November 2017

Previous work has suggested that maternal developmental disorder traits related to autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) are significantly associated with child maltreatment. However, there may be other important maternal characteristics that contribute to child maltreatment. We hypothesized that maternal impulse control disability may also affect child maltreatment in addition to maternal developmental disorder traits. We aimed to test this hypothesis via a cohort study performed in Tokyo (n = 1,260). Linear regression analyses using the Behavioural Inhibition/Behavioural Activation Scales, the self-administered short version of the Pervasive Developmental Disorders Autism Society Japan Rating Scale, the short form of the Adult Attention-Deficit Hyperactivity Disorder Self-Report Scale, and the Child Maltreatment Scale, revealed that excessive inhibition of behaviour and affect, which is impulse control disability, is significantly associated with child maltreatment (b = 0.031, p = 0.018) in addition to maternal developmental disorder traits (ASD: b = 0.052, p = 0.004; ADHD: b = 0.178, p < 0.001). Logistic regression analyses revealed that ASD (adjusted odds ratio [AOR] = 1.083, p = 0.014) and high behavioural inhibition (AOR = 1.068, p = 0.016) were significantly associated with moderate child maltreatment, while ADHD was associated (AOR = 1.034, p = 0.022) with severe child maltreatment. These maternal characteristics may inform the best means for prevention and management of child maltreatment cases.
Publisher Correction: Electron momentum densities near Dirac cones: Anisotropic Umklapp scattering and momentum broadening
Authors: Hiraoka N. , Nomura T.
Published: November 2017

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.
Quantifying quantum coherence with quantum Fisher information
Authors: Feng X. N. , Wei L. F.
Published: November 2017

Quantum coherence is one of the old but always important concepts in quantum mechanics, and now it has been regarded as a necessary resource for quantum information processing and quantum metrology. However, the question of how to quantify the quantum coherence has just been paid the attention recently (see, e.g., Baumgratz et al. PRL, 113. 140401 (2014)). In this paper we verify that the well-known quantum Fisher information (QFI) can be utilized to quantify the quantum coherence, as it satisfies the monotonicity under the typical incoherent operations and the convexity under the mixing of the quantum states. Differing from most of the pure axiomatic methods, quantifying quantum coherence by QFI could be experimentally testable, as the bound of the QFI is practically measurable. The validity of our proposal is specifically demonstrated with the typical phase-damping and depolarizing evolution processes of a generic single-qubit state, and also by comparing it with the other quantifying methods proposed previously.
mPeriod2 Brdm1 and other single Period mutant mice have normal food anticipatory activity
Authors: Pendergast Julie S. , Wendroth Robert H. , Stenner Rio C. , Keil Charles D. , Yamazaki Shin
Published: November 2017

Animals anticipate the timing of food availability via the food-entrainable oscillator (FEO). The anatomical location and timekeeping mechanism of the FEO are unknown. Several studies showed the circadian gene,Period 2, is critical for FEO timekeeping. However, other studies concluded that canonical circadian genes are not essential for FEO timekeeping. In this study, we re-examined the effects of thePer2Brdm1mutation on food entrainment using methods that have revealed robust food anticipatory activity in other mutant lines. We examined food anticipatory activity, which is the output of the FEO, in singlePeriodmutant mice. SinglePer1,Per2, andPer3mutant mice had robust food anticipatory activity during restricted feeding. In addition, we found that two different lines ofPer2mutant mice (ldcandBrdm1) anticipated restricted food availability. To determine if FEO timekeeping persisted in the absence of the food cue, we assessed activity during fasting. Food anticipatory (wheel-running) activity in allPeriodmutant mice was also robust during food deprivation. Together, our studies demonstrate that thePeriodgenes are not necessary for the expression of food anticipatory activity.
Potential Application of 1H NMR for Routine Serum Lipidome Analysis –Evaluation of Effects of Bariatric Surgery
Authors: Mika Adriana , Kaczynski Zbigniew , Stepnowski Piotr , Kaczor Maciej , Proczko-Stepaniak Monika , Kaska Lukasz , Sledzinski Tomasz
Published: November 2017

Routine laboratory lipid assays include simple measurements of total cholesterol, triacylglycerols and HDL. However, lipids are a large group of compounds involved in many metabolic pathways, and their alterations may have serious health consequences. In this study, we used 1H NMR to analyze lipids extracted from sera of 16 obese patients prior to and after bariatric surgeries. We observed a post-surgery decrease in serum concentrations of lipids from various groups. The hereby presented findings imply that 1H NMR is suitable for rapid, simple and non-invasive detection of lipids from 30 structural groups, among them triacylglycerols, phosphatidylcholine, phosphatidylethanolamine, sphingomyelin, total phospholipids, total, free and esterified cholesterol, total and unsaturated fatty acids. NMR-based analysis of serum lipids may contribute to a substantial increase in the number of routinely determined markers from this group; therefore, it may find application in clinical assessment of obese subjects prior to and after bariatric surgeries, as well as in the examination of patients with other metabolic diseases.
Laser Thinning and Patterning of MoS2 with Layer-by-Layer Precision
Authors: Hu Lili , Shan Xinyan , Wu Yanling , Zhao Jimin , Lu Xinghua
Published: November 2017

The recently discovered novel properties of two dimensional materials largely rely on the layer-critical variation in their electronic structure and lattice symmetry. Achieving layer-by-layer precision patterning is thus crucial for junction fabrications and device engineering, which hitherto poses an unprecedented challenge. Here we demonstrate laser thinning and patterning with layer-by-layer precision in a two dimensional (2D) quantum material MoS2. Monolayer, bilayer and trilayer of MoS2films are produced with precise vertical and lateral control, which removes the extruding barrier for fabricating novel three dimensional (3D) devices composed of diverse layers and patterns. By tuning the laser fluence and exposure time we demonstrate producing MoS2patterns with designed layer numbers. The underlying physics mechanism is identified to be temperature-dependent evaporation of the MoS2lattice, verified by our measurements and calculations. Our investigation paves way for 3D device fabrication based on 2D layered quantum materials.
Expression of both poly r(C) binding protein 1 (PCBP1) and miRNA-3978 is suppressed in peritoneal gastric cancer metastasis
Authors: Ji Fu-jian , Wu Yuan-yu , An Zhe , Liu Xue-song , Jiang Jun-nan , Chen Fang-fang , Fang Xue-dong
Published: November 2017

The expression of legumain which has been shown overexpressed in patients with metastatic gastric cancer is positively correlated to both disease progression and outcome, and negatively correlated to microRNA (miR)−3978 expression. The RNA-binding protein, poly r(C) binding protein 1 (PCBP1) was the most downregulated protein in the metastatic tissue specimens. Quantitative real-time PCR showed that PCBP1 expression is transcriptionally downregulated in peritoneal metastasis tissues. RNA immunoprecipitation experiments showed that PCBP1 and miR-3978 are sequestered in normal peritoneal tissue, but the complex is disrupted following metastatic progression. PCBP1 expression mimicked miR-3978 expression across gastric cancer patients. Finally, replenishment of PCBP1 or miR-3978 expression in the peritoneal metastasis cell line MKN45 decreased legumain protein expression and chemosensitized the cells to treatment with docetaxel. However, replenishment of one and concomitant depletion of the other failed to induce chemosensitivity to docetaxel. Replenishment of miR-3978 also resulted in induction of PCBP1 protein expression, potentially indicating that miR-3978 expression might downregulate a negative regulator targeting PCBP1. Our current study reveals PCBP1 as an additional biomarker in peritoneal metastasis. PCBP1 and miR-3978 expression were correlated and suggests a potential interplay of differential miRNA biogenesis and RNA binding protein during metastatic progression.
Structure-function relationships in ABCG2: insights from molecular dynamics simulations and molecular docking studies
Authors: Ferreira Ricardo J. , Bonito Cátia A. , Cordeiro M. Natália D. S. , Ferreira Maria-José U. , dos Santos Daniel J. V. A.
Published: November 2017

Efflux pumps of the ATP-binding cassette transporters superfamily (ABC transporters) are frequently involved in the multidrug-resistance (MDR) phenomenon in cancer cells. Herein, we describe a new atomistic model for the MDR-relatedABCG2efflux pump, also named breast cancer resistance protein (BCRP), based on the recently published crystallographic structure of theABCG5/G8heterodimer sterol transporter, a member of the ABCG family involved in cholesterol homeostasis. By means of molecular dynamics simulations and molecular docking, a far-reaching characterization of theABCG2homodimer was obtained. The role of important residues and motifs in the structural stability of the transporter was comprehensively studied and was found to be in good agreement with the available experimental data published in literature. Moreover, structural motifs potentially involved in signal transmission were identified, along with two symmetrical drug-binding sites that are herein described for the first time, in a rational attempt to better understand how drug binding and recognition occurs inABCG2homodimeric transporters.
Changing trends in the prevalence of H. pylori infection in Japan (1908–2003): a systematic review and meta-regression analysis of 170,752 individuals
Authors: Wang Chaochen , Nishiyama Takeshi , Kikuchi Shogo , Inoue Manami , Sawada Norie , Tsugane Shoichiro , Lin Yingsong
Published: November 2017

Changing trends in the prevalence of H. pylori infection in the general population over time are thought to be the main driving force behind the declining gastric cancer mortality in Japan. However, whether the prevalence of H. pylori infection itself shows a birth-cohort pattern needs to be corroborated. We performed a systematic review of studies that reported the prevalence of H. pylori infection among Japanese individuals. Meta-regression was conducted in the framework of a generalized additive mixed model (GAMM) to account for heterogeneity in the prevalence of H. pylori infection as a function of birth year. The prevalence of H. pylori infection confirmed a clear birth cohort pattern: the predicted prevalence (%, 95% CI) was 60.9 (56.3–65.4), 65.9 (63.9–67.9), 67.4 (66.0–68.7), 64.1 (63.1–65.1), 59.1 (58.2–60.0), 49.1 (49.0–49.2), 34.9 (34.0–35.8), 24.6 (23.5–25.8), 15.6 (14.0–17.3), and 6.6 (4.8–8.9) among those who were born in the year 1910, 1920, 1930, 1940, 1950, 1960, 1970, 1980, 1990, and 2000, respectively. The present study demonstrated a clear birth-cohort pattern of H. pylori infection in the Japanese population. The decreased prevalence of H. pylori infection in successive generations should be weighed in future gastric cancer control programs.
The photocycle of orange carotenoid protein conceals distinct intermediates and asynchronous changes in the carotenoid and protein components
Authors: Maksimov E. G. , Sluchanko N. N. , Slonimskiy Y. B. , Slutskaya E. A. , Stepanov A. V. , Argentova-Stevens A. M. , Shirshin E. A. , Tsoraev G. V. , Klementiev K. E. , Slatinskaya O. V. , Lukashev E. P. , Friedrich T. , Paschenko V. Z. , Rubin A. B.
Published: November 2017

The 35-kDa Orange Carotenoid Protein (OCP) is responsible for photoprotection in cyanobacteria. It acts as a light intensity sensor and efficient quencher of phycobilisome excitation. Photoactivation triggers large-scale conformational rearrangements to convert OCP from the orange OCPO state to the red active signaling state, OCPR, as demonstrated by various structural methods. Such rearrangements imply a complete, yet reversible separation of structural domains and translocation of the carotenoid. Recently, dynamic crystallography of OCPO suggested the existence of photocycle intermediates with small-scale rearrangements that may trigger further transitions. In this study, we took advantage of single 7 ns laser pulses to study carotenoid absorption transients in OCP on the time-scale from 100 ns to 10 s, which allowed us to detect a red intermediate state preceding the red signaling state, OCPR. In addition, time-resolved fluorescence spectroscopy and the assignment of carotenoid-induced quenching of different tryptophan residues derived thereof revealed a novel orange intermediate state, which appears during the relaxation of photoactivated OCPR to OCPO. Our results show asynchronous changes between the carotenoid- and protein-associated kinetic components in a refined mechanistic model of the OCP photocycle, but also introduce new kinetic signatures for future studies of OCP photoactivity and photoprotection.
Differences in mitochondrial function and morphology during cooling and rewarming between hibernator and non-hibernator derived kidney epithelial cells
Authors: Hendriks Koen D. W. , Lupi Eleonora , Hardenberg Maarten C. , Hoogstra-Berends Femke , Deelman Leo E. , Henning Robert H.
Published: November 2017

Hibernators show superior resistance to ischemia and hypothermia, also outside the hibernation season. Therefore, hibernation is a promising strategy to decrease cellular damage in a variety of fields, such as organ transplantation. Here, we explored the role of mitochondria herein, by comparing epithelial cell lines from a hibernator (hamster kidney cells, HaK) and a non-hibernator (human embryonic kidney cells, HEK293) during cold preservation at 4 °C and rewarming. Cell survival (Neutral Red), ATP and MDA levels, mitochondrial membrane potential (MMP), mitochondrial morphology (using fluorescent probes) and metabolism (seahorse XF) were assessed. Hypothermia induced dispersion of the tubular mitochondrial network, a loss of MMP, increased oxygen radical (MDA) and decreased ATP production in HEK293. In contrast, HaK maintained MMP and ATP production without an increase in oxygen radicals during cooling and rewarming, resulting in superior cell survival compared to HEK293. Further, normothermic HaK showed a dispersed mitochondrial network and higher respiratory and glycolysis capacity compared to HEK293. Disclosing the mechanisms that hibernators use to counteract cell death in hypothermic and ischemic circumstances may help to eventually improve organ preservation in a variety of fields, including organ transplantation.
Divide-and-conquer Tournament on Social Networks
Authors: Wang Jiasheng , Zhang Yichao , Guan Jihong , Zhou Shuigeng
Published: November 2017

In social gaming networks, previous studies extensively investigated the influence of a variety of strategies on reciprocal behaviors in the prisoner’s dilemma game. The studied frameworks range from the case that an individual uniformly cooperates or defects with all social contacts, to the recently reported divide-and-conquer games, where an individual can choose a particular move to play with each neighbor. In this paper, we investigate a divide-and-conquer tournament among 14 well-known strategies on social gaming networks. In the tournament, an individual’s fitness is measured by accumulated and average payoff aggregated for a certain number of rounds. On the base of their fitness, the evolution of the population follows a local learning mechanism. Our observation indicates that the distribution of individuals adopting a strategy in degree ranking fundamentally changes the frequency of the strategy. In the divide-and-conquer gaming networks, our result suggests that the connectivity in social networks and strategy are two key factors that govern the evolution of the population.
α subunits in GABAA receptors are dispensable for GABA and diazepam action
Authors: Wongsamitkul Nisa , Maldifassi Maria C. , Simeone Xenia , Baur Roland , Ernst Margot , Sigel Erwin
Published: November 2017

The major isoform of the GABAA receptor is α1β2γ2. The binding sites for the agonist GABA are located at the β2+/α1− subunit interfaces and the modulatory site for benzodiazepines at α1+/γ2−. In the absence of α1 subunits, a receptor was formed that was gated by GABA and modulated by diazepam similarly. This indicates that alternative subunits can take over the role of the α1 subunits. Point mutations were introduced in β2 or γ2 subunits at positions homologous to α1− benzodiazepine binding and GABA binding positions, respectively. From this mutation work we conclude that the site for GABA is located at a β2+/β2− subunit interface and that the diazepam site is located at the β2+/γ2− subunit interface. Computational docking leads to a structural hypothesis attributing this non-canonical interaction to a binding mode nearly identical with the one at the α1+/γ2− interface. Thus, the β2 subunit can take over the role of the α1 subunit for the formation of both sites, its minus side for the GABA binding site and its plus side for the diazepam binding site.
Screening based approach and dehydrogenation kinetics for MgH2: Guide to find suitable dopant using first-principles approach
Authors: Kumar E. Mathan , Rajkamal A. , Thapa Ranjit
Published: November 2017

First-principles based calculations are performed to investigate the dehydrogenation kinetics considering doping at various layers of MgH2 (110) surface. Doping at first and second layer of MgH2 (110) has a significant role in lowering the H2 desorption (from surface) barrier energy, whereas the doping at third layer has no impact on the barrier energy. Molecular dynamics calculations are also performed to check the bonding strength, clusterization, and system stability. We study in details about the influence of doping on dehydrogenation, considering the screening factors such as formation enthalpy, bulk modulus, and gravimetric density. Screening based approach assist in finding Al and Sc as the best possible dopant in lowering of desorption temperature, while preserving similar gravimetric density and Bulk modulus as of pure MgH2 system. The electron localization function plot and population analysis illustrate that the bond between Dopant-Hydrogen is mainly covalent, which weaken the Mg-Hydrogen bonds. Overall we observed that Al as dopant is suitable and surface doping can help in lowering the desorption temperature. So layer dependent doping studies can help to find the best possible reversible hydride based hydrogen storage materials.
Drying in a microfluidic chip: experiments and simulations
Authors: Fantinel Paolo , Borgman Oshri , Holtzman Ran , Goehring Lucas
Published: November 2017

We present an experimental micro-model of drying porous media, based on microfluidic cells made of arrays of pillars on a regular grid, and complement these experiments with a matching two-dimensional pore-network model of drying. Disorder, or small-scale heterogeneity, was introduced into the cells by randomly varying the radii of the pillars. The microfluidic chips were filled with a volatile oil and then dried horizontally, such that gravitational effects were excluded. The experimental and simulated drying rates and patterns were then compared in detail, for various levels of disorder. The geometrical features were reproduced well, although the model under-predicted the formation of trapped clusters of drying fluid. Reproducing drying rates proved to be more challenging, but improved if the additional trapped clusters were added to the model. The methods reported can be adapted to a wide range of multi-phase flow problems, and allow for the rapid development of high-precision micro-models containing tens of thousands of individual elements.
Non-thermal atmospheric plasma ameliorates imiquimod-induced psoriasis-like skin inflammation in mice through inhibition of immune responses and up-regulation of PD-L1 expression
Authors: Lee Yun Sang , Lee Myung-Hoon , Kim Hang-Jun , Won Ho-Ryun , Kim Chul-Ho
Published: November 2017

Plasma medicine is an emerging novel therapeutic field. It has been reported that plasma can kill bacteria, promote wound healing and induce apoptosis of tumor cells. However, the effects of plasma on immune cells and immune related skin diseases have not been well studied. In this study, we demonstrated that non-thermal atmospheric plasma (NTP) treatment could inhibit psoriasis-like skin inflammation in mice. NTP treatment in imiquimod-induced psoriasis-like mouse skin inhibited increases in epithelial cell thickness and expression of pro-inflammatory molecules compared to ones without the NTP treatment. In addition, differentiation of Th17 cells, an important cell type for pathogenesis of psoriasis, was inhibited in the NTP-treated mouse lymph nodes. It was also demonstrated that liquid type plasma (LTP), which is also known as indirect plasma, inhibited Th17 cell differentiation in vitro. Other in vitro experiments showed that LTP inhibited bone marrow-derived dendritic cell activation. Interestingly, LTP enhanced PD-L1 expression in HaCaT cells, suggesting that NTP may inhibit unwanted over-activation of T cells through increased PD-L1 expression. Taken together, these results suggest that NTP may be used in treatment of CD4+ T cell-mediated autoimmune diseases such as psoriasis.
A scale to measure MRI contrast agent sensitivity
Authors: Alvares Rohan D. A. , Szulc Daniel A. , Cheng Hai-Ling M.
Published: November 2017

Magnetic resonance imaging (MRI) provides superior resolution of anatomical features and the best soft tissue contrast, and is one of the predominant imaging modalities. With this technique, contrast agents are often used to aid discrimination by enhancing specific features. Over the years, a rich diversity of such agents has evolved and with that, so has a need to systematically sort contrast agents based on their efficiency, which directly determines sensitivity. Herein, we present a scale to rank MRI contrast agents. The scale is based on analytically determining the minimum detectable concentration of a contrast agent, and employing a ratiometric approach to standardize contrast efficiency to a benchmark contrast agent. We demonstrate the approach using several model contrast agents and compare the relative sensitivity of these agents for the first time. As the first universal metric of contrast agent sensitivity, this scale will be vital to easily assessing contrast agent efficiency and thus important to promoting use of some of the elegant and diverse contrast agents in research and clinical practice.
Inhibition activity of a traditional Chinese herbal formula Huang-Lian-Jie-Du-Tang and its major components found in its plasma profile on neuraminidase-1
Authors: Zhou Xuelin , Li Haotian , Shi Zhilong , Gao Sijia , Wei Shizhang , Li Kun , Wang Jiabo , Li Jianyu , Wang Ruilin , Gong Man , Zhao Yanling , Xiao Xiaohe
Published: November 2017

Huang-Lian-Jie-Du-Tang (HLJDT), a traditional formula with four TCM herbs, has been used for hundred years for different diseases. The current study aimed to assess the inhibitory activity of HLJDT against H1N1 neuraminidase (NA-1), and identify potent NA-1 inhibitors from its plasma profile. Thein vitroNA-1 study has shown that the water extract of HLJDT potently inhibited NA-1 (IC50 = 112.6 μg/ml; Ki = 55.6 μg/ml) in a competitive mode. The IC50values of the water extracts of its four herbs were as follows: Coptidis Rhizoma, 96.1 μg/ml; Phellodendri Chinensis Cortex, 108.6 μg/ml; Scutellariae Radix, 303.5 μg/ml; Gardeniae Fructus, 285.0 μg/ml. Thirteen compounds found in the plasma profile of HLJDT were also identified as potent NA-1 inhibitors, which included jatrorrhizine, palmatine, epiberberine, geniposide, oroxylin A, berberine, coptisine, baicalein, wogonoside, phellodendrine, wogonin, oroxylin A-7-O-glucuronide and baicalin (sorted in ascending order by their IC50values). Their inhibitory activities were consistent with molecular docking analysis when considering crystallographic water molecules in the ligand-binding pocket of NA-1. Our current findings suggested that HLJDT can be used as a complementary medicine for H1N1 infection and its potent active compounds can be developed as NA-1 inhibitors.
Increased Complement 3a Receptor is Associated with Behcet’s disease and Vogt-Koyanagi-Harada disease
Authors: Wang Chaokui , Cao Shuang , Zhang Dike , Li Hong , Kijlstra Aize , Yang Peizeng
Published: November 2017

Behcet’s disease (BD) and Vogt-Koyanagi-Harada disease (VKH) are systemic and recurrent autoimmune diseases associated with abnormal T cell immune response. Complement 3a receptor (C3aR) and complement 5a receptor (C5aR) have been reported to be involved in T cell mediated autoimmune disease. This study aimed to investigate the role of C3aR and C5aR in these two diseases. The C3aR expression in PBMCs was increased in patients with active BD (aBD) and active VKH (aVKH). No statistical difference was found concerning the expression of C5aR in PBMCs between patients with aBD or aVKH and normal controls. After the intraocular inflammation in BD and VKH patients was controlled, the C3aR expression returned back to normal levels. The serum from patients with aBD and aVKH significantly induced C3aR expression by PBMCs. C3a induced IL-6, IL-1β and TNF-α secretion, while inhibited the production of IL-10 by monocytes. Activation of C3aR in CD4+T cells could upregulate IL-17 production and inhibit IL-10 production, but had no detectable influence on IFN-γ production. Our data indicates that increased C3aR expression may lead to over activation of the Th17 cell response and may therefore contribute to the pathogenesis of BD and VKH disease.
Social Support as a Key Protective Factor against Depression in HIV-Infected Patients: Report from large HIV clinics in Hanoi, Vietnam
Authors: Matsumoto Shoko , Yamaoka Kazue , Takahashi Kenzo , Tanuma Junko , Mizushima Daisuke , Do Cuong Duy , Nguyen Dung Thi , Nguyen Hoai Dung Thi , Nguyen Kinh Van , Oka Shinichi
Published: November 2017

Depression is the most common mental health issue among people living with HIV/AIDS (PLWHA). This study explored how different types and sources of social support are associated with depression among HIV-infected patients in Vietnam. We carried out a cross-sectional survey on 1,503 HIV-infected patients receiving antiretroviral therapy at two HIV clinics in Hanoi in 2016. Depression was prevalent in 26.2% of participants. Higher score of social support, especially emotional/informational support and positive social interaction, showed significant association with lower depression rate. Although family was primary source of all types of social support, receiving emotional/informational support not only from family but also from outside of family correlated with a lower proportion of depression. In countries with constrained social resources and/or with family-oriented social structures, as in Vietnam, expanding social networks between HIV populations and society is a potentially important option for reducing depression.
UV irradiation to mouse skin decreases hippocampal neurogenesis and synaptic protein expression via HPA axis activation
Authors: Han Mira , Ban Jae-Jun , Bae Jung-Soo , Shin Chang-Yup , Lee Dong Hun , Chung Jin Ho
Published: November 2017

The skin senses external environment, including ultraviolet light (UV). Hippocampus is a brain region that is responsible for memory and emotion. However, changes in hippocampus by UV irradiation to the skin have not been studied. In this study, after 2 weeks of UV irradiation to the mouse skin, we examined molecular changes related to cognitive functions in the hippocampus and activation of the hypothalamic-pituitary-adrenal (HPA) axis. UV exposure to the skin decreased doublecortin-positive immature neurons and synaptic proteins, including N-methyl-D-aspartate receptor 2 A and postsynaptic density protein-95, in the hippocampus. Moreover, we observed that UV irradiation to the skin down-regulated brain-derived neurotrophic factor expression and ERK signaling in the hippocampus, which are known to modulate neurogenesis and synaptic plasticity. The cutaneous and central HPA axes were activated by UV, which resulted in significant increases in serum levels of corticosterone. Subsequently, UV irradiation to the skin activated the glucocorticoid-signaling pathway in the hippocampal dentate gyrus. Interestingly, after 6 weeks of UV irradiation, mice showed depression-like behavior in the tail suspension test. Taken together, our data suggest that repeated UV exposure through the skin may negatively affect hippocampal neurogenesis and synaptic plasticity along with HPA axis activation.
Visuospatial attention in the lateralised brain of pigeons – a matter of ontogenetic light experiences
Authors: Letzner Sara , Güntürkün Onur , Lor Stephanie , Pawlik Robert Jan , Manns Martina
Published: November 2017

The ontogenetic mechanisms leading to complementary hemispheric specialisations of the two brain halves are poorly understood. In pigeons, asymmetrical light stimulation during development triggers the left-hemispheric dominance for visuomotor control but light effects on right-hemispheric specialisations are largely unknown. We therefore tested adult pigeons with and without embryonic light experience in a visual search task in which the birds pecked peas regularly scattered on an area in front of them. Comparing the pecking pattern of both groups indicates that the embryonic light conditions differentially influence biased visuospatial attention under mono- and binocular seeing conditions. When one eye was occluded, dark-incubated pigeons peck only within the limits of the visual hemifield of the seeing eye. Light-exposed pigeons also peck into the contralateral field indicating enlarged monocular visual fields of both hemispheres. While dark-incubated birds evinced an attentional bias to the right halfspace when seeing with both eyes, embryonic light exposure shifted this to the left. Thus, embryonic light experience modifies processes regulating biased visuospatial attention of the adult birds depending on the seeing conditions during testing. These data support the impact of light onto the emergence of functional dominances in both hemispheres and point to the critical role of interhemispheric processes.
Manganese availability is negatively associated with carbon storage in northern coniferous forest humus layers
Authors: Stendahl Johan , Berg Björn , Lindahl Björn D.
Published: November 2017

Carbon sequestration below ground depends on organic matter input and decomposition, but regulatory bottlenecks remain unclear. The relative importance of plant production, climate and edaphic factors has to be elucidated to better predict carbon storage in forests. In Swedish forest soil inventory data from across the entire boreal latitudinal range (n = 2378), the concentration of exchangeable manganese was singled out as the strongest predictor (R2 = 0.26) of carbon storage in the extensive organic horizon (mor layer), which accounts for one third of the total below ground carbon. In comparison, established ecosystem models applied on the same data have failed to predict carbon stocks (R2 < 0.05), and in our study manganese availability overshadowed both litter production and climatic factors. We also identified exchangeable potassium as an additional strong predictor, however strongly correlated with manganese. The negative correlation between manganese and carbon highlights the importance of Mn-peroxidases in oxidative decomposition of recalcitrant organic matter. The results support the idea that the fungus-driven decomposition could be a critical factor regulating humus carbon accumulation in boreal forests, as Mn-peroxidases are specifically produced by basidiomycetes.
Predicted molecular targets and pathways for germacrone, curdione, and furanodiene in the treatment of breast cancer using a bioinformatics approach
Authors: Kong Qi , Ma Yong , Yu Jie , Chen Xiuping
Published: November 2017

Germacrone, curdione, and furanodiene have been shown to be useful in the treatment of breast cancer but the pharmacological mechanism of action is unclear. In this paper, we explored a new method to study the molecular network and function of Traditional Chinese Medicine (TCM) herbs and their corresponding ingredients with bioinformatics tools, including PubChem Compound Database, BATMAN-TCM, SystemsDock, Coremine Medical, Gene ontology, and KEGG. Eleven targeted genes/proteins, 4 key pathways, and 10 biological processes were identified to participate in the mechanism of action in treating breast cancer with germacrone, curdione, and furanodiene. The information achieved by the bioinformatics tools was useful to interpretation the molecular mechanism for the treatment of germacrone, curdione, and furanodiene on breast cancers.
Dihydrotestosterone levels at birth associate positively with higher proportions of circulating immature/naïve CD5+ B cells in boys
Authors: Lundell Anna-Carin , Nordström Inger , Andersson Kerstin , Strömbeck Anna , Ohlsson Claes , Tivesten Åsa , Rudin Anna
Published: November 2017

Boys present with higher proportions of immature/naïve CD5+B cells than girls up to 3 years of age. Boys also have higher fractions of regulatory T cells (Tregs) in early infancy, but the mechanisms for these sex-related differences are unknown. In the prospective FARMFLORA follow-up study of 23 boys and 25 girls, we investigated if these immunological differences remained at 8 years of age. We also examined if testosterone or dihydrotestosterone (DHT) levels at birth and at 8 years of age were associated with immune maturation. Immunological variables and androgen levels were examined and measured in blood samples obtained at birth, 3–5 days and at 8 years of age. Boys had higher proportions of CD5+and immature/transitional CD24hiCD38hiB cells, whereas girls had higher fractions of B cells with a memory phenotype at 8 years of age. School-aged boys also presented with higher frequencies of Tregs, and a greater capacity to produce T-cell-associated cytokines. Among boys, higher cord blood DHT levels were associated with higher proportions of CD5+B cells in early infancy and at 8 years of life. These results suggest that DHT actionsin uteromight be involved in the mechanism for delayed peripheral B-cell maturation in boys.
High-fat diet-induced obesity and insulin resistance are characterized by differential beta oscillatory signaling of the limbic cortico-basal ganglia loop
Authors: Maurer Lukas , Tang Hui , Haumesser Jens K. , Altschüler Jennifer , Kühn Andrea A. , Spranger Joachim , van Riesen Christoph
Published: November 2017

The concept of brain circuit disorders has been proposed for a variety of neuropsychiatric diseases, characterized by pathological disturbances of neuronal networks including changes in oscillatory signaling of re-entrant cortico-subcortical loops in the basal ganglia system. Parts of this circuitry play a pivotal role in energy homeostasis. We therefore investigated whether high-fat diet (HFD) induced obesity is associated with changes in oscillatory signaling in the limbic cortico-basal ganglia loop. We performed multi-site in-vivo electrophysiological recordings of local field potentials within this network under urethane anesthesia in adult rats after 4 weeks of HFD feeding compared to age-matched controls. Recordings were performed at baseline and during systemic glucose challenge. Our analysis demonstrates increased oscillatory beta power in the nucleus accumbens (NAC) associated with decreased beta coherence between cortex and NAC in animals fed a HFD. Spontaneous beta oscillatory power strongly correlated with endocrine markers of obesity. The glucose challenge increased beta oscillations in control animals but not in animals receiving the HFD. Furthermore direct intracerebroventricular insulin injection increased beta oscillations in the NAC. The present study provides evidence for aberrant oscillatory signaling in the limbic cortico-basal ganglia loop that might contribute to the dysfunctional information processing in obesity.