bluuebunny/crossref_metadata_2025 huggingface dataset:
MARCH1 regulates insulin sensitivity by controlling cell surface insulin receptor levels
Authors: Nagarajan Arvindhan , Petersen Max C. , Nasiri Ali R. , Butrico Gina , Fung Annie , Ruan Hai-Bin , Kursawe Romy , Caprio Sonia , Thibodeau Jacques , Bourgeois-Daigneault Marie-Claude , Sun Lisha , Gao Guangping , Bhanot Sanjay , Jurczak Michael J. , Green Michael R. , Shulman Gerald I. , Wajapeyee Narendra
Published: August 2016

Insulin resistance is a key driver of type 2 diabetes (T2D) and is characterized by defective insulin receptor (INSR) signalling. Although surface INSR downregulation is a well-established contributor to insulin resistance, the underlying molecular mechanisms remain obscure. Here we show that the E3 ubiquitin ligase MARCH1 impairs cellular insulin action by degrading cell surface INSR. Using a large-scale RNA interference screen, we identify MARCH1 as a negative regulator of INSR signalling. March1 loss-of-function enhances, and March1 overexpression impairs, hepatic insulin sensitivity in mice. MARCH1 ubiquitinates INSR to decrease cell surface INSR levels, but unlike other INSR ubiquitin ligases, MARCH1 acts in the basal state rather than after insulin stimulation. Thus, MARCH1 may help set the basal gain of insulin signalling. MARCH1 expression is increased in white adipose tissue of obese humans, suggesting that MARCH1 contributes to the pathophysiology of T2D and could be a new therapeutic target.
Neutrophil recruitment limited by high-affinity bent β2 integrin binding ligand in cis
Authors: Fan Zhichao , McArdle Sara , Marki Alex , Mikulski Zbigniew , Gutierrez Edgar , Engelhardt Britta , Deutsch Urban , Ginsberg Mark , Groisman Alex , Ley Klaus
Published: August 2016

Neutrophils are essential for innate immunity and inflammation and many neutrophil functions are β2 integrin-dependent. Integrins can extend (E+) and acquire a high-affinity conformation with an ‘open’ headpiece (H+). The canonical switchblade model of integrin activation proposes that the E+ conformation precedes H+, and the two are believed to be structurally linked. Here we show, using high-resolution quantitative dynamic footprinting (qDF) microscopy combined with a homogenous conformation-reporter binding assay in a microfluidic device, that a substantial fraction of β2 integrins on human neutrophils acquire an unexpected E−H+ conformation. E−H+ β2 integrins bind intercellular adhesion molecules (ICAMs) in cis, which inhibits leukocyte adhesion in vitro and in vivo. This endogenous anti-inflammatory mechanism inhibits neutrophil aggregation, accumulation and inflammation.
Correlated anomalous phase diffusion of coupled phononic modes in a sideband-driven resonator
Authors: Sun F. , Dong X. , Zou J. , Dykman M. I. , Chan H. B.
Published: August 2016

The dynamical backaction from a periodically driven optical cavity can reduce the damping of a mechanical resonator, leading to parametric instability accompanied by self-sustained oscillations. Here we study experimentally and theoretically new aspects of the backaction and the discrete time-translation symmetry of a driven system using a micromechanical resonator with two nonlinearly coupled vibrational modes with strongly differing frequencies and decay rates. We find self-sustained oscillations in both the low- and high-frequency modes. Their frequencies and amplitudes are determined by the nonlinearity, which also leads to bistability and hysteresis. The phase fluctuations of the two modes show near-perfect anti-correlation, a consequence of the discrete time-translation symmetry. Concurrently, the phase of each mode undergoes anomalous diffusion. The phase variance follows a power law time dependence, with an exponent determined by the 1/f-type resonator frequency noise. Our findings enable compensating for the fluctuations using a feedback scheme to achieve stable frequency downconversion.
Unravelling the electrochemical double layer by direct probing of the solid/liquid interface
Authors: Favaro Marco , Jeong Beomgyun , Ross Philip N. , Yano Junko , Hussain Zahid , Liu Zhi , Crumlin Ethan J.
Published: August 2016

The electrochemical double layer plays a critical role in electrochemical processes. Whilst there have been many theoretical models predicting structural and electrical organization of the electrochemical double layer, the experimental verification of these models has been challenging due to the limitations of available experimental techniques. The induced potential drop in the electrolyte has never been directly observed and verified experimentally, to the best of our knowledge. In this study, we report the direct probing of the potential drop as well as the potential of zero charge by means of ambient pressure X-ray photoelectron spectroscopy performed under polarization conditions. By analyzing the spectra of the solvent (water) and a spectator neutral molecule with numerical simulations of the electric field, we discern the shape of the electrochemical double layer profile. In addition, we determine how the electrochemical double layer changes as a function of both the electrolyte concentration and applied potential.
Insulin post-transcriptionally modulates Bmal1 protein to affect the hepatic circadian clock
Authors: Dang Fabin , Sun Xiujie , Ma Xiang , Wu Rong , Zhang Deyi , Chen Yaqiong , Xu Qian , Wu Yuting , Liu Yi
Published: August 2016

Although food availability is a potent synchronizer of the peripheral circadian clock in mammals, the underlying mechanisms are unclear. Here, we show that hepatic Bmal1, a core transcription activator of the molecular clock, is post-transcriptionally regulated by signals from insulin, an important hormone that is temporally controlled by feeding. Insulin promotes postprandial Akt-mediated Ser42-phosphorylation of Bmal1 to induce its dissociation from DNA, interaction with 14-3-3 protein and subsequently nuclear exclusion, which results in the suppression of Bmal1 transcriptional activity. Inverted feeding cycles not only shift the phase of daily insulin oscillation, but also elevate the amplitude due to food overconsumption. This enhanced and reversed insulin signalling initiates the reset of clock gene rhythms by altering Bmal1 nuclear accumulation in mouse liver. These results reveal the molecular mechanism of insulin signalling in regulating peripheral circadian rhythms.
Association of Adiponectin Polymorphism with Metabolic Syndrome Risk and Adiponectin Level with Stroke Risk: A Meta-Analysis
Authors: Yuan Hui-Ping , Sun Liang , Li Xing-Hui , Che Fu-Gang , Zhu Xiao-Quan , Yang Fan , Han Jing , Jia Chun-Yuan , Yang Ze
Published: August 2016

Many previous studies have provided evidence that the ADIPOQ +45T>G polymorphism (rs2241766) might cause metabolic syndrome (MS). As a cardiovascular manifestation of MS, the incidence of stroke is associated with adiponectin; however, the results remain controversial and inconsistent. Systematic searches of relevant studies published up to Dec 2014 and Jan 2016 on the ADIPOQ +45T>G polymorphism and the risk of MS and adiponectin levels and the risk of stroke, respectively, were conducted in MEDLINE and EMBASE. The odds ratio (OR) or risk ratio (RR) and their 95% confidence interval (95% CI) were extracted. Sixteen studies containing 4,113 MS cases and 3,637 healthy controls indicated a weak positive association between ADIPOQ +45 T>G and MS in the dominant genetic model (OR = 1.30, 95% CI = 1.03–1.65), which was also validated by stratified subgroup analyses. Twelve studies including 26,213 participants and 4,246 stroke cases indicated that 5 μg/ml increments in adiponectin level were not relevant to stroke risk (RR = 1.05, 95% CI = 1.00–1.10, P = 0.069). This study suggested a weak positive association of ADIPOQ +45T>G with MS and a strong association with metabolic-related disease. Additionally, adiponectin level was not a causal factor of increasing stroke risk.
Differential expression of genes in the alate and apterous morphs of the brown citrus aphid, Toxoptera citricida
Authors: Shang Feng , Ding Bi-Yue , Xiong Ying , Dou Wei , Wei Dong , Jiang Hong-Bo , Wei Dan-Dan , Wang Jin-Jun
Published: August 2016

Winged and wingless morphs in insects represent a trade-off between dispersal ability and reproduction. We studied key genes associated with apterous and alate morphs in Toxoptera citricida (Kirkaldy) using RNAseq, digital gene expression (DGE) profiling and RNA interference. The de novo assembly of the transcriptome was obtained through Illumina short-read sequencing technology. A total of 44,199 unigenes were generated and 27,640 were annotated. The transcriptomic differences between alate and apterous adults indicated that 279 unigenes were highly expressed in alate adults, whereas 5,470 were expressed at low levels. Expression patterns of the top 10 highly expressed genes in alate adults agreed with wing bud development trends. Silencing of the lipid synthesis and degradation gene (3-ketoacyl-CoA thiolase, mitochondrial-like) and glycogen genes (Phosphoenolpyruvate carboxykinase [GTP]-like and Glycogen phosphorylase-like isoform 2) resulted in underdeveloped wings. This suggests that both lipid and glycogen metabolism provide energy for aphid wing development. The large number of sequences and expression data produced from the transcriptome and DGE sequencing, respectively, increases our understanding of wing development mechanisms.
Chronic Rhinosinusitis Associated with Erectile Dysfunction: A Population-Based Study
Authors: Tai Shu-Yu , Wang Ling-Feng , Tai Chih-Feng , Huang Yu-Ting , Chien Chen-Yu
Published: August 2016

Few studies have investigated the relationship between chronic rhinosinusitis (CRS) and erectile dysfunction (ED). This case-control study aimed to investigate the association between CRS and the risk of ED in a large national sample. Tapping Taiwan’s National Health Insurance Research Database, we identified people 30 years or older with a new primary diagnosis of CRS between 1996 and 2007. The cases were compared with sex- and age-matched controls. We identified 14 039 cases and recruited 140 387 matched controls. Both groups were followed up in the same database until the end of 2007 for instances of ED. Of those with CRS, 294 (2.1%) developed ED during a mean (SD) follow-up of 3.20 (2.33) years, while 1 661 (1.2%) of the matched controls developed ED, mean follow up 2.97 (2.39) years. Cox regression analyses were performed adjusting for sex, age, insurance premium, residence, hypertension, hyperlipidemia, diabetes, obesity, coronary heart disease, chronic kidney disease, chronic obstructive pulmonary disease, asthma, allergic rhinitis, arrhythmia, ischemic stroke, intracerebral hemorrhage, and medications. CRS was revealed to be an independent predictor of ED in the fully adjusted model (HR = 1.51; 95% CI = 1.33–1.73; P < 0.0001).
Individual dispersal decisions affect fitness via maternal rank effects in male rhesus macaques
Authors: Weiß Brigitte M. , Kulik Lars , Ruiz-Lambides Angelina V. , Widdig Anja
Published: August 2016

Natal dispersal may have considerable social, ecological and evolutionary consequences. While species-specific dispersal strategies have received much attention, individual variation in dispersal decisions and its fitness consequences remain poorly understood. We investigated causes and consequences of natal dispersal age in rhesus macaques (Macaca mulatta), a species with male dispersal. Using long-term demographic and genetic data from a semi-free ranging population on Cayo Santiago, Puerto Rico, we analysed how the social environment such as maternal family, group and population characteristics affected the age at which males leave their natal group. While natal dispersal age was unrelated to most measures of group or population structure, our study confirmed earlier findings that sons of high-ranking mothers dispersed later than sons of low-ranking ones. Natal dispersal age did not affect males’ subsequent survival, but males dispersing later were more likely to reproduce. Late dispersers were likely to start reproducing while still residing in their natal group, frequently produced extra-group offspring before natal dispersal and subsequently dispersed to the group in which they had fathered offspring more likely than expected. Hence, the timing of natal dispersal was affected by maternal rank and influenced male reproduction, which, in turn affected which group males dispersed to.
Effect of BI-1 on insulin resistance through regulation of CYP2E1
Authors: Lee Geum-Hwa , Oh Kyoung-Jin , Kim Hyung-Ryong , Han Hye-Sook , Lee Hwa-Young , Park Keun-Gyu , Nam Ki-Hoan , Koo Seung-Hoi , Chae Han-Jung
Published: August 2016

Diet-induced obesity is a major contributing factor to the progression of hepatic insulin resistance. Increased free fatty acids in liver enhances endoplasmic reticulum (ER) stress and production of reactive oxygen species (ROS), both are directly responsible for dysregulation of hepatic insulin signaling. BI-1, a recently studied ER stress regulator, was examined to investigate its association with ER stress and ROS in insulin resistance models. To induce obesity and insulin resistance, BI-1 wild type and BI-1 knock-out mice were fed a high-fat diet for 8 weeks. The BI-1 knock-out mice had hyperglycemia, was associated with impaired glucose and insulin tolerance under high-fat diet conditions. Increased activity of NADPH-dependent CYP reductase-associated cytochrome p450 2E1 (CYP2E1) and exacerbation of ER stress in the livers of BI-1 knock-out mice was also observed. Conversely, stable expression of BI-1 in HepG2 hepatocytes was shown to reduce palmitate-induced ER stress and CYP2E1-dependent ROS production, resulting in the preservation of intact insulin signaling. Stable expression of CYP2E1 led to increased ROS production and dysregulation of insulin signaling in hepatic cells, mimicking palmitate-mediated hepatic insulin resistance. We propose that BI-1 protects against obesity-induced hepatic insulin resistance by regulating CYP2E1 activity and ROS production.
Homogeneity and variation of donor doping in Verneuil-grown SrTiO3:Nb single crystals
Authors: Rodenbücher C. , Luysberg M. , Schwedt A. , Havel V. , Gunkel F. , Mayer J. , Waser R.
Published: August 2016

The homogeneity of Verneuil-grown SrTiO3:Nb crystals was investigated. Due to the fast crystal growth process, inhomogeneities in the donor dopant distribution and variation in the dislocation density are expected to occur. In fact, for some crystals optical studies show variations in the density of Ti3+states on the microscale and a cluster-like surface conductivity was reported in tip-induced resistive switching studies. However, our investigations by TEM, EDX mapping and 3D atom probe reveal that the Nb donors are distributed in a statistically random manner, indicating that there is clearly no inhomogeneity on the macro-, micro- and nanoscale in high quality Verneuil-grown crystals. In consequence, the electronic transport in the bulk of donor-doped crystals is homogeneous and it is not significantly channelled by extended defects such as dislocations which justifies using this material, for example, as electronically conducting substrate for epitaxial oxide film growth.
Intron retention-dependent gene regulation in Cryptococcus neoformans
Authors: Gonzalez-Hilarion Sara , Paulet Damien , Lee Kyung-Tae , Hon Chung-Chau , Lechat Pierre , Mogensen Estelle , Moyrand Frédérique , Proux Caroline , Barboux Rony , Bussotti Giovanni , Hwang Jungwook , Coppée Jean-Yves , Bahn Yong-Sun , Janbon Guilhem
Published: August 2016

The biological impact of alternative splicing is poorly understood in fungi, although recent studies have shown that these microorganisms are usually intron-rich. In this study, we re-annotated the genome of C. neoformans var. neoformans using RNA-Seq data. Comparison with C. neoformans var. grubii revealed that more than 99% of ORF-introns are in the same exact position in the two varieties whereas UTR-introns are much less evolutionary conserved. We also confirmed that alternative splicing is very common in C. neoformans, affecting nearly all expressed genes. We also observed specific regulation of alternative splicing by environmental cues in this yeast. However, alternative splicing does not appear to be an efficient method to diversify the C. neoformans proteome. Instead, our data suggest the existence of an intron retention-dependent mechanism of gene expression regulation that is not dependent on NMD. This regulatory process represents an additional layer of gene expression regulation in fungi and provides a mechanism to tune gene expression levels in response to any environmental modification.
Acetylated α-Tubulin Regulated by N-Acetyl-Seryl-Aspartyl-Lysyl-Proline(Ac-SDKP) Exerts the Anti-fibrotic Effect in Rat Lung Fibrosis Induced by Silica
Authors: Xiaojun Wang , Yan Liu , Hong Xu , Xianghong Zhang , Shifeng Li , Dingjie Xu , Xuemin Gao , Lijuan Zhang , Bonan Zhang , Zhongqiu Wei , Ruimin Wang , Brann Darrell , Fang Yang
Published: August 2016

Silicosis is the most serious occupational disease in China. The objective of this study was to screen various proteins related to mechanisms of the pathogenesis of silicosis underlying the anti-fibrotic effect of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) using proteomic profile analysis. We also aimed to explore a potential mechanism of acetylated α-tubulin (α-Ac-Tub) regulation by Ac-SDKP. Two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF/TOF MS) were used to assess the different protein expression profiles between control and silicosis rats treated with or without Ac-SDKP. Twenty-nine proteins were identified to be potentially involved in the progression of silicosis and the anti-fibrotic effect of Ac-SDKP. Our current study finds that 1) the lost expression of Ac-Tub-α may be a new mechanism in rat silicosis; 2) treatment of silicotic rats with N-acetyl-Seryl-Aspartyl-Lysyl-Proline (Ac-SDKP) inhibits myofibroblast differentiation and collagen deposition accompanied by stabilizing the expression of α-Ac-Tub in vivo and in vitro, which is related with deacetylase family member 6 (HDAC6) and α-tubulin acetyl transferase (α-TAT1). Our data suggest that α-Ac-Tub regulation by Ac-SDKP may potentially be a new anti-fibrosis mechanism.
Path (un)predictability of two interacting cracks in polycarbonate sheets using Digital Image Correlation
Authors: Koivisto J. , Dalbe M.-J. , Alava M. J. , Santucci S.
Published: August 2016

Crack propagation is tracked here with Digital Image Correlation analysis in the test case of two cracks propagating in opposite directions in polycarbonate, a material with high ductility and a large Fracture Process Zone (FPZ). Depending on the initial distances between the two crack tips, one may observe different complex crack paths with in particular a regime where the two cracks repel each other prior to being attracted. We show by strain field analysis how this can be understood according to the principle of local symmetry: the propagation is to the direction where the local shear - mode KII in fracture mechanics language - is zero. Thus the interactions exhibited by the cracks arise from symmetry, from the initial geometry, and from the material properties which induce the FPZ. This complexity makes any long-range prediction of the path(s) impossible.
Observation of the Chiral and Achiral Hexatic Phases of Self-assembled Micellar polymers
Authors: Pal Antara , Kamal Md. Arif , Raghunathan V. A.
Published: August 2016

We report the discovery of a thermodynamically stable line hexatic (N + 6) phase in a three-dimensional (3D) system made up of self-assembledpolymer-likemicelles of amphiphilic molecules. The experimentally observed phase transition sequencenematic (N) "Equation missing" N + 6 "Equation missing" two-dimensional hexagonal (2D-H) is in good agreement with the theoretical predictions. Further, the present study also brings to light the effect of chirality on the N + 6 phase. In the chiral N + 6 phase the bond-orientational order within each “polymer” bundle is found to be twisted about an axis parallel to the average polymer direction. This structure is consistent with the theoretically envisaged Moiré state, thereby providing the first experimental demonstration of the Moiré structure. In addition to confirming the predictions of fundamental theories of two-dimensional melting, these results are relevant in a variety of situations in chemistry, physics and biology, where parallel packing of polymer-like objects are encountered.
Triclosan Resistome from Metagenome Reveals Diverse Enoyl Acyl Carrier Protein Reductases and Selective Enrichment of Triclosan Resistance Genes
Authors: Khan Raees , Kong Hyun Gi , Jung Yong-Hoon , Choi Jinhee , Baek Kwang-Yeol , Hwang Eul Chul , Lee Seon-Woo
Published: August 2016

Triclosan (TCS) is a widely used antimicrobial agent and TCS resistance is considered to have evolved in diverse organisms with extensive use of TCS, but distribution of TCS resistance has not been well characterized. Functional screening of the soil metagenome in this study has revealed that a variety of target enoyl acyl carrier protein reductases (ENR) homologues are responsible for the majority of TCS resistance. Diverse ENRs similar to 7-α-hydroxysteroid dehydrogenase (7-α-HSDH), FabG, or the unusual YX7K-type ENR conferred extreme tolerance to TCS. The TCS-refractory 7-α HSDH-like ENR and the TCS-resistant YX7K-type ENR seem to be prevalent in human pathogenic bacteria, suggesting that a selective enrichment occurred in pathogenic bacteria in soil. Additionally, resistance to multiple antibiotics was found to be mediated by antibiotic resistance genes that co-localize with TCS resistance determinants. Further comparative analysis of ENRs from 13 different environments has revealed a huge diversity of both prototypic and metagenomic TCS-resistant ENRs, in addition to a selective enrichment of TCS-resistant specific ENRs in presumably TCS-contaminated environments with reduced ENR diversity. Our results suggest that long-term extensive use of TCS can lead to the selective emergence of TCS-resistant bacterial pathogens, possibly with additional resistance to multiple antibiotics, in natural environments.
A measure of the concentration of rare events
Authors: Prieto Curiel Rafael , Bishop Steven
Published: August 2016

We introduce here an index, which we call the Rare Event Concentration Coefficient (RECC), that is a measure of the dispersion/concentration of events which have a low frequency but tend to have a high level of concentration, such as the number of crimes suffered by a person. The Rare Event Concentration Coefficient is a metric based on a statistical mixture model, with a value closer to zero meaning that events are homogeneously distributed, and a value closer to one meaning that the events have a higher degree of concentration. This measure may be used to compare the concentration of events over different time periods and over different regions. Other traditional approaches for the dispersion/concentration of a variable tend to be blind to structural changes in the pattern of occurrence of rare events. The RECC overcomes this issue and we show here two simple applications, first by using the number of burglaries suffered in Netherlands and then by using the number of volcanic eruptions in the world.
N-acetylcysteine attenuates lipopolysaccharide-induced impairment in lamination of Ctip2-and Tbr1- expressing cortical neurons in the developing rat fetal brain
Authors: Chao Ming-Wei , Chen Chie-Pein , Yang Yu-Hsiu , Chuang Yu-Chen , Chu Tzu-Yun , Tseng Chia-Yi
Published: August 2016

Oxidative stress and inflammatory insults are the major instigating events of bacterial intrauterine infection that lead to fetal brain injury. The purpose of this study is to investigate the remedial effects of N-acetyl-cysteine (NAC) for inflammation-caused deficits in brain development. We found that lipopolysaccharide (LPS) induced reactive oxygen species (ROS) production by RAW264.7 cells. Macrophage-conditioned medium caused noticeable cortical cell damage, specifically in cortical neurons. LPS at 25 μg/kg caused more than 75% fetal loss in rats. An increase in fetal cortical thickness was noted in the LPS-treated group. In the enlarged fetal cortex, laminar positioning of the early born cortical cells expressing Tbr1 and Ctip2 was disrupted, with a scattered distribution. The effect was similar, but minor, in later born Satb2-expressing cortical cells. NAC protected against LPS-induced neuron toxicity in vitro and counteracted pregnancy loss and alterations in thickness and lamination of the neocortex in vivo. Fetal loss and abnormal fetal brain development were due to LPS-induced ROS production. NAC is an effective protective agent against LPS-induced damage. This finding highlights the key therapeutic impact of NAC in LPS-caused abnormal neuronal laminar distribution during brain development.
Fluorometric Measurement of Individual Stomata Activity and Transpiration via a “Brush-on”, Water-Responsive Polymer
Authors: Seo Minjeong , Park Dong-Hoon , Lee Chan Woo , Jaworski Justyn , Kim Jong-Man
Published: August 2016

Much of atmospheric water originates from transpiration, the process by which plants release H2O from pores, known as stomata, that simultaneously intake CO2 for photosynthesis. Controlling stomatal aperture can regulate the extent of water transport in response to dynamic environmental factors including osmotic stress, temperature, light, and wind. While larger leaf regions are often examined, the extent of water vapor release from individual stomata remains unexplored. Using a “brush-on” sensing material, we can now assess transpiration using a water-responsive, polydiacetylene-based coating on the leaves surfaces. By eliciting a fluorometric signal to passing water vapor, we obtained information regarding the activity of individual stomata. In this demonstration, our results prove that this coating can identify the proportion of active stomata and the extent of transpirational diffusion of water in response to different conditions.
Large-Scale Discovery of Disease-Disease and Disease-Gene Associations
Authors: Gligorijevic Djordje , Stojanovic Jelena , Djuric Nemanja , Radosavljevic Vladan , Grbovic Mihajlo , Kulathinal Rob J. , Obradovic Zoran
Published: August 2016

Data-driven phenotype analyses on Electronic Health Record (EHR) data have recently drawn benefits across many areas of clinical practice, uncovering new links in the medical sciences that can potentially affect the well-being of millions of patients. In this paper, EHR data is used to discover novel relationships between diseases by studying their comorbidities (co-occurrences in patients). A novel embedding model is designed to extract knowledge from disease comorbidities by learning from a large-scale EHR database comprising more than 35 million inpatient cases spanning nearly a decade, revealing significant improvements on disease phenotyping over current computational approaches. In addition, the use of the proposed methodology is extended to discover novel disease-gene associations by including valuable domain knowledge from genome-wide association studies. To evaluate our approach, its effectiveness is compared against a held-out set where, again, it revealed very compelling results. For selected diseases, we further identify candidate gene lists for which disease-gene associations were not studied previously. Thus, our approach provides biomedical researchers with new tools to filter genes of interest, thus, reducing costly lab studies.
Thermodynamic and hydrochemical controls on CH4 in a coal seam gas and overlying alluvial aquifer: new insights into CH4 origins
Authors: Owen D. Des. R. , Shouakar-Stash O. , Morgenstern U. , Aravena R.
Published: August 2016

Using a comprehensive data set (dissolved CH4, δ13C-CH4, δ2H-CH4, δ13C-DIC, δ37Cl, δ2H-H2O, δ18O-H2O, Na, K, Ca, Mg, HCO3, Cl, Br, SO4, NO3 and DO), in combination with a novel application of isometric log ratios, this study describes hydrochemical and thermodynamic controls on dissolved CH4 from a coal seam gas reservoir and an alluvial aquifer in the Condamine catchment, eastern Surat/north-western Clarence-Moreton basins, Australia. δ13C-CH4 data in the gas reservoir (−58‰ to −49‰) and shallow coal measures underlying the alluvium (−80‰ to −65‰) are distinct. CO2 reduction is the dominant methanogenic pathway in all aquifers, and it is controlled by SO4 concentrations and competition for reactants such as H2. At isolated, brackish sites in the shallow coal measures and alluvium, highly depleted δ2H-CH4 (<310‰) indicate acetoclastic methanogenesis where SO4 concentrations inhibit CO2 reduction. Evidence of CH4 migration from the deep gas reservoir (200–500 m) to the shallow coal measures (<200 m) or the alluvium was not observed. The study demonstrates the importance of understanding CH4 at different depth profiles within and between aquifers. Further research, including culturing studies of microbial consortia, will improve our understanding of the occurrence of CH4 within and between aquifers in these basins.
Giant Polymersome Protocells Dock with Virus Particle Mimics via Multivalent Glycan-Lectin Interactions
Authors: Kubilis Artur , Abdulkarim Ali , Eissa Ahmed M. , Cameron Neil R.
Published: August 2016

Despite the low complexity of their components, several simple physical systems, including microspheres, coacervate droplets and phospholipid membrane structures (liposomes), have been suggested as protocell models. These, however, lack key cellular characteristics, such as the ability to replicate or to dock with extracellular species. Here, we report a simple method for the de novo creation of synthetic cell mimics in the form of giant polymeric vesicles (polymersomes), which are capable of behavior approaching that of living cells. These polymersomes form by self-assembly, under electroformation conditions, of amphiphilic, glycosylated block copolymers in aqueous solution. The glycosylated exterior of the resulting polymeric giant unilamellar vesicles (GUVs) allows their selective interaction with carbohydrate-binding receptor-functionalized particles, in a manner reminiscent of the cell-surface docking of virus particles. We believe that this is the first example of a simple protocell model displaying cell-like behavior through a native receptor-ligand interaction.
Pre-B-cell colony-enhancing factor protects against apoptotic neuronal death and mitochondrial damage in ischemia
Authors: Wang Xiaowan , Li Hailong , Ding Shinghua
Published: August 2016

We previously demonstrated that Pre-B-cell colony-enhancing factor (PBEF), also known as nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in mammalian NAD+ biosynthesis pathway, plays a brain and neuronal protective role in ischemic stroke. In this study, we further investigated the mechanism of its neuroprotective effect after ischemia in the primary cultured mouse cortical neurons. Using apoptotic cell death assay, fluorescent imaging, molecular biology, mitochondrial biogenesis measurements and Western blotting analysis, our results show that the overexpression of PBEF in neurons can significantly promote neuronal survival, reduce the translocation of apoptosis inducing factor (AIF) from mitochondria to nuclei and inhibit the activation of capase-3 after glutamate-induced excitotoxicity. We further found that the overexpression of PBEF can suppress glutamate-induced mitochondrial fragmentation, the loss of mitochondrial DNA (mtDNA) content and the reduction of PGC-1 and NRF-1 expressions. Furthermore, these beneficial effects by PBEF are dependent on its enzymatic activity of NAD+ synthesis. In summary, our study demonstrated that PBEF ameliorates ischemia-induced neuronal death through inhibiting caspase-dependent and independent apoptotic signaling pathways and suppressing mitochondrial damage and dysfunction. Our study provides novel insights into the mechanisms underlying the neuroprotective effect of PBEF and helps to identify potential targets for ischemic stroke therapy.
Proliferation in cardiac fibroblasts induced by β1-adrenoceptor autoantibody and the underlying mechanisms
Authors: Lv Tingting , Du Yunhui , Cao Ning , Zhang Suli , Gong Yulin , Bai Yan , Wang Wen , Liu Huirong
Published: August 2016

Chronic sustained stimulation of β-adrenoceptor is closely related to cardiac fibrosis which is bad for cardiac function. Growing evidence showed that the high prevalence of β1-adrenoceptor autoantibody (β1-AA) in the sera of patients with various types of cardiovascular diseases decreased cardiac function. In the current study, we demonstrated that β1-AA impaired the cardiac function evaluated by echocardiography and that β1-AA triggered cardiac fibrosis in terms of increased expression of α-smooth muscle actin as the marker of myofibroblast and collagen deposition in a passive β1-AA immunized mice model during 16 weeks. Further, we showed that β1-AA activated β1-AR/cAMP/PKA pathway and promoted proliferation in primary cardiac fibroblasts through specific binding to β1-AR but not to β2-AR. Moreover, β1-AA was also likely to promote proliferation in cardiac fibroblasts through activating p38MAPK and ERK1/2 as p38MAPK inhibitor SB203580 and ERK1/2 inhibitor PD98059 partially reversed the proliferative effect. The persistent activating signalling of PKA and P38MAPK in 1 h induced by β1-AA was associated with lacking agonist-induced desensitization phenomena. The conditioned medium from β1-AA-stimulated cardiac fibroblasts induced cardiomyocyte apoptosis, which indicated that β1-AA changed the secretion of cardiac fibroblasts contributing to cardiac injury. These findings will contribute to our understanding of the pathological mechanisms of β1-AA.
A Synergistic Effect of Surfactant and ZrO2 Underlayer on Photocurrent Enhancement and Cathodic Shift of Nanoporous Fe2O3 Photoanode
Authors: Shinde Pravin S. , Lee Su Yong , Choi Sun Hee , Lee Hyun Hwi , Ryu Jungho , Jang Jum Suk
Published: August 2016

Augmenting the donor density and nanostructure engineering are the crucial points to improve solar water oxidation performance of hematite (α-Fe2O3). This work addresses the sluggish water oxidation reaction associated with hematite photoanode by tweaking its internal porosity. The porous hematite photoanodes are fabricated by a novel synthetic strategy via pulse reverse electrodeposition (PRED) method that involves incorporation of a cationic CTAB surfactant in a sulfate electrolyte and spin-coated ZrO2 underlayer (UL) on FTO. CTAB is found to be beneficial in promoting the film growth rate during PRED. Incorporation of Zr4+ ions from ZrO2 UL and Sn4+ ions from FTO into the Fe2O3 lattice via solid-state diffusion reaction during pertinent annihilation of surfactant molecules at 800 °C produced internally porous hematite films with improved carrier concentration. The porous hematite demonstrated a sustained photocurrent enhancement and a significant cathodic shift of 130 mV relative to the planar hematite under standard illumination conditions (AM 1.5G) in 1 M NaOH electrolyte. The absorption, electrochemical impedance spectroscopy and Mott-Schottky analyses revealed that the ZrO2 UL and CTAB not only increased the carrier density and light harvesting but also accelerated the surface oxidation reaction kinetics, synergistically boosting the performance of internally porous hematite photoanodes.
Optical nano artifact metrics using silicon random nanostructures
Authors: Matsumoto Tsutomu , Yoshida Naoki , Nishio Shumpei , Hoga Morihisa , Ohyagi Yasuyuki , Tate Naoya , Naruse Makoto
Published: August 2016

Nano-artifact metrics exploit unique physical attributes of nanostructured matter for authentication and clone resistance, which is vitally important in the age of Internet-of-Things where securing identities is critical. However, expensive and huge experimental apparatuses, such as scanning electron microscopy, have been required in the former studies. Herein, we demonstrate an optical approach to characterise the nanoscale-precision signatures of silicon random structures towards realising low-cost and high-value information security technology. Unique and versatile silicon nanostructures are generated via resist collapse phenomena, which contains dimensions that are well below the diffraction limit of light. We exploit the nanoscale precision ability of confocal laser microscopy in the height dimension; our experimental results demonstrate that the vertical precision of measurement is essential in satisfying the performances required for artifact metrics. Furthermore, by using state-of-the-art nanostructuring technology, we experimentally fabricate clones from the genuine devices. We demonstrate that the statistical properties of the genuine and clone devices are successfully exploited, showing that the liveness-detection-type approach, which is widely deployed in biometrics, is valid in artificially-constructed solid-state nanostructures. These findings pave the way for reasonable and yet sufficiently secure novel principles for information security based on silicon random nanostructures and optical technologies.
Development of functionalized multi-walled carbon-nanotube-based alginate hydrogels for enabling biomimetic technologies
Authors: Joddar Binata , Garcia Eduardo , Casas Atzimba , Stewart Calvin M.
Published: August 2016

Alginate is a hydrogel commonly used for cell culture by ionically crosslinking in the presence of divalent Ca2+ ions. However these alginate gels are mechanically unstable, not permitting their use as scaffolds to engineer robust biological bone, breast, cardiac or tumor tissues. This issue can be addressed via encapsulation of multi-walled carbon nanotubes (MWCNT) serving as a reinforcing phase while being dispersed in a continuous phase of alginate. We hypothesized that adding functionalized MWCNT to alginate, would yield composite gels with distinctively different mechanical, physical and biological characteristics in comparison to alginate alone. Resultant MWCNT-alginate gels were porous, and showed significantly less degradation after 14 days compared to alginate alone. In vitro cell-studies showed enhanced HeLa cell adhesion and proliferation on the MWCNT-alginate compared to alginate. The extent of cell proliferation was greater when cultured atop 1 and 3 mg/ml MWCNT-alginate; although all MWCNT-alginates lead to enhanced cell cluster formation compared to alginate alone. Among all the MWCNT-alginates, the 1 mg/ml gels showed significantly greater stiffness compared to all other cases. These results provide an important basis for the development of the MWCNT-alginates as novel substrates for cell culture applications, cell therapy and tissue engineering.
A novel P2X4 receptor-selective antagonist produces anti-allodynic effect in a mouse model of herpetic pain
Authors: Matsumura Yuta , Yamashita Tomohiro , Sasaki Atsushi , Nakata Eriko , Kohno Keita , Masuda Takahiro , Tozaki-Saitoh Hidetoshi , Imai Toshiyasu , Kuraishi Yasushi , Tsuda Makoto , Inoue Kazuhide
Published: August 2016

Accumulating evidence indicates that purinergic P2X4 receptors (P2X4R: cation channels activated by extracellular ATP) expressed in spinal microglia are crucial for pathological chronic pain caused by nerve damage, suggesting a potential target for drug discovery. We identified NP-1815-PX (5-[3-(5-thioxo-4H-[1,2,4]oxadiazol-3-yl)phenyl]-1H-naphtho[1, 2-b][1,4]diazepine-2,4(3H,5H)-dione) as a novel antagonist selective for P2X4R with high potency and selectivity compared with other P2XR subtypes. In in vivo assay for acute and chronic pain, intrathecal administration of NP-1815-PX produced an anti-allodynic effect in mice with traumatic nerve damage without affecting acute nociceptive pain and motor function (although its oral administration did not produce the effect). Furthermore, in a mouse model of herpetic pain, P2X4R upregulation in the spinal cord exclusively occurred in microglia and intrathecal NP-1815-PX suppressed induction of mechanical allodynia. This model also showed K+/Cl− cotransporter 2 (KCC2) downregulation, which is implicated in dorsal horn neuron hyperexcitability; this downregulation was restored by intrathecal treatment with NP-1815-PX or by interfering with brain-derived neurotrophic factor (BDNF) signaling, a P2X4R-activated microglial factor implicated in KCC2 downregulation. Taken together, the newly developed P2X4R antagonist NP-1815-PX produces anti-allodynic effects in chronic pain models without altering acute pain sensitivity, suggesting that microglial P2X4R could be an attractive target for treating chronic pain.
Post-response βγ power predicts the degree of choice-based learning in internally guided decision-making
Authors: Nakao Takashi , Kanayama Noriaki , Katahira Kentaro , Odani Misaki , Ito Yosuke , Hirata Yuki , Nasuno Reika , Ozaki Hanako , Hiramoto Ryosuke , Miyatani Makoto , Northoff Georg
Published: August 2016

Choosing an option increases a person’s preference for that option. This phenomenon, called choice-based learning (CBL), has been investigated separately in the contexts of internally guided decision-making (IDM, e.g., preference judgment), for which no objectively correct answer exists and externally guided decision making (EDM, e.g., perceptual decision making), for which one objectively correct answer exists. For the present study, we compared decision making of these two types to examine differences of underlying neural processes of CBL. As IDM and EDM tasks, occupation preference judgment and salary judgment were used, respectively. To compare CBL for the two types of decision making, we developed a novel measurement of CBL: decision consistency. When CBL occurs, decision consistency is higher in the last-half trials than in first-half trials. Electroencephalography (EEG) data have demonstrated that the change of decision consistency is positively correlated with the fronto-central beta–gamma power after response in the first-half trials for IDM, but not for EDM. Those results demonstrate for the first time the difference of CBL between IDM and EDM. The fronto-central beta–gamma power is expected to reflect a key process of CBL, specifically for IDM.
Tracking objects outside the line of sight using 2D intensity images
Authors: Klein Jonathan , Peters Christoph , Martín Jaime , Laurenzis Martin , Hullin Matthias B.
Published: August 2016

The observation of objects located in inaccessible regions is a recurring challenge in a wide variety of important applications. Recent work has shown that using rare and expensive optical setups, indirect diffuse light reflections can be used to reconstruct objects and two-dimensional (2D) patterns around a corner. Here we show that occluded objects can be tracked in real time using much simpler means, namely a standard 2D camera and a laser pointer. Our method fundamentally differs from previous solutions by approaching the problem in an analysis-by-synthesis sense. By repeatedly simulating light transport through the scene, we determine the set of object parameters that most closely fits the measured intensity distribution. We experimentally demonstrate that this approach is capable of following the translation of unknown objects and translation and orientation of a known object, in real time.
Interspecific comparison of traffic noise effects on dove coo transmission in urban environments
Authors: Shieh Bao-Sen , Liang Shih-Hsiung , Chiu Yuh-Wen , Lin Szu-Ying
Published: August 2016

Most previous studies concerning avian adaptation to anthropogenic noise have focused on songbirds, but few have focused on non-songbirds commonly found in urban environments such as doves. We conducted field playback-recording experiments on the perch-coos of five dove species, including four native Taiwan species (the spotted dove, Spilopelia chinensis, the oriental turtle-dove, Streptopelia orientalis, the red collared-dove, Streptopelia tranquebarica and the emerald dove, Chalcophaps indica) and one species not native to Taiwan (the zebra dove, Geopelia striata) to evaluate the detection and recognition of dove coos in habitats with differing levels of traffic noise. Our results suggest that traffic noise has selected dominant urban species such as the spotted dove to temporally and spatially adjust cooing to reduce the masking effects of traffic noise and rare urban species such as the emerald dove to avoid areas of high traffic noise. Additionally, although the zebra dove had the highest coo frequency among the study species, its coos showed the highest detection value but not the highest recognition value. We conclude that traffic noise is an important factor in shaping the distribution of rare and dominant dove species in urban environments through its significant effects on coo transmission.
Thin film depth profiling by ion beam analysis
Authors: Jeynes Chris , Colaux Julien L.
Published: August 2016

The analysis of thin films is of central importance for functional materials, including the very large and active field of nanomaterials.
Simultaneous determination of tocopherols and tocotrienols in vegetable oils by GC-MS
Authors: Zhang Rui , Shen Weijian , Wei Xueyuan , Zhang Feifang , Shen Chongyu , Wu Bin , Zhao Zengyun , Liu Han , Deng Xiaojun
Published: August 2016

A simple and rapid gas chromatography-mass spectrometry (GC-MS) method was developed and validated for the simultaneous determination of α-, β-, γ- and δ-tocopherols and α-, β-, γ- and δ-tocotrienols in vegetable oils.
A quantitative, in vitro appraisal of experimental low-glucose storage solutions used for blood banking
Authors: Mu Ruipeng , Chen Chengpeng , Wang Yimeng , Spence Dana M.
Published: August 2016

A combination of 3D printed tools and classic cellular analyses reveals the benefits of reducing the glucose content of currently approved solutions used to process and store red blood cells for transfusion medicine.
A mechanistic study and computational prediction of iron, cobalt and manganese cyclopentadienone complexes for hydrogenation of carbon dioxide
Authors: Ge Hongyu , Chen Xiangyang , Yang Xinzheng
Published: August 2016

A series of cobalt and manganese cyclopentadienone complexes are proposed and examined computationally as promising catalysts for hydrogenation of CO2.
End-capping of amphiphilic nanotubes with phospholipid vesicles: impact of the phospholipid on the cap formation and vesicle loading under osmotic conditions
Authors: Erne Petra M. , Štacko Peter , van Dijken Derk Jan , Chen Jiawen , Stuart Marc C. A. , Feringa Ben L.
Published: August 2016

Amphiphilic nanotubes are capped with vesicles of phospholipids. The phase transition temperature and type of the phospholipids plays a crucial role in the phase separation that leads to the end-capped nanotubes, and subsequent vesicle-loading by osmosis.
Mechanistic analysis of aliphatic β-lactones in Vibrio harveyi reveals a quorum sensing independent mode of action
Authors: Zhao Weining , Lorenz Nicola , Jung Kirsten , Sieber Stephan A.
Published: August 2016

β-Lactone analogs of autoinducers potently inhibitVibrio harveyibioluminescence using a quorum sensing independent mechanism interfering with fatty acid biosynthesis.
A high performance three-dimensional thiophene-annulated perylene dye as an acceptor for organic solar cells
Authors: Fan Wei , Liang Ningning , Meng Dong , Feng Jiajing , Li Yan , Hou Jianhui , Wang Zhaohui
Published: August 2016

A new three-dimensional thiophene-annulated perylene dye, namely tetra-PBI-S, was designed and synthesized. Organic solar cells based on the tetra-PBI-S acceptor show a much higher power conversion efficiency than tetra-PBI based solar cells.
High-efficiency water collection on biomimetic material with superwettable patterns
Authors: Zhu Hai , Yang Fuchao , Li Jing , Guo Zhiguang
Published: August 2016

A superhydrophilic surface with two superhydrophobic circular patterns was successfully prepared, which showed outstanding fog-harvesting efficiency with a water collection rate (WCR) of 1316.9 mg h−1 cm−2. The water collection process can be repeated 10 times without obvious variation in the WCR.