bluuebunny/crossref_metadata_2025 huggingface dataset:
A Magmatic Seafloor Source at an Ultraslow-Spreading Ridge
Authors: Wheeling Kate
Published: September 2015

An ultraslow-spreading stretch of the Southwest Indian Ridge is thicker than expected: both tectonic and volcanic processes may be feeding the growing seafloor there.
Ablation of hippocampal neurogenesis in mice impairs the response to stress during the dark cycle
Authors: Tsai Cheng-Yu , Tsai Ching-Yen , Arnold Sebastian J. , Huang Guo-Jen
Published: September 2015

The functional role of adult neurogenesis in the hippocampus remains the subject of intense speculation. One recent hypothesis is that adult-born neurons contribute to the endocrine and behavioural outputs of the stress response. Here we show a genetic model system to ablate neurogenesis by inducibly deleting Tbr2 gene function specifically in the hippocampus and corroborate our findings in a radiation-based model of neurogenesis deprivation. We found that mice with ablation of new neurons in the dentate gyrus exhibit reduced anxiety during the dark cycle. After restraint stress, corticosterone levels in neurogenesis-deficient mice decreased more quickly than controls and were more sensitive to suppression by dexamethasone. Furthermore, glucocorticoid receptor target genes and neuronal activity markers showed reduced expression after stress in neurogenesis-deficient mice. These findings suggest that newborn neurons in the hippocampus are involved in sensing and eliciting an appropriate response to stress.
Antibiotics in neonatal life increase murine susceptibility to experimental psoriasis
Authors: Zanvit Peter , Konkel Joanne E. , Jiao Xue , Kasagi Shimpei , Zhang Dunfang , Wu Ruiqing , Chia Cheryl , Ajami Nadim J. , Smith Daniel P. , Petrosino Joseph F. , Abbatiello Brittany , Nakatsukasa Hiroko , Chen Qianming , Belkaid Yasmine , Chen Zi-Jiang , Chen WanJun
Published: September 2015

Psoriasis is an inflammatory skin disease affecting ∼2% of the world’s population, but the aetiology remains incompletely understood. Recently, microbiota have been shown to differentially regulate the development of autoimmune diseases, but their influence on psoriasis is incompletely understood. We show here that adult mice treated with antibiotics that target Gram-negative and Gram-positive bacteria develop ameliorated psoriasiform dermatitis induced by imiquimod, with decreased pro-inflammatory IL-17- and IL-22-producing T cells. Surprisingly, mice treated neonatally with these antibiotics develop exacerbated psoriasis induced by imiquimod or recombinant IL-23 injection when challenged as adults, with increased IL-22-producing γδ+ T cells. 16S rRNA gene compositional analysis reveals that neonatal antibiotic-treatment dysregulates gut and skin microbiota in adults, which is associated with increased susceptibility to experimental psoriasis. This link between neonatal antibiotic-mediated imbalance in microbiota and development of experimental psoriasis provides precedence for further investigation of its specific aetiology as it relates to human psoriasis.
Lower glycolysis carries a higher flux than any biochemically possible alternative
Authors: Court Steven J. , Waclaw Bartlomiej , Allen Rosalind J.
Published: September 2015

The universality of many pathways of core metabolism suggests a strong role for evolutionary selection, but it remains unclear whether existing pathways have been selected from a large or small set of biochemical possibilities. To address this question, we constructin silicoall possible biochemically feasible alternatives to the trunk pathway of glycolysis and gluconeogenesis, one of the most highly conserved pathways in metabolism. We show that, even though a large number of alternative pathways exist, the alternatives carry lower flux than the real pathway under typical physiological conditions. We also find that if physiological conditions were different, different pathways could outperform those found in nature. Together, our results demonstrate how thermodynamic and biophysical constraints restrict the biochemical alternatives that are open to evolution, and suggest that the existing trunk pathway of glycolysis and gluconeogenesis may represent a maximal flux solution.
Raman spectroscopy as probe of nanometre-scale strain variations in graphene
Authors: Neumann C. , Reichardt S. , Venezuela P. , Drögeler M. , Banszerus L. , Schmitz M. , Watanabe K. , Taniguchi T. , Mauri F. , Beschoten B. , Rotkin S. V. , Stampfer C.
Published: September 2015

Confocal Raman spectroscopy has emerged as a major, versatile workhorse for the non-invasive characterization of graphene. Although it is successfully used to determine the number of layers, the quality of edges, and the effects of strain, doping and disorder, the nature of the experimentally observed broadening of the most prominent Raman 2D line has remained unclear. Here we show that the observed 2D line width contains valuable information on strain variations in graphene on length scales far below the laser spot size, that is, on the nanometre-scale. This finding is highly relevant as it has been shown recently that such nanometre-scaled strain variations limit the carrier mobility in high-quality graphene devices. Consequently, the 2D line width is a good and easily accessible quantity for classifying the crystalline quality, nanometre-scale flatness as well as local electronic properties of graphene, all important for future scientific and industrial applications.
Dose–response curve slope helps predict therapeutic potency and breadth of HIV broadly neutralizing antibodies
Authors: Webb Nicholas E. , Montefiori David C. , Lee Benhur
Published: September 2015

A new generation of HIV broadly neutralizing antibodies (bnAbs) with remarkable potency, breadth and epitope diversity has rejuvenated interest in immunotherapeutic strategies. Potencies defined by in vitro IC50 and IC80 values (50 and 80% inhibitory concentrations) figure prominently into the selection of clinical candidates; however, much higher therapeutic levels will be required to reduce multiple logs of virus and impede escape. Here we predict bnAb potency at therapeutic levels by analysing dose–response curve slopes, and show that slope is independent of IC50/IC80 and specifically relates to bnAb epitope class. With few exceptions, CD4-binding site and V3-glycan bnAbs exhibit slopes >1, indicative of higher expected therapeutic effectiveness, whereas V2-glycan, gp41 membrane-proximal external region (MPER) and gp120–gp41 bnAbs exhibit less favourable slopes <1. Our results indicate that slope is one major predictor of both potency and breadth for bnAbs at clinically relevant concentrations, and may better coordinate the relationship between bnAb epitope structure and therapeutic expectations.
Exciton dynamics of C60-based single-photon emitters explored by Hanbury Brown–Twiss scanning tunnelling microscopy
Authors: Merino P. , Große C. , Rosławska A. , Kuhnke K. , Kern K.
Published: September 2015

Exciton creation and annihilation by charges are crucial processes for technologies relying on charge-exciton-photon conversion. Improvement of organic light sources or dye-sensitized solar cells requires methods to address exciton dynamics at the molecular scale. Near-field techniques have been instrumental for this purpose; however, characterizing exciton recombination with molecular resolution remained a challenge. Here, we study exciton dynamics by using scanning tunnelling microscopy to inject current with sub-molecular precision and Hanbury Brown–Twiss interferometry to measure photon correlations in the far-field electroluminescence. Controlled injection allows us to generate excitons in solid C60 and let them interact with charges during their lifetime. We demonstrate electrically driven single-photon emission from localized structural defects and determine exciton lifetimes in the picosecond range. Monitoring lifetime shortening and luminescence saturation for increasing carrier injection rates provides access to charge-exciton annihilation dynamics. Our approach introduces a unique way to study single quasi-particle dynamics on the ultimate molecular scale.
Causal mechanisms and balancing selection inferred from genetic associations with polycystic ovary syndrome
Authors: Day Felix R. , Hinds David A. , Tung Joyce Y. , Stolk Lisette , Styrkarsdottir Unnur , Saxena Richa , Bjonnes Andrew , Broer Linda , Dunger David B. , Halldorsson Bjarni V. , Lawlor Debbie A. , Laval Guillaume , Mathieson Iain , McCardle Wendy L. , Louwers Yvonne , Meun Cindy , Ring Susan , Scott Robert A. , Sulem Patrick , Uitterlinden André G. , Wareham Nicholas J. , Thorsteinsdottir Unnur , Welt Corrine , Stefansson Kari , Laven Joop S. E. , Ong Ken K. , Perry John R. B.
Published: September 2015

Polycystic ovary syndrome (PCOS) is the most common reproductive disorder in women, yet there is little consensus regarding its aetiology. Here we perform a genome-wide association study of PCOS in up to 5,184 self-reported cases of White European ancestry and 82,759 controls, with follow-up in a further ∼2,000 clinically validated cases and ∼100,000 controls. We identify six signals for PCOS at genome-wide statistical significance (P<5 × 10−8), in/near genes ERBB4/HER4, YAP1, THADA, FSHB, RAD50 and KRR1. Variants in/near three of the four epidermal growth factor receptor genes (ERBB2/HER2, ERBB3/HER3 and ERBB4/HER4) are associated with PCOS at or near genome-wide significance. Mendelian randomization analyses indicate causal roles in PCOS aetiology for higher BMI (P=2.5 × 10−9), higher insulin resistance (P=6 × 10−4) and lower serum sex hormone binding globulin concentrations (P=5 × 10−4). Furthermore, genetic susceptibility to later menopause is associated with higher PCOS risk (P=1.6 × 10−8) and PCOS-susceptibility alleles are associated with higher serum anti-Müllerian hormone concentrations in girls (P=8.9 × 10−5). This large-scale study implicates an aetiological role of the epidermal growth factor receptors, infers causal mechanisms relevant to clinical management and prevention, and suggests balancing selection mechanisms involved in PCOS risk.
Genomic analyses reveal recurrent mutations in epigenetic modifiers and the JAK–STAT pathway in Sézary syndrome
Authors: Kiel Mark J. , Sahasrabuddhe Anagh A. , Rolland Delphine C. M. , Velusamy Thirunavukkarasu , Chung Fuzon , Schaller Matthew , Bailey Nathanael G. , Betz Bryan L. , Miranda Roberto N. , Porcu Pierluigi , Byrd John C. , Medeiros L. Jeffrey , Kunkel Steven L. , Bahler David W. , Lim Megan S. , Elenitoba-Johnson Kojo S. J.
Published: September 2015

Sézary syndrome (SS) is an aggressive leukaemia of mature T cells with poor prognosis and limited options for targeted therapies. The comprehensive genetic alterations underlying the pathogenesis of SS are unknown. Here we integrate whole-genome sequencing (n=6), whole-exome sequencing (n=66) and array comparative genomic hybridization-based copy-number analysis (n=80) of primary SS samples. We identify previously unknown recurrent loss-of-function aberrations targeting members of the chromatin remodelling/histone modification and trithorax families, including ARID1A in which functional loss from nonsense and frameshift mutations and/or targeted deletions is observed in 40.3% of SS genomes. We also identify recurrent gain-of-function mutations targeting PLCG1 (9%) and JAK1, JAK3, STAT3 and STAT5B (JAK/STAT total ∼11%). Functional studies reveal sensitivity of JAK1-mutated primary SS cells to JAK inhibitor treatment. These results highlight the complex genomic landscape of SS and a role for inhibition of JAK/STAT pathways for the treatment of SS.
A database to enable discovery and design of piezoelectric materials
Authors: de Jong Maarten , Chen Wei , Geerlings Henry , Asta Mark , Persson Kristin Aslaug
Published: September 2015

Piezoelectric materials are used in numerous applications requiring a coupling between electrical fields and mechanical strain. Despite the technological importance of this class of materials, for only a small fraction of all inorganic compounds which display compatible crystallographic symmetry, has piezoelectricity been characterized experimentally or computationally. In this work we employ first-principles calculations based on density functional perturbation theory to compute the piezoelectric tensors for nearly a thousand compounds, thereby increasing the available data for this property by more than an order of magnitude. The results are compared to select experimental data to establish the accuracy of the calculated properties. The details of the calculations are also presented, along with a description of the format of the database developed to make these computational results publicly available. In addition, the ways in which the database can be accessed and applied in materials development efforts are described.
Downregulating p22phox ameliorates inflammatory response in Angiotensin II-induced oxidative stress by regulating MAPK and NF-κB pathways in ARPE-19 cells
Authors: Qiu Yiguo , Tao Lifei , Lei Chunyan , Wang Jiaming , Yang Peizeng , Li Qiuhong , Lei Bo
Published: September 2015

Oxidative stress and inflammation are two interrelated biological events implicated in the pathogenesis of many diseases. Reactive oxygen species (ROS) produced under oxidative stress play a key role in pathological conditions. Inhibition of p22phox, an indispensable component of the NADPH oxidase (NOX) complex comprising the main source of ROS, plays a protective role in many ocular conditions by inhibiting the activation of NOXs and the generation of ROS. However, little is understood regarding the role of p22phox in oxidative stress-related inflammation in the eye. We used a p22phox small interfering RNA (siRNA) to transfect the retinal pigment epithelium (RPE)-derived cell line ARPE-19 and human primary RPE (hRPE) cells, then stimulated with Ang II. We observed a potent anti-inflammatory effect and studied the underlying mechanism. Downregulating p22phox resulted in decreased ROS generation, a reduction of NOXs (NOX1, 2, 4) and a decrease in inflammatory cytokine. In addition, p22phox downregulation reduced the activation of the MAPK and NF-κB signaling pathways. We conclude that inhibition of p22phox has an anti-inflammatory effect in Ang II-induced oxidative stress. Suppressing the MAPK and NF-κB pathways is involved in this protective effect. These results suggest that p22phox may provide a promising therapeutic target for oxidative stress-induced ocular inflammation
Tuning all-Optical Analog to Electromagnetically Induced Transparency in nanobeam cavities using nanoelectromechanical system
Authors: Shi Peng , Zhou Guangya , deng Jie , Tian Feng , Chau Fook Siong
Published: September 2015

We report the observations of all-optical electromagnetically induced transparency in nanostructures using waveguide side-coupled with photonic crystal nanobeam cavities, which has measured linewidths much narrower than individual resonances. The quality factor of transparency resonance can be 30 times larger than those of measured individual resonances. When the gap between cavity and waveguide is reduced to 10 nm, the bandwidth of destructive interference region can reach 10 nm while the width of transparency resonance is 0.3 nm. Subsequently, a comb-drive actuator is introduced to tune the line shape of the transparency resonance. The width of the peak is reduced to 15 pm and the resulting quality factor exceeds 105.
Differential Plasma-cell evolution is linked with Dermatophagoides pteronyssinus immunotherapy response
Authors: Fernández Tahia D. , Gómez Enrique , Doña Inmaculada , Campo Paloma , Rondon Carmen , Gonzalez Miguel , Gomez Francisca , Palomares Francisca , Salas Maria , Blanca Miguel , Mayorga Cristobalina , Torres Maria J.
Published: September 2015

Allergic rhinitis is highly prevalent worldwide. Immunotherapy has been shown to control its symptoms, however, up to 30% of patients may not respond. Previous studies of the immunological mechanisms involved in allergen-immunotherapy (AIT) have focused on the humoral and T-cell response and several studies have evaluated some B-cell subpopulations during AIT and their role in immunological tolerance. However, although B and plasma-cell subpopulations are two of the most important cellular subtypes involved in allergic reactions, their relation with AIT efficacy remains unelucidated. The objective was to analyze the effects of immunotherapy on different B and plasma-cell subpopulations and whether these changes correlate with the clinical response to the treatment. Although no changes are found in B-cell subpopulations, responder patients show increased levels of memory B-cells even before the beginning of treatment. Changes in plasma-cell subpopulations are found, mainly in circulating inflammatory plasma-cells that could affect the response to the allergen. Moreover, an early increase of specific-IgG4 and IgG4 secreting-cells was found. All these suggest that the determination of the memory B-cells before the initiation of the treatment and the quantification of IgG4 and IgG4-secreting-cells in the first months of immunotherapy, could serve as markers for the clinical response to treatment.
Direct Observation of Long Electron-Hole Diffusion Distance in CH3NH3PbI3 Perovskite Thin Film
Authors: Li Yu , Yan Weibo , Li Yunlong , Wang Shufeng , Wang Wei , Bian Zuqiang , Xiao Lixin , Gong Qihuang
Published: September 2015

In high performance perovskite based solar cells, CH3NH3PbI3 is the key material. We carried out a study on charge diffusion in spin-coated CH3NH3PbI3 perovskite thin film by transient fluorescent spectroscopy. A thickness-dependent fluorescent lifetime was found. By coating the film with an electron or hole transfer layer, [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) or 2,2′,7,7′-tetrakis(N,N-di-p-methoxyphenylamine)-9,9′-spirobifluorene (Spiro-OMeTAD) respectively, we observed the charge transfer directly through the fluorescence quenching. One-dimensional diffusion model was applied to obtain long charge diffusion distances in thick films, which is ~1.7 μm for electrons and up to ~6.3 μm for holes. Short diffusion distance of few hundreds of nanometer was also observed in thin film. This thickness dependent charge diffusion explained the formerly reported short charge diffusion distance (~100 nm) in films and resolved its confliction to thick working layer (300–500 nm) in real devices. This study presents direct support to the high performance perovskite solar cells and will benefit the devices’ design.
Oxidative Etching of Hexagonal Boron Nitride Toward Nanosheets with Defined Edges and Holes
Authors: Liao Yunlong , Tu Kaixiong , Han Xiaogang , Hu Liangbing , Connell John W. , Chen Zhongfang , Lin Yi
Published: September 2015

Lateral surface etching of two-dimensional (2D) nanosheets results in holey 2D nanosheets that have abundant edge atoms. Recent reports on holey graphene showed that holey 2D nanosheets can outperform their intact counterparts in many potential applications such as energy storage, catalysis, sensing, transistors and molecular transport/separation. From both fundamental and application perspectives, it is desirable to obtain holey 2D nanosheets with defined hole morphology and hole edge structures. This remains a great challenge for graphene and is little explored for other 2D nanomaterials. Here, a facile, controllable and scalable method is reported to carve geometrically defined pit/hole shapes and edges on hexagonal boron nitride (h-BN) basal plane surfaces via oxidative etching in air using silver nanoparticles as catalysts. The etched h-BN was further purified and exfoliated into nanosheets that inherited the hole/edge structural motifs and, under certain conditions, possess altered optical bandgap properties likely induced by the enriched zigzag edge atoms. This method opens up an exciting approach to further explore the physical and chemical properties of hole- and edge-enriched boron nitride and other 2D nanosheets, paving the way toward applications that can take advantage of their unique structures and performance characteristics.
Preimplantation death of xenomitochondrial mouse embryo harbouring bovine mitochondria
Authors: Kawahara Manabu , Koyama Shiori , Iimura Satomi , Yamazaki Wataru , Tanaka Aiko , Kohri Nanami , Sasaki Keisuke , Takahashi Masashi
Published: September 2015

Mitochondria, cellular organelles playing essential roles in eukaryotic cell metabolism, are thought to have evolved from bacteria. The organization of mtDNA is remarkably uniform across species, reflecting its vital and conserved role in oxidative phosphorylation (OXPHOS). Our objectives were to evaluate the compatibility of xenogeneic mitochondria in the development of preimplantation embryos in mammals. Mouse embryos harbouring bovine mitochondria (mtB-M embryos) were prepared by the cell-fusion technique employing the haemagglutinating virus of Japan (HVJ). The mtB-M embryos showed developmental delay at embryonic days (E) 3.5 after insemination. Furthermore, none of the mtB-M embryos could implant into the maternal uterus after embryo transfer, whereas control mouse embryos into which mitochondria from another mouse had been transferred developed as well as did non-manipulated embryos. When we performed quantitative PCR (qPCR) of mouse and bovine ND5, we found that the mtB-M embryos contained 8.3% of bovine mitochondria at the blastocyst stage. Thus, contamination with mitochondria from another species induces embryonic lethality prior to implantation into the maternal uterus. The heteroplasmic state of these xenogeneic mitochondria could have detrimental effects on preimplantation development, leading to preservation of species-specific mitochondrial integrity in mammals.
Synergy of multi-scale toughening and protective mechanisms at hierarchical branch-stem interfaces
Authors: Müller Ulrich , Gindl-Altmutter Wolfgang , Konnerth Johannes , Maier Günther A. , Keckes Jozef
Published: September 2015

Biological materials possess a variety of artful interfaces whose size and properties are adapted to their hierarchical levels and functional requirements. Bone, nacre and wood exhibit an impressive fracture resistance based mainly on small crystallite size, interface organic adhesives and hierarchical microstructure. Currently, little is known about mechanical concepts in macroscopic biological interfaces like the branch-stem junction with estimated 1014 instances on earth and sizes up to few meters. Here we demonstrate that the crack growth in the upper region of the branch-stem interface of conifer trees proceeds along a narrow predefined region of transversally loaded tracheids, denoted as sacrificial tissue, which fail upon critical bending moments on the branch. The specific arrangement of the tracheids allows disconnecting the overloaded branch from the stem in a controlled way by maintaining the stem integrity. The interface microstructure based on the sharply adjusted cell orientation and cell helical angle secures a zig-zag crack propagation path, mechanical interlock closing after the bending moment is removed, crack gap bridging and self-repairing by resin deposition. The multi-scale synergetic concepts allows for a controllable crack growth between stiff stem and flexible branch, as well as mechanical tree integrity, intact physiological functions and recovery after the cracking.
A new nanocomposite forward osmosis membrane custom-designed for treating shale gas wastewater
Authors: Qin Detao , Liu Zhaoyang , Delai Sun Darren , Song Xiaoxiao , Bai Hongwei
Published: September 2015

Managing the wastewater discharged from oil and shale gas fields is a big challenge, because this kind of wastewater is normally polluted by high contents of both oils and salts. Conventional pressure-driven membranes experience little success for treating this wastewater because of either severe membrane fouling or incapability of desalination. In this study, we designed a new nanocomposite forward osmosis (FO) membrane for accomplishing simultaneous oil/water separation and desalination. This nanocomposite FO membrane is composed of an oil-repelling and salt-rejecting hydrogel selective layer on top of a graphene oxide (GO) nanosheets infused polymeric support layer. The hydrogel selective layer demonstrates strong underwater oleophobicity that leads to superior anti-fouling capability under various oil/water emulsions and the infused GO in support layer can significantly mitigate internal concentration polarization (ICP) through reducing FO membrane structural parameter by as much as 20%. Compared with commercial FO membrane, this new FO membrane demonstrates more than three times higher water flux, higher removals for oil and salts (>99.9% for oil and >99.7% for multivalent ions) and significantly lower fouling tendency when investigated with simulated shale gas wastewater. These combined merits will endorse this new FO membrane with wide applications in treating highly saline and oily wastewaters.
Identification of an iridium(III) complex with anti-bacterial and anti-cancer activity
Authors: Lu Lihua , Liu Li-Juan , Chao Wei-chieh , Zhong Hai-Jing , Wang Modi , Chen Xiu-Ping , Lu Jin-Jian , Li Ruei-nian , Ma Dik-Lung , Leung Chung-Hang
Published: September 2015

Group 9 transition metal complexes have been widely explored as therapeutic agents due to their unique geometry, their propensity to undergo ligand exchanges with biomolecules and their diverse steric and electronic properties. These metal complexes can offer distinct modes of action in living organisms compared to carbon-based molecules. In this study, we investigated the antimicrobial and anti-proliferative abilities of a series of cyclometallated iridium(III) complexes. The iridium(III) complex 1 inhibited the growth of S. aureus with MIC and MBC values of 3.60 and 7.19 μM, respectively, indicating its potent bactericidal activity. Moreover, complex 1 also exhibited cytotoxicity against a number of cancer cell lines, with particular potency against ovarian, cervical and melanoma cells. This cyclometallated iridium(III) complex is the first example of a substitutionally-inert, Group 9 organometallic compound utilized as a direct and selective inhibitor of S. aureus.
Inhibition of the Rho/Rho kinase pathway prevents lipopolysaccharide-induced hyperalgesia and the release of TNF-α and IL-1β in the mouse spinal cord
Authors: Wang Cunjin , Song Siyuan , Zhang Yang , Ge Yali , Fang Xiangzhi , Huang Tianfeng , Du Jin , Gao Ju
Published: September 2015

Administration of lipopolysaccharide (LPS) by various routes produces profound inflammatory pain hypersensitivity. However, the molecular events that induce this response remain largely uncharacterized. In the present study, we sought to elucidate the role of the Rho/Rho kinase (ROCK) pathway in the release of tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β) following injection of LPS into the mouse paw, which is associated with nociceptive behavior. The spinal cord of LPS-treated mice showed increased active GTP-bound RhoA and upregulation of ROCK2 and c-fos compared to the normal saline group. Furthermore, the inflammation-related cytokines TNF-α and IL-1β were markedly increased in the spinal dorsal horn after intraplantar injection of LPS. However, the latter effects were prevented by prophylactic intrathecal administration of the Rho inhibitor (C3 exoenzyme) or the ROCK inhibitor (Y27632). Collectively, our results suggest that the Rho/ROCK signaling pathway plays a critical role in LPS-induced inflammatory pain and that this pathway is coincident with the release of the pro-nociceptive cytokines TNF-α and IL-1β, which produces hyperalgesia.
Local bacteria affect the efficacy of chemotherapeutic drugs
Authors: Lehouritis Panos , Cummins Joanne , Stanton Michael , Murphy Carola T. , McCarthy Florence O. , Reid Gregor , Urbaniak Camilla , Byrne William L. , Tangney Mark
Published: September 2015

In this study, the potential effects of bacteria on the efficacy of frequently used chemotherapies was examined. Bacteria and cancer cell lines were examined in vitro and in vivo for changes in the efficacy of cancer cell killing mediated by chemotherapeutic agents. Of 30 drugs examined in vitro, the efficacy of 10 was found to be significantly inhibited by certain bacteria, while the same bacteria improved the efficacy of six others. HPLC and mass spectrometry analyses of sample drugs (gemcitabine, fludarabine, cladribine, CB1954) demonstrated modification of drug chemical structure. The chemoresistance or increased cytotoxicity observed in vitro with sample drugs (gemcitabine and CB1954) was replicated in in vivo murine subcutaneous tumour models. These findings suggest that bacterial presence in the body due to systemic or local infection may influence tumour responses or off-target toxicity during chemotherapy.
The shadow of the future promotes cooperation in a repeated prisoner’s dilemma for children
Authors: Blake Peter R. , Rand David G. , Tingley Dustin , Warneken Felix
Published: September 2015

Cooperation among genetically unrelated individuals can be supported by direct reciprocity. Theoretical models and experiments with adults show that the possibility of future interactions with the same partner can promote cooperation via conditionally cooperative strategies such as tit-for-tat (TFT). Here, we introduce a novel implementation of the repeated Prisoner’s Dilemma (PD) designed for children to examine whether repeated interactions can successfully promote cooperation in 10 and 11 year olds. We find that children cooperate substantially more in repeated PDs than in one-shot PDs. We also find that girls cooperate more than boys and that children with more conduct problems cooperate less. Finally, we find that children use conditional cooperation strategies but that these strategies vary by gender and conduct problem rating. Specifically, girls and children with few conduct problems appear to follow an altruistic version of win-stay, lose-shift (WSLS), attempting to re-establish cooperation after they had defected. Boys and children with more conduct problems appear to follow a Grim strategy, defecting for the duration after the partner defects. Thus we provide evidence that children utilize the power of direct reciprocity to promote cooperation in strategic interactions and that, by late elementary school, distinct strategies of conditional cooperation have emerged.
Novel non-local effects in three-terminal hybrid devices with quantum dot
Authors: Michałek G. , Domański T. , Bułka B.R. , Wysokiński K.I.
Published: September 2015

We predict non-local effect in the three-terminal hybrid device consisting of the quantum dot (QD) tunnel coupled to two normal and one superconducting reservoirs. It manifests itself as the negative non-local resistance and results from the competition between the ballistic electron transfer (ET) and the crossed Andreev scattering (CAR). The effect is robust both in the linear and non-linear regimes. In the latter case the screening of charges and the long-range interactions play significant role. We show that sign change of the non-local conductance depends on the subgap Shiba/Andreev states and it takes place even in absence of the Coulomb interactions. The effect is large and can be experimentally verified using the four probe setup. Since the induced non-local voltage changes sign and magnitude upon varying the gate potential and/or coupling of the quantum dot to the superconducting lead, such measurement could hence provide a controlled and precise method to determine the positions of the Shiba/Andreev states. Our predictions ought to be contrasted with non-local effects observed hitherto in the three-terminal planar junctions where the residual negative non-local conductance has been observed at large voltages, related to the Thouless energy of quasiparticles tunneling through the superconducting slab.
Response of plant nutrient stoichiometry to fertilization varied with plant tissues in a tropical forest
Authors: Mo Qifeng , Zou Bi , Li Yingwen , Chen Yao , Zhang Weixin , Mao Rong , Ding Yongzhen , Wang Jun , Lu Xiankai , Li Xiaobo , Tang Jianwu , Li Zhian , Wang Faming
Published: September 2015

Plant N:P ratios are widely used as indices of nutrient limitation in terrestrial ecosystems, but the response of these metrics in different plant tissues to altered N and P availability and their interactions remains largely unclear. We evaluated changes in N and P concentrations, N:P ratios of new leaves (<1 yr), older leaves (>1 yr), stems and mixed fine roots of seven species after 3-years of an N and P addition experiment in a tropical forest. Nitrogen addition only increased fine root N concentrations. P addition increased P concentrations among all tissues. The N × P interaction reduced leaf and stem P concentrations, suggesting a negative effect of N addition on P concentrations under P addition. The reliability of using nutrient ratios as indices of soil nutrient availability varied with tissues: the stoichiometric metrics of stems and older leaves were more responsive indicators of changed soil nutrient availability than those of new leaves and fine roots. However, leaf N:P ratios can be a useful indicator of inter-specific variation in plant response to nutrients availability. This study suggests that older leaf is a better choice than other tissues in the assessment of soil nutrient status and predicting plant response to altered nutrients using nutrients ratios.
The role of shear in crystallization kinetics: From suppression to enhancement
Authors: Richard David , Speck Thomas
Published: September 2015

In many technical applications crystallization proceeds in the presence of stresses and flows, hence the importance to understand the crystallization mechanism in simple situations. We employ molecular dynamics simulations to study the crystallization kinetics of a nearly hard sphere liquid that is weakly sheared. We demonstrate that shear flow both enhances and suppresses the crystallization kinetics of hard spheres. The effect of shear depends on the quiescent mechanism: suppression in the activated regime and enhancement in the diffusion-limited regime for small strain rates. At higher strain rates crystallization again becomes an activated process even at densities close to the glass transition.
Development of ‘Redox Arrays’ for identifying novel glutathionylated proteins in the secretome
Authors: Mullen Lisa , Seavill Miles , Hammouz Raneem , Bottazzi Barbara , Chan Philippe , Vaudry David , Ghezzi Pietro
Published: September 2015

Proteomics techniques for analysing the redox status of individual proteins in complex mixtures tend to identify the same proteins due to their high abundance. We describe here an array-based technique to identify proteins undergoing glutathionylation and apply it to the secretome and the proteome of human monocytic cells. The method is based on incorporation of biotinylated glutathione (GSH) into proteins, which can then be identified following binding to a 1000-protein antibody array. We thus identify 38 secreted and 55 intracellular glutathionylated proteins, most of which are novel candidates for glutathionylation. Two of the proteins identified in these experiments, IL-1 sRII and Lyn, were then confirmed to be susceptible to glutathionylation. Comparison of the redox array with conventional proteomic methods confirmed that the redox array is much more sensitive and can be performed using more than 100-fold less protein than is required for methods based on mass spectrometry. The identification of novel targets of glutathionylation, particularly in the secretome where the protein concentration is much lower, shows that redox arrays can overcome some of the limitations of established redox proteomics techniques.
Implementation of an antenatal magnesium sulfate protocol for fetal neuroprotection in preterm infants
Authors: Bouet Pierre-Emmanuel , Brun Stéphanie , Madar Hugo , Baisson Anne-Laure , Courtay Véronique , Gascoin-Lachambre Géraldine , Lasocki Sigismond , Sentilhes Loïc
Published: September 2015

The aim of our study was to assess the feasibility of implementing a protocol for the use of magnesium sulfate to prevent cerebral palsy. This retrospective single-center study included all women with fetuses of gestational age <33 weeks of gestation whose birth was planned or expected within 24 hours from September 2011 to December 2012. They were to receive magnesium sulfate, administered intravenously as a 4-g bolus followed by a constant infusion of 1 g per hour. If delivery had not occurred after 12 hours and was no longer considered imminent, the infusion was to be discontinued. The study included 119 women, 81 (68.1%) of whom received magnesium sulfate. Among the latter, 71 (87.5%) gave birth within 24 hours. The reasons treatment was not given were: omission by medical team (19/38, 50%), urgent delivery (18/38, 47.4%) and contraindication to treatment (1/38, 2.6%). The mean gestational age at protocol implementation was 29.6 +/− 2.1 weeks. Maternal monitoring, especially at the onset of infusion, appeared suboptimal. No major maternal side effects were observed. Our study shows that implementing a protocol for prevention of cerebral palsy by magnesium sulfate is feasible in a tertiary obstetric center.
Pathophysiology of major depressive disorder: mechanisms involved in etiology are not associated with clinical progression
Authors: Verduijn J , Milaneschi Y , Schoevers R A , van Hemert A M , Beekman A T F , Penninx B W J H
Published: September 2015

Meta-analyses support the involvement of different pathophysiological mechanisms (inflammation, hypothalamic–pituitary (HPA)-axis, neurotrophic growth and vitamin D) in major depressive disorder (MDD). However, it remains unknown whether dysregulations in these mechanisms are more pronounced when MDD progresses toward multiple episodes and/or chronicity. We hypothesized that four central pathophysiological mechanisms of MDD are not only involved in etiology, but also associated with clinical disease progression. Therefore, we expected to find increasingly more dysregulation across consecutive stages of MDD progression. The sample from the Netherlands Study of Depression and Anxiety (18–65 years) consisted of 230 controls and 2333 participants assigned to a clinical staging model categorizing MDD in eight stages (0, 1A, 1B, 2, 3A, 3B, 3C and 4), from familial risk at MDD (stage 0) to chronic MDD (stage 4). Analyses of covariance examined whether pathophysiological mechanism markers (interleukin (IL)-6, C-reactive protein (CRP), cortisol, brain-derived neurotrophic factor and vitamin D) showed a linear trend across controls, those at risk for MDD (stages 0, 1A and 1B), and those with full-threshold MDD (stages 2, 3A, 3B, 3C and 4). Subsequently, pathophysiological differences across separate stages within those at risk and with full-threshold MDD were examined. A linear increase of inflammatory markers (CRP P=0.026; IL-6 P=0.090), cortisol (P=0.025) and decrease of vitamin D (P<0.001) was found across the entire sample (for example, from controls to those at risk and those with full-threshold MDD). Significant trends of dysregulations across stages were present in analyses focusing on at-risk individuals (IL-6 P=0.050; cortisol P=0.008; vitamin D P<0.001); however, no linear trends were found in dysregulations for any of the mechanisms across more progressive stages of full-threshold MDD. Our results support that the examined pathophysiological mechanisms are involved in MDD’s etiology. These same mechanisms, however, are less important in clinical progression from first to later MDD episodes and toward chronicity.
Effects of depressive symptoms and peripheral DAT methylation on neural reactivity to alcohol cues in alcoholism
Authors: Wiers C E , Shumay E , Volkow N D , Frieling H , Kotsiari A , Lindenmeyer J , Walter H , Bermpohl F
Published: September 2015

In alcohol-dependent (AD) patients, alcohol cues induce strong activations in brain areas associated with alcohol craving and relapse, such as the nucleus accumbens (NAc) and amygdala. However, little is known about the influence of depressive symptoms, which are common in AD patients, on the brain’s reactivity to alcohol cues. The methylation state of the dopamine transporter gene (DAT) has been associated with alcohol dependence, craving and depression, but its influence on neural alcohol cue reactivity has not been tested. Here, we compared brain reactivity to alcohol cues in 38 AD patients and 17 healthy controls (HCs) using functional magnetic resonance imaging and assessed the influence of depressive symptoms and peripheral DAT methylation in these responses. We show that alcoholics with low Beck’s Depression Inventory scores (n=29) had higher cue-induced reactivity in NAc and amygdala than those with mild/moderate depression scores (n=9), though subjective perception of craving was higher in those with mild/moderate depression scores. We corroborated a higher DAT methylation in AD patients than HCs, and showed higher DAT methylation in AD patients with mild/moderate than low depression scores. Within the AD cohort, higher methylation predicted craving and, at trend level (P=0.095), relapse 1 year after abstinence. Finally, we show that amygdala cue reactivity correlated with craving and DAT methylation only in AD patients with low depression scores. These findings suggest that depressive symptoms and DAT methylation are associated with alcohol craving and associated brain processes in alcohol dependence, which may have important consequences for treatment. Moreover, peripheral DAT methylation may be a clinically relevant biomarker in AD patients.
Aqueous Equilibrium Constants of Formation for Bromamines, Chloramines, and Bromochloramines: Quantum Chemistry Estimates.
Authors: Trogolo Daniela , von Gunten Urs , Samuel Arey J.
Published: September 2015

Chloramines, bromamines, and bromochloramines are halogen-containing species that can be formed from the reaction between ammonia and hypohalous acids in water. These species are halogen oxidants implicated in the formation of potentially dangerous disinfection byproducts during water disinfection treatments. Despite these concerns, halamine speciation is not fully understood and halamine reactivities towards naturally-occurring compounds is difficult to investigate by experimental means only. Thus, we assessed the aqueous equilibrium constants for the formation of halamines by exploiting quantum chemical modeling. A benchmark-level composite method, termed TA14, was employed to obtain accurate estimates of thermodynamic equilibria of halamine formation in aqueous systems.
Nitrosamines, Not Only Disinfection By-Products (DBPs)
Authors: Pallez C. , Dauchy X. , Munoz J. F. , Rosin C.
Published: September 2015

The main objectives of this study were to develop a sensitive method to analyze nine nitrosamines in drinking water and to evaluate their occurrence in raw water and treated water samples from public water systems. About 600 samples (raw water and treated water) equally distributed across the 100 French departments, were collected from October 2011 to May 2012. This sampling, represents about 20% of the national water supply flow. In raw water samples, no molecule was detected for 95% of the samples. Only N-nitrosodimethylamine (NDMA) and N-nitrosomorpholine (NMOR) were identified. In treated water, among the nine nitrosamines analysed, only NDMA, NMOR and N-nitrosodiethylamine (NDEA) were quantified. This campaign also revealed concentrations higher than 1000 ng/l for NMOR in raw and treated water of a municipality. Further investigations highlighted concentrations of NMOR up to 3000 ng/L in close water supplies and up to 17500 ng/L in the nearby river downstream to an industrial site. This pharmaceutical site uses annually several thousand tons of morpholine in its process of manufacturing, and produces unintentionally NMOR in its wastewater treatment plant, due to acidic conditions.
The Removal Effect of Volatile Halocarbon Compounds in Drinking Water Using Household Water Purifier
Authors: Goto Masayuki , Takanashi Reiko , Kaneko Takehiko , Manaka Yumi , Kishida Koji , Nakajima Hadjime
Published: September 2015

We examined the effectiveness of filtration using water purifying cartridges to remove volatile halocarbon compounds (VHCs) in drinking water. The purpose of this study was to evaluate the usefulness of commercial filters in comparison with the effect of boiling in removing VHCs. The standard pure waters were adulterated with eight VHCs of concentration such as CHCl3 0.1–100 µg/L, CHCl2Br 0.025–25 µg/L, CHClBr2 0.04–40 µg/L, CHBr3 0.2–200 µg/L, C2HCl3 0.15–150 µg/L, C2Cl4 0.04–40 µg/L, C2H3Cl3 0.04–40 µg/L and CCl4 0.01–10 µg/L. In almost all boiled samples except CHBr3, the concentration levels of VHCs were decreased to undetectable levels. However, in the highest level of CHBr3, the level of 200 μg/L was reduced to 1 instead of undetectable level after 10-minutes boiling. The total 200L of each adulterated sample was filtered using a commercial cartridge filter and the VHCs levels analyzed. The highest concentration of CHCl3 was decreased to 43% of the original level. However, in the series of CHCl2Br, CHClBr2, CHBr3, C2HCl3, C2Cl4, and C2H3Cl3, only 0.5% of these VHCs were detected after filtering, and an undetectable amount of CCl4 was also revealed. We also evaluated the VHCs contamination level such as CHCl3, CHCl2Br, CHClBr2, CHBr3 and CCl4 in samples of drinkable tap water, which were measured as 6.6, 5.7, 2.5, 1.0 and 0.4 µg/L, respectively. By filtering 1,800 L of contaminated water, the removal capability of VHCs fell. The levels of CHCl3, CHCl2Br, CHClBr2, CHBr3 and CCl4 remained at 95, 67, 60, 20 and 0% of the original amount, respectively.
Investigation of the interaction modes between nonpolar organic pollutants with ionizable functional groups and natural organic matter via AuNP-based colorimetric assays
Authors: Niu Hongyun , Wang Saihua , Tan Yixin , Cai Yaqi
Published: September 2015

Natural organic matter (NOM) modified AuNP sensors can “observe” the specific interactions between organic compounds and NOM using colorimetric assays.
Asymmetric bromine–lithium exchange: on the importance of both the diamine ligand and the organolithium reagent
Authors: Praz Jézabel , Graff Julien , Egger Léo , Guénée Laure , Wagschal Simon , Kündig E. Peter , Alexakis Alexandre
Published: September 2015

The asymmetric bromine–lithium exchange on a series of prochiral biphenyls was investigated.
Aminothiazole-derived N,S,Fe-doped graphene nanosheets as high performance electrocatalysts for oxygen reduction
Authors: Chen Chi , Yang Xiao-Dong , Zhou Zhi-You , Lai Yu-Jiao , Rauf Muhammad , Wang Ying , Pan Jing , Zhuang Lin , Wang Qiang , Wang Yu-Cheng , Tian Na , Zhang Xin-Sheng , Sun Shi-Gang
Published: September 2015

N,S,Fe-doped graphene nanosheets with high ORR electrocatalytic activity were directly synthesized from aminothiazole through Fe catalysis under heat-treatment.
Intracellular Zn2+ detection with quantum dot-based FLIM nanosensors
Authors: Ripoll Consuelo , Martin Miguel , Roldan Mar , Talavera Eva M. , Orte Angel , Ruedas-Rama Maria J.
Published: September 2015

Fluorescence Lifetime Imaging Microscopy (FLIM) has been employed for the detection of intracellular Zn2+ levels, implicated in various signalling pathways, using a family of quantum dot (QD) nanosensors.
Hierarchically structured catalysts for cascade and selective steam reforming/hydrodeoxygenation reactions
Authors: Sun Junming , Karim Ayman M. , Li Xiaohong Shari , Rainbolt James , Kovarik Libor , Shin Yongsoon , Wang Yong
Published: September 2015

A hierarchically structured catalyst with combined steam reforming and hydrodeoxygenation active sites is reported to efficiently upgrade the pyrolysis vapors of lignocellulosic biomass via size-exclusion.
Nickel-catalysed para-CH activation of pyridine with switchable regioselective hydroheteroarylation of allylarenes
Authors: Lee Wei-Chih , Chen Chien-Hung , Liu Cheng-Yuan , Yu Ming-Shiuan , Lin Yung-Huei , Ong Tiow-Gan
Published: September 2015

para-CH activation of pyridine with allylbenzene is described by Ni/Al cooperative catalysis to achieve branch and linear selectivity.