bluuebunny/crossref_metadata_2025 huggingface dataset:
Toll-like receptor-5 agonist, entolimod, suppresses metastasis and induces immunity by stimulating an NK-dendritic-CD8
+
T-cell axis
Authors: Brackett Craig M. , Kojouharov Bojidar , Veith Jean , Greene Kellee F. , Burdelya Lyudmila G. , Gollnick Sandra O. , Abrams Scott I. , Gudkov Andrei V.
Published: February 2016

Significance

Innate immune modulators can generate a potent antitumor T-cell response and are thus a desirable approach to immunotherapy. However, their use is limited by the risk of induction of acute inflammation. In this regard, bacterial flagellin is unique among other innate immune modulators because of a significantly safer cytokine profile induced upon activation by its target, Toll-like receptor 5 (TLR5). We show here that systemic administration of entolimod, a pharmacologically optimized flagellin derivative, induces a cascade of cell–cell signaling resulting in mobilization to the liver of various components of innate and adaptive immunity, followed by suppression of liver metastases and development of long-term antitumor immune memory. Thus, TLR5 agonists can be considered as an organ-specific immunotherapy for the treatment and prevention of metastases.
Identification of a small molecule inhibitor of 3-phosphoglycerate dehydrogenase to target serine biosynthesis in cancers
Authors: Mullarky Edouard , Lucki Natasha C. , Beheshti Zavareh Reza , Anglin Justin L. , Gomes Ana P. , Nicolay Brandon N. , Wong Jenny C. Y. , Christen Stefan , Takahashi Hidenori , Singh Pradeep K. , Blenis John , Warren J. David , Fendt Sarah-Maria , Asara John M. , DeNicola Gina M. , Lyssiotis Costas A. , Lairson Luke L. , Cantley Lewis C.
Published: February 2016

Significance

Serine supports a number of anabolic processes, including protein, lipid, and nucleic acid synthesis. Cells can either import serine or synthesize it de novo. Recently, overexpression of 3-phosphoglycerate dehydrogenase (
PHGDH
), the gene encoding the first committed step of serine synthesis, via focal amplification and other mechanisms, has been identified in human cancers. Cancer cell lines that overexpress
PHGDH
are uniquely sensitive to PHGDH knockdown whereas lines that express little PHGDH are insensitive, suggesting that PHGDH may be a clinically interesting target. Here, we report the discovery of a specific small molecule inhibitor of PHGDH, which enables preclinical evaluation of PHGDH as a target in cancer and provides a tool to study the biology of de novo serine synthesis.
Redundant function of DNA ligase 1 and 3 in alternative end-joining during immunoglobulin class switch recombination
Authors: Masani Shahnaz , Han Li , Meek Katheryn , Yu Kefei
Published: February 2016

Significance

DNA ligase IV (Lig4) is essential for nonhomologous end-joining (NHEJ), the major pathway for repairing DNA double-strand breaks in mammalian cells. An ill-defined alternative end-joining (A-EJ) pathway can also mediate end-joining in cells deficient in NHEJ, although A-EJ is kinetically slower and less accurate than NHEJ. Here, we report that either Lig1 or Lig3 can mediate alternative end-joining in Lig4 knockout cells. Cells having only one ligase (Lig1 or nuclear Lig3) are capable of DNA replication and DNA repair after exposure to a wide range of genotoxins. These results demonstrate the remarkable (and unexpected) plasticity of DNA ligases in mammalian cells.
Autoimmune vitiligo is associated with gain-of-function by a transcriptional regulator that elevates expression ofHLA-A*02:01in vivo
Authors: Hayashi Masahiro , Jin Ying , Yorgov Daniel , Santorico Stephanie A. , Hagman James , Ferrara Tracey M. , Jones Kenneth L. , Cavalli Giulio , Dinarello Charles A. , Spritz Richard A.
Published: February 2016

Significance

Vitiligo is an autoimmune disease in which spots of white skin and hair result from destruction of melanocytes. Vitiligo is associated withHLA-A*02:01, which presents multiple vitiligo melanocyte autoantigens. We localize vitiligo risk to a SNP haplotype 20 kb downstream of theHLA-Agene, spanning a transcriptional regulatory element. Blood cells from healthy subjects carrying the high-risk haplotype expressed moreHLA-ARNA than subjects carrying only nonhigh-risk haplotypes. Vitiligo risk in the MHC class I region thus derives from combined quantitative and qualitative phenomena: an SNP haplotype in a transcriptional regulator that induces elevated expression ofHLA-ARNA in vivo, and strong linkage disequilibrium with anHLA-Aallele that confers *02:01 specificity. These combine to increase HLA-A2 available to present melanocyte autoantigens.
PP2A-3 interacts with ACR4 and regulates formative cell division in the
Arabidopsis
root
Authors: Yue Kun , Sandal Priyanka , Williams Elisabeth L. , Murphy Evan , Stes Elisabeth , Nikonorova Natalia , Ramakrishna Priya , Czyzewicz Nathan , Montero-Morales Laura , Kumpf Robert , Lin Zhefeng , van de Cotte Brigitte , Iqbal Mudassar , Van Bel Michiel , Van De Slijke Eveline , Meyer Matthew R. , Gadeyne Astrid , Zipfel Cyril , De Jaeger Geert , Van Montagu Marc , Van Damme Daniël , Gevaert Kris , Rao A. Gururaj , Beeckman Tom , De Smet Ive
Published: February 2016

Significance

Plant growth and development are mediated through a wide range of proteins, including receptor kinases and phosphatases. The receptor kinase ARABIDOPSIS CRINKLY 4 (ACR4) is part of a mechanism controlling formative cell divisions in the
Arabidopsis
root. However, the regulation of ACR4 signaling and how it affects cell divisions remains completely unknown. We discovered that ACR4 phosphorylates the PROTEIN PHOSPHATASE 2A-3 (PP2A-3) catalytic subunit of the PP2A phosphatase holoenzyme and that PP2A dephosphorylates ACR4. These data exposed a tightly regulated point in the associated biochemical network regulating formative cell divisions in plant roots.
Disentangling the mechanisms behind climate effects on zooplankton
Authors: Kvile Kristina Ø. , Langangen Øystein , Prokopchuk Irina , Stenseth Nils C. , Stige Leif C.
Published: February 2016

Significance

Underlying mechanisms behind observed associations between zooplankton dynamics and climate are often unclear. We investigate how drift patterns, temperature, mixed layer depth, and wind influence the biomass ofCalanus finmarchicus, a dominant North Atlantic copepod. To address the underlying mechanisms, we include drift modeling results in statistical analyses of survey data, analyze spatial and interannual variability, and investigate effects across trophic levels. Chlorophyll biomass in spring andC. finmarchicusbiomass in summer relate positively to shallow mixed layer depth and high wind speed in spring, suggesting climate effects on zooplankton through food availability. High temperatures increaseC. finmarchicusbiomass in spring but not summer. The results imply how climate change might influence future feeding conditions for predators on zooplankton.
Idh1
mutations contribute to the development of T-cell malignancies in genetically engineered mice
Authors: Hao Zhenyue , Cairns Rob A. , Inoue Satoshi , Li Wanda Y. , Sheng Yi , Lemonnier François , Wakeham Andrew , Snow Bryan E. , Dominguez-Brauer Carmen , Ye Jing , Larsen Dana M. , Straley Kimberly S. , Tobin Erica R. , Narayanaswamy Rohini , Gaulard Philippe , Mak Tak W.
Published: February 2016

Significance

Isocitrate dehydrogenase 1 (
IDH1
) mutations are drivers of hematological malignancy. Although these mutations are most often associated with myeloid disease, they are also found in lymphoid malignancies, including T-cell acute lymphoblastic leukemia (T-ALL). Treatment strategies targeting these mutations are currently being devised, including small-molecule inhibitors of the mutant IDH1 enzyme. A better understanding of the role of these mutations in tumorigenesis and their effects on tumor cells will allow these treatment strategies to be effectively translated to the clinic. Here we show that
Idh1
mutations can contribute to the development of T-cell malignancies, including T-ALL, using a conditional knock-in mouse model. These mouse models provide a platform for further evaluation of treatment strategies for T-cell malignancy.
General 2.5 power law of metallic glasses
Authors: Zeng Qiaoshi , Lin Yu , Liu Yijin , Zeng Zhidan , Shi Crystal Y. , Zhang Bo , Lou Hongbo , Sinogeikin Stanislav V. , Kono Yoshio , Kenney-Benson Curtis , Park Changyong , Yang Wenge , Wang Weihua , Sheng Hongwei , Mao Ho-kwang , Mao Wendy L.
Published: February 2016

Significance

This work establishes a general rule correlating the bulk properties [volume (
V
)] with atomic structure information (principal diffraction peak position
q
1
) for metallic glasses, i.e.,
V
∝(1/
q
1
)
2.5
. It is shown that the 2.5 power law is strictly followed by any metallic glass with its volume tuned by pressure and/or composition. This general 2.5 power law is attributed to the well-constrained structure change/modification that inevitably happens during pressure and/or composition tuning of metallic glasses, which brings insight into the structure of metallic glasses.
The SPOT Effect: People Spontaneously Prefer their Own Theories
Authors: Gregg Aiden P. , Mahadevan Nikhila , Sedikides Constantine
Published: February 2016

People often exhibit confirmation bias: They process information bearing on the truth of their theories in a way that facilitates their continuing to regard those theories as true. Here, we tested whether confirmation bias would emerge even under the most minimal of conditions. Specifically, we tested whether drawing a nominal link between the self and a theory would suffice to bias people towards regarding that theory as true. If, all else equal, people regard the self as good (i.e., engage in self-enhancement), and good theories are true (in accord with their intended function), then people should regard their own theories as true; otherwise put, they should manifest a spontaneous preference for their own theories (i.e., a SPOT effect). In three experiments, participants were introduced to a theory about which of two imaginary alien species preyed upon the other. Participants then considered in turn several items of evidence bearing on the theory and each time evaluated the likelihood that the theory was true versus false. As hypothesized, participants regarded the theory as more likely to be true when it was arbitrarily ascribed to them as opposed to an “Alex” (Experiment 1) or to no one (Experiment 2). We also found that the SPOT effect failed to converge with four different indices of self-enhancement (Experiment 3), suggesting that it may be distinctive in character.
RAG-mediated DNA double-strand breaks activate a cell type–specific checkpoint to inhibit pre–B cell receptor signals
Authors: Bednarski Jeffrey J. , Pandey Ruchi , Schulte Emily , White Lynn S. , Chen Bo-Ruei , Sandoval Gabriel J. , Kohyama Masako , Haldar Malay , Nickless Andrew , Trott Amanda , Cheng Genhong , Murphy Kenneth M. , Bassing Craig H. , Payton Jacqueline E. , Sleckman Barry P.
Published: February 2016

DNA double-strand breaks (DSBs) activate a canonical DNA damage response, including highly conserved cell cycle checkpoint pathways that prevent cells with DSBs from progressing through the cell cycle. In developing B cells, pre–B cell receptor (pre–BCR) signals initiate immunoglobulin light (Igl) chain gene assembly, leading to RAG-mediated DNA DSBs. The pre–BCR also promotes cell cycle entry, which could cause aberrant DSB repair and genome instability in pre–B cells. Here, we show that RAG DSBs inhibit pre–BCR signals through the ATM- and NF-κB2–dependent induction of SPIC, a hematopoietic-specific transcriptional repressor. SPIC inhibits expression of the SYK tyrosine kinase and BLNK adaptor, resulting in suppression of pre–BCR signaling. This regulatory circuit prevents the pre–BCR from inducing additional Igl chain gene rearrangements and driving pre–B cells with RAG DSBs into cycle. We propose that pre–B cells toggle between pre–BCR signals and a RAG DSB-dependent checkpoint to maintain genome stability while iteratively assembling Igl chain genes.
Expanding the antimalarial toolkit: Targeting host–parasite interactions
Authors: Langhorne Jean , Duffy Patrick E.
Published: February 2016

Recent successes in malaria control are threatened by drug-resistant Plasmodium parasites and insecticide-resistant Anopheles mosquitoes, and first generation vaccines offer only partial protection. New research approaches have highlighted host as well as parasite molecules or pathways that could be targeted for interventions. In this study, we discuss host–parasite interactions at the different stages of the Plasmodium life cycle within the mammalian host and the potential for therapeutics that prevent parasite migration, invasion, intracellular growth, or egress from host cells, as well as parasite-induced pathology.
Fast photoresponse of zinc ferrite nanotube arrays fabricated by electrodeposition
Authors: Liu Hao , Sun Qi , Zhang Zili , Zheng Zhiyuan , lü Zhiqing , Zhao Kun
Published: February 2016

Although nano-sized zinc ferrite materials exhibit excellent visible light activity, their photoresponse characteristics as photodetectors have rarely been investigated. In this paper, zinc ferrite nanotube arrays were fabricated using electrodeposition with the aid of zinc oxide nanowire arrays as a template. These nanotube arrays showed tens of milliseconds-response photocurrents under the irradiation of a 532 nm solid-state laser, and the magnitudes of the photocurrents were linearly increased with increasing laser power. These features of ZnFe2O4 nanotube arrays revealed their potential applications in high-frequency or high-speed photodevices.
ALMA resolves extended star formation in high-z AGN host galaxies
Authors: Harrison C. M. , Simpson J. M. , Stanley F. , Alexander D. M. , Daddi E. , Mullaney J. R. , Pannella M. , Rosario D. J. , Smail Ian
Published: February 2016

We present high-resolution (0.3 arcsec) Atacama Large Millimeter Array (ALMA) 870 μm imaging of five z ≈ 1.5–4.5 X-ray detected AGN (with luminosities of L2–8keV > 1042 erg s−1). These data provide a ≳20 times improvement in spatial resolution over single-dish rest-frame far-infrared (FIR) measurements. The sub-millimetre emission is extended on scales of FWHM ≈ 0.2 arcsec–0.5 arcsec, corresponding to physical sizes of 1–3 kpc (median value of 1.8 kpc). These sizes are comparable to the majority of z=1–5 sub-millimetre galaxies (SMGs) with equivalent ALMA measurements. In combination with spectral energy distribution analyses, we attribute this rest-frame FIR emission to dust heated by star formation. The implied star-formation rate surface densities are ≈20–200 M⊙ yr−1 kpc−2, which are consistent with SMGs of comparable FIR luminosities (i.e. LIR ≈ [1–5] × 1012 L⊙). Although limited by a small sample of AGN, which all have high-FIR luminosities, our study suggests that the kpc-scale spatial distribution and surface density of star formation in high-redshift star-forming galaxies is the same irrespective of the presence of X-ray detected AGN.
Spatially resolved radio-to-far-infrared SED of the luminous merger remnant NGC 1614 with ALMA and VLA
Authors: Saito Toshiki , Iono Daisuke , Xu Cong K. , Ueda Junko , Nakanishi Kouichiro , Yun Min S. , Kaneko Hiroyuki , Yamashita Takuji , Lee Minju , Espada Daniel , Motohara Kentaro , Kawabe Ryohei
Published: February 2016

We present the results of Atacama Large Millimeter/Submillimeter Array (ALMA) 108-, 233-, 352-, and 691-GHz continuum observations and Very Large Array (VLA) 4.81- and 8.36-GHz observations of the nearby luminous merger remnant NGC 1614. By analyzing the beam (1${^{\prime\prime}_{.}}$0 × 1${^{\prime\prime}_{.}}$0) and uv (≥45 kλ) matched ALMA and VLA maps, we find that the deconvolved source size of lower-frequency emission (≤108 GHz) is more compact (420 pc × 380 pc) compared to the higher-frequency emission (≥233 GHz) (560 pc × 390 pc), suggesting different physical origins for the continuum emission. Based on a spectral energy distribution (SED) model for a dusty starburst galaxy, it is found that the SED can be explained by three components: (1) non-thermal synchrotron emission (traced in the 4.81- and 8.36-GHz continua), (2) thermal free–free emission (traced in the 108-GHz continuum), and (3) thermal dust emission (traced in the 352- and 691-GHz continua). We also present the spatially resolved (sub-kpc scale) Kennicutt–Schmidt relation of NGC 1614. The result suggests a systematically shorter molecular gas depletion time in NGC 1614 (average τgas of 49–77 Myr and 70–226 Myr at the starburst ring and the outer region, respectively) than that of normal disk galaxies (∼2 Gyr) and a mid-stage merger VV 114 (= 0.1–1 Gyr). This implies that the star formation activities in (ultra-)luminous infrared galaxies are efficiently enhanced as the merger stage proceeds, which is consistent with the results from high-resolution numerical merger simulations.
Suzaku confirms NGC 3660 is an unabsorbed Seyfert 2
Authors: Rivers Elizabeth , Brightman Murray , Bianchi Stefano , Matt Giorgio , Nandra Kirpal , Ueda Yoshihiro
Published: February 2016

An enigmatic group of objects, unabsorbed Seyfert 2s may have intrinsically weak broad line regions, obscuration in the line of sight to the BLR but not to the X-ray corona, or so much obscuration that the X-ray continuum is completely suppressed and the observed spectrum is actually scattered into the line of sight from nearby material. NGC 3660 has been shown to have weak broad optical/near-infrared lines, no obscuration in the soft X-ray band, and no indication of “changing look” behavior. The only previous hard X-ray detection of this source by Beppo-SAX seemed to indicate that the source might harbor a heavily obscured nucleus. However, our analysis of a long-look Suzaku observation of this source shows that this is not the case, and that this source has a typical power-law X-ray continuum with normal reflection and no obscuration. We conclude that NGC 3660 is confirmed to have no unidentified obscuration and that the anomolously high Beppo-SAX measurement must be due to source confusion or similar, being inconsistent with our Suzaku measurements as well as non-detections from Swift-Burst Alert Telescope (BAT) and Rossi X-ray Timing Explorer (RXTE).
Morphological and Functional Assessment of Oesophageal Mucosa Integrity in Children With Cystic Fibrosis
Authors: Brecelj Jernej , Zidar Nina , Jeruc Jera , Orel Rok
Published: February 2016

Objectives:

The aim of the study was to investigate morphological and functional characteristics of oesophageal epithelial barrier in children with cystic fibrosis (CF) with or without gastro‐oesophageal reflux disease (GORD) in comparison to healthy controls.

Methods:

Oesophagogastroduodenoscopy with oesophageal biopsies and combined oesophageal multichannel intraluminal impedance‐pH monitoring was performed in 17 children with CF (CFtot) with (CFgord) or without GORD (CFnorm). Histological combined severity score was calculated and widths of spaces between epithelial cells were measured. Basal impedance value was used to assess functional integrity of epithelial barrier. Results of each investigation were compared with a group of children without oesophageal disease.

Results:

CFtot, but also CFnorm, had more severe pathohistological changes included in the compound severity score than controls (0.75 ± 0.32 and 0.75 ± 0.20 vs 0.27 ± 0.25; P < 0.001 and P = 0.001, respectively). They also had more dilated intercellular spaces (2.6 μm ± 0.6 and 2.7 μm ± 0.5 vs 1.9 μm ± 0.2; P = 0.001 and P < 0.001, respectively). Baseline impedance values between proximal and distal pairs of electrodes were significantly lower in CFtot (2876 Ω ± 484, 2590 Ω ± 1013) and also in CFnorm (2922 Ω ± 363, 2844 Ω ± 457) than in controls (3703 Ω ± 859, 3753 Ω ± 1070) (P = 0.012 and P = 0.002; and P = 0.027 and P = 0.005, respectively). The treatment of CFgord with proton pump inhibitor increased, but did not normalise the baseline impedance values (2860 Ω ± 560 to 3355 Ω ± 750 and 2178 Ω ± 1564 to 3057 Ω ± 594).

Conclusions:

Children with CF had morphological and functional changes of oesophageal mucosal integrity even in the absence of GORD.
Infliximab‐Associated Immunomediated Hepatitis in Children With Inflammatory Bowel Disease
Authors: Mostamand Shikib , Schroeder Shauna , Schenkein Jacqueline , Miloh Tamir
Published: February 2016

Infliximab (IFX) is commonly used to induce and maintain remission in inflammatory bowel disease (IBD). We report the first 2 cases of children with ulcerative colitis who had normal liver transaminases before IFX and were diagnosed with immunomediated hepatitis after IFX induction. Both the cases had negative antibodies for antinuclear, smooth muscle, and liver kidney microsome, with 1 patient having positive autoimmune serology (dsDNA) and overlap primary sclerosing cholangitis. IFX was discontinued and transaminases normalized without steroid administration. Clinicians treating pediatric patients with IBD with IFX should be aware of IFX immunomediated hepatitis. This phenomenon is previously reported in adult patients with IBD. To our knowledge, these are the first cases reported in pediatric patients with IBD.
Multifaceted origins of sex differences in the brain
Authors: McCarthy Margaret M.
Published: February 2016

Studies of sex differences in the brain range from reductionistic cell and molecular analyses in animal models to functional imaging in awake human subjects, with many other levels in between. Interpretations and conclusions about the importance of particular differences often vary with differing levels of analyses and can lead to discord and dissent. In the past two decades, the range of neurobiological, psychological and psychiatric endpoints found to differ between males and females has expanded beyond reproduction into every aspect of the healthy and diseased brain, and thereby demands our attention. A greater understanding of all aspects of neural functioning will only be achieved by incorporating sex as a biological variable. The goal of this review is to highlight the current state of the art of the discipline of sex differences research with an emphasis on the brain and to contextualize the articles appearing in the accompanying special issue.
Genetic dissection of neural circuits underlying sexually dimorphic social behaviours
Authors: Bayless Daniel W. , Shah Nirao M.
Published: February 2016

The unique hormonal, genetic and epigenetic environments of males and females during development and adulthood shape the neural circuitry of the brain. These differences in neural circuitry result in sex-typical displays of social behaviours such as mating and aggression. Like other neural circuits, those underlying sex-typical social behaviours weave through complex brain regions that control a variety of diverse behaviours. For this reason, the functional dissection of neural circuits underlying sex-typical social behaviours has proved to be difficult. However, molecularly discrete neuronal subpopulations can be identified in the heterogeneous brain regions that control sex-typical social behaviours. In addition, the actions of oestrogens and androgens produce sex differences in gene expression within these brain regions, thereby highlighting the neuronal subpopulations most likely to control sexually dimorphic social behaviours. These conditions permit the implementation of innovative genetic approaches that, in mammals, are most highly advanced in the laboratory mouse. Such approaches have greatly advanced our understanding of the functional significance of sexually dimorphic neural circuits in the brain. In this review, we discuss the neural circuitry of sex-typical social behaviours in mice while highlighting the genetic technical innovations that have advanced the field.
The importance of having two X chromosomes
Authors: Arnold Arthur P. , Reue Karen , Eghbali Mansoureh , Vilain Eric , Chen Xuqi , Ghahramani Negar , Itoh Yuichiro , Li Jingyuan , Link Jenny C. , Ngun Tuck , Williams-Burris Shayna M.
Published: February 2016

Historically, it was thought that the number of X chromosomes plays little role in causing sex differences in traits. Recently, selected mouse models have been used increasingly to compare mice with the same type of gonad but with one versus two copies of the X chromosome. Study of these models demonstrates that mice with one X chromosome can be strikingly different from those with two X chromosomes, when the differences are not attributable to confounding group differences in gonadal hormones. The number of X chromosomes affects adiposity and metabolic disease, cardiovascular ischaemia/reperfusion injury and behaviour. The effects of X chromosome number are likely the result of inherent differences in expression of X genes that escape inactivation, and are therefore expressed from both X chromosomes in XX mice, resulting in a higher level of expression when two X chromosomes are present. The effects of X chromosome number contribute to sex differences in disease phenotypes, and may explain some features of X chromosome aneuploidies such as in Turner and Klinefelter syndromes.
Epigenetic mechanisms in sexual differentiation of the brain and behaviour
Authors: Forger Nancy G.
Published: February 2016

Circumstantial evidence alone argues that the establishment and maintenance of sex differences in the brain depend on epigenetic modifications of chromatin structure. More direct evidence has recently been obtained from two types of studies: those manipulating a particular epigenetic mechanism, and those examining the genome-wide distribution of specific epigenetic marks. The manipulation of histone acetylation or DNA methylation disrupts the development of several neural sex differences in rodents. Taken together, however, the evidence suggests there is unlikely to be a simple formula for masculine or feminine development of the brain and behaviour; instead, underlying epigenetic mechanisms may vary by brain region or even by dependent variable within a region. Whole-genome studies related to sex differences in the brain have only very recently been reported, but suggest that males and females may use different combinations of epigenetic modifications to control gene expression, even in cases where gene expression does not differ between the sexes. Finally, recent findings are discussed that are likely to direct future studies on the role of epigenetic mechanisms in sexual differentiation of the brain and behaviour.
An examination of sex differences in the effects of early-life opiate and alcohol exposure
Authors: Terasaki Laurne S. , Gomez Julie , Schwarz Jaclyn M.
Published: February 2016

Early-life exposure to drugs and alcohol is one of the most preventable causes of developmental, behavioural and learning disorders in children. Thus a significant amount of basic, animal and human research has focused on understanding the behavioural consequences and the associated neural effects of exposure to drugs and alcohol during early brain development. Despite this, much of the previous research that has been done on this topic has used predominantly male subjects or rodents. While many of the findings from these male-specific studies may ultimately apply to females, the purpose of this review is to highlight the research that has also examined sex as a factor and found striking differences between the sexes in their response to early-life opiate and alcohol exposure. Finally, we will also provide a framework for scientists interested in examining sex as a factor in future experiments that specifically examine the consequences of early-life drug and alcohol exposure.
Short template switch events explain mutation clusters in the human genome
Authors: Löytynoja Ari , Goldman Nick
Published: February 2016

Resequencing efforts are uncovering the extent of genetic variation in humans and provide data to study the evolutionary processes shaping our genome. One recurring puzzle in both intra- and inter-species studies is the high frequency of complex mutations comprising multiple nearby base substitutions or insertion-deletions. We devised a generalized mutation model of template switching during replication that extends existing models of genome rearrangement, and used this to study the role of template switch events in the origin of such mutation clusters. Applied to the human genome, our model detects thousands of template switch events during the evolution of human and chimp from their common ancestor, and hundreds of events between two independently sequenced human genomes. While many of these are consistent with the template switch mechanism previously proposed for bacteria but not thought significant in higher organisms, our model also identifies new types of mutations that create short inversions, some flanked by paired inverted repeats. The local template switch process can create numerous complex mutation patterns, including hairpin loop structures, and explains multi-nucleotide mutations and compensatory substitutions without invoking positive selection, complicated and speculative mechanisms, or implausible coincidence. Clustered sequence differences are challenging for mapping and variant calling methods, and we show that detection of mutation clusters with current resequencing methodologies is difficult and many erroneous variant annotations exist in human reference data. Template switch events such as those we have uncovered may have been neglected as an explanation for complex mutations because of biases in commonly used analyses. Incorporation of our model into reference-based analysis pipelines and comparisons ofde novo-assembled genomes will lead to improved understanding of genome variation and evolution.
Human Longevity is Influenced by Many Genetic Variants: Evidence from 75,000 UK Biobank Participants
Authors: Pilling Luke C. , Atkins Janice L. , Bowman Kirsty , Jones Samuel E. , Tyrrell Jessica , Beaumont Robin N. , Ruth Katherine S. , Tuke Marcus A. , Yaghootkar Hanieh , Wood Andrew R. , Freathy Rachel M. , Murray Anna , Weedon Michael N. , Xue Luting , Lunetta Kathryn , Murabito Joanne M. , Harries Lorna W. , Robine Jean-Marie , Brayne Carol , Kuchel George A. , Ferrucci Luigi , Frayling Timothy M. , Melzer David
Published: February 2016

Variation in human lifespan is 20 to 30% heritable but few genetic variants have been identified. We undertook a Genome Wide Association Study (GWAS) using age at death of parents of middle-aged UK Biobank participants of European decent (n=75,244 with father’s and/or mother’s data). Genetic risk scores for 19 phenotypes (n=777 proven variants) were also tested.

Genotyped variants (n=845,997) explained 10.2% (SD=1.3%) of combined parental longevity. In GWAS, a locus in the nicotine receptorCHRNA3– previously associated with increased smoking and lung cancer - was associated with paternal age at death, with each protective allele (rs1051730[G]) being associated with 0.03 years later age at father’s death (p=3x10-8). Offspring of longer lived parents had more protective alleles (lower genetic risk scores) for coronary artery disease, systolic blood pressure, body mass index, cholesterol and triglyceride levels, type-1 diabetes, inflammatory bowel disease and Alzheimer’s disease. In candidate gene analyses, variants in theTOMM40/APOElocus were associated with longevity (including rs429358, p=3x10-5), butFOXOvariants were not associated.

These results support a multiple protective factors model for achieving longer lifespans in humans, with a prominent role for cardiovascular-related pathways. Several of these genetically influenced risks, including blood pressure and tobacco exposure, are potentially modifiable.
Crystal structure of bis(1,4-diazabicyclo[2.2.2]octan-1-ium) thiosulfate dihydrate
Authors: Seck Gorgui Awa , Sene Aboubacary , Diop Libasse , Maris Thierry
Published: February 2016

The crystal structure of the hydrated title salt, 2C6H13N2+·S2O32−·2H2O, contains a centrosymmetric cyclic motif of eight hydrogen-bonded molecular subunits. Two DABCOH+cations (DABCO = 1,4-diazabicyclo[2.2.2]octane) are linked to two water molecules and two thiosulfate anionsviaO—H...N and O—H...O hydrogen bonds, respectively. Two other water molecules close the cyclic motif through O—H...O contacts to the first two water molecules and to the two thiosulfate anions. A second pair of DABCOH+cations is N—H...O hydrogen bonded to the two anions and is pendant to the ring. Adjacent cyclic motifs are bridged into a block-like arrangement extending along [100] through O—H...O interactions involving the second pair of water molecules and neighbouring thiosulfate anions.
Crystal structure of the 1:1 adduct of 2,3-diphenyl-3,4,5,6-tetrahydro-2H-1,3-thiazin-4-one with triphenyltin chloride
Authors: Yennawar Hemant P. , Fox Ryan , Silverberg Lee J.
Published: February 2016

The title adduct, chlorido(2,3-diphenyl-3,4,5,6-tetrahydro-2H-1,3-thiazin-4-one-κO)triphenyltin, [Sn(C6H5)3Cl(C16H15NOS)], resulted from reaction of 2,3-diphenyl-3,4,5,6-tetrahydro-2H-1,3-thiazin-4-one with triphenyltin chloride. The thiazine ring has an envelope conformation with the S atom forming the flap. The molecule has five phenyl rings, two of them attached to the thiazine ring at positions 2 and 3, and three in coordination with the SnIVatom. The three rings of the triphenyltin group are involved in intramolecular interactions of different types, C—H...O, edge-to-face (or T-type) π–π interactions with the 3-phenyl ring of the thiazine, T-type interactions with both phenyl rings of the thiazineetc. On the other hand, all the phenyl rings participate in intermolecular π–π interactions. There is one instance of a `parallel-displaced'-type interaction extending continuously along thea-axis direction and seven instances of T-type interactions stabilizing the crystal lattice.
1-Ethyl-3-nitroquinolin-4(1H)-one
Authors: Limbach Daniel , Stengelin Elena , Schollmeyer Dieter , Detert Heiner
Published: February 2016

The title compound, C11H10N2O3, was obtained as side-product in a project focussing on the synthesis of carbolines. It was prepared from nitroquinolinone, ethanol and phosphoryl chloride. With the exception of the methyl group [C—N—C—Cmethyltorsion angle = −96.4 (2)°], the molecule is essentially planar (r.m.s. deviation = 0.033 Å). In the molecular packing, undulating ribbons along thebaxis are connectedviaC—H...O hydrogen bonds; an intramolecular C—H...O interaction is also noted.
6-Fluoro-1H-indole-2,3-dione
Authors: Golen James A. , Manke David R.
Published: February 2016

The title compound, C8H4FNO2, has a single, almost planar, molecule in the asymmetric unit, with the non-H atoms having a mean deviation from planarity of 0.042 Å. Intermolecular N—H...O hydrogen bonds result in infinite chains along [100]. The molecules are further linked through weak C—H...O and C—H...F interactions.
(5,7-Dimethyl-2-oxo-2H-chromen-4-yl)methyl morpholine-4-carbodithioate
Authors: Anitha B. R. , Roopashree K. R. , Kumar K. Mahesh , Ravi A. J. , Devarajegowda H. C.
Published: February 2016

In the title compound, C17H19NO3S2, the 2H-chromene ring system is nearly planar, with a maximum deviation of 0.080 (2) Å, and the morpholine ring adopts a chair conformation. The bond-angle sum at the N atom is 358°. The coumarin unit makes dihedral angle of 86.34 (9)° with the morpholine ring. A short intramolecular C—H...S contact generates anS(7) ring. In the crystal, inversion dimers linked by pairs of weak C—H...O hydrogen bonds generateR22(16) loops. Aromatic π–π interactions interactions [shortest centroid–centroid distance = 3.8599 (13) Å] also occur.
2-(5-Methyl-1-benzofuran-3-yl)acetic acid
Authors: Ramprasad N. , Gowda Ramakrishna , Gowda K. V. Arjuna , Basanagouda Mahantesha
Published: February 2016

The asymmetric unit of the title compound, C11H10O3, contains two crystallographically independent molecules,AandB, with closely matching conformations (r.m.s. overlay fit = 0.105 Å). In each case, the OH group of the acetic acid residue occupies a position approximately antiperiplanar to the C atom of the heterocycle. A short intramolecular C—H...O contact occurs within each molecule. In the crystal, carboxylic acidA+Bdimers generateR22(8) loops.
(7,8-Dimethyl-2-oxo-2H-chromen-4-yl)methyl piperidine-1-carbodithioate
Authors: Ravi A. J. , Kumar K. Mahesh , Devarajegowda H. C.
Published: February 2016

In the title compound, C18H21NO2S2, the 2H-chromene ring systems is nearly planar, with a maximum deviation of 0.023 (2) Å. The coumarin unit makes a dihedral angle of 60.54 (8)° with the piperidine ring, which adopts a chair conformation. The carbodithioate group is present in a synperiplanar conformation with respect to the piperidine ring, as indicated by the torsion angle of −4.7 (2)°. A short intramolecular C—H...S conatct generates anS(5) ring. No directional interactions beyond van der Waals contacts could be identified in the crystal.
Strategic corporate communication and impact in Indian service sector
Authors: Sinha Mala , Bhatia Perveen
Published: February 2016

Purpose

– The purpose of this paper is to examine the nature of strategic corporate communication (SCC) activities and its impact in Indian service sector organizations.

Design/methodology/approach

– A descriptive research design was used with data obtained from 227 executives from service sector organizations. A research instrument was constructed and measures of SCC and its impact were derived through factor analysis.

Findings

– Multiple regression analysis led to formulation of new relationships among the variables (messages, medium and stakeholders) involved in SCC and its impact. For example, in crisis situations, messages related to identity and image were associated with greater communication impact than were other types of messages. Similarly communicating with primary stakeholders like employees and customers was more important than with other stakeholders. Among the different types of medium used in SCC, virtual medium and disclosures led to greater communication impact.

Originality/value

– Communication impact due to SCC was a multi-dimensional construct comprising of three kinds of impacts: communication synergy; value representation; and organizational reliability. The relationships of messages, mediums and stakeholders with different types of SCC Impact can help practitioners design and implement effective strategies of corporate communication.
Integrated reporting with CSR practices
Authors: Lueg Klarissa , Lueg Rainer , Andersen Karina , Dancianu Veronica
Published: February 2016

Purpose

– The purpose of this paper is to illustrate how standards and guidelines for corporate social responsibility (CSR) can help a company in its integrated reporting (IR). The authors investigate the motivations of diverse stakeholders (including shareholders) in fostering the adoption of standards and guidelines for CSR after IR became mandatory in Denmark.

Design/methodology/approach

– The authors conduct a case study at the Danish carpet manufacturer EGE. The authors interpret the case from the perspective of pragmatic constructivism, which focuses on the integration of four dimensions: facts, possibilities, values, and communication.

Findings

– The authors find that the family-owned EGE follows a strategy of “enlightened shareholder value,” in which CSR is an essential value driver. This strategy fostered IR with guidelines and standards for CSR. The CSR practices appeared to be helpful for integrating measureable plans to the strategy and for controlling CSR implementation. However, the long and technical CSR reports did not effectively communicate EGE’s values and possibilities. The authors outline how EGE overcame these barriers.

Originality/value

– The authors suggest that IR implementation depends on the context, and the authors explain why the case company has opted to issue two separate reports for their IR. In addition, the authors suggest that standardized approaches to CSR may be suitable for internal planning and control purposes; however, companies must go beyond these measurements to achieve IR.
Optimizing on hydrostatic structural parameters for regulatable dry gas seal based on central composite design test
Authors: Jin Zhaoxu , Li Shuangxi , Cai Jining , zhang qiuxiang
Published: February 2016

Purpose

– This paper aims to introduce a new type of analysis method to seek the actual working performance of the regulatable dry gas seal, including equilibrium film thickness, stiffness-leakage ratio and so on. Additionally, a parametric optimization of the hydrostatic structure is completed for this kind of seal.

Design/methodology/approach

– From the point of axial force balance based on gas lubrication theory, a new analysis method, the Gas Film Divided Method, has been introduced. A four-factor and three-level hydrostatic structural parameters test scheme is designed by means of Central Composite Design test and then the hydrostatic structural parameters of regulatable dry gas seal were optimized. Three types of regulatable dry gas seal have been designed and manufactured to verify the theoretical analysis by measuring the equilibrium film thickness and inward leakage.

Findings

– The results indicate that the numerical values of the Gas Film Divided (GFD) method agree well with the experimental ones. Test proves that the Central Composite Design test could achieve optimized hydrostatic structural parameters of regulatable dry gas seal effectively.

Research limitations/implications

– For validating the correctness of the GFD method, an experiment study of the regulatable dry gas seal is being carried out where atmosphere is selected as the lubricant for the sake of safety. Soon after, the author will discuss the application in the new paper.

Originality/value

– The introduction of the GFD method proffers important insights to seek the performances of regulatable dry gas seal under the actual working conditions. The detailed optimal values of the hydrostatic structural parameters were given by the theoretical research which may be helpful for the design of regulatable dry gas seal.
A new temperature parameter set for characterizing the frictional temperature rise of disc brakes
Authors: Yin Yan , Xiao Xingming , Bao Jiusheng , Liu Jinge , Lu Yuhao , Ji Yangyang
Published: February 2016

Purpose

– The purpose of this study is to establish a new temperature set for characterizing the frictional temperature rise (FTR) of disc brakes. The FTR produced by braking is an important factor which directly affects the tribological properties of disc brakes. Presently, most existing researches characterize the FTR only by several static parameters such as average temperature or maximum temperature, which cannot reflect accurately the dynamic characteristics of temperature variation in the process of braking. In this paper, a new temperature parameter set was extracted and the influences of braking conditions on these parameters were investigated by experiments.

Design/methodology/approach

– First, several simulated braking experiments of disc brakes were conducted to reveal the dynamic variation rules and mechanisms of the FTR in braking. Second, the characteristic parameter subset of the FTR was extracted with five significant parameters, namely, initial temperature, average temperature, end temperature, maximum temperature and the ratio of maximum temperature time. Furthermore, the fitting parameter subset of the FTR was constructed based on the temperature rise curve. Finally, the influence and mechanisms of initial braking velocity and braking pressure on the new temperature parameter set were investigated through braking experiments.

Findings

– This paper extracted a new temperature parameter set including a characteristic parameter subset and a fitting parameter subset and revealed the influences of braking conditions on it by experiments.

Originality/value

– The results showed that the new temperature parameter set extracted in this paper can characterize the dynamic characteristics of disc brake’s FTR variations more objectively and comprehensively. The research results will provide a theoretical basis for extracting the fault feature of friction properties.
Dynamic balance analysis of contamination control for hydraulic systems based on dynamic filtration ratio
Authors: Ma Guangying , Ning Shurong , Hu Yunlong , Gao jun
Published: February 2016

Purpose

– The aim of this study is to establish a dynamic model of the filtration ratio. For the problem that the measured value of the filtration ratio is far less than the theoretical value in the actual hydraulic filtering system, the paper aims to find the relationship between the filtration ratio and the parameters of the hydraulic systems, such as the contamination level and the dirt-holding quantity of the filter.

Design/methodology/approach

– The paper opted for the method of experimental analysis and simulation to determine the relationship between the filtration ratio and the parameters of the hydraulic system, and established a dynamic filtration ratio model.

Findings

– The paper provides a preliminary model of dynamic filtration ratio, and the model shows that the filtration ratio is exponentially related to the contamination level and the dirt-holding quantity. Different filters have different influence coefficients. The filtering capacity for a certain particle size and the contamination level control of the filter for different hydraulic systems can be judged according to the dynamic balance equation of hydraulic systems.

Originality/value

– The paper is useful in the selection of filters and in the precise control of the contamination level of the hydraulic system.
Communication in the heart of policy and the conduct of conduct
Authors: Kraaier Niels Martijn
Published: February 2016

Purpose

– In 2001, Dutch politician Jacques Wallage introduced the concept of “communication in the heart of policy”, which sought to bridge the perceived gap between the government and the populace. He also advocated for a stronger focus on the proper representation of cabinet ministers in the mass media. The purpose of this paper is to explore the implications experienced by communication professionals in the Dutch public service in terms of integrating this approach.

Design/methodology/approach

– This paper is based on a series of 17 qualitative semi-structured interviews held with communication professionals either previously or currently employed in the Dutch public service.

Findings

– The findings show that it has become increasingly difficult for communication professionals in the Dutch public service to maintain the strict separation between government communication and political communication that once characterised their work.

Research limitations/implications

– The focus of this paper is on government communication in the Netherlands at a national level.

Practical implications

– This paper argues that a stronger focus on the image and reputation of cabinet members blurs the line between government communication and political communication, which may defeat the purpose of “communication in the heart of policy”.

Originality/value

– This paper offers a unique insight into government communication practices in a consociational state, where politics are marked by negotiation and a common striving for broad consensus, and where the public service is controlled by coalition governments rather than one particular party.