bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD36 regulates lipopolysaccharide-induced signaling pathways and mediates the internalization of Escherichia coli in cooperation with TLR4 in goat mammary gland epithelial cells
Authors: Cao Duoyao , Luo Jun , Chen Dekun , Xu Huifen , Shi Huaiping , Jing Xiaoqi , Zang Wenjuan 
Published: March 2016

AbstractThe scavenger receptor CD36 is involved in pathogen recognition, phagocytosis, and pathogen-induced signaling. This study investigated the relationship between CD36 and TLR4 in modifying lipopolysaccharide (LPS)-induced signaling pathways and mediating Escherichia coli (E. coli) endocytosis in primary goat mammary epithelial cells (pGMECs). The manipulation of CD36 expression significantly influenced TLR4 and nuclear factor kappa B (NF-κB) mRNA expression in pGMECs stimulated with LPS for 12 h. NF-κB and activator protein-1 (AP-1) activity was regulated by the manipulation of CD36 expression in LPS-induced pGMECs. However, CD36-mediated AP-1 activation occurred primarily through c-Jun N-terminal kinase (c-JNK). Adaptor proteins and proinflammatory cytokines were also involved in these signaling pathways and acted by regulating CD36 expression in LPS-stimulated cells. Moreover, CD36 cooperated with TLR4 in TLR4-mediated phagocytosis following E. coli simulation, but this complex was not induced by LPS treatment. Our study is the first to illuminate CD36 as a scavenger receptor in ruminants. Additionally, this study indicates that CD36 plays a vital role in the LPS-induced activation of downstream signaling cascades and mediates E. coli phagocytosis via TLR4 in pGMECs, which offers a novel treatment strategy for mastitis.
Bioavailability of Polycyclic Aromatic Hydrocarbons and their Potential Application in Eco-risk Assessment and Source Apportionment in Urban River Sediment
Authors: Yang Xunan , Yu Liuqian , Chen Zefang , Xu Meiying 
Published: March 2016

AbstractTraditional risk assessment and source apportionment of sediments based on bulk polycyclic aromatic hydrocarbons (PAHs) can introduce biases due to unknown aging effects in various sediments. We used a mild solvent (hydroxypropyl-β-cyclodextrin) to extract the bioavailable fraction of PAHs (a-PAHs) from sediment samples collected in Pearl River, southern China. We investigated the potential application of this technique for ecological risk assessments and source apportionment. We found that the distribution of PAHs was associated with human activities and that the a-PAHs accounted for a wide range (4.7%–21.2%) of total-PAHs (t-PAHs) and high risk sites were associated with lower t-PAHs but higher a-PAHs. The correlation between a-PAHs and the sediment toxicity assessed using tubificid worms (r = −0.654, P = 0.021) was greater than that from t-PAH-based risk assessment (r = −0.230, P = 0.472). Moreover, the insignificant correlation between a-PAH content and mPEC-Q of low molecular weight PAHs implied the potiential bias of t-PAH-based risk assessment. The source apportionment from mild extracted fractions was consistent across different indicators and was in accordance with typical pollution sources. Our results suggested that mild extraction-based approaches reduce the potential error from aging effects because the mild extracted PAHs provide a more direct indicator of bioavailability and fresher fractions in sediments.
A strategy to optimize the thermoelectric performance in a spark plasma sintering process
Authors: Chiu Wan-Ting , Chen Cheng-Lung , Chen Yang-Yuan 
Published: March 2016

AbstractSpark plasma sintering (SPS) is currently widely applied to existing alloys as a means of further enhancing the alloys’ figure of merit. However, the determination of the optimal sintering condition is challenging in the SPS process. This report demonstrates a systematic way to independently optimize the Seebeck coefficient S and the ratio of electrical to thermal conductivity (σ/κ) and thus achieve the maximum figure of merit zT = S2(σ/κ)T. Sb2−xInxTe3 (x = 0–0.2) were chosen as examples to validate the method. Although high sintering temperature and pressure are helpful in enhancing the compactness and electrical conductivity of pressed samples, the resultant deteriorated Seebeck coefficient and increasing thermal conductivity eventually offset the benefit. We found that the optimal sintering temperature coincides with temperatures at which the maximum Seebeck coefficient begins to degrade, whereas the optimal sintering pressure coincided with the pressure at which the σ/κ ratio reaches a maximum. Based on this principle, the optimized sintering conditions were determined and the zT of Sb1.9In0.1Te3 is raised to 0.92 at 600 K, showing an approximately 84% enhancement. This work develops a facile strategy for selecting the optimal SPS sintering condition to further enhance the zT of bulk specimens.
Computational analysis of the MCoTI-II plant defence knottin reveals a novel intermediate conformation that facilitates trypsin binding
Authors: Jones Peter M. , George Anthony M. 
Published: March 2016

AbstractMCoTI-I and II are plant defence proteins, potent trypsin inhibitors from the bitter gourd Momordica cochinchinensis. They are members of the Knottin Family, which display exceptional stability due to unique topology comprising three interlocked disulfide bridges. Knottins show promise as scaffolds for new drug development. A crystal structure of trypsin-bound MCoTI-II suggested that loop 1, which engages the trypsin active site, would show decreased dynamics in the bound state, an inference at odds with an NMR analysis of MCoTI-I, which revealed increased dynamics of loop 1 in the presence of trypsin. To investigate this question, we performed unrestrained MD simulations of trypsin-bound and free MCoTI-II. This analysis found that loop 1 of MCoTI-II is not more dynamic in the trypsin-bound state than in the free state. However, it revealed an intermediate conformation, transitional between the free and bound MCoTI-II states. The data suggest that MCoTI-II binding involves a process in which initial interaction with trypsin induces transitions between the free and intermediate conformations and fluctuations between these states account for the increase in dynamics of loop 1 observed for trypsin-bound MCoTI-I. The MD analysis thus revealed new aspects of the inhibitors’ dynamics that may be of utility in drug design.
A Stress-Activated Transposon in Arabidopsis Induces Transgenerational Abscisic Acid Insensitivity
Authors: Ito Hidetaka , Kim Jong-Myong , Matsunaga Wataru , Saze Hidetoshi , Matsui Akihiro , Endo Takaho A. , Harukawa Yoshiko , Takagi Hiroki , Yaegashi Hiroki , Masuta Yukari , Masuda Seiji , Ishida Junko , Tanaka Maho , Takahashi Satoshi , Morosawa Taeko , Toyoda Tetsuro , Kakutani Tetsuji , Kato Atsushi , Seki Motoaki 
Published: March 2016

AbstractTransposable elements (TEs), or transposons, play an important role in adaptation. TE insertion can affect host gene function and provides a mechanism for rapid increases in genetic diversity, particularly because many TEs respond to environmental stress. In the current study, we show that the transposition of a heat-activated retrotransposon,ONSEN, generated a mutation in an abscisic acid (ABA) responsive gene, resulting in an ABA-insensitive phenotype inArabidopsis, suggesting stress tolerance. Our results provide direct evidence that a transposon activated by environmental stress could alter the genome in a potentially positive manner. Furthermore, the ABA-insensitive phenotype was inherited when the transcription was disrupted by anONSENinsertion, whereas ABA sensitivity was recovered when the effects ofONSENwere masked by IBM2. These results suggest that epigenetic mechanisms in host plants typically buffered the effect of a new insertion, but could selectively “turn on” TEs when stressed.
Multi-functional magnesium alloys containing interstitial oxygen atoms
Authors: Kang H. , Choi H. J. , Kang S. W. , Shin S. E. , Choi G. S. , Bae D. H. 
Published: March 2016

AbstractA new class of magnesium alloys has been developed by dissolving large amounts of oxygen atoms into a magnesium lattice (Mg-O alloys). The oxygen atoms are supplied by decomposing titanium dioxide nanoparticles in a magnesium melt at 720 °C; the titanium is then completely separated out from the magnesium melt after solidification. The dissolved oxygen atoms are located at the octahedral sites of magnesium, which expand the magnesium lattice. These alloys possess ionic and metallic bonding characteristics, providing outstanding mechanical and functional properties. A Mg-O-Al casting alloy made in this fashion shows superior mechanical performance, chemical resistance to corrosion, and thermal conductivity. Furthermore, a similar Mg-O-Zn wrought alloy shows high elongation to failure (>50%) at room temperature, because the alloy plastically deforms with only multiple slips in the sub-micrometer grains (<300 nm) surrounding the larger grains (~15 μm). The metal/non-metal interstitial alloys are expected to open a new paradigm in commercial alloy design.
Reconstruction of diaminopimelic acid biosynthesis allows characterisation of Mycobacterium tuberculosis N-succinyl-L,L-diaminopimelic acid desuccinylase
Authors: Usha Veeraraghavan , Lloyd Adrian J. , Roper David I. , Dowson Christopher G. , Kozlov Guennadi , Gehring Kalle , Chauhan Smita , Imam Hasan T. , Blindauer Claudia A. , Besra Gurdyal S. 
Published: March 2016

AbstractWith the increased incidence of tuberculosis (TB) caused by Mycobacterium tuberculosis there is an urgent need for new and better anti-tubercular drugs. N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE) is a key enzyme in the succinylase pathway for the biosynthesis of meso-diaminopimelic acid (meso-DAP) and L-lysine. DapE is a zinc containing metallohydrolase which hydrolyses N-succinyl L,L diaminopimelic acid (L,L-NSDAP) to L,L-diaminopimelic acid (L,L-DAP) and succinate. M. tuberculosis DapE (MtDapE) was cloned, over-expressed and purified as an N-terminal hexahistidine ((His)6) tagged fusion containing one zinc ion per DapE monomer. We redesigned the DAP synthetic pathway to generate L,L-NSDAP and other L,L-NSDAP derivatives and have characterised MtDapE with these substrates. In contrast to its other Gram negative homologues, the MtDapE was insensitive to inhibition by L-captopril which we show is consistent with novel mycobacterial alterations in the binding site of this drug.
A common NTRK2 variant is associated with emotional arousal and brain white-matter integrity in healthy young subjects
Authors: Spalek K , Coynel D , Freytag V , Hartmann F , Heck A , Milnik A , de Quervain D , Papassotiropoulos A 
Published: March 2016

AbstractDysregulation of emotional arousal is observed in many psychiatric diseases such as schizophrenia, mood and anxiety disorders. The neurotrophic tyrosine kinase receptor type 2 gene (NTRK2) has been associated with these disorders. Here we investigated the relation between genetic variability of NTRK2 and emotional arousal in healthy young subjects in two independent samples (n1=1171; n2=707). In addition, diffusion tensor imaging (DTI) data in a subgroup of 342 participants were used to identify NTRK2-related white-matter structure differences. After correction for multiple testing, we identified a NTRK2 single nucleotide polymorphism associated with emotional arousal in both samples (n1: Pnominal=0.0003, Pcorrected=0.048; n2: Pnominal=0.0141, Pcorrected=0.036). DTI revealed significant, whole-brain corrected correlations between emotional arousal and brain white-matter mean diffusivity (MD), as well as significant, whole-brain corrected NTRK2 genotype-related differences in MD (PFWE<0.05). Our study demonstrates that genetic variability of NTRK2, a susceptibility gene for psychiatric disorders, is related to emotional arousal and—independently—to brain white-matter properties in healthy individuals.
Is increased antidepressant exposure a contributory factor to the obesity pandemic?
Authors: Lee S H , Paz-Filho G , Mastronardi C , Licinio J , Wong M-L 
Published: March 2016

AbstractMajor depressive disorder (MDD) and obesity are both common heterogeneous disorders with complex aetiology, with a major impact on public health. Antidepressant prescribing has risen nearly 400% since 1988, according to data from the Centers for Disease Control and Prevention (CDC). In parallel, adult obesity rates have doubled since 1980, from 15 to 30 percent, while childhood obesity rates have more than tripled. Rising obesity rates have significant health consequences, contributing to increased rates of more than thirty serious diseases. Despite the concomitant rise of antidepressant use and of the obesity rates in Western societies, the association between the two, as well as the mechanisms underlying antidepressant-induced weight gain, remain under explored. In this review, we highlight the complex relationship between antidepressant use, MDD and weight gain. Clinical findings have suggested that obesity may increase the risk of developing MDD, andvice versa. Hypothalamic–pituitary–adrenal (HPA) axis activation occurs in the state of stress; concurrently, the HPA axis is also dysregulated in obesity and metabolic syndrome, making it the most well-understood shared common pathophysiological pathway with MDD. Numerous studies have investigated the effects of different classes of antidepressants on body weight. Previous clinical studies suggest that the tricyclics amitriptyline, nortriptyline and imipramine, and the serotonin norepinephrine reuptake inhibitor mirtazapine are associated with weight gain. Despite the fact that selective serotonin reuptake inhibitor (SSRI) use has been associated with weight loss during acute treatment, a number of studies have shown that SSRIs may be associated with long-term risk of weight gain; however, because of high variability and multiple confounds in clinical studies, the long-term effect of SSRI treatment and SSRI exposure on body weight remains unclear. A recently developed animal paradigm shows that the combination of stress and antidepressants followed by long-term high-fat diet results, long after discontinuation of antidepressant treatment, in markedly increased weight, in excess of what is caused by high-fat diet alone. On the basis of existing epidemiological, clinical and preclinical data, we have generated the testable hypothesis that escalating use of antidepressants, resulting in high rates of antidepressant exposure, might be a contributory factor to the obesity epidemic.
Human DC-SIGN binds specific human milk glycans
Authors: Noll Alexander J. , Yu Ying , Lasanajak Yi , Duska-McEwen Geralyn , Buck Rachael H. , Smith David F. , Cummings Richard D. 
Published: March 2016

Human milk glycans (HMGs) are prebiotics, pathogen receptor decoys and regulators of host physiology and immune responses. Mechanistically, human lectins (glycan-binding proteins, hGBP) expressed by dendritic cells (DCs) are of major interest, as these cells directly contact HMGs. To explore such interactions, we screened many C-type lectins and sialic acid-binding immunoglobulin-like lectins (Siglecs) expressed by DCs for glycan binding on microarrays presenting over 200 HMGs. Unexpectedly, DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) showed robust binding to many HMGs, whereas other C-type lectins failed to bind, and Siglec-5 and Siglec-9 showed weak binding to a few glycans. By contrast, most hGBP bound to multiple glycans on other microarrays lacking HMGs. An α-linked fucose residue was characteristic of HMGs bound by DC-SIGN. Binding of DC-SIGN to the simple HMGs 2′-fucosyl-lactose (2′-FL) and 3-fucosyl-lactose (3-FL) was confirmed by flow cytometry to beads conjugated with 2′-FL or 3-FL, as well as the ability of the free glycans to inhibit DC-SIGN binding. 2′-FL had an IC50 of ∼1 mM for DC-SIGN, which is within the physiological concentration of 2′-FL in human milk. These results demonstrate that DC-SIGN among the many hGBP expressed by DCs binds to α-fucosylated HMGs, and suggest that such interactions may be important in influencing immune responses in the developing infant.
Ethics, performativity and gender: porous and expansive concepts of selving in the performance work of Gretchen Jude and of Nicole Peisl
Authors: Hunter Lynette 
Published: March 2016

AbstractSituated knowledge theories that focused on processes and contexts for knowing were developed by women in response to finding that what they knew was unspoken or unspeakable not only in various disciplinary fields but also in their lived lives. And it is not surprising that the performativities that sustain knowing rather than knowledge are often the focus of women performers attempting to give form to those not-saids to make living worthwhile. This article discusses the gendered contexts of two women performers for making performative forms and for carrying those forms into performance. Yet the primary focus is on what their work does, and how it generates a felt sense of the somatic complexity of becoming through performative practices and rehearsals. The dancer/choreographer Nicole Peisl and musician/multimedia artist Gretchen Jude are from quite different parts of the Anglo European West yet in practising for non-individual porous and expansive selving, and for collaborative differences that generate emergent form, the work is remarkably similar. In their focus on ethico-poetic politics rather than the politics of social ethics, they offer ways to sustain an engaged situated ethics in the performativity of gender in lived lives as well as in the performance of gender as necessarily multiple. This paper is published as part of a thematic collection dedicated to gender studies.
Impacts of classifying New York City students as overweight
Authors: Almond Douglas , Lee Ajin , Schwartz Amy Ellen 
Published: March 2016

Significance
One third of US children are overweight. Childhood obesity is strongly associated with academic performance, predicts obesity in adulthood, and may be easier to modify than adult weight. Parents who are unaware their children are overweight may impede healthier weight ranges. We consider an informational intervention of New York City’s obesity report cards using a regression discontinuity design framework. To a surprising degree, discontinuous assignment rules are commonplace in allocating program services and shaping clinical care decisions by health care providers. Regression discontinuity designs offer a relatively untapped methodological approach for isolating causal effects, particularly as they relate to health.
Small genome of the fungus
Escovopsis weberi
, a specialized disease agent of ant agriculture
Authors: de Man Tom J. B. , Stajich Jason E. , Kubicek Christian P. , Teiling Clotilde , Chenthamara Komal , Atanasova Lea , Druzhinina Irina S. , Levenkova Natasha , Birnbaum Stephanie S. L. , Barribeau Seth M. , Bozick Brooke A. , Suen Garret , Currie Cameron R. , Gerardo Nicole M. 
Published: March 2016

Significance
Many organisms are specialists living within a narrow range of conditions. Pathogens are often adapted to efficiently exploit only a few hosts species, or sometimes, only some genotypes within a species. The genomes of such parasites are predicted to maintain genes critical for host utilization and to lose genes no longer necessary outside their constrained lifestyle. We demonstrate that the genomic content of a fungal pathogen specialized to attack and consume fungus cultivated by ants meets these predictions. Despite a reduced genome size and gene content in comparison with less specialized relatives, the genome of this agricultural pathogen retains genes necessary for production of toxins, a step critical to host attack, and for breaking down nutrients abundant in its host.
Identification and characterization of influenza variants resistant to a viral endonuclease inhibitor
Authors: Song Min-Suk , Kumar Gyanendra , Shadrick William R. , Zhou Wei , Jeevan Trushar , Li Zhenmei , Slavish P. Jake , Fabrizio Thomas P. , Yoon Sun-Woo , Webb Thomas R. , Webby Richard J. , White Stephen W. 
Published: March 2016

Significance
The endonuclease domain within the influenza virus heterotrimeric replication machinery is essential and represents an attractive drug target. It is important to understand the structural basis of potential inhibitor resistance, to design appropriate inhibitors and to prioritize drug candidates that are unlikely to cause the rapid development of clinically-relevant resistance mutations. Using a prototypical endonuclease inhibitor (L-742,001), we used mutagenesis to select for replication competent resistant mutants and studied the structural and functional basis for the observed resistance. These studies confirm that the endonuclease domain is an excellent drug target for treating influenza. They also provide reagents (mutant viruses and constructs) and crucial pharmacophore knowledge that will aid in the development of new drug candidates for urgently needed influenza therapies.
Autocratic strategies for iterated games with arbitrary action spaces
Authors: McAvoy Alex , Hauert Christoph 
Published: March 2016

SignificanceGames with two actions (“cooperate” and “defect”) have been extremely useful in modeling biological interactions. Despite their utility, however, there are many naturally occurring encounters that these games cannot fully capture. For example, the effort expended in animal grooming or the rate of siderophore production by microbes can take on a continuous range of values. Such interactions are better modeled by games with more general (continuous) action spaces. In this setting, we prove the existence of autocratic strategies that unilaterally enforce linear relationships on the payoffs for repeated games. In particular, we show that a player can often enforce such a relationship by playing only two actions throughout the repeated game.
Acetyl-CoA carboxylase inhibition by ND-630 reduces hepatic steatosis, improves insulin sensitivity, and modulates dyslipidemia in rats
Authors: Harriman Geraldine , Greenwood Jeremy , Bhat Sathesh , Huang Xinyi , Wang Ruiying , Paul Debamita , Tong Liang , Saha Asish K. , Westlin William F. , Kapeller Rosana , Harwood H. James 
Published: March 2016

Significance
Using structure-based drug design, we have identified a series of potent allosteric protein–protein interaction acetyl-CoA carboxylase inhibitors, exemplified by ND-630, that interact within the acetyl-CoA carboxylase subunit phosphopeptide acceptor and dimerization site to prevent dimerization and inhibit enzymatic activity. ND-630 reduces fatty acid synthesis and stimulates fatty acid oxidation in cultured cells and experimental animals, reduces hepatic steatosis, improves insulin sensitivity, reduces weight gain without affecting food intake, and favorably affects dyslipidemia in diet-induced obese rats and reduces hepatic steatosis, improves glucose-stimulated insulin secretion, and reduces hemoglobin A1c in Zucker diabetic fatty rats. These data suggest that ND-630 may be useful in treating a variety of metabolic disorders, including metabolic syndrome, type 2 diabetes, and fatty liver disease.