bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trans-omics approaches used to characterise fish nutritional biorhythms in leopard coral grouper (Plectropomus leopardus)
Authors: Mekuchi Miyuki , Sakata Kenji , Yamaguchi Tomofumi , Koiso Masahiko , Kikuchi Jun 
Published: August 2017

AbstractAquaculture is now a major supplier of fish, and has the potential to be a major source of protein in the future. Leopard coral groupers are traded in Asian markets as superior fish, and production via aquaculture has commenced. As feeding efficiency is of great concern in aquaculture, we sought to examine the metabolism of leopard coral groupers using trans-omics approaches. Metabolic mechanisms were comprehensively analysed using transcriptomic and metabolomic techniques. This study focused on the dynamics of muscular metabolites and gene expression. The omics data were discussed in light of circadian rhythms and fasting/feeding. The obtained data suggest that branched-chain amino acids played a role in energy generation in the fish muscle tissues during fasting. Moreover, glycolysis, TCA cycles, and purine metabolic substances exhibited circadian patterns, and gene expression also varied. This study is the first step to understanding the metabolic mechanisms of the leopard coral grouper.
Structural basis for therapeutic inhibition of influenza A polymerase PB2 subunit
Authors: Ma Xiaolei , Xie Lili , Wartchow Charles , Warne Robert , Xu Yongjin , Rivkin Alexey , Tully David , Shia Steven , Uehara Kyoko , Baldwin Dianna M. , Muiru Gladys , Zhong Weidong , Zaror Isabel , Bussiere Dirksen E. , Leonard Vincent H. J. 
Published: August 2017

AbstractInfluenza virus uses a unique mechanism to initiate viral transcription named cap-snatching. The PB2 subunit of the viral heterotrimeric RNA polymerase binds the cap structure of cellular pre-mRNA to promote its cleavage by the PA subunit. The resulting 11–13 capped oligomer is used by the PB1 polymerase subunit to initiate transcription of viral proteins. VX-787 is an inhibitor of the influenza A virus pre-mRNA cap-binding protein PB2. This clinical stage compound was shown to bind the minimal cap-binding domain of PB2 to inhibit the cap-snatching machinery. However, the binding of this molecule in the context of an extended form of the PB2 subunit has remained elusive. Here we generated a collection of PB2 truncations to identify a PB2 protein representative of its structure in the viral heterotrimeric protein. We present the crystal structure of VX-787 bound to a PB2 construct that recapitulates VX-787's biological antiviral activity in vitro. This co-structure reveals more extensive interactions than previously identified and provides insight into the observed resistance profile, affinity, binding kinetics, and conformational rearrangements induced by VX-787.
The effect of the TM6SF2 E167K variant on liver steatosis and fibrosis in patients with chronic hepatitis C: a meta-analysis
Authors: Liu Zhengtao , Que Shuping , Zhou Lin , Zheng Shusen , Romeo Stefano , Mardinoglu Adil , Valenti Luca 
Published: August 2017

AbstractThe impact of Transmembrane 6 superfamily member 2 (TM6SF2) E167K variant, which causes hepatocellular fat retention by altering lipoprotein secretion, on liver damage and metabolic traits in chronic hepatitis C patients is still debated. We performed a systematic review and meta-analysis to clarify this relationship. Four studies with a total of 4325 patients were included. The risk of histologically-determined advanced steatosis, fibrosis, and cirrhosis (but not of severe inflammation) were increased in carriers of the TM6SF2 variant (P < 0.05). Unlike the inconsistent association with steatosis severity, due to the confounding effect of infection by the genotype-3 hepatitis C virus, the TM6SF2 variant was robustly associated with advanced fibrosis (OR = 1.07; 95% confidence interval [CI] = 1.01–1.14) and in particular with cirrhosis (OR = 2.05; 95% CI = 1.39–3.02). Regarding metabolic features, individuals positive for the TM6SF2 variant exhibited 5.8–12.0% lower levels of circulating triglycerides and non-HDL cholesterol (P < 0.05). Carriers of the variant were leaner, but there was high heterogeneity across studies (I2 = 97.2%). No significant association was observed between the TM6SF2 variant and insulin resistance or hepatitis C viral load (both P > 0.05). In conclusion, the TM6SF2 E167K variant promotes the development of steatosis, fibrosis and cirrhosis in patients with chronic hepatitis C. Conversely, this variant reduces circulating atherogenic lipid fractions.
Identification and ranking of environmental threats with ecosystem vulnerability distributions
Authors: Zijp Michiel C. , Huijbregts Mark A. J. , Schipper Aafke M. , Mulder Christian , Posthuma Leo 
Published: August 2017

AbstractResponses of ecosystems to human-induced stress vary in space and time, because both stressors and ecosystem vulnerabilities vary in space and time. Presently, ecosystem impact assessments mainly take into account variation in stressors, without considering variation in ecosystem vulnerability. We developed a method to address ecosystem vulnerability variation by quantifying ecosystem vulnerability distributions (EVDs) based on monitoring data of local species compositions and environmental conditions. The method incorporates spatial variation of both abiotic and biotic variables to quantify variation in responses among species and ecosystems. We show that EVDs can be derived based on a selection of locations, existing monitoring data and a selected impact boundary, and can be used in stressor identification and ranking for a region. A case study on Ohio’s freshwater ecosystems, with freshwater fish as target species group, showed that physical habitat impairment and nutrient loads ranked highest as current stressors, with species losses higher than 5% for at least 6% of the locations. EVDs complement existing approaches of stressor assessment and management, which typically account only for variability in stressors, by accounting for variation in the vulnerability of the responding ecosystems.
The conserved tyrosine residue 940 plays a key structural role in membrane interaction of Bordetella adenylate cyclase toxin
Authors: Masin Jiri , Roderova Jana , Osickova Adriana , Novak Petr , Bumba Ladislav , Fiser Radovan , Sebo Peter , Osicka Radim 
Published: August 2017

AbstractThe adenylate cyclase toxin-hemolysin (CyaA, ACT or AC-Hly) translocates its adenylate cyclase (AC) enzyme domain into target cells in a step that depends on membrane cholesterol content. We thus examined what role in toxin activities is played by the five putative cholesterol recognition amino acid consensus (CRAC) motifs predicted in CyaA hemolysin moiety. CRAC-disrupting phenylalanine substitutions had no impact on toxin activities and these were not inhibited by free cholesterol, showing that the putative CRAC motifs are not involved in cholesterol binding. However, helix-breaking proline substitutions in these segments uncovered a structural role of the Y632, Y658, Y725 and Y738 residues in AC domain delivery and pore formation by CyaA. Substitutions of Y940 of the fifth motif, conserved in the acylated domains of related RTX toxins, did not impact on fatty-acylation of CyaA by CyaC and the CyaA-Y940F mutant was intact for toxin activities on erythrocytes and myeloid cells. However, the Y940A or Y940P substitutions disrupted the capacity of CyaA to insert into artificial lipid bilayers or target cell membranes. The aromatic ring of tyrosine 940 side chain thus appears to play a key structural role in molecular interactions that initiate CyaA penetration into target membranes.
Compact flexible multi-pass rotary delay line using spinning micro-machined mirrors
Authors: Fleddermann Roland , Lee Woei Ming , Huang Keshu , Campbell Geoff T. , Lam Ping Koy , Chow Jong H. 
Published: August 2017

AbstractWe propose a new method to extend the path length tunability of rotary delay-lines. This method was shown to achieve a duty cycle of >80% and repetition rates of over 40 kHz. The new method relies on a new multi-segmented micro-machined mirror and serial injection of a single reflection onto separate segments of this mirror. The tunability is provided by the relative positioning of each reflective point on the mirror segments. There are two distinct modes of operation: synchronous and asynchronous. By simply manipulating the spatial position of the returning paths over the respective mirror segments, we can switch between increasing the repetition rate (asynchronous mode) or the total delay path (synchronous mode). We experimentally demonstrated up to 8 m/s scans with repetition rates of up to 42.7 kHz. Furthermore, we present numerical simulations of 18 reflection points to illustrate possibility of achieving a scan speed of up to 80 m/s. Through intermediate combinations of synchronous and asynchronous operation modes with 4 or more passes, we also show that the system can simultaneously increase both repetition rate and scan depth.
Fungal Hybrid B heme peroxidases – unique fusions of a heme peroxidase domain with a carbohydrate-binding domain
Authors: Zámocký Marcel , Janeček Štefan , Obinger Christian 
Published: August 2017

AbstractHeme peroxidases, essential peroxide converting oxidoreductases are divided into four independently evolved superfamilies. Within the largest one – the peroxidase-catalase superfamily - two hybrid lineages were described recently. Whereas Hybrid A heme peroxidases represent intermediate enzymes between ascorbate peroxidases and cytochrome c peroxidases, Hybrid B heme peroxidases are unique fusion proteins comprised of a conserved N-terminal heme peroxidase domain and a C-terminal domain of various sugar binding motifs. So far these peculiar peroxidases are only found in the kingdom of Fungi. Here we present a phylogenetic reconstruction of the whole superfamily with focus on Hybrid B peroxidases. We analyse the domain assembly and putative structure and function of the newly discovered oligosaccharide binding domains. Two distinct carbohydrate binding modules (CBM21 and CBM34) are shown to occur in phytopathogenic ascomycetous orthologs of Hybrid B heme peroxidases only. Based on multiple sequence alignment and homology modeling the structure-function relationships are discussed with respect to physiological function. A concerted action of peroxide cleavage with specific cell-wall carbohydrate binding can support phytopathogens survival within the plant host.
Antisense oligonucleotide and thyroid hormone conjugates for obesity treatment
Authors: Cao Yang , Matsubara Tomoko , Zhao Can , Gao Wei , Peng Linxiu , Shan Jinjun , Liu Zhengxia , Yuan Fang , Tang Lingyi , Li Peixin , Guan Zhibin , Fang Zhuyuan , Lu Xiang , Huang Hu , Yang Qin 
Published: August 2017

AbstractUsing the principle of antibody-drug conjugates that deliver highly potent cytotoxic agents to cancer cells for cancer therapy, we here report the synthesis of antisense-oligonucleotides (ASO) and thyroid hormone T3 conjugates for obesity treatment. ASOs primarily target fat and liver with poor penetrance to other organs. Pharmacological T3 treatment increases energy expenditure and causes weight loss, but is contraindicated for obesity treatment due to systemic effects on multiple organs. We hypothesize that ASO-T3 conjugates may knock down target genes and enrich T3 action in fat and liver. Two established ASOs are tested. Nicotinamide N-methyltransferase (NNMT)-ASO prevents diet-induced obesity in mice. Apolipoprotein B (ApoB)-ASO is an FDA approved drug for treating familial hypercholesterolemia. NNMT-ASO and ApoB-ASO are chemically conjugated with T3 using a non-cleavable sulfo-SMCC linker. Both NNMT-ASO-T3 (NAT3) and ApoB-ASO-T3 (AAT3) enhance thyroid hormone receptor activity. Treating obese mice with NAT3 or AAT3 decreases adiposity and increases lean mass. ASO-T3 enhances white fat browning, decreases genes for fatty acid synthesis in liver, and shows limited effects on T3 target genes in heart and muscle. Furthermore, AAT3 augments LDL cholesterol-lowering effects of ApoB-ASO. Therefore, ASO and hormone/drug conjugation may provide a novel strategy for obesity and hyperlipidemia treatment.
Homophilic binding of the neural cell adhesion molecule CHL1 regulates development of ventral midbrain dopaminergic pathways
Authors: Alsanie W. F. , Penna V. , Schachner M. , Thompson L. H. , Parish C. L. 
Published: August 2017

AbstractAbnormal development of ventral midbrain (VM) dopaminergic (DA) pathways, essential for motor and cognitive function, may underpin a number of neurological disorders and thereby highlight the importance of understanding the birth and connectivity of the associated neurons. While a number of regulators of VM DA neurogenesis are known, processes involved in later developmental events, including terminal differentiation and axon morphogenesis, are less well understood. Recent transcriptional analysis studies of the developing VM identified genes expressed during these stages, including the cell adhesion molecule with homology to L1 (Chl1). Here, we map the temporal and spatial expression of CHL1 and assess functional roles of substrate-bound and soluble-forms of the protein during VM DA development. Results showed early CHL1 in the VM, corresponding with roles in DA progenitor migration and differentiation. Subsequently, we demonstrated roles for CHL1 in both axonal extension and repulsion, selectively of DA neurons, suggestive of a role in guidance towards forebrain targets and away from hindbrain nuclei. In part, CHL1 mediates these roles through homophilic CHL1-CHL1 interactions. Collectively, these findings enhance our knowledge of VM DA pathways development, and may provide new insights into understanding DA developmental conditions such as autism spectrum disorders.
Complete sequences of two novel bla
NDM-1-harbouring plasmids from two Acinetobacter towneri isolates in China associated with the acquisition of Tn125
Authors: Zou Dayang , Huang Yong , Liu Wei , Yang Zhan , Dong Derong , Huang Simo , He Xiaoming , Ao Da , Liu Ningwei , Wang Shengshu , Wang Yong , Tong Yigang , Yuan Jing , Huang Liuyu 
Published: August 2017

AbstractTwo novel New Delhi metallo-β-lactamase-1 (NDM-1)-positive plasmids containing a complete composite transposon, Tn125, from two respective Acinetobacter towneri isolates were characterized. Plasmid pNDM-GJ01 (30,293 bp) isolated from A. towneri G165 did not show homology to any known plasmid structure, except for the transposon Tn125 containing blaNDM-1. A novel repB gene and two XRE-type transcriptional regulators were found in pNDM-GJ01. Plasmid pNDM-GJ02 (62,011 bp) isolated from A. towneri G295 showed the highest homology to pBJAB0715 (41% coverage, 99% nucleotide identity). In addition to the blaNDM-1-harbouring transposon Tn125, pNDM-GJ02 also had an IS26-composite transposon, which contains ISCR1 and two class 1 integrons carrying different cassette arrays. Both clinical isolates were highly resistant to β-lactams and susceptible to tigecycline and colistin. Ten other resistance genes were detected in G295, and one other resistance gene was detected in G165. No transconjugant was obtained from any of the donors by broth and filter mating. The emergence of these two novel plasmids carrying NDM-1 in Acinetobacter spp., pNDM-GJ01 and pNDM-GJ02, suggests Tn125 mobile integration.
Assessing the relationship between surface urban heat islands and landscape patterns across climatic zones in China
Authors: Yang Qiquan , Huang Xin , Li Jiayi 
Published: August 2017

AbstractThe urban heat island (UHI) effect exerts a great influence on the Earth’s environment and human health and has been the subject of considerable attention. Landscape patterns are among the most important factors relevant to surface UHIs (SUHIs); however, the relationship between SUHIs and landscape patterns is poorly understood over large areas. In this study, the surface UHI intensity (SUHII) is defined as the temperature difference between urban and suburban areas, and the landscape patterns are quantified by the urban-suburban differences in several typical landscape metrics (ΔLMs). Temperature and land-cover classification datasets based on satellite observations were applied to analyze the relationship between SUHII and ΔLMs in 332 cities/city agglomerations distributed in different climatic zones of China. The results indicate that SUHII and its correlations with ΔLMs are profoundly influenced by seasonal, diurnal, and climatic factors. The impacts of different land-cover types on SUHIs are different, and the landscape patterns of the built-up and vegetation (including forest, grassland, and cultivated land) classes have the most significant effects on SUHIs. The results of this study will help us to gain a deeper understanding of the relationship between the SUHI effect and landscape patterns.
Combined effects of increased temperature and endocrine disrupting pollutants on sex determination, survival, and development across generations
Authors: DeCourten Bethany M. , Brander Susanne M. 
Published: August 2017

AbstractUnderstanding the combined effects of anthropogenic impacts such as climate change and pollution on aquatic ecosystems is critical. However, little is known about how predicted temperature increases may affect the activity of endocrine disrupting compounds (EDCs), particularly in species with plasticity in sex determination. We investigated the effects of a concomitant increase in temperature and exposure to estrogenic EDCs on reproduction and development in an estuarine model organism (Menidia beryllina) across multiple generations. Parents (P) were exposed to environmental levels of the estrogenic insecticide bifenthrin or ethinylestradiol (EE2) at 22 °C and 28 °C for 14 days prior to the initiation of spawning trials. Embryos in the F1 generation were exposed to EDCs until 21 days post hatch (dph), reared to adulthood in clean water at elevated temperatures, and spawned. F1 sex ratios were significantly influenced by elevated temperature and EDCs, potentially altering adaptive development. We also observed fewer viable offspring and increased developmental deformities in the F1 and F2 generations, with a greater impact on F2 juveniles. These findings enhance our understanding of responses to EDCs in the context of climate change and may demonstrate heritable effects. Our study represents the first multigenerational assessment of elevated temperatures in combination with environmentally relevant concentrations of commonly detected endocrine disruptors in a model vertebrate species.
Yttrium Copper Titanate as a Highly Efficient Electrocatalyst for Oxygen Reduction Reaction in Fuel Cells, Synthesized via Ultrafast Automatic Flame Technique
Authors: Singh Laxman , Azad Uday Pratap , Singh Satendra Pal , Ganesan Vellaichamy , Rai U. S. , Lee Youngil 
Published: August 2017

AbstractReplacing platinum (Pt) metal-based electrocatalysts used in the oxygen reduction reaction (ORR) in fuel cells is an important research topic due to the high cost and scarcity of Pt, which have restricted the commercialization of these clean-energy technologies. The ABO3-type perovskite family of an ACu3Ti4O12 (A = Ca, Y, Bi, and La) polycrystalline material can serve as an alternative electrocatalyst for the ORR in terms of low-cost, activity, and stability. These perovskite materials may be considered the next generation electro-catalyst for the ORR because of their photocatalytic activity and physical and chemical properties capable of containing a wide range of A- and B-site metals. This paper reports the ORR activity of a new Y2/3Cu3Ti4O12 perovskite, synthesized via a rapid and facile automatic flame synthesis technique using rotating disk electrode (RDE) measurements. Y2/3Cu3Ti4O12/C has superior ORR activity, stability, and durability compared to commercial Pt/C. The results presented in this article will provide the future perspectives to research based on ACu3Ti4O12 (A = Ca, Y, Bi, Sm, Cd, and La) perovskite as the next generation electro-catalyst for the ORR in various electrochemical devices, such as fuel cells, metal–air batteries, and electrolysis.
A Systematic Protein Refolding Screen Method using the DGR Approach Reveals that Time and Secondary TSA are Essential Variables
Authors: Wang Yuanze , van Oosterwijk Niels , Ali Ameena M. , Adawy Alaa , Anindya Atsarina L. , Dömling Alexander S. S. , Groves Matthew R. 
Published: August 2017

AbstractRefolding of proteins derived from inclusion bodies is very promising as it can provide a reliable source of target proteins of high purity. However, inclusion body-based protein production is often limited by the lack of techniques for the detection of correctly refolded protein. Thus, the selection of the refolding conditions is mostly achieved using trial and error approaches and is thus a time-consuming process. In this study, we use the latest developments in the differential scanning fluorimetry guided refolding approach as an analytical method to detect correctly refolded protein. We describe a systematic buffer screen that contains a 96-well primary pH-refolding screen in conjunction with a secondary additive screen. Our research demonstrates that this approach could be applied for determining refolding conditions for several proteins. In addition, it revealed which “helper” molecules, such as arginine and additives are essential. Four different proteins: HA-RBD, MDM2, IL-17A and PD-L1 were used to validate our refolding approach. Our systematic protocol evaluates the impact of the “helper” molecules, the pH, buffer system and time on the protein refolding process in a high-throughput fashion. Finally, we demonstrate that refolding time and a secondary thermal shift assay buffer screen are critical factors for improving refolding efficiency.
The role of the immunoproteasome in interferon-γ-mediated microglial activation
Authors: Moritz Kasey E. , McCormack Nikki M. , Abera Mahlet B. , Viollet Coralie , Yauger Young J. , Sukumar Gauthaman , Dalgard Clifton L. , Burnett Barrington G. 
Published: August 2017

AbstractMicroglia regulate the brain microenvironment by sensing damage and neutralizing potentially harmful insults. Disruption of central nervous system (CNS) homeostasis results in transition of microglia to a reactive state characterized by morphological changes and production of cytokines to prevent further damage to CNS tissue. Immunoproteasome levels are elevated in activated microglia in models of stroke, infection and traumatic brain injury, though the exact role of the immunoproteasome in neuropathology remains poorly defined. Using gene expression analysis and native gel electrophoresis we characterize the expression and assembly of the immunoproteasome in microglia following interferon-gamma exposure. Transcriptome analysis suggests that the immunoproteasome regulates multiple features of microglial activation including nitric oxide production and phagocytosis. We show that inhibiting the immunoproteasome attenuates expression of pro-inflammatory cytokines and suppresses interferon-gamma-dependent priming of microglia. These results imply that targeting immunoproteasome function following CNS injury may attenuate select microglial activity to improve the pathophysiology of neurodegenerative conditions or the progress of inflammation-mediated secondary injury following neurotrauma.