bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural basis for the broad substrate specificity of the human tyrosylprotein sulfotransferase-1
Authors: Tanaka Shinnosuke , Nishiyori Toshiaki , Kojo Hidetaka , Otsubo Reo , Tsuruta Moe , Kurogi Katsuhisa , Liu Ming-Cheh , Suiko Masahito , Sakakibara Yoichi , Kakuta Yoshimitsu 
Published: August 2017

AbstractTyrosylprotein sulfotransferases (TPSTs) are enzymes that catalyze post-translational tyrosine sulfation of proteins. In humans, there are only two TPST isoforms, designated TPST1 and TPST2. In a previous study, we reported the crystal structure of TPST2, which revealed the catalytic mechanism of the tyrosine sulfation reaction. However, detailed molecular mechanisms underlying how TPSTs catalyse a variety of substrate proteins with different efficiencies and how TPSTs catalyze the sulfation of multiple tyrosine residues in a substrate protein remain unresolved. Here, we report two crystal structures of the human TPST1 complexed with two substrate peptides that are catalysed by human TPST1 with significantly different efficiencies. The distinct binding modes found in the two complexes provide insight into the sulfation mechanism for these substrates. The present study provides valuable information describing the molecular mechanism of post-translational protein modifications catalysed by TPSTs.
Predicting the murine enterocyte metabolic response to diets that differ in lipid and carbohydrate composition
Authors: Sinha Neeraj , Suarez-Diez Maria , van Schothorst Evert M. , Keijer Jaap , Martins dos Santos Vitor A. P. , Hooiveld Guido J. E. J. 
Published: August 2017

AbstractThe small intestine serves as gatekeeper at the interface between body and diet and is thought to play an important role in the etiology of obesity and associated metabolic disorders. A computational modelling approach was used to improve our understanding of the metabolic responses of epithelial cells to different diets. A constraint based, mouse-specific enterocyte metabolic model (named mmu_ENT717) was constructed to describe the impact of four fully characterized semi-purified diets, that differed in lipid and carbohydrate composition, on uptake, metabolism, as well as secretion of carbohydrates and lipids. Our simulation results predicted luminal sodium as a limiting factor for active glucose absorption; necessity of apical localization of glucose transporter GLUT2 for absorption of all glucose in the postprandial state; potential for gluconeogenesis in enterocytes; and the requirement of oxygen for the formation of endogenous cholesterol needed for chylomicron formation under luminal cholesterol-free conditions. In addition, for a number of enzymopathies related to intestinal carbohydrate and lipid metabolism it was found that their effects might be ameliorated through dietary interventions. In conclusion, our improved enterocyte-specific model was shown to be a suitable platform to study effects of dietary interventions on enterocyte metabolism, and provided novel and deeper insights into enterocyte metabolism.
Interplay between maternal Slc6a4 mutation and prenatal stress: a possible mechanism for autistic behavior development
Authors: Sjaarda Calvin P. , Hecht Patrick , McNaughton Amy J. M. , Zhou Audrina , Hudson Melissa L. , Will Matt J. , Smith Garth , Ayub Muhammad , Liang Ping , Chen Nansheng , Beversdorf David , Liu Xudong 
Published: August 2017

AbstractThe low activity allele of the maternal polymorphism, 5HTTLPR, in the serotonin transporter, SLC6A4, coupled with prenatal stress is reported to increase the risk for children to develop autism spectrum disorder (ASD). Similarly, maternal Slc6a4 knock-out and prenatal stress in rodents results in offspring demonstrating ASD-like characteristics. The present study uses an integrative genomics approach to explore mechanistic changes in early brain development in mouse embryos exposed to this maternal gene-environment phenomenon. Restraint stress was applied to pregnant Slc6a4+/+ and Slc6a4+/− mice and post-stress embryonic brains were assessed for whole genome level profiling of methylome, transcriptome and miRNA using Next Generation Sequencing. Embryos of stressed Slc6a4+/+ dams exhibited significantly altered methylation profiles and differential expression of 157 miRNAs and 1009 genes affecting neuron development and cellular adhesion pathways, which may function as a coping mechanism to prenatal stress. In striking contrast, the response of embryos of stressed Slc6a4+/− dams was found to be attenuated, shown by significantly reduced numbers of differentially expressed genes (458) and miRNA (0) and genome hypermethylation. This attenuated response may pose increased risks on typical brain development resulting in development of ASD-like characteristics in offspring of mothers with deficits in serotonin related pathways during stressful pregnancies.
Metabolomics and genomics combine to unravel the pathway for the presence of fragrance in rice
Authors: Daygon Venea Dara , Calingacion Mariafe , Forster Louise C. , Voss James J. De , Schwartz Brett D. , Ovenden Ben , Alonso David E. , McCouch Susan R. , Garson Mary J. , Fitzgerald Melissa A. 
Published: August 2017

AbstractSince it was first characterised in 1983, 2-acetyl-1-pyrroline (2AP) has been considered to be the most important aroma compound in rice. In this study, we show four other amine heterocycles: 6-methyl, 5-oxo-2,3,4,5-tetrahydropyridine (6M5OTP), 2-acetylpyrrole, pyrrole and 1-pyrroline, that correlate strongly with the production of 2AP, and are present in consistent proportions in a set of elite aromatic rice varieties from South East Asia and Australia as well as in a collection of recombinant inbred lines (RILs) derived from indica Jasmine-type varieties, Australian long grain varieties (temperate japonica) and Basmati-type rice (Grp V). These compounds were detected through untargeted metabolite profiling by two-dimensional gas chromatography-time-of-flight mass spectrometry (GC × GC-TOF-MS), and their identity were confirmed by comparison with authentic standards analysed using gas chromatography mass spectrometry (GC-MS) and High Resolution GC × GC-TOF-MS (GC × GC HRT-4D). Genome-wide association analysis indicates that all compounds co-localised with a single quantitative trait locus (QTL) that harbours the FGR gene responsible for the production of GABA. Together, these data provide new insights into the production of 2AP, and evidence for understanding the pathway leading to the accumulation of aroma in fragrant rice.
Sensitive genotyping of mutations in the EGFR gene from NSCLC patients using PCR-GoldMag lateral flow device
Authors: Li Xian-Ying , Zhang Chao , Zhang Qin-Lu , Zhu Juan-Li , Liu Qian , Chen Ming-Wei , Yang Xue-Min , Hui Wen-Li , Cui Ya-Li 
Published: August 2017

AbstractEpidermal growth factor receptor (EGFR) mutations predict better outcomes with EGFR tyrosine kinase inhibitors in patients with non-small cell lung cancer (NSCLC). Most common activating mutations include in-frame deletion in exon 19 and L858R substitution in exon 21, which account for >90% of all EGFR mutations in NSCLC. In this study, a PCR-GoldMag lateral flow assay (PCR-GoldMag LFA) was developed for the visual detection of delE746-A750 and L858R of EGFR mutations. Forty formalin-fixed paraffin-embedded (FFPE) tissue samples of NSCLC patients were analyzed using PCR-GoldMag LFA system and verified by direct sequencing and TaqMan-PCR detection methods. Results showed that EGFR mutations were detected in 34 cases among the 40 samples (85%) by PCR-GoldMag LFA method. Among the 34 cases, 5 cases were simultaneously detected with delE746-A750 in exon 19 and L858R mutation in exon 21. Compared with sequencing, only 4 samples were detected as delE746-A750, which revealed higher sensitivity of PCR-GoldMag LFA detection method than direct sequencing. TaqMan-PCR method verified the L858R mutation and was in 100% agreement with our method. These results indicated that our method has obvious advantages to analyze clinical samples and offers a more sensitive alternative to direct sequencing for the detection of EGFR mutations.
Exploring the Sequence-based Prediction of Folding Initiation Sites in Proteins
Authors: Raimondi Daniele , Orlando Gabriele , Pancsa Rita , Khan Taushif , Vranken Wim F. 
Published: August 2017

AbstractProtein folding is a complex process that can lead to disease when it fails. Especially poorly understood are the very early stages of protein folding, which are likely defined by intrinsic local interactions between amino acids close to each other in the protein sequence. We here present EFoldMine, a method that predicts, from the primary amino acid sequence of a protein, which amino acids are likely involved in early folding events. The method is based on early folding data from hydrogen deuterium exchange (HDX) data from NMR pulsed labelling experiments, and uses backbone and sidechain dynamics as well as secondary structure propensities as features. The EFoldMine predictions give insights into the folding process, as illustrated by a qualitative comparison with independent experimental observations. Furthermore, on a quantitative proteome scale, the predicted early folding residues tend to become the residues that interact the most in the folded structure, and they are often residues that display evolutionary covariation. The connection of the EFoldMine predictions with both folding pathway data and the folded protein structure suggests that the initial statistical behavior of the protein chain with respect to local structure formation has a lasting effect on its subsequent states.
Neural circuitry governing anxious individuals’ mis-allocation of working memory to threat
Authors: Stout Daniel M. , Shackman Alexander J. , Pedersen Walker S. , Miskovich Tara A. , Larson Christine L. 
Published: August 2017

AbstractDispositional anxiety is a trait-like phenotype that confers increased risk for a range of debilitating neuropsychiatric disorders. Like many patients with anxiety disorders, individuals with elevated levels of dispositional anxiety are prone to intrusive and distressing thoughts in the absence of immediate threat. Recent electrophysiological research suggests that these symptoms are rooted in the mis-allocation of working memory (WM) resources to threat-related information. Here, functional MRI was used to identify the network of brain regions that support WM for faces and to quantify the allocation of neural resources to threat-related distracters in 81 young adults. Results revealed widespread evidence of mis-allocation. This was evident in both face-selective regions of the fusiform cortex and domain-general regions of the prefrontal and parietal cortices. This bias was exaggerated among individuals with a more anxious disposition. Mediation analyses provided compelling evidence that anxious individuals’ tendency to mis-allocate WM resources to threat-related distracters is statistically explained by heightened amygdala reactivity. Collectively, these results provide a neurocognitive framework for understanding the pathways linking anxious phenotypes to the development of internalizing psychopathology and set the stage for developing improved intervention strategies.
Peptide biomarkers used for the selective breeding of a complex polygenic trait in honey bees
Authors: Guarna M. Marta , Hoover Shelley E. , Huxter Elizabeth , Higo Heather , Moon Kyung-Mee , Domanski Dominik , Bixby Miriam E. F. , Melathopoulos Andony P. , Ibrahim Abdullah , Peirson Michael , Desai Suresh , Micholson Derek , White Rick , Borchers Christoph H. , Currie Robert W. , Pernal Stephen F. , Foster Leonard J. 
Published: August 2017

AbstractWe present a novel way to select for highly polygenic traits. For millennia, humans have used observable phenotypes to selectively breed stronger or more productive livestock and crops. Selection on genotype, using single-nucleotide polymorphisms (SNPs) and genome profiling, is also now applied broadly in livestock breeding programs; however, selection on protein/peptide or mRNA expression markers has not yet been proven useful. Here we demonstrate the utility of protein markers to select for disease-resistant hygienic behavior in the European honey bee (Apis mellifera L.). Robust, mechanistically-linked protein expression markers, by integrating cis- and trans- effects from many genomic loci, may overcome limitations of genomic markers to allow for selection. After three generations of selection, the resulting marker-selected stock outperformed an unselected benchmark stock in terms of hygienic behavior, and had improved survival when challenged with a bacterial disease or a parasitic mite, similar to bees selected using a phenotype–based assessment for this trait. This is the first demonstration of the efficacy of protein markers for industrial selective breeding in any agricultural species, plant or animal.
Analysis of population-specific pharmacogenomic variants using next-generation sequencing data
Authors: Ahn Eunyong , Park Taesung 
Published: August 2017

AbstractFunctional rare variants in drug-related genes are believed to be highly differentiated between ethnic- or racial populations. However, knowledge of population differentiation (PD) of rare single-nucleotide variants (SNVs), remains widely lacking, with the highest fixation indices, (Fst values), from both rare and common variants annotated to specific genes, having only been marginally used to understand PD at the gene level. In this study, we suggest a new, gene-based PD method, PD of Rare and Common variants (PDRC), for analyzing rare variants, as inspired by Generalized Cochran-Mantel-Haenszel (GCMH) statistics, to identify highly population-differentiated drug response-related genes (“pharmacogenes”). Through simulation studies, we reveal that PDRC adequately summarizes rare and common variants, due to PD, over a specific gene. We also applied the proposed method to a real whole-exome sequencing dataset, consisting of 10,000 datasets, from the Type 2 Diabetes Genetic Exploration by Next-generation sequencing in multi-Ethnic Samples (T2D-GENES) initiative, and 3,000 datasets from the Genetics of Type 2 diabetes (Go-T2D) repository. Among the 48 genes annotated with Very Important Pharmacogenetic summaries (VIPgenes), in the PharmGKB database, our PD method successfully identified candidate genes with high PD, including ACE, CYP2B6, DPYD, F5, MTHFR, and SCN5A.
A complex of Neuroplastin and Plasma Membrane Ca2+ ATPase controls T cell activation
Authors: Korthals Mark , Langnaese Kristina , Smalla Karl-Heinz , Kähne Thilo , Herrera-Molina Rodrigo , Handschuh Juliane , Lehmann Anne-Christin , Mamula Dejan , Naumann Michael , Seidenbecher Constanze , Zuschratter Werner , Tedford Kerry , Gundelfinger Eckart D. , Montag Dirk , Fischer Klaus-Dieter , Thomas Ulrich 
Published: August 2017

AbstractThe outcome of T cell activation is determined by mechanisms that balance Ca2+influx and clearance. Here we report that murine CD4 T cells lacking Neuroplastin (Nptn−/−), an immunoglobulin superfamily protein, display elevated cytosolic Ca2+and impaired post-stimulation Ca2+clearance, along with increased nuclear levels of NFAT transcription factor and enhanced T cell receptor-induced cytokine production. On the molecular level, we identified plasma membrane Ca2+ATPases (PMCAs) as the main interaction partners of Neuroplastin. PMCA levels were reduced by over 70% inNptn−/−T cells, suggesting an explanation for altered Ca2+handling. Supporting this, Ca2+extrusion was impaired while Ca2+levels in internal stores were increased. T cells heterozygous for PMCA1 mimicked the phenotype ofNptn−/−T cells. Consistent with sustained Ca2+levels, differentiation ofNptn−/−T helper cells was biased towards the Th1 versus Th2 subset. Our study thus establishes Neuroplastin-PMCA modules as important regulators of T cell activation.
Enhanced wintertime greenhouse effect reinforcing Arctic amplification and initial sea-ice melting
Authors: Cao Yunfeng , Liang Shunlin , Chen Xiaona , He Tao , Wang Dongdong , Cheng Xiao 
Published: August 2017

AbstractThe speeds of both Arctic surface warming and sea-ice shrinking have accelerated over recent decades. However, the causes of this unprecedented phenomenon remain unclear and are subjects of considerable debate. In this study, we report strong observational evidence, for the first time from long-term (1984–2014) spatially complete satellite records, that increased cloudiness and atmospheric water vapor in winter and spring have caused an extraordinary downward longwave radiative flux to the ice surface, which may then amplify the Arctic wintertime ice-surface warming. In addition, we also provide observed evidence that it is quite likely the enhancement of the wintertime greenhouse effect caused by water vapor and cloudiness has advanced the time of onset of ice melting in mid-May through inhibiting sea-ice refreezing in the winter and accelerating the pre-melting process in the spring, and in turn triggered the positive sea-ice albedo feedback process and accelerated the sea ice melting in the summer.
Ultrafast photonic reinforcement learning based on laser chaos
Authors: Naruse Makoto , Terashima Yuta , Uchida Atsushi , Kim Song-Ju 
Published: August 2017

AbstractReinforcement learning involves decision making in dynamic and uncertain environments and constitutes an important element of artificial intelligence (AI). In this work, we experimentally demonstrate that the ultrafast chaotic oscillatory dynamics of lasers efficiently solve the multi-armed bandit problem (MAB), which requires decision making concerning a class of difficult trade-offs called the exploration–exploitation dilemma. To solve the MAB, a certain degree of randomness is required for exploration purposes. However, pseudorandom numbers generated using conventional electronic circuitry encounter severe limitations in terms of their data rate and the quality of randomness due to their algorithmic foundations. We generate laser chaos signals using a semiconductor laser sampled at a maximum rate of 100 GSample/s, and combine it with a simple decision-making principle called tug of war with a variable threshold, to ensure ultrafast, adaptive, and accurate decision making at a maximum adaptation speed of 1 GHz. We found that decision-making performance was maximized with an optimal sampling interval, and we highlight the exact coincidence between the negative autocorrelation inherent in laser chaos and decision-making performance. This study paves the way for a new realm of ultrafast photonics in the age of AI, where the ultrahigh bandwidth of light wave can provide new value.
A model for relative biological effectiveness of therapeutic proton beams based on a global fit of cell survival data
Authors: Abolfath Ramin , Peeler Christopher R. , Newpower Mark , Bronk Lawrence , Grosshans David , Mohan Radhe 
Published: August 2017

AbstractWe introduce an approach for global fitting of the recently published high-throughput and high accuracy clonogenic cell-survival data for therapeutic scanned proton beams. Our fitting procedure accounts for the correlation between the cell-survival, the absorbed (physical) dose and the proton linear energy transfer (LET). The fitting polynomials and constraints have been constructed upon generalization of the microdosimetric kinetic model (gMKM) adapted to account for the low energy and high lineal-energy spectrum of the beam where the current radiobiological models may underestimate the reported relative biological effectiveness (RBE). The parameters (α, β) of the linear-quadratic (LQ) model calculated by the presented method reveal a smooth transition from low to high LETs which is an advantage of the current method over methods previously employed to fit the same clonogenic data. Finally, the presented approach provides insight into underlying microscopic mechanisms which, with future study, may help to elucidate radiobiological responses along the Bragg curve and resolve discrepancies between experimental data and current RBE models.
The protective action of osmolytes on the deleterious effects of gamma rays and atmospheric pressure plasma on protein conformational changes
Authors: Attri Pankaj , Kim Minsup , Sarinont Thapanut , Ha Choi Eun , Seo Hyunwoong , Cho Art E. , Koga Kazunori , Shiratani Masaharu 
Published: August 2017

AbstractBoth gamma rays and atmospheric pressure plasma are known to have anticancer properties. While their mechanism actions are still not clear, in some contexts they work in similar manner, while in other contexts they work differently. So to understand these relationships, we have studied Myoglobin protein after the treatment of gamma rays and dielectric barrier discharge (DBD) plasma, and analyzed the changes in thermodynamic properties and changes in the secondary structure of protein after both treatments. The thermodynamic properties were analyzed using chemical and thermal denaturation after both treatments. We have also studied the action of gamma rays and DBD plasma on myoglobin in the presence of osmolytes, such as sorbitol and trehalose. For deep understanding of the action of gamma rays and DBD plasma, we have analyzed the reactive species generated by them in buffer at all treatment conditions. Finally, we have used molecular dynamic simulation to understand the hydrogen peroxide action on myoglobin with or without osmolytes, to gain deeper insight into how the osmolytes can protect the protein structure from the reactive species generated by gamma rays and DBD plasma.
High copy and stable expression of the xylanase XynHB in Saccharomyces cerevisiae by rDNA-mediated integration
Authors: Fang Cheng , Wang Qinhong , Selvaraj Jonathan Nimal , Zhou Yuling , Ma Lixin , Zhang Guimin , Ma Yanhe 
Published: August 2017

AbstractXylanase is a widely-used additive in baking industry for enhancing dough and bread quality. Several xylanases used in baking industry were expressed in different systems, but their expression in antibiotic free vector system is highly essential and safe. In the present study, an alternative rDNA-mediated technology was developed to increase the copy number of target gene by integrating it into Saccharomyces cerevisiae genome. A xylanase-encoding gene xynHB from Bacillus sp. was cloned into pHBM367H and integrated into S. cerevisiae genome through rDNA-mediated recombination. Exogenous XynHB expressed by recombinant S. cerevisiae strain A13 exhibited higher degradation activity towards xylan than other transformants. The real-time PCR analysis on A13 genome revealed the presence of 13.64 copies of xynHB gene. Though no antibiotics have been used, the genetic stability and the xylanase activity of xynHB remained stable up to 1,011 generations of cultivation. S. cerevisiae strain A13 expressing xylanase reduced the required kneading time and increased the height and diameter of the dough size, which would be safe and effective in baking industry as no antibiotics-resistance risk. The new effective rDNA-mediated technology without using antibiotics here provides a way to clone other food related industrial enzymes for applications.