bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipidomic Signatures and Associated Transcriptomic Profiles of Clear Cell Renal Cell Carcinoma
Authors: Saito Kosuke , Arai Eri , Maekawa Keiko , Ishikawa Masaki , Fujimoto Hiroyuki , Taguchi Ryo , Matsumoto Kenji , Kanai Yae , Saito Yoshiro 
Published: June 2016

AbstractRenal cell carcinoma (RCC) is the most common histological type of adult kidney cancer. In this study, we obtained lipidomic profiles of clear cell RCC (ccRCC), a major RCC subtype, by performing a lipidomic analysis of specimens of cancerous tissue and the surrounding normal renal cortex obtained from the same patients (N = 49). We also compared the lipidomic profiles with the lipogenic transcriptome of specimens of cancerous tissue and the surrounding normal renal cortex for an additional set of patient samples (N = 95). Overall, we detected 326 lipids, including phospholipids, sphingolipids, neutral lipids, and eicosanoids. The levels of more than 70% of the detected lipids were significantly different (P < 0.01, corrected by the false discovery rate). The cancerous tissue was distinguished by higher levels of ether-type phospholipids, cholesterol esters, and triacylglycerols, as well as by lower levels of phospholipids (except for phosphatidylcholines) and polyunsaturated fatty acids. Characteristic changes in the levels of mRNAs and metabolites suggested that the phosphatidylethanolamine (PE) synthesis pathway is suppressed in ccRCC and associated with cell proliferation. The present study represents the lipidomic profiles of ccRCC, which provides novel information about the metabolic changes in renal cancerous tissue and RCC pathophysiology.
The first characterization of multidrug and toxin extrusion (MATE/SLC47) proteins in zebrafish (Danio rerio)
Authors: Lončar Jovica , Popović Marta , Krznar Petra , Zaja Roko , Smital Tvrtko 
Published: June 2016

AbstractMultidrug and toxin extrusion (MATE) proteins are involved in the extrusion of endogenous compounds and xenobiotics across the plasma membrane. They are conserved from bacteria to mammals, with different numbers of genes within groups. Here, we present the first data on identification and functional characterization of Mate proteins in zebrafish (Danio rerio). Phylogenetic analysis revealed six Mates in teleost fish, annotated as Mate3–8, which form a distinct cluster separated from the tetrapod MATEs/Mates. Synteny analysis showed that zebrafish mate genes are orthologous to human MATEs. Gene expression analysis revealed that all the mate transcripts were constitutively and differentially expressed during embryonic development, followed by pronounced and tissue-specific expression in adults. Functional analyses were performed using transport activity assays with model substrates after heterologous overexpression of five zebrafish Mates in HEK293T cells. The results showed that zebrafish Mates interact with both physiological and xenobiotic substances but also substantially differ with respect to the interacting compounds and interaction strength in comparison to mammalian MATEs/Mates. Taken together, our data clearly indicate a potentially important role for zebrafish Mate transporters in zebrafish embryos and adults and provide a basis for detailed functional characterizations of single zebrafish Mate transporters.
Quantitative and compositional responses of ammonia-oxidizing archaea and bacteria to long-term field fertilization
Authors: Xue Chao , Zhang Xu , Zhu Chen , Zhao Jun , Zhu Ping , Peng Chang , Ling Ning , Shen Qirong 
Published: June 2016

AbstractArchaeal (AOA) and bacterial (AOB) ammonia-oxidizer responses to long-term field fertilization in a Mollisol soil were assessed through pyrosequencing of amoA genes. Long-term fertilization treatments including chemical fertilizer (NPK), NPK plus manure (NPKM) and no fertilization over 23 years altered soil properties resulting in significant shifts in AOA and AOB community composition and abundance. NPK exhibited a strong influence on AOA and AOB composition while the addition of manure neutralized the community change induced by NPK. NPK also led to significant soil acidification and enrichment of Nitrosotalea. Nitrosospira cluster 9 and 3c were the most abundant AOB populations with opposing responses to fertilization treatments. NPKM had the largest abundance of ammonia-oxidizers and highest potential nitrification activity (PNA), suggesting high N loss potential due to a doubling of nutrient input compared to NPK. PNA was strongly correlated to AOA and AOB community composition indicating that both were important in ammonium oxidization in this Mollisol soil. Total N and organic C were the most important factors driving shifts in AOA and AOB community composition. The AOA community was strongly correlated to the activities of all sugar hydrolysis associated soil enzymes and was more responsive to C and N input than AOB.
Loss of cortactin causes endothelial barrier dysfunction via disturbed adrenomedullin secretion and actomyosin contractility
Authors: García Ponce Alexander , Citalán Madrid Alí F. , Vargas Robles Hilda , Chánez Paredes Sandra , Nava Porfirio , Betanzos Abigail , Zarbock Alexander , Rottner Klemens , Vestweber Dietmar , Schnoor Michael 
Published: June 2016

AbstractChanges in vascular permeability occur during inflammation and the actin cytoskeleton plays a crucial role in regulating endothelial cell contacts and permeability. We demonstrated recently that the actin-binding protein cortactin regulates vascular permeability via Rap1. However, it is unknown if the actin cytoskeleton contributes to increased vascular permeability without cortactin. As we consistently observed more actin fibres in cortactin-depleted endothelial cells, we hypothesised that cortactin depletion results in increased stress fibre contractility and endothelial barrier destabilisation. Analysing the contractile machinery, we found increased ROCK1 protein levels in cortactin-depleted endothelium. Concomitantly, myosin light chain phosphorylation was increased while cofilin, mDia and ERM were unaffected. Secretion of the barrier-stabilising hormone adrenomedullin, which activates Rap1 and counteracts actomyosin contractility, was reduced in plasma from cortactin-deficient mice and in supernatants of cortactin-depleted endothelium. Importantly, adrenomedullin administration and ROCK1 inhibition reduced actomyosin contractility and rescued the effect on permeability provoked by cortactin deficiency in vitro and in vivo. Our data suggest a new role for cortactin in controlling actomyosin contractility with consequences for endothelial barrier integrity.
Transcriptome sequencing and marker development in winged bean (Psophocarpus tetragonolobus; Leguminosae)
Authors: Vatanparast Mohammad , Shetty Prateek , Chopra Ratan , Doyle Jeff J. , Sathyanarayana N. , Egan Ashley N. 
Published: June 2016

AbstractWinged bean, Psophocarpus tetragonolobus (L.) DC., is similar to soybean in yield and nutritional value but more viable in tropical conditions. Here, we strengthen genetic resources for this orphan crop by producing a de novo transcriptome assembly and annotation of two Sri Lankan accessions (denoted herein as CPP34 [PI 491423] and CPP37 [PI 639033]), developing simple sequence repeat (SSR) markers and identifying single nucleotide polymorphisms (SNPs) between geographically separated genotypes. A combined assembly based on 804,757 reads from two accessions produced 16,115 contigs with an N50 of 889 bp, over 90% of which has significant sequence similarity to other legumes. Combining contigs with singletons produced 97,241 transcripts. We identified 12,956 SSRs, including 2,594 repeats for which primers were designed and 5,190 high-confidence SNPs between Sri Lankan and Nigerian genotypes. The transcriptomic data sets generated here provide new resources for gene discovery and marker development in this orphan crop and will be vital for future plant breeding efforts. We also analyzed the soybean trypsin inhibitor (STI) gene family, important plant defense genes, in the context of related legumes and found evidence for radiation of the Kunitz trypsin inhibitor (KTI) gene family within winged bean.
Temporal tuning in the bat auditory cortex is sharper when studied with natural echolocation sequences
Authors: Beetz M. Jerome , Hechavarría Julio C. , Kössl Manfred 
Published: June 2016

AbstractPrecise temporal coding is necessary for proper acoustic analysis. However, at cortical level, forward suppression appears to limit the ability of neurons to extract temporal information from natural sound sequences. Here we studied how temporal processing can be maintained in the bats’ cortex in the presence of suppression evoked by natural echolocation streams that are relevant to the bats’ behavior. We show that cortical neurons tuned to target-distance actually profit from forward suppression induced by natural echolocation sequences. These neurons can more precisely extract target distance information when they are stimulated with natural echolocation sequences than during stimulation with isolated call-echo pairs. We conclude that forward suppression does for time domain tuning what lateral inhibition does for selectivity forms such as auditory frequency tuning and visual orientation tuning. When talking about cortical processing, suppression should be seen as a mechanistic tool rather than a limiting element.
Tunnelling current-voltage characteristics of Angstrom gaps measured with terahertz time-domain spectroscopy
Authors: Kim Joon-Yeon , Kang Bong Joo , Bahk Young-Mi , Kim Yong Seung , Park Joohyun , Kim Won Tae , Rhie Jiyeah , Han Sanghoon , Jeon Hyeongtag , Park Cheol-Hwan , Rotermund Fabian , Kim Dai-Sik 
Published: June 2016

AbstractQuantum tunnelling becomes inevitable as gap dimensions in metal structures approach the atomic length scale, and light passing through these gaps can be used to examine the quantum processes at optical frequencies. Here, we report on the measurement of the tunnelling current through a 3-Å-wide metal-graphene-metal gap using terahertz time-domain spectroscopy. By analysing the waveforms of the incident and transmitted terahertz pulses, we obtain the tunnelling resistivity and the time evolution of the induced current and electric fields in the gap and show that the ratio of the applied voltage to the tunnelling current is constant, i.e., the gap shows ohmic behaviour for the strength of the incident electric field up to 30 kV/cm. We further show that our method can be extended and applied to different types of nanogap tunnel junctions using suitable equivalent RLC circuits for the corresponding structures by taking an array of ring-shaped nanoslots as an example.
Iron overload by Superparamagnetic Iron Oxide Nanoparticles is a High Risk Factor in Cirrhosis by a Systems Toxicology Assessment
Authors: Wei Yushuang , Zhao Mengzhu , Yang Fang , Mao Yang , Xie Hang , Zhou Qibing 
Published: June 2016

AbstractSuperparamagnetic iron oxide nanoparticles (SPIONs) as a contrast agent have been widely used in magnetic resonance imaging for tumor diagnosis and theranostics. However, there has been safety concern of SPIONs with cirrhosis related to excess iron-induced oxidative stress. In this study, the impact of iron overload by SPIONs was assessed on a mouse cirrhosis model. A single dose of SPION injection at 0.5 or 5 mg Fe/kg in the cirrhosis group induced a septic shock response at 24 h with elevated serum levels of liver and kidney function markers and extended impacts over 14 days including high levels of serum cholesterols and persistent low serum iron level. In contrast, full restoration of liver functions was found in the normal group with the same dosages over time. Analysis with PCR array of the toxicity pathways revealed the high dose of SPIONs induced significant expression changes of a distinct subset of genes in the cirrhosis liver. All these results suggested that excess iron of the high dose of SPIONs might be a risk factor for cirrhosis because of the marked impacts of elevated lipid metabolism, disruption of iron homeostasis and possibly, aggravated loss of liver functions.
PhyloToAST: Bioinformatics tools for species-level analysis and visualization of complex microbial datasets
Authors: Dabdoub Shareef M. , Fellows Megan L. , Paropkari Akshay D. , Mason Matthew R. , Huja Sarandeep S. , Tsigarida Alexandra A. , Kumar Purnima S. 
Published: June 2016

AbstractThe 16S rRNA gene is widely used for taxonomic profiling of microbial ecosystems; and recent advances in sequencing chemistry have allowed extremely large numbers of sequences to be generated from minimal amounts of biological samples. Analysis speed and resolution of data to species-level taxa are two important factors in large-scale explorations of complex microbiomes using 16S sequencing. We present here new software, Phylogenetic Tools for Analysis of Species-level Taxa (PhyloToAST), that completely integrates with the QIIME pipeline to improve analysis speed, reduce primer bias (requiring two sequencing primers), enhance species-level analysis and add new visualization tools. The code is free and open source and can be accessed at http://phylotoast.org.
Determination of GLUT1 Oligomerization Parameters using Bioluminescent Förster Resonance Energy Transfer
Authors: Looyenga Brendan , VanOpstall Calvin , Lee Zion , Bell Jed , Lodge Evans , Wrobel Katherine , Arnoys Eric , Louters Larry 
Published: June 2016

AbstractThe facilitated glucose transporter GLUT1 (SLC2A1) is an important mediator of glucose homeostasis in humans. Though it is found in most cell types to some extent, the level of GLUT1 expression across different cell types can vary dramatically. Prior studies in erythrocytes—which express particularly high levels of GLUT1—have suggested that GLUT1 is able to form tetrameric complexes with enhanced transport activity. Whether dynamic aggregation of GLUT1 also occurs in cell types with more modest expression of GLUT1, however, is unclear. To address this question, we developed a genetically encoded bioluminescent Förster resonance energy transfer (BRET) assay using the luminescent donor Nanoluciferase and fluorescent acceptor mCherry. By tethering these proteins to the N-terminus of GLUT1 and performing saturation BRET analysis, we were able to demonstrate the formation of multimeric complexes in live cells. Parallel use of flow cytometry and immunoblotting further enabled us to estimate the density of GLUT1 proteins required for spontaneous oligomerization. These data provide new insights into the physiological relevance of GLUT1 multimerization as well as a new variant of BRET assay that is useful for measuring the interactions among other cell membrane proteins in live cells.
A HIV-Tat/C4-binding protein chimera encoded by a DNA vaccine is highly immunogenic and contains acute EcoHIV infection in mice
Authors: Tomusange Khamis , Wijesundara Danushka , Gummow Jason , Garrod Tamsin , Li Yanrui , Gray Lachlan , Churchill Melissa , Grubor-Bauk Branka , Gowans Eric J. 
Published: June 2016

AbstractDNA vaccines are cost-effective to manufacture on a global scale and Tat-based DNA vaccines have yielded protective outcomes in preclinical and clinical models of human immunodeficiency virus (HIV), highlighting the potential of such vaccines. However, Tat-based DNA vaccines have been poorly immunogenic and despite the administration of multiple doses and/or the addition of adjuvants, these vaccines are not in general use. In this study, we improved Tat immunogenicity by fusing it with the oligomerisation domain of a chimeric C4-binding protein (C4b-p), termed IMX313, resulting in Tat heptamerisation and linked Tat to the leader sequence of tissue plasminogen activator (TPA) to ensure that the bulk of heptamerised Tat is secreted. Mice vaccinated with secreted Tat fused to IMX313 (pVAX-sTat-IMX313) developed higher titres of Tat-specific serum IgG, mucosal sIgA and cell-mediated immune (CMI) responses and showed superior control of EcoHIV infection, a surrogate murine HIV challenge model, compared with animals vaccinated with other test vaccines. Given the crucial contribution of Tat to HIV-1 pathogenesis and the precedent of Tat-based DNA vaccines in conferring some level of protection in animal models, we believe that the virologic control demonstrated with this novel multimerised Tat vaccine highlights the promise of this vaccine candidate for humans.
Oligonucleotide-based systems: DNA, microRNAs, DNA/RNA aptamers
Authors: Jolly Pawan , Estrela Pedro , Ladomery Michael 
Published: June 2016

There are an increasing number of applications that have been developed for oligonucleotide-based biosensing systems in genetics and biomedicine. Oligonucleotide-based biosensors are those where the probe to capture the analyte is a strand of deoxyribonucleic acid (DNA), ribonucleic acid (RNA) or a synthetic analogue of naturally occurring nucleic acids. This review will shed light on various types of nucleic acids such as DNA and RNA (particularly microRNAs), their role and their application in biosensing. It will also cover DNA/RNA aptamers, which can be used as bioreceptors for a wide range of targets such as proteins, small molecules, bacteria and even cells. It will also highlight how the invention of synthetic oligonucleotides such as peptide nucleic acid (PNA) or locked nucleic acid (LNA) has pushed the limits of molecular biology and biosensor development to new perspectives. These technologies are very promising albeit still in need of development in order to bridge the gap between the laboratory-based status and the reality of biomedical applications.
Early multisensory integration of self and source motion in the auditory system
Authors: Wigderson Eyal , Nelken Israel , Yarom Yosef 
Published: June 2016

SignificanceA moving organism is constantly bombarded by sensory information, much of which originates from the movement itself. The organism has to disentangle self-generated sensations from the rest of the sensory input to correctly guide its behavior. This study addresses this problem in the sound localization system where the organism has to discriminate between movement of a sound source and a perceived movement of sound due to self-movement. Here, we demonstrate that the dorsal cochlear nucleus (DCN), at the very first stage of central auditory processing, integrates its auditory and vestibular information. We show that, as a result of this multisensory integration, the DCN already holds the information necessary to accomplish this task.
Sleeping Beautyscreen revealsPpargactivation in metastatic prostate cancer
Authors: Ahmad Imran , Mui Ernest , Galbraith Laura , Patel Rachana , Tan Ee Hong , Salji Mark , Rust Alistair G. , Repiscak Peter , Hedley Ann , Markert Elke , Loveridge Carolyn , van der Weyden Louise , Edwards Joanne , Sansom Owen J. , Adams David J. , Leung Hing Y. 
Published: June 2016

SignificanceUsing an unbiased forward mutagenesis screen, we were able to successfully identify candidate genes that drive advanced and metastatic prostate cancer (CaP). Alterations of peroxisome proliferator-activated receptor gamma (PPARG), encoding a regulator crucial of lipid metabolism, appear to play a role in the development of metastatic CaP in both humans and mice.
Cluster failure: Why fMRI inferences for spatial extent have inflated false-positive rates
Authors: Eklund Anders , Nichols Thomas E. , Knutsson Hans 
Published: June 2016

Significance
Functional MRI (fMRI) is 25 years old, yet surprisingly its most common statistical methods have not been validated using real data. Here, we used resting-state fMRI data from 499 healthy controls to conduct 3 million task group analyses. Using this null data with different experimental designs, we estimate the incidence of significant results. In theory, we should find 5% false positives (for a significance threshold of 5%), but instead we found that the most common software packages for fMRI analysis (SPM, FSL, AFNI) can result in false-positive rates of up to 70%. These results question the validity of a number of fMRI studies and may have a large impact on the interpretation of weakly significant neuroimaging results.
Mapping transcription factor interactome networks using HaloTag protein arrays
Authors: Yazaki Junshi , Galli Mary , Kim Alice Y. , Nito Kazumasa , Aleman Fernando , Chang Katherine N. , Carvunis Anne-Ruxandra , Quan Rosa , Nguyen Hien , Song Liang , Alvarez José M. , Huang Shao-shan Carol , Chen Huaming , Ramachandran Niroshan , Altmann Stefan , Gutiérrez Rodrigo A. , Hill David E. , Schroeder Julian I. , Chory Joanne , LaBaer Joshua , Vidal Marc , Braun Pascal , Ecker Joseph R. 
Published: June 2016

Significance
Using a newly developed technology, HaloTag nucleic acid programmable protein array (HaloTag-NAPPA), we increase the capacity of in situ protein microarray technology several-fold, such that proteome-scale screening becomes feasible. Many examples of novel protein–protein interactions (PPIs) among plant signaling pathways were observed. With few exceptions, nearly all of these connections are undocumented in the existing literature. This study has resulted in an important new resource for the plant biology community—a plant transcription factor-anchored protein–protein interaction network map. Such transcription factor- and transcriptional regulator-based PPI networks may help in the identification of novel genes for use in the improvement of agronomic traits such as grain quality, disease resistance, and stress tolerance.
Macronutrient ratios in pollen shape bumble bee (
Bombus impatiens
) foraging strategies and floral preferences
Authors: Vaudo Anthony D. , Patch Harland M. , Mortensen David A. , Tooker John F. , Grozinger Christina M. 
Published: June 2016

Significance
Bees pollinate the majority of flowering plant species, including agricultural crops. The pollen they obtain is their main protein and lipid source that fuels development and reproduction. Bee populations are declining globally, in large part because of landscape-level loss of host-plant species contributing to a nutritional shortage. To mitigate declines, we must understand how the nutritional requirements of bees influence foraging behavior. We demonstrate that bumble bees selectively collect pollen from host-plant species based on the protein:lipid ratios of pollen. Our research indicates that bees evaluate pollen quality and adjust foraging decisions to meet their nutritional needs. To be effective, conservation initiatives must include host-plant species that provide pollen that satisfies the nutritional demands of bees to support their populations.
Htm1p–Pdi1p is a folding-sensitive mannosidase that marks N-glycoproteins for ER-associated protein degradation
Authors: Liu Yi-Chang , Fujimori Danica Galonić , Weissman Jonathan S. 
Published: June 2016

Significance
During the biogenesis of proteins destined for the secretory pathway, proteins that fail to fold correctly are retained in the endoplasmic reticulum (ER) and targeted for degradation through a quality-control system called “ER-associated protein degradation” (ERAD), but how misfolded proteins are defined has remained unknown. Here we studied the ERAD pathway for misfolded N-glycoproteins, whose ERAD commitment requires the generation of a unique N-glycan structure by the action of the complex of the mannosidase Htm1p and the protein disulfide isomerase Pdi1p (Htm1p–Pdi1p). We found that Htm1p–Pdi1p differentiates the conformations of different N-glycoproteins and preferentially targets proteins trapped in partially structured states. In summary, our study reveals a conformational standard of how ERAD targets the right proteins for degradation.