bluuebunny/crossref_metadata_2025_split huggingface dataset:
The calcium-activated potassium channel KCa3.1 is an important modulator of hepatic injury
Authors: Sevelsted Møller Linda , Fialla Annette Dam , Schierwagen Robert , Biagini Matteo , Liedtke Christian , Laleman Wim , Klein Sabine , Reul Winfried , Koch Hansen Lars , Rabjerg Maj , Singh Vikrant , Surra Joaquin , Osada Jesus , Reinehr Roland , de Muckadell Ove B. Schaffalitzky , Köhler Ralf , Trebicka Jonel 
Published: June 2016

AbstractThe calcium-activated potassium channel KCa3.1 controls different cellular processes such as proliferation and volume homeostasis. We investigated the role of KCa3.1 in experimental and human liver fibrosis. KCa3.1 gene expression was investigated in healthy and injured human and rodent liver. Effect of genetic depletion and pharmacological inhibition of KCa3.1 was evaluated in mice during carbon tetrachloride induced hepatic fibrogenesis. Transcription, protein expression and localisation of KCa3.1 was analysed by reverse transcription polymerase chain reaction, Western blot and immunohistochemistry. Hemodynamic effects of KCa3.1 inhibition were investigated in bile duct-ligated and carbon tetrachloride intoxicated rats. In vitro experiments were performed in rat hepatic stellate cells and hepatocytes. KCa3.1 expression was increased in rodent and human liver fibrosis and was predominantly observed in the hepatocytes. Inhibition of KCa3.1 aggravated liver fibrosis during carbon tetrachloride challenge but did not change hemodynamic parameters in portal hypertensive rats. In vitro, KCa3.1 inhibition leads to increased hepatocyte apoptosis and DNA damage, whereas proliferation of hepatic stellate cells was stimulated by KCa3.1 inhibition. Our data identifies KCa3.1 channels as important modulators in hepatocellular homeostasis. In contrast to previous studies in vitro and other tissues this channel appears to be anti-fibrotic and protective during liver injury.
Anti-tumor effect of β-glucan from Lentinus edodes and the underlying mechanism
Authors: Xu Hui , Zou Siwei , Xu Xiaojuan , Zhang Lina 
Published: June 2016

Abstractβ-Glucans are well known for its various bioactivities, but the underlying mechanism has not been fully understood. This study focuses on the anti-tumor effect and the potential mechanism of a branched β-(1, 3)-glucan (LNT) extracted from Lentinus edodes. The in vivo data indicated that LNT showed a profound inhibition ratio of ~75% against S-180 tumor growth, even significantly higher than the positive control of Cytoxan (~54%). Interestingly, LNT sharply promoted immune cells accumulation into tumors accompanied by cell apoptosis and inhibition of cell proliferation during tumor development. Furthermore, LNT not only up-regulated expressions of the tumor suppressor p53, cell cycle arrestin p21 and pro-apoptotic proteins of Bax and caspase 3/9, but also down-regulated PARP1 and anti-apoptotic protein Bcl-2 expressions in tumor tissues. It was first found that LNT initiated p53-dependent signaling pathway to suppress cell proliferation in vitro and the caspase-dependent pathway to induce cell apoptosis in vivo. The underlying anti-tumor mechanism was proposed that LNT activated immune responses to induce cell apoptosis through caspase 3-dependent signaling pathway and to inhibit cell proliferation possibly via p53-dependent signaling pathway in vivo. Besides, LNT inhibited angiogenesis by suppressing VEGF expression, leading to slow progression of tumors.
Site-specific covalent modifications of human insulin by catechol estrogens: Reactivity and induced structural and functional changes
Authors: Ku Ming-Chun , Fang Chieh-Ming , Cheng Juei-Tang , Liang Huei-Chen , Wang Tzu-Fan , Wu Chih-Hsing , Chen Chiao-Chen , Tai Jung-Hsiang , Chen Shu-Hui 
Published: June 2016

AbstractProteins, covalently modified by catechol estrogens (CEs), were identified recently from the blood serum of diabetic patients and referred to as estrogenized proteins. Estrogenization of circulating insulin may occur and affect its molecular functioning. Here, the chemical reactivity of CEs towards specific amino acid residues of proteins and the structural and functional changes induced by the estrogenization of insulin were studied using cyclic voltammetry, liquid chromatography-mass spectrometry, circular dichroism spectroscopy, molecular modeling, and bioassays. Our results indicate that CEs, namely, 2- and 4-hydroxyl estrogens, were thermodynamically and kinetically more reactive than the catechol moiety. Upon co-incubation, intact insulin formed a substantial number of adducts with one or multiple CEs via covalent conjugation at its Cys 7 in the A or B chain, as well as at His10 or Lys29 in the B chain. Such conjugation was coupled with the cleavage of inter-chain disulfide linkages. Estrogenization on these sites may block the receptor-binding pockets of insulin. Insulin signaling and glucose uptake levels were lower in MCF-7 cells treated with modified insulin than in cells treated with native insulin. Taken together, our findings demonstrate that insulin molecules are susceptible to active estrogenization, and that such modification may alter the action of insulin.
Protein-directed synthesis of highly monodispersed, spherical gold nanoparticles and their applications in multidimensional sensing
Authors: Leng Yumin , Fu Ling , Ye Liqun , Li Bo , Xu Xiumei , Xing Xiaojing , He Junbao , Song Yuling , Leng Chaoliang , Guo Yongming , Ji Xiaoxu , Lu Zhiwen 
Published: June 2016

AbstractAn in-situ reduction method has been reported to prepare gold nanoparticles (GNPs) of 40–110 nm by using the green reducing agents of proteins, which are activated by H2O2 and the superoxide anion ("Equation missing"). The protein of collagen turns HAuCl4 to the aqueous Au(I) ainions, which are further reduced by other proteins to be highly monodispersed and spherical GNPs of different sizes. The GNPs reduced by different proteins are found to be with the exposed {100} facets, the distinctive UV-vis absorption spectra and various colors (See Fig. 1). By means of extracting the color responses, such as red, green and blue (RGB) alterations, an in-situ reduction method-based multidimensional sensing platform is fabricated in the process of GNPs synthesis. Without further modification of GNPs, nine common proteins are found to be well detected and discriminated at different concentrations. Moreover, this sensing platform also demonstrates great potentials in qualitative and semiquantitative analysis on the individuals of these proteins with high sensitivity. Furthermore, the validation of this multidimensional sensing platform has been carried out by analysis on the spiked proteins in human urine and the target proteins in complex matrix (e.g. lysozyme in human tear).
Role of IL-10-producing regulatory B cells in modulating T-helper cell immune responses during silica-induced lung inflammation and fibrosis
Authors: Liu Fangwei , Dai Wujing , Li Chao , Lu Xiaowei , Chen Ying , Weng Dong , Chen Jie 
Published: June 2016

AbstractSilicosis is characterized by chronic lung inflammation and fibrosis, which are seriously harmful to human health. Previous research demonstrated that uncontrolled T-helper (Th) cell immune responses were involved in the pathogenesis of silicosis. Lymphocytes also are reported to have important roles. Existing studies on lymphocyte regulation of Th immune responses were limited to T cells, such as the regulatory T (Treg) cell, which could negatively regulate inflammation and promote the process of silicosis. However, other regulatory subsets in silicosis have not been investigated in detail, and the mechanism of immune homeostasis modulation needs further exploration. Another regulatory lymphocyte, the regulatory B cell, has recently drawn increasing attention. In this study, we comprehensively showed the role of IL-10-producing regulatory B cell (B10) in a silicosis model of mice. B10 was inducible by silica instillation. Insufficient B10 amplified inflammation and attenuated lung fibrosis by promoting the Th1 immune response. Insufficient B10 clearly inhibited Treg and decreased the level of IL-10. Our study indicated that B10 could control lung inflammation and exacerbate lung fibrosis by inhibiting Th1 response and modulating the Th balance. The regulatory function of B10 could be associated with Treg induction and IL-10 secretion.
Mesenchymal stem cells alleviate experimental rheumatoid arthritis through microRNA-regulated IκB expression
Authors: Yan Xin , Cen Yurong , Wang Qin 
Published: June 2016

AbstractPrevious studies have demonstrated that mesenchymal stem cell (MSC) transplantation reduces the severity of collagen-induced arthritis (CIA) in mice, which is a model for rheumatoid arthritis (RA) in humans. However, the underlying molecular mechanisms remain ill-defined. Here, we showed that MSC transplantation reduced the activities of NF-κB signaling and decreased microRNA-548e (miR-548e) levels in the joint tissue in CIA-mice, seemingly through activation of transforming growth factor β receptor signaling. Bioinformatics analyses revealed that miR-548e inhibited protein translation of the NF-κB inhibitor, IκB, through binding to the 3′-UTR of the IκB mRNA. MSCs co-transplanted with adeno-associated virus (AAV) carrying miR-548e abolished the therapeutic effects of MSCs on CIA. On the other hand, transplantation of AAV carrying antisense of miR-548e (as-miR-548e) partially mimicked the effects of MSC transplantation on CIA. Together, these data suggest that MSC transplantation may alleviate experimental RA partially through suppressing miR-548e-mediated IκB inhibition.
A metagenomic-based survey of microbial (de)halogenation potential in a German forest soil
Authors: Weigold Pascal , El-Hadidi Mohamed , Ruecker Alexander , Huson Daniel H. , Scholten Thomas , Jochmann Maik , Kappler Andreas , Behrens Sebastian 
Published: June 2016

AbstractIn soils halogens (fluorine, chlorine, bromine, iodine) are cycled through the transformation of inorganic halides into organohalogen compounds and vice versa. There is evidence that these reactions are microbially driven but the key enzymes and groups of microorganisms involved are largely unknown. Our aim was to uncover the diversity, abundance and distribution of genes encoding for halogenating and dehalogenating enzymes in a German forest soil by shotgun metagenomic sequencing. Metagenomic libraries of three soil horizons revealed the presence of genera known to be involved in halogenation and dehalogenation processes such as Bradyrhizobium or Pseudomonas. We detected a so far unknown diversity of genes encoding for (de)halogenating enzymes in the soil metagenome including specific and unspecific halogenases as well as metabolic and cometabolic dehalogenases. Genes for non-heme, no-metal chloroperoxidases and haloalkane dehalogenases were the most abundant halogenase and dehalogenase genes, respectively. The high diversity and abundance of (de)halogenating enzymes suggests a strong microbial contribution to natural halogen cycling. This was also confirmed in microcosm experiments in which we quantified the biotic formation of chloroform and bromoform. Knowledge on microorganisms and genes that catalyze (de)halogenation reactions is critical because they are highly relevant to industrial biotechnologies and bioremediation applications.
Use of fluorescent nanoparticles to investigate nutrient acquisition by developing Eimeria maxima macrogametocytes
Authors: Frölich Sonja , Wallach Michael 
Published: June 2016

AbstractThe enteric disease coccidiosis, caused by the unicellular parasite Eimeria, is a major and reoccurring problem for the poultry industry. While the molecular machinery driving host cell invasion and oocyst wall formation has been well documented in Eimeria, relatively little is known about the host cell modifications which lead to acquisition of nutrients and parasite growth. In order to understand the mechanism(s) by which nutrients are acquired by developing intracellular gametocytes and oocysts, we have performed uptake experiments using polystyrene nanoparticles (NPs) of 40 nm and 100 nm in size, as model NPs typical of organic macromolecules. Cytochalasin D and nocodazole were used to inhibit, respectively, the polymerization of the actin and microtubules. The results indicated that NPs entered the parasite at all stages of macrogametocyte development and early oocyst maturation via an active energy dependent process. Interestingly, the smaller NPs were found throughout the parasite cytoplasm, while the larger NPs were mainly localised to the lumen of large type 1 wall forming body organelles. NP uptake was reduced after microfilament disruption and treatment with nocodazole. These observations suggest that E. maxima parasites utilize at least 2 or more uptake pathways to internalize exogenous material during the sexual stages of development.
Transcriptome analysis revealed chimeric RNAs, single nucleotide polymorphisms and allele-specific expression in porcine prenatal skeletal muscle
Authors: Yang Yalan , Tang Zhonglin , Fan Xinhao , Xu Kui , Mu Yulian , Zhou Rong , Li Kui 
Published: June 2016

AbstractPrenatal skeletal muscle development genetically determines postnatal muscle characteristics such as growth and meat quality in pigs. However, the molecular mechanisms underlying prenatal skeletal muscle development remain unclear. Here, we performed the first genome-wide analysis of chimeric RNAs, single nuclear polymorphisms (SNPs) and allele-specific expression (ASE) in prenatal skeletal muscle in pigs. We identified 14,810 protein coding genes and 163 high-confidence chimeric RNAs expressed in prenatal skeletal muscle. More than 94.5% of the chimeric RNAs obeyed the canonical GT/AG splice rule and were trans-splicing events. Ten and two RNAs were aligned to human and mouse chimeric transcripts, respectively. We detected 106,457 high-quality SNPs (6,955 novel), which were mostly (89.09%) located within QTLs for production traits. The high proportion of non-exonic SNPs revealed the incomplete annotation status of the current swine reference genome. ASE analysis revealed that 11,300 heterozygous SNPs showed allelic imbalance, whereas 131 ASE variants were located in the chimeric RNAs. Moreover, 4 ASE variants were associated with various economically relevant traits of pigs. Taken together, our data provide a source for studies of chimeric RNAs and biomarkers for pig breeding, while illuminating the complex transcriptional events underlying prenatal skeletal muscle development in mammals.
Integrating roots into a whole plant network of flowering time genes in Arabidopsis thaliana
Authors: Bouché Frédéric , D’Aloia Maria , Tocquin Pierre , Lobet Guillaume , Detry Nathalie , Périlleux Claire 
Published: June 2016

AbstractMolecular data concerning the involvement of roots in the genetic pathways regulating floral transition are lacking. In this study, we performed global analyses of the root transcriptome in Arabidopsis in order to identify flowering time genes that are expressed in the roots and genes that are differentially expressed in the roots during the induction of flowering. Data mining of public microarray experiments uncovered that about 200 genes whose mutations are reported to alter flowering time are expressed in the roots (i.e.were detected in more than 50% of the microarrays). However, only a few flowering integrator genes passed the analysis cutoff. Comparison of root transcriptome in short days and during synchronized induction of flowering by a single 22-h long day revealed that 595 genes were differentially expressed. Enrichment analyses of differentially expressed genes in root tissues, gene ontology categories, and cis-regulatory elements converged towards sugar signaling. We concluded that roots are integrated in systemic signaling, whereby carbon supply coordinates growth at the whole plant level during the induction of flowering. This coordination could involve the root circadian clock and cytokinin biosynthesis as a feed forward loop towards the shoot.
Substrate-assisted mechanism of RNP disruption by the spliceosomal Brr2 RNA helicase
Authors: Theuser Matthias , Höbartner Claudia , Wahl Markus C. , Santos Karine F. 
Published: June 2016

Significance
RNA helicases can remodel substrate RNA–protein complexes in diverse ways. However, these activities have typically been studied using noncognate helicase-substrate systems, because the in vivo targets of many helicases are unknown. We investigated how the Brr2 protein disrupts its cognate U4/U6 di-small nuclear RNA–protein complex (di-snRNP), a reaction required for spliceosome catalytic activation. Our results suggest that Brr2 acts like a switch, initiating displacement of U6 snRNA, thereby inducing it to adopt an alternative conformation incompatible with base pairing to U4 snRNA. This mechanism explains how one U4/U6-bound protein, pre-mRNA processing factor 3 (Prp3), is displaced, whereas Prp31 and small nuclear ribonucleoprotein-associated protein 1 (Snu13) are released in complex with U4 snRNA. This unprecedented mode of RNP disruption minimizes requirements for reassembly of the U4/U6 di-snRNP after splicing.
Computational and experimental investigations of one-step conversion of poly(carbonate)s into value-added poly(aryl ether sulfone)s
Authors: Jones Gavin O. , Yuen Alexander , Wojtecki Rudy J. , Hedrick James L. , García Jeannette M. 
Published: June 2016

SignificanceThis work describes a convenient, quantitative, and robust one-step transformation of polycarbonates into high-value poly(aryl ether sulfone)s in the presence of a carbonate salt and bis(aryl fluorides). This strategy has important implications for the repurposing of plastic waste into value-added materials by the use of carefully controlled depolymerization conditions. Computational studies used to support these findings show how carbonate salts decompose organic carbonates and form the poly(aryl ether sulfone) products. Determining the role of the metal salt in the depolymerization/repolymerization process will enable future design for economic recycling and synthesis methods.
Enzyme surface rigidity tunes the temperature dependence of catalytic rates
Authors: Isaksen Geir Villy , Åqvist Johan , Brandsdal Bjørn Olav 
Published: June 2016

Significance
Faced with an exponential decrease in chemical reaction rates as the temperature is lowered, cold-adapted organisms require specialized enzymes to maintain a functional metabolism. Such enzymes catalyze their reactions with lower activation enthalpies counterbalanced by more negative entropies, yielding higher rates at low temperatures compared with mesophilic enzymes, although the rates at room temperature are often similar. The structural mechanisms behind this universal property still remain largely unknown. We attack this problem with extensive computer simulations and high-precision Arrhenius plots, showing that the protein surface rigidity outside the active site region tunes the enthalpy–entropy balance. This enables significantly higher rates at low to moderate temperatures for cold-active enzymes compared with their warm-active counterparts.
Chromosome-level assembly ofArabidopsis thalianaLerreveals the extent of translocation and inversion polymorphisms
Authors: Zapata Luis , Ding Jia , Willing Eva-Maria , Hartwig Benjamin , Bezdan Daniela , Jiao Wen-Biao , Patel Vipul , Velikkakam James Geo , Koornneef Maarten , Ossowski Stephan , Schneeberger Korbinian 
Published: June 2016

SignificanceDespite widespread reports on deciphering the sequences of all kinds of genomes, most of these reconstructed genomes rely on a comparison of short DNA sequencing reads to a reference sequence, rather than being independently reconstructed. This method limits the insights on genomic differences to local, mostly small-scale variation, because large rearrangements are likely overlooked by current methods. We have de novo assembled the genome of a common strain ofArabidopsis thalianaLandsbergerectaand revealed hundreds of rearranged regions. Some of these differences suppress meiotic recombination, impacting the haplotypes of a worldwide population ofA. thaliana. In addition to sequence changes, this work, which, to our knowledge is the first comparison of an independent, chromosome-level assembledA. thalianagenome, revealed hundreds of unknown, accession-specific genes.
Large deviations of the shifted index number in the Gaussian ensemble
Authors: Pérez Castillo Isaac 
Published: June 2016

Abstract
We show that, using the Coulomb fluid approach, we are able to derive a rate function

Ψ
(
c
,
x
)

of two variables that captures: (i) the large deviations of bulk eigenvalues; (ii) the large deviations of extreme eigenvalues (both left and right large deviations); (iii) the statistics of the fraction c of eigenvalues to the left of a position x. Thus,

Ψ
(
c
,
x
)

explains the full order statistics of the eigenvalues of large random Gaussian matrices as well as the statistics of the shifted index number. All our analytical findings are thoroughly compared with Monte Carlo simulations, obtaining excellent agreement. A summary of preliminary results has already been presented in Pérez Castillo (2014 Phys. Rev. E 90 040102) in the context of one-dimensional trapped spinless fermions in a harmonic potential.
The chemical identity of intervessel pit membranes inAcerchallenges hydrogel control of xylem hydraulic conductivity
Authors: Klepsch Matthias M. , Schmitt Marco , Paul Knox J. , Jansen Steven 
Published: June 2016

AbstractIon-mediated enhancement of the hydraulic conductivity of xylem tissue (i.e. the ionic effect) has been reported for various angiosperm species. One explanation of the ionic effect is that it is caused by the swelling and shrinking of intervessel pit membranes due to the presence of pectins and/or other cell-wall matrix polymers such as heteroxylans or arabinogalactan–proteins (AGPs) that may contain acidic sugars. Here, we examined the ionic effect for six Acer species and their pit membrane chemistry using immunocytochemistry, including antibodies against glycoproteins. Moreover, anatomical features related to the bordered pit morphology and vessel dimensions were investigated using light and electron microscopy. The ionic effect varied from 18 % (± 9) to 32 % (± 13). Epitopes of homogalacturonan (LM18) and xylan (LM11) were not detected in intervessel pit membranes. Negative results were also obtained for glycoproteins (extensin: LM1, JIM20; AGP glycan: LM2), although AGP (JIM13)-related epitopes were detected in parenchyma cells. The mean vessel length was significantly correlated with the magnitude of the ionic effect, unlike other pit or vessel-related characteristics. Our results suggest that intervessel pit membranes of Acer are unlikely to contain pectic or other acidic polysaccharides. Therefore, alternative explanations should be tested to clarify the ionic effect.