bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kindlin-2 controls TGF-β signalling and Sox9 expression to regulate chondrogenesis
Authors: Wu Chuanyue , Jiao Hongli , Lai Yumei , Zheng Wei , Chen Ka , Qu Hong , Deng Weimin , Song Pingping , Zhu Ke , Cao Huiling , Galson Deborah L. , Fan Jie , Im Hee-Jeong , Liu Yujie , Chen Ju , Chen Di , Xiao Guozhi 
Published: July 2015

AbstractThe signals that control skeletogenesis are incompletely understood. Here we show that deleting Kindlin-2 in Prx1-expressing mesenchymal progenitors in mice causes neonatal lethality, chondrodysplasia and loss of the skull vault. Kindlin-2 ablation reduces chondrocyte density by decreasing cell proliferation and increasing apoptosis, and disrupts column formation, thus impairing the formation of the primary ossification center and causing severe limb shortening. Remarkably, Kindlin-2 localizes to not only focal adhesions, but also to the nuclei of chondrocytes. Loss of Kindlin-2 reduces, while the overexpression of Kindlin-2 increases, Sox9 expression. Furthermore, the overexpression of Sox9 restores the defects in chondrogenic differentiation induced by Kindlin-2 deletion in vitro. In addition, Kindlin-2 ablation inhibits TGF-β1-induced Smad2 phosphorylation and chondrocyte differentiation. Finally, deleting Kindlin-2 in chondrocytes directly impairs chondrocyte functions, resulting in progressive dwarfism and kyphosis in mice. These studies uncover a previously unrecognized function for Kindlin-2 and a mechanism for regulation of the chondrocyte differentiation programme and chondrogenesis.
Structural basis for cellobiose dehydrogenase action during oxidative cellulose degradation
Authors: Tan Tien-Chye , Kracher Daniel , Gandini Rosaria , Sygmund Christoph , Kittl Roman , Haltrich Dietmar , Hällberg B. Martin , Ludwig Roland , Divne Christina 
Published: July 2015

AbstractA new paradigm for cellulose depolymerization by fungi focuses on an oxidative mechanism involving cellobiose dehydrogenases (CDH) and copper-dependent lytic polysaccharide monooxygenases (LPMO); however, mechanistic studies have been hampered by the lack of structural information regarding CDH. CDH contains a haem-binding cytochrome (CYT) connected via a flexible linker to a flavin-dependent dehydrogenase (DH). Electrons are generated from cellobiose oxidation catalysed by DH and shuttled via CYT to LPMO. Here we present structural analyses that provide a comprehensive picture of CDH conformers, which govern the electron transfer between redox centres. Using structure-based site-directed mutagenesis, rapid kinetics analysis and molecular docking, we demonstrate that flavin-to-haem interdomain electron transfer (IET) is enabled by a haem propionate group and that rapid IET requires a closed CDH state in which the propionate is tightly enfolded by DH. Following haem reduction, CYT reduces LPMO to initiate oxygen activation at the copper centre and subsequent cellulose depolymerization.
Recessive mutations in POLR1C cause a leukodystrophy by impairing biogenesis of RNA polymerase III
Authors: Thiffault Isabelle , Wolf Nicole I. , Forget Diane , Guerrero Kether , Tran Luan T. , Choquet Karine , Lavallée-Adam Mathieu , Poitras Christian , Brais Bernard , Yoon Grace , Sztriha Laszlo , Webster Richard I. , Timmann Dagmar , van de Warrenburg Bart P. , Seeger Jürgen , Zimmermann Alíz , Máté Adrienn , Goizet Cyril , Fung Eva , van der Knaap Marjo S. , Fribourg Sébastien , Vanderver Adeline , Simons Cas , Taft Ryan J. , Yates III John R. , Coulombe Benoit , Bernard Geneviève 
Published: July 2015

AbstractA small proportion of 4H (Hypomyelination, Hypodontia and Hypogonadotropic Hypogonadism) or RNA polymerase III (POLR3)-related leukodystrophy cases are negative for mutations in the previously identified causative genesPOLR3AandPOLR3B. Here we report eight of these cases carrying recessive mutations inPOLR1C, a gene encoding a shared POLR1 and POLR3 subunit, also mutated in some Treacher Collins syndrome (TCS) cases. Using shotgun proteomics and ChIP sequencing, we demonstrate that leukodystrophy-causative mutations, but not TCS mutations, inPOLR1Cimpair assembly and nuclear import of POLR3, but not POLR1, leading to decreased binding to POLR3 target genes. This study is the first to show that distinct mutations in a gene coding for a shared subunit of two RNA polymerases lead to selective modification of the enzymes’ availability leading to two different clinical conditions and to shed some light on the pathophysiological mechanism of one of the most common hypomyelinating leukodystrophies, POLR3-related leukodystrophy.
Genetic determinants of antithyroid drug-induced agranulocytosis by human leukocyte antigen genotyping and genome-wide association study
Authors: Chen Pei-Lung , Shih Shyang-Rong , Wang Pei-Wen , Lin Ying-Chao , Chu Chen-Chung , Lin Jung-Hsin , Chen Szu-Chi , Chang Ching-Chung , Huang Tien-Shang , Tsai Keh Sung , Tseng Fen-Yu , Wang Chih-Yuan , Lu Jin-Ying , Chiu Wei-Yih , Chang Chien-Ching , Chen Yu-Hsuan , Chen Yuan-Tsong , Fann Cathy Shen-Jang , Yang Wei-Shiung , Chang Tien-Chun 
Published: July 2015

AbstractGraves’ disease is the leading cause of hyperthyroidism affecting 1.0–1.6% of the population. Antithyroid drugs are the treatment cornerstone, but may cause life-threatening agranulocytosis. Here we conduct a two-stage association study on two separate subject sets (in total 42 agranulocytosis cases and 1,208 Graves’ disease controls), using direct human leukocyte antigen genotyping and SNP-based genome-wide association study. We demonstrate HLA-B*38:02 (Armitage trend Pcombined=6.75 × 10−32) and HLA-DRB1*08:03 (Pcombined=1.83 × 10−9) as independent susceptibility loci. The genome-wide association study identifies the same signals. Estimated odds ratios for these two loci comparing effective allele carriers to non-carriers are 21.48 (95% confidence interval=11.13–41.48) and 6.13 (95% confidence interval=3.28–11.46), respectively. Carrying both HLA-B*38:02 and HLA-DRB1*08:03 increases odds ratio to 48.41 (Pcombined=3.32 × 10−21, 95% confidence interval=21.66–108.22). Our results could be useful for antithyroid-induced agranulocytosis and potentially for agranulocytosis caused by other chemicals.
The minimal work cost of information processing
Authors: Faist Philippe , Dupuis Frédéric , Oppenheim Jonathan , Renner Renato 
Published: July 2015

AbstractIrreversible information processing cannot be carried out without some inevitable thermodynamical work cost. This fundamental restriction, known as Landauer’s principle, is increasingly relevant today, as the energy dissipation of computing devices impedes the development of their performance. Here we determine the minimal work required to carry out any logical process, for instance a computation. It is given by the entropy of the discarded information conditional to the output of the computation. Our formula takes precisely into account the statistically fluctuating work requirement of the logical process. It enables the explicit calculation of practical scenarios, such as computational circuits or quantum measurements. On the conceptual level, our result gives a precise and operational connection between thermodynamic and information entropy, and explains the emergence of the entropy state function in macroscopic thermodynamics.
Microsecond protein dynamics observed at the single-molecule level
Authors: Otosu Takuhiro , Ishii Kunihiko , Tahara Tahei 
Published: July 2015

AbstractHow polypeptide chains acquire specific conformations to realize unique biological functions is a central problem of protein science. Single-molecule spectroscopy, combined with fluorescence resonance energy transfer, is utilized to study the conformational heterogeneity and the state-to-state transition dynamics of proteins on the submillisecond to second timescales. However, observation of the dynamics on the microsecond timescale is still very challenging. This timescale is important because the elementary processes of protein dynamics take place and direct comparison between experiment and simulation is possible. Here we report a new single-molecule technique to reveal the microsecond structural dynamics of proteins through correlation of the fluorescence lifetime. This method, two-dimensional fluorescence lifetime correlation spectroscopy, is applied to clarify the conformational dynamics of cytochromec. Three conformational ensembles and the microsecond transitions in each ensemble are indicated from the correlation signal, demonstrating the importance of quantifying microsecond dynamics of proteins on the folding free energy landscape.
Green to red photoconversion of GFP for protein tracking in vivo
Authors: Sattarzadeh Amirali , Saberianfar Reza , Zipfel Warren R. , Menassa Rima , Hanson Maureen R. 
Published: July 2015

AbstractA variety of fluorescent proteins have been identified that undergo shifts in spectral emission properties over time or once they are irradiated by ultraviolet or blue light. Such proteins are finding application in following the dynamics of particular proteins or labelled organelles within the cell. However, before genes encoding these fluorescent proteins were available, many proteins have already been labelled with GFP in transgenic cells; a number of model organisms feature collections of GFP-tagged lines and organisms. Here we describe a fast, localized and non-invasive method for GFP photoconversion from green to red. We demonstrate its use in transgenic plant, Drosophila and mammalian cells in vivo. While genes encoding fluorescent proteins specifically designed for photoconversion will usually be advantageous when creating new transgenic lines, our method for photoconversion of GFP allows the use of existing GFP-tagged transgenic lines for studies of dynamic processes in living cells.
Rhein prevents endotoxin-induced acute kidney injury by inhibiting NF-κB activities
Authors: Yu Chen , Qi Dong , Sun Ju-Feng , Li Peng , Fan Hua-Ying 
Published: July 2015

AbstractThis study aimed to explore the effect and mechanisms of rhein on sepsis-induced acute kidney injury by injecting lipopolysaccharide (LPS) and cecal ligation and puncture (CLP) in vivo and on LPS-induced HK-2 cells in vitro. For histopathological analysis, rhein effectively attenuated the severity of renal injury. Rhein could significantly decrease concentration of BUN and SCr and level of TNF-α and IL-1β in two different mouse models of experimental sepsis. Moreover, rhein could markedly attenuate circulating leukocyte infiltration and enhance phagocytic activity of macrophages partly impaired at 12 h after CLP. Rhein could enhance cell viability and suppresse the release of MCP-1 and IL-8 in LPS-stimulated HK-2 cells Furthermore, rhein down regulated the expression of phosphorylated NF-κB p65, IκBα and IKKβ stimulated by LPS both in vivo and in vitro. All these results suggest that rhein has protective effects on endotoxin-induced kidney injury. The underlying mechanism of rhein on anti-endotoxin kidney injury may be closely related with its anti-inflammatory and immunomodulatory properties by decreasing NF-κB activation through restraining the expression and phosphorylation of the relevant proteins in NF-κB signal pathway, hindering transcription of NF-κB p65.These evidence suggest that rhein has a potential application to treat endotoxemia-associated acute kidney injury.
Synthesis of magnetic metal-organic framework (MOF) for efficient removal of organic dyes from water
Authors: Zhao Xiaoli , Liu Shuangliu , Tang Zhi , Niu Hongyun , Cai Yaqi , Meng Wei , Wu Fengchang , Giesy John P. 
Published: July 2015

AbstractA novel, simple and efficient strategy for fabricating a magnetic metal-organic framework (MOF) as sorbent to remove organic compounds from simulated water samples is presented and tested for removal of methylene blue (MB) as an example. The novel adsorbents combine advantages of MOFs and magnetic nanoparticles and possess large capacity, low cost, rapid removal and easy separation of the solid phase, which makes it an excellent sorbent for treatment of wastewaters. The resulting magnetic MOFs composites (also known as MFCs) have large surface areas (79.52 m2 g−1), excellent magnetic response (14.89 emu g−1) and large mesopore volume (0.09 cm3 g−1), as well as good chemical inertness and mechanical stability. Adsorption was not drastically affected by pH, suggesting π–π stacking interaction and/or hydrophobic interactions between MB and MFCs. Kinetic parameters followed pseudo-second-order kinetics and adsorption was described by the Freundlich isotherm. Adsorption capacity was 84 mg MB g−1 at an initial MB concentration of 30 mg L−1, which increased to 245 mg g−1 when the initial MB concentration was 300 mg L−1. This capacity was much greater than most other adsorbents reported in the literature. In addition, MFC adsorbents possess excellent reusability, being effective after at least five consecutive cycles.
Structural insights into the unique inhibitory mechanism of the silkworm protease inhibitor serpin18
Authors: Guo Peng-Chao , Dong Zhaoming , Zhao Ping , Zhang Yan , He Huawei , Tan Xiang , Zhang Weiwei , Xia Qingyou 
Published: July 2015

AbstractSerpins generally serve as inhibitors that utilize a mobile reactive center loop (RCL) as bait to trap protease targets. Here, we present the crystal structure of serpin18 from Bombyx mori at 1.65 Å resolution, which has a very short and stable RCL. Activity analysis showed that the inhibitory target of serpin18 is a cysteine protease rather than a serine protease. Notably, this inhibitiory reaction results from the formation of an intermediate complex, which then follows for the digestion of protease and inhibitor into small fragments. This activity differs from previously reported modes of inhibition for serpins. Our findings have thus provided novel structural insights into the unique inhibitory mechanism of serpin18. Furthermore, one physiological target of serpin18, fibroinase, was identified, which enables us to better define the potential role for serpin18 in regulating fibroinase activity during B. mori development.
Predictability Bounds of Electronic Health Records
Authors: Dahlem Dominik , Maniloff Diego , Ratti Carlo 
Published: July 2015

AbstractThe ability to intervene in disease progression given a person’s disease history has the potential to solve one of society’s most pressing issues: advancing health care delivery and reducing its cost. Controlling disease progression is inherently associated with the ability to predict possible future diseases given a patient’s medical history. We invoke an information-theoretic methodology to quantify the level of predictability inherent in disease histories of a large electronic health records dataset with over half a million patients. In our analysis, we progress from zeroth order through temporal informed statistics, both from an individual patient’s standpoint and also considering the collective effects. Our findings confirm our intuition that knowledge of common disease progressions results in higher predictability bounds than treating disease histories independently. We complement this result by showing the point at which the temporal dependence structure vanishes with increasing orders of the time-correlated statistic. Surprisingly, we also show that shuffling individual disease histories only marginally degrades the predictability bounds. This apparent contradiction with respect to the importance of time-ordered information is indicative of the complexities involved in capturing the health-care process and the difficulties associated with utilising this information in universal prediction algorithms.
Intermediate monocytes in ANCA vasculitis: increased surface expression of ANCA autoantigens and IL-1β secretion in response to anti-MPO antibodies
Authors: O’Brien Eóin C. , Abdulahad Wayel H. , Rutgers Abraham , Huitema Minke G. , O’Reilly Vincent P. , Coughlan Alice M. , Harrington Mark , Heeringa Peter , Little Mark A. , Hickey Fionnuala B. 
Published: July 2015

AbstractANCA vasculitis encompasses several autoimmune conditions characterised by destruction of small vessels, inflammation of the respiratory tract and glomerulonephritis. Most patients harbour autoantibodies to myeloperoxidase (MPO) or proteinase 3 (PR3). Clinical and experimental data suggest that pathogenesis is driven by ANCA-mediated activation of neutrophils and monocytes. We investigated a potential role for distinct monocyte subsets. We found that the relative proportion of intermediate monocytes is increased in patients versus control individuals and both MPO and PR3 are preferentially expressed on these cells. We demonstrate that MPO and PR3 are expressed independently of each other on monocytes and that PR3 is not associated with CD177. MPO expression correlates with that of Fc receptor CD16 on intermediate monocytes. Monocyte subsets respond differently to antibodies directed against MPO and PR3, with anti-MPO but not anti-PR3 leading to increased IL-1β, IL-6 and IL-8 production. In concordance with the observed higher surface expression of MPO on intermediate monocytes, this subset produces the highest quantity of IL-1β in response to anti-MPO stimulation. These data suggest that monocytes, specifically, the intermediate subset, may play a role in ANCA vasculitis and also indicate that substantial differences exist between the effect of anti-MPO and anti-PR3 antibodies on these cells.
In situ microscopic observation of chitin and fungal cells with chitinous cell walls in hydrothermal conditions
Authors: Deguchi Shigeru , Tsujii Kaoru , Horikoshi Koki 
Published: July 2015

AbstractRecent findings of intact chitin in fossil records suggest surprisingly high recalcitrance of this biopolymer during hydrothermal treatments. We also know in the experience of everyday life that mushroom, cells of which have chitinous cell walls, do not fall apart however long they are simmered. We used in situ optical microscopy to examine chitin and fungal cells with chitinous cell walls during hydrothermal treatments and obtained direct evidence that they remained undegraded at temperatures well over 200 °C. The results show very hot and compressed water is needed to make mushrooms mushy.
Single Nanoparticle Detection Using Far-field Emission of Photonic Molecule around the Exceptional Point
Authors: Zhang Nan , Liu Shuai , Wang Kaiyang , Gu Zhiyuan , Li Meng , Yi Ningbo , Xiao Shumin , Song Qinghai 
Published: July 2015

AbstractHighly sensitive, label-free detection methods have important applications in fundamental research and healthcare diagnostics. To date, the detection of single nanoparticles has remained largely dependent on extremely precise spectral measurement, which relies on high-cost equipment. Here, we demonstrate a simple but very nontrivial mechanism for the label-free sizing of nanoparticles using the far-field emission of a photonic molecule (PM) around an exceptional point (EP). By attaching a nanoparticle to a PM around an EP, the main resonant behaviors are strongly disturbed. In addition to typical mode splitting, we find that the far-field pattern of the PM is significantly changed. Taking a heteronuclear diatomic PM as an example, we demonstrate that a single nanoparticle, whose radius is as small as 1 nm to 7 nm, can be simply monitored through the variation of the far-field pattern. Compared with conventional methods, our approach is much easier and does not rely on high-cost equipment. In addition, this research will illuminate new advances in single nanoparticle detection.
Trace element fingerprinting of cockle (Cerastoderma edule) shells can reveal harvesting location in adjacent areas
Authors: Ricardo Fernando , Génio Luciana , Costa Leal Miguel , Albuquerque Rui , Queiroga Henrique , Rosa Rui , Calado Ricardo 
Published: July 2015

AbstractDetermining seafood geographic origin is critical for controlling its quality and safeguarding the interest of consumers. Here, we use trace element fingerprinting (TEF) of bivalve shells to discriminate the geographic origin of specimens. Barium (Ba), manganese (Mn), magnesium (Mg), strontium (Sr) and lead (Pb) were quantified in cockle shells (Cerastoderma edule) captured with two fishing methods (by hand and by hand-raking) and from five adjacent fishing locations within an estuarine system (Ria de Aveiro, Portugal). Results suggest no differences in TEF of cockle shells captured by hand or by hand-raking, thus confirming that metal rakes do not act as a potential source of metal contamination that could somehow bias TEF results. In contrast, significant differences were recorded among locations for all trace elements analysed. A Canonical Analysis of Principal Coordinates (CAP) revealed that 92% of the samples could be successfully classified according to their fishing location using TEF. We show that TEF can be an accurate, fast and reliable method to determine the geographic origin of bivalves, even among locations separated less than 1 km apart within the same estuarine system. Nonetheless, follow up studies are needed to determine if TEF can reliably discriminate between bivalves originating from different ecosystems.
Rice_Phospho 1.0: a new rice-specific SVM predictor for protein phosphorylation sites
Authors: Lin Shoukai , Song Qi , Tao Huan , Wang Wei , Wan Weifeng , Huang Jian , Xu Chaoqun , Chebii Vivien , Kitony Justine , Que Shufu , Harrison Andrew , He Huaqin 
Published: July 2015

AbstractExperimentally-determined or computationally-predicted protein phosphorylation sites for distinctive species are becoming increasingly common. In this paper, we compare the predictive performance of a novel classification algorithm with different encoding schemes to develop a rice-specific protein phosphorylation site predictor. Our results imply that the combination of Amino acid occurrence Frequency with Composition of K-Spaced Amino Acid Pairs (AF-CKSAAP) provides the best description of relevant sequence features that surround a phosphorylation site. A support vector machine (SVM) using AF-CKSAAP achieves the best performance in classifying rice protein phophorylation sites when compared to the other algorithms. We have used SVM with AF-CKSAAP to construct a rice-specific protein phosphorylation sites predictor, Rice_Phospho 1.0 (http://bioinformatics.fafu.edu.cn/rice_phospho1.0). We measure the Accuracy (ACC) and Matthews Correlation Coefficient (MCC) of Rice_Phospho 1.0 to be 82.0% and 0.64, significantly higher than those measures for other predictors such as Scansite, Musite, PlantPhos and PhosphoRice. Rice_Phospho 1.0 also successfully predicted the experimentally identified phosphorylation sites in LOC_Os03g51600.1, a protein sequence which did not appear in the training dataset. In summary, Rice_phospho 1.0 outputs reliable predictions of protein phosphorylation sites in rice and will serve as a useful tool to the community.