bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual regulatory switch through interactions of Tcf7l2/Tcf4 with stage-specific partners propels oligodendroglial maturation
Authors: Zhao Chuntao , Deng Yaqi , Liu Lei , Yu Kun , Zhang Liguo , Wang Haibo , He Xuelian , Wang Jincheng , Lu Changqing , Wu Laiman N , Weng Qinjie , Mao Meng , Li Jianrong , van Es Johan H , Xin Mei , Parry Lee , Goldman Steven A , Clevers Hans , Lu Q. Richard 
Published: March 2016

AbstractConstitutive activation of Wnt/β-catenin inhibits oligodendrocyte myelination. Tcf7l2/Tcf4, a β-catenin transcriptional partner, is required for oligodendrocyte differentiation. How Tcf7l2 modifies β-catenin signalling and controls myelination remains elusive. Here we define a stage-specific Tcf7l2-regulated transcriptional circuitry in initiating and sustaining oligodendrocyte differentiation. Multistage genome occupancy analyses reveal that Tcf7l2 serially cooperates with distinct co-regulators to control oligodendrocyte lineage progression. At the differentiation onset, Tcf7l2 interacts with a transcriptional co-repressor Kaiso/Zbtb33 to block β-catenin signalling. During oligodendrocyte maturation, Tcf7l2 recruits and cooperates with Sox10 to promote myelination. In that context, Tcf7l2 directly activates cholesterol biosynthesis genes and cholesterol supplementation partially rescues oligodendrocyte differentiation defects in Tcf712 mutants. Together, we identify stage-specific co-regulators Kaiso and Sox10 that sequentially interact with Tcf7l2 to coordinate the switch at the transitions of differentiation initiation and maturation during oligodendrocyte development, and point to a previously unrecognized role of Tcf7l2 in control of cholesterol biosynthesis for CNS myelinogenesis.
The Gq signalling pathway inhibits brown and beige adipose tissue
Authors: Klepac Katarina , Kilić Ana , Gnad Thorsten , Brown Loren M. , Herrmann Beate , Wilderman Andrea , Balkow Aileen , Glöde Anja , Simon Katharina , Lidell Martin E. , Betz Matthias J. , Enerbäck Sven , Wess Jürgen , Freichel Marc , Blüher Matthias , König Gabi , Kostenis Evi , Insel Paul A. , Pfeifer Alexander 
Published: March 2016

AbstractBrown adipose tissue (BAT) dissipates nutritional energy as heat via the uncoupling protein-1 (UCP1) and BAT activity correlates with leanness in human adults. Here we profile G protein-coupled receptors (GPCRs) in brown adipocytes to identify druggable regulators of BAT. Twenty-one per cent of the GPCRs link to the Gq family, and inhibition of Gq signalling enhances differentiation of human and murine brown adipocytes. In contrast, activation of Gq signalling abrogates brown adipogenesis. We further identify the endothelin/Ednra pathway as an autocrine activator of Gq signalling in brown adipocytes. Expression of a constitutively active Gq protein in mice reduces UCP1 expression in BAT, whole-body energy expenditure and the number of brown-like/beige cells in white adipose tissue (WAT). Furthermore, expression of Gq in human WAT inversely correlates with UCP1 expression. Thus, our data indicate that Gq signalling regulates brown/beige adipocytes and inhibition of Gq signalling may be a novel therapeutic approach to combat obesity.
Editing of mouse and human immunoglobulin genes by CRISPR-Cas9 system
Authors: Cheong Taek-Chin , Compagno Mara , Chiarle Roberto 
Published: March 2016

AbstractApplications of the CRISPR-Cas9 system to edit the genome have widely expanded to include DNA gene knock-out, deletions, chromosomal rearrangements, RNA editing and genome-wide screenings. Here we show the application of CRISPR-Cas9 technology to edit the mouse and human immunoglobulin (Ig) genes. By delivering Cas9 and guide-RNA (gRNA) with retro- or lenti-virus to IgM+ mouse B cells and hybridomas, we induce class-switch recombination (CSR) of the IgH chain to the desired subclass. Similarly, we induce CSR in all human B cell lines tested with high efficiency to targeted IgH subclass. Finally, we engineer mouse hybridomas to secrete Fab′ fragments instead of the whole Ig. Our results indicate that Ig genes in mouse and human cells can be edited to obtain any desired IgH switching helpful to study the biology of normal and lymphoma B cells. We also propose applications that could transform the technology of antibody production.
FAM21 directs SNX27–retromer cargoes to the plasma membrane by preventing transport to the Golgi apparatus
Authors: Lee Seongju , Chang Jaerak , Blackstone Craig 
Published: March 2016

AbstractThe endosomal network maintains cellular homeostasis by sorting, recycling and degrading endocytosed cargoes. Retromer organizes the endosomal sorting pathway in conjunction with various sorting nexin (SNX) proteins. The SNX27–retromer complex has recently been identified as a major endosomal hub that regulates endosome-to-plasma membrane recycling by preventing lysosomal entry of cargoes. Here, we show that SNX27 directly interacts with FAM21, which also binds retromer, within the Wiskott–Aldrich syndrome protein and SCAR homologue (WASH) complex. This interaction is required for the precise localization of SNX27 at an endosomal subdomain as well as for recycling of SNX27-retromer cargoes. Furthermore, FAM21 prevents cargo transport to the Golgi apparatus by controlling levels of phosphatidylinositol 4-phosphate, which facilitates cargo dissociation at the Golgi. Together, our results demonstrate that the SNX27–retromer–WASH complex directs cargoes to the plasma membrane by blocking their transport to lysosomes and the Golgi.
Open-gate mutants of the mammalian proteasome show enhanced ubiquitin-conjugate degradation
Authors: Choi Won Hoon , de Poot Stefanie A. H. , Lee Jung Hoon , Kim Ji Hyeon , Han Dong Hoon , Kim Yun Kyung , Finley Daniel , Lee Min Jae 
Published: March 2016

AbstractWhen in the closed form, the substrate translocation channel of the proteasome core particle (CP) is blocked by the convergent N termini of α-subunits. To probe the role of channel gating in mammalian proteasomes, we deleted the N-terminal tail of α3; the resulting α3ΔN proteasomes are intact but hyperactive in the hydrolysis of fluorogenic peptide substrates and the degradation of polyubiquitinated proteins. Cells expressing the hyperactive proteasomes show markedly elevated degradation of many established proteasome substrates and resistance to oxidative stress. Multiplexed quantitative proteomics revealed ∼200 proteins with reduced levels in the mutant cells. Potentially toxic proteins such as tau exhibit reduced accumulation and aggregate formation. These data demonstrate that the CP gate is a key negative regulator of proteasome function in mammals, and that opening the CP gate may be an effective strategy to increase proteasome activity and reduce levels of toxic proteins in cells.
Tracking the shape-dependent sintering of platinum–rhodium model catalysts under operando conditions
Authors: Hejral Uta , Müller Patrick , Balmes Olivier , Pontoni Diego , Stierle Andreas 
Published: March 2016

AbstractNanoparticle sintering during catalytic reactions is a major cause for catalyst deactivation. Understanding its atomic-scale processes and finding strategies to reduce it is of paramount scientific and economic interest. Here, we report on the composition-dependent three-dimensional restructuring of epitaxial platinum–rhodium alloy nanoparticles on alumina during carbon monoxide oxidation at 550 K and near-atmospheric pressures employing in situ high-energy grazing incidence x-ray diffraction, online mass spectrometry and a combinatorial sample design. For platinum-rich particles our results disclose a dramatic reaction-induced height increase, accompanied by a corresponding reduction of the total particle surface coverage. We find this restructuring to be progressively reduced for particles with increasing rhodium composition. We explain our observations by a carbon monoxide oxidation promoted non-classical Ostwald ripening process during which smaller particles are destabilized by the heat of reaction. Its driving force lies in the initial particle shape which features for platinum-rich particles a kinetically stabilized, low aspect ratio.
SCARB2 variants and glucocerebrosidase activity in Parkinson’s disease
Authors: Alcalay Roy N , Levy Oren A , Wolf Pavlina , Oliva Petra , Zhang Xiaokui Kate , Waters Cheryl H , Fahn Stanley , Kang Un Jung , Liong Christopher , Ford Blair , Mazzoni Pietro , Kuo Sheng , Johnson Amelie , Xiong Lan , Rouleau Guy A , Chung Wendy K , Marder Karen S , Gan-Or Ziv 
Published: March 2016

AbstractMutations in glucocerebrosidase (GBA) are a common risk factor for Parkinson's disease (PD). The scavenger receptor class B member 2 (SCARB2) gene encodes a receptor responsible for the transport of glucocerebrosidase (GCase) to the lysosome. Two common SNPs in linkage disequilibrium with SCARB2, rs6812193 and rs6825004, have been associated with PD and Lewy Body Disease in genome-wide association studies. Whether these SNPs are associated with altered glucocerebrosidase enzymatic activity is unknown. Our objective was to determine whether SCARB2 SNPs are associated with PD and with reduced GCase activity. The GBA gene was fully sequenced, and the LRRK2 G2019S and SCARB2 rs6812193 and rs6825004 SNPs were genotyped in 548 PD patients and 272 controls. GCase activity in dried blood spots was measured by tandem mass spectrometry. We tested the association between SCARB2 genotypes and PD risk in regression models adjusted for gender, age, and LRRK2 G2019S and GBA mutation status. We compared GCase activity between participants with different genotypes at rs6812193 and rs6825004. Genotype at rs6812193 was associated with PD status. PD cases were less likely to carry the T allele than the C allele (OR=0.71; P=0.004), but GCase enzymatic activity was similar across rs6812193 genotypes (C/C: 11.88 μmol/l/h; C/T: 11.80 μmol/l/h; T/T: 12.02 μmol/l/h; P=0.867). Genotype at rs6825004 was not associated with either PD status or GCase activity. In conclusion, our results support an association between SCARB2 genotype at rs6812193 and PD, but suggest that the increased risk is not mediated by GCase activity.
Dependence of fluorescent protein brightness on protein concentration in solution and enhancement of it
Authors: Morikawa Takamitsu J. , Fujita Hideaki , Kitamura Akira , Horio Takashi , Yamamoto Johtaro , Kinjo Masataka , Sasaki Akira , Machiyama Hiroaki , Yoshizawa Keiko , Ichimura Taro , Imada Katsumi , Nagai Takeharu , Watanabe Tomonobu M. 
Published: March 2016

AbstractFluorescent proteins have been widely used in biology because of their compatibility and varied applications in living specimens. Fluorescent proteins are often undesirably sensitive to intracellular conditions such as pH and ion concentration, generating considerable issues at times. However, harnessing these intrinsic sensitivities can help develop functional probes. In this study, we found that the fluorescence of yellow fluorescent protein (YFP) depends on the protein concentration in the solution and that this dependence can be enhanced by adding a glycine residue in to the YFP; we applied this finding to construct an intracellular protein-crowding sensor. A Förster resonance energy transfer (FRET) pair, involving a cyan fluorescent protein (CFP) insensitive to protein concentration and a glycine-inserted YFP, works as a genetically encoded probe to evaluate intracellular crowding. By measuring the fluorescence of the present FRET probe, we were able to detect dynamic changes in protein crowding in living cells.
Epstein Barr Virus and Mycobacterium avium subsp. paratuberculosis peptides are recognized in sera and cerebrospinal fluid of MS patients
Authors: Mameli Giuseppe , Cocco Eleonora , Frau Jessica , Marrosu Maria Giovanna , Sechi Leonardo Antonio 
Published: March 2016

AbstractMycobacterium avium subsp. paratuberculosis (MAP) and Epstein-Barr virus (EBV) epitopes elicit a consistent humoral response in serum of multiple sclerosis patients, but the cross reactivity against the homologous myelin basic protein (MBP) and human interferon regulatory factor 5 (IRF5) has not been searched within the Cerebral Spinal Fluid (CSF). We evaluated in sera and CSF of patients with MS and with other neurological diseases (OND) the humoral response against EBV/MAP peptides and the IRF5/MBP. Our data showed that EBV and MAP peptides are able to induce a specific humoral immune response in MS patients compared to OND controls both in serum and in CSF. An intrathecal specific synthesis of IgG against MBP and their EBV and MAP homologous as indicated by the antibody index was observed in MS patients. The humoral response against EBV, MAP, MBP and IRF5 was significantly higher in MS patients compared to OND both in serum and in CSF. The higher presence of antibodies against MBP and their MAP and EBV homologous in CSF during relapses suggests a possible role of the pathogens in enhancing inflammation.
Plant Phenotyping using Probabilistic Topic Models: Uncovering the Hyperspectral Language of Plants
Authors: Wahabzada Mirwaes , Mahlein Anne-Katrin , Bauckhage Christian , Steiner Ulrike , Oerke Erich-Christian , Kersting Kristian 
Published: March 2016

AbstractModern phenotyping and plant disease detection methods, based on optical sensors and information technology, provide promising approaches to plant research and precision farming. In particular, hyperspectral imaging have been found to reveal physiological and structural characteristics in plants and to allow for tracking physiological dynamics due to environmental effects. In this work, we present an approach to plant phenotyping that integrates non-invasive sensors, computer vision, as well as data mining techniques and allows for monitoring how plants respond to stress. To uncover latent hyperspectral characteristics of diseased plants reliably and in an easy-to-understand way, we “wordify” the hyperspectral images, i.e., we turn the images into a corpus of text documents. Then, we apply probabilistic topic models, a well-established natural language processing technique that identifies content and topics of documents. Based on recent regularized topic models, we demonstrate that one can track automatically the development of three foliar diseases of barley. We also present a visualization of the topics that provides plant scientists an intuitive tool for hyperspectral imaging. In short, our analysis and visualization of characteristic topics found during symptom development and disease progress reveal the hyperspectral language of plant diseases.
Element substitution by living organisms: the case of manganese in mollusc shell aragonite
Authors: Soldati Analia L. , Jacob Dorrit E. , Glatzel Pieter , Swarbrick Janine C. , Geck Jochen 
Published: March 2016

AbstractDetermining the manganese concentration in shells of freshwater bivalves provides a unique way to obtain information about climate and environmental changes during time-intervals that pre-date instrumental data records. This approach, however, relies on a thorough understanding of how manganese is incorporated into the shell material –a point that remained controversial so far. Here we clarify this issue, using state-of-the-art X-ray absorption and X-ray emission spectroscopy in combination with band structure calculations. We verify that in the shells of all studied species manganese is incorporated as high-spin Mn2+, i.e. manganese always has the same valence as calcium. More importantly, the unique chemical sensitivity of valence-to-core X-ray emission enables us to show that manganese is always coordinated by a CO3-octahedron. This, firstly, provides firm experimental evidence for manganese being primarily located in the inorganic carbonate. Secondly, it indicates that the structure of the aragonitic host is locally altered such that manganese attains an octahedral, calcitic coordination. This modification at the atomic level enables the bivalve to accommodate many orders of magnitude more manganese in its aragonitic shell than found in any non-biogenic aragonite. This outstanding feature is most likely facilitated through the non-classical crystallization pathway of bivalve shells.
Short range magnetic exchange interaction favors ferroelectricity
Authors: Wan Xiangang , Ding Hang-Chen , Savrasov Sergey Y. , Duan Chun-Gang 
Published: March 2016

AbstractMultiferroics, where two or more ferroic order parameters coexist, is one of the hottest fields in condensed matter physics and materials science. To search multiferroics, currently most researches are focused on frustrated magnets, which usually have complicated magnetic structure and low magnetic ordering temperature. Here, we argue that actually simple interatomic magnetic exchange interaction already contains a driving force for ferroelectricity, thus providing a new microscopic mechanism for the coexistence and strong coupling between ferroelectricity and magnetism. We demonstrate this mechanism by showing that even the simplest antiferromagnetic insulator like MnO, could display a magnetically induced ferroelectricity under a biaxial strain. In addition, we show that such mechanism also exists in the most important single phase multiferroics, i.e. BiFeO3, suggesting that this mechanism is ubiquitous in systems with superexchange interaction.
RETRACTED ARTICLE: Sepsis-induced elevation in plasma serotonin facilitates endothelial hyperpermeability
Authors: Li Yicong , Hadden Coedy , Cooper Anthonya , Ahmed Asli , Wu Hong , Lupashin Vladimir V. , Mayeux Philip R. , Kilic Fusun 
Published: March 2016

AbstractHyperpermeability of the endothelial barrier and resulting microvascular leakage are a hallmark of sepsis. Our studies describe the mechanism by which serotonin (5-HT) regulates the microvascular permeability during sepsis. The plasma 5-HT levels are significantly elevated in mice made septic by cecal ligation and puncture (CLP). 5-HT-induced permeability of endothelial cells was associated with the phosphorylation of p21 activating kinase (PAK1), PAK1-dependent phosphorylation of vimentin (P-vimentin) filaments and a strong association between P-vimentin and ve-cadherin. These findings were in good agreement with the findings with the endothelial cells incubated in serum from CLP mice. In vivo, reducing the 5-HT uptake rates with the 5-HT transporter (SERT) inhibitor, paroxetine blocked renal microvascular leakage and the decline in microvascular perfusion. Importantly, mice that lack SERT showed significantly less microvascular dysfunction after CLP. Based on these data, we propose that the increased endothelial 5-HT uptake together with 5-HT signaling disrupts the endothelial barrier function in sepsis. Therefore, regulating intracellular 5-HT levels in endothelial cells represents a novel approach in improving sepsis-associated microvascular dysfunction and leakage. These new findings advance our understanding of the mechanisms underlying cellular responses to intracellular/extracellular 5-HT ratio in sepsis and refine current views of these signaling processes during sepsis.
A Facile Strategy to Prepare Dendrimer-stabilized Gold Nanorods with Sub-10-nm Size for Efficient Photothermal Cancer Therapy
Authors: Wang Xinyu , Wang Hanling , Wang Yitong , Yu Xiangtong , Zhang Sanjun , Zhang Qiang , Cheng Yiyun 
Published: March 2016

AbstractGold (Au) nanoparticles are promising photothermal agents with the potential of clinical translation. However, the safety concerns of Au photothermal agents including the potential toxic compositions such as silver and copper elements in their structures and the relative large size-caused retention and accumulation in the body post-treatment are still questionable. In this article, we successfully synthesized dendrimer-stabilized Au nanorods (DSAuNRs) with pure Au composition and a sub-10-nm size in length, which represented much higher photothermal effect compared with dendrimer-encapsulated Au nanoparticles due to their significantly enhanced absorption in the near-infrared region. Furthermore, glycidol-modified DSAuNRs exhibited the excellent biocompatibility and further showed the high photothermal efficiency of killing cancer cells in vitro and retarding tumor growth in vivo. The investigation depicted an optimal photothermal agent with the desirable size and safe composition.
Two overlapping two-component systems in Xanthomonas oryzae pv. oryzae contribute to full fitness in rice by regulating virulence factors expression
Authors: Zheng Dehong , Yao Xiaoyan , Duan Meng , Luo Yufeng , Liu Biao , Qi Pengyuan , Sun Ming , Ruan Lifang 
Published: March 2016

AbstractTwo-component signal transduction systems (TCSs) are widely used by bacteria to adapt to the environment. In the present study, StoS (stress tolerance-related oxygen sensor) and SreKRS (salt response kinase, regulator, and sensor) were found to positively regulate extracellular polysaccharide (EPS) production and swarming in the rice pathogen Xanthomonas oryzae pv. oryzae (Xoo). Surprisingly, the absence of stoS or sreKRS did not attenuate virulence. To better understand the intrinsic functions of StoS and SreKRS, quantitative proteomics isobaric tags for relative and absolute quantitation (iTRAQ) was employed. Consistent with stoS and sreK mutants exhibiting a similar phenotype, the signalling circuits of StoS and SreKRS overlapped. Carbohydrate metabolism proteins and chemotaxis proteins, which could be responsible for EPS and swarming regulation, respectively, were reprogrammed in stoS and sreK mutants. Moreover, StoS and SreKRS demonstrated moderate expression of the major virulence factor, hypersensitive response and pathogenicity (Hrp) proteins through the HrpG-HrpX circuit. Most importantly, Xoo equipped with StoS and SreKRS outcompetes strains without StoS or SreKRS in co-infected rice and grows outside the host. Therefore, we propose that StoS and SreKRS adopt a novel strategy involving the moderation of Hrp protein expression and the promotion of EPS and motility to adapt to the environment.
Distinctive Pattern of Serum Elements During the Progression of Alzheimer’s Disease
Authors: Paglia Giuseppe , Miedico Oto , Cristofano Adriana , Vitale Michela , Angiolillo Antonella , Chiaravalle Antonio Eugenio , Corso Gaetano , Di Costanzo Alfonso 
Published: March 2016

AbstractElement profiling is an interesting approach for understanding neurodegenerative processes, considering that compelling evidences show that element toxicity might play a crucial role in the onset and progression of Alzheimer’s disease (AD). Aim of this study was to profile 22 serum elements in subjects with or at risk of AD. Thirtyfour patients with probable AD, 20 with mild cognitive impairment (MCI), 24 with subjective memory complaint (SMC) and 40 healthy subjects (HS) were included in the study. Manganese, iron, copper, zinc, selenium, thallium, antimony, mercury, vanadium and molybdenum changed significantly among the 4 groups. Several essential elements, such as manganese, selenium, zinc and iron tended to increase in SMC and then progressively to decrease in MCI and AD. Toxic elements show a variable behavior, since some elements tended to increase, while others tended to decrease in AD. A multivariate model, built using a panel of six essential elements (manganese, iron, copper, zinc, selenium and calcium) and their ratios, discriminated AD patients from HS with over 90% accuracy. These findings suggest that essential and toxic elements contribute to generate a distinctive signature during the progression of AD, and their monitoring in elderly might help to detect preclinical stages of AD.