bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mtf2-PRC2 control of canonical Wnt signaling is required for definitive erythropoiesis
Authors: Rothberg Janet L. Manias , Maganti Harinad B. , Jrade Hani , Porter Christopher J. , Palidwor Gareth A. , Cafariello Christopher , Battaion Hannah L. , Khan Safwat T. , Perkins Theodore J. , Paulson Robert F. , Ito Caryn Y. , Stanford William L. 
Published: April 2018

AbstractPolycomb repressive complex 2 (PRC2) accessory proteins play substoichiometric, tissue-specific roles to recruit PRC2 to specific genomic loci or increase enzymatic activity, while PRC2 core proteins are required for complex stability and global levels of trimethylation of histone 3 at lysine 27 (H3K27me3). Here, we demonstrate a role for the classical PRC2 accessory protein Mtf2/Pcl2 in the hematopoietic system that is more akin to that of a core PRC2 protein. Mtf2
−/−
erythroid progenitors demonstrate markedly decreased core PRC2 protein levels and a global loss of H3K27me3 at promoter-proximal regions. The resulting de-repression of transcriptional and signaling networks blocks definitive erythroid development, culminating in Mtf2
−/−
embryos dying by e15.5 due to severe anemia. Gene regulatory network (GRN) analysis demonstrated Mtf2 directly regulates Wnt signaling in erythroblasts, leading to activated canonical Wnt signaling in Mtf2-deficient erythroblasts, while chemical inhibition of canonical Wnt signaling rescued Mtf2-deficient erythroblast differentiation in vitro. Using a combination of in vitro, in vivo and systems analyses, we demonstrate that Mtf2 is a critical epigenetic regulator of Wnt signaling during erythropoiesis and recast the role of polycomb accessory proteins in a tissue-specific context.
Dkk3 dependent transcriptional regulation controls age related skeletal muscle atrophy
Authors: Yin Jie , Yang Lele , Xie Yangli , Liu Yan , Li Sheng , Yang Wenjun , Xu Bo , Ji Hongbin , Ding Lianghua , Wang Kun , Li Gang , Chen Lin , Hu Ping 
Published: April 2018

AbstractAge-related muscle atrophy (sarcopenia) is the leading cause for disability in aged population, but the underlying molecular mechanisms are poorly understood. Here we identify a novel role for the secreted glycoprotein Dickkopf 3 (Dkk3) in sarcopenia. Forced expression of Dkk3 in muscles in young mice leads to muscle atrophy. Conversely, reducing its expression in old muscles restores both muscle size and function. Dkk3 induces nuclear import of β-catenin and enhances its interaction with FoxO3, which in turn activates the transcription of E3 ubiquitin ligase Fbxo32 and Trim63, driving muscle atrophy. These findings suggest that Dkk3 may be used as diagnostic marker and as therapeutic target for age-related muscle atrophy, and reveal a distinct transcriptional control of Fbxo32 and Trim63.
Frizzled-8 integrates Wnt-11 and transforming growth factor-β signaling in prostate cancer
Authors: Murillo-Garzón Virginia , Gorroño-Etxebarria Irantzu , Åkerfelt Malin , Puustinen Mikael Christer , Sistonen Lea , Nees Matthias , Carton James , Waxman Jonathan , Kypta Robert M. 
Published: April 2018

AbstractWnt-11 promotes cancer cell migration and invasion independently of β-catenin but the receptors involved remain unknown. Here, we provide evidence that FZD8 is a major Wnt-11 receptor in prostate cancer that integrates Wnt-11 and TGF-β signals to promote EMT. FZD8 mRNA is upregulated in multiple prostate cancer datasets and in metastatic cancer cell lines in vitro and in vivo. Analysis of patient samples reveals increased levels of FZD8 in cancer, correlating with Wnt-11. FZD8 co-localizes and co-immunoprecipitates with Wnt-11 and potentiates Wnt-11 activation of ATF2-dependent transcription. FZD8 silencing reduces prostate cancer cell migration, invasion, three-dimensional (3D) organotypic cell growth, expression of EMT-related genes, and TGF-β/Smad-dependent signaling. Mechanistically, FZD8 forms a TGF-β-regulated complex with TGF-β receptors that is mediated by the extracellular domains of FZD8 and TGFBR1. Targeting FZD8 may therefore inhibit aberrant activation of both Wnt and TGF-β signals in prostate cancer.
Substrate-bound outward-open structure of a Na+-coupled sialic acid symporter reveals a new Na+ site
Authors: Wahlgren Weixiao Y. , Dunevall Elin , North Rachel A. , Paz Aviv , Scalise Mariafrancesca , Bisignano Paola , Bengtsson-Palme Johan , Goyal Parveen , Claesson Elin , Caing-Carlsson Rhawnie , Andersson Rebecka , Beis Konstantinos , Nilsson Ulf J. , Farewell Anne , Pochini Lorena , Indiveri Cesare , Grabe Michael , Dobson Renwick C. J. , Abramson Jeff , Ramaswamy S. , Friemann Rosmarie 
Published: April 2018

AbstractMany pathogenic bacteria utilise sialic acids as an energy source or use them as an external coating to evade immune detection. As such, bacteria that colonise sialylated environments deploy specific transporters to mediate import of scavenged sialic acids. Here, we report a substrate-bound 1.95 Å resolution structure and subsequent characterisation of SiaT, a sialic acid transporter from Proteus mirabilis. SiaT is a secondary active transporter of the sodium solute symporter (SSS) family, which use Na+ gradients to drive the uptake of extracellular substrates. SiaT adopts the LeuT-fold and is in an outward-open conformation in complex with the sialic acid N-acetylneuraminic acid and two Na+ ions. One Na+ binds to the conserved Na2 site, while the second Na+ binds to a new position, termed Na3, which is conserved in many SSS family members. Functional and molecular dynamics studies validate the substrate-binding site and demonstrate that both Na+ sites regulate N-acetylneuraminic acid transport.
Sulfenate anions as organocatalysts for benzylic chloromethyl coupling polymerization via C=C bond formation
Authors: Li Minyan , Berritt Simon , Wang Carol , Yang Xiaodong , Liu Yang , Sha Sheng-Chun , Wang Bo , Wang Rui , Gao Xuyu , Li Zhanyong , Fan Xinyuan , Tao Youtian , Walsh Patrick J. 
Published: April 2018

AbstractOrganocatalytic polymerization reactions have a number of advantages over their metal-catalyzed counterparts, including environmental friendliness, ease of catalyst synthesis and storage, and alternative reaction pathways. Here we introduce an organocatalytic polymerization method called benzylic chloromethyl-coupling polymerization (BCCP). BCCP is catalyzed by organocatalysts not previously employed in polymerization processes (sulfenate anions), which are generated from bench-stable sulfoxide precatalysts. The sulfenate anion promotes an umpolung polycondensation via step-growth propagation cycles involving sulfoxide intermediates. BCCP represents an example of an organocatalyst that links monomers by C=C double bond formation and offers transition metal-free access to a wide variety of polymers that cannot be synthesized by traditional precursor routes.
Catalytic condensation for the formation of polycyclic heteroaromatic compounds
Authors: Forberg Daniel , Schwob Tobias , Kempe Rhett 
Published: April 2018

AbstractThe conservation of our global element resources is a challenge of the utmost urgency. Since aliphatic and aromatic alcohols are accessible from abundant indigestible kinds of biomass, first and foremost lignocellulose, the development of novel chemical reactions converting alcohols into important classes of compounds is a particularly attractive carbon conservation and CO2-emission reduction strategy. Herein, we report the catalytic condensation of phenols and aminophenols or aminoalcohols. The overall reaction of this synthesis concept proceeds via three steps: hydrogenation, dehydrogenative condensation and dehydrogenation. Reusable catalysts recently developed in our laboratory mediate these reactions highly efficient. The scope of the concept is exemplarily demonstrated by the synthesis of carbazoles, quinolines and acridines, the structural motifs of which figure prominently in many important natural products, drugs and materials.
Architecture of the U6 snRNP reveals specific recognition of 3′-end processed U6 snRNA
Authors: Montemayor Eric J. , Didychuk Allison L. , Yake Allyson D. , Sidhu Gurnimrat K. , Brow David A. , Butcher Samuel E. 
Published: April 2018

AbstractThe spliceosome removes introns from precursor messenger RNA (pre-mRNA) to produce mature mRNA. Prior to catalysis, spliceosomes are assembled de novo onto pre-mRNA substrates. During this assembly process, U6 small nuclear RNA (snRNA) undergoes extensive structural remodeling. The early stages of this remodeling process are chaperoned by U6 snRNP proteins Prp24 and the Lsm2–8 heteroheptameric ring. We now report a structure of the U6 snRNP from Saccharomyces cerevisiae. The structure reveals protein–protein contacts that position Lsm2–8 in close proximity to the chaperone “active site” of Prp24. The structure also shows how the Lsm2–8 ring specifically recognizes U6 snRNA that has been post-transcriptionally modified at its 3′ end, thereby elucidating the mechanism by which U6 snRNPs selectively recruit 3′ end-processed U6 snRNA into spliceosomes. Additionally, the structure reveals unanticipated homology between the C-terminal regions of Lsm8 and the cytoplasmic Lsm1 protein involved in mRNA decay.
High frequency neural spiking and auditory signaling by ultrafast red-shifted optogenetics
Authors: Mager Thomas , Lopez de la Morena David , Senn Verena , Schlotte Johannes , D´Errico Anna , Feldbauer Katrin , Wrobel Christian , Jung Sangyong , Bodensiek Kai , Rankovic Vladan , Browne Lorcan , Huet Antoine , Jüttner Josephine , Wood Phillip G. , Letzkus Johannes J. , Moser Tobias , Bamberg Ernst 
Published: April 2018

AbstractOptogenetics revolutionizes basic research in neuroscience and cell biology and bears potential for medical applications. We develop mutants leading to a unifying concept for the construction of various channelrhodopsins with fast closing kinetics. Due to different absorption maxima these channelrhodopsins allow fast neural photoactivation over the whole range of the visible spectrum. We focus our functional analysis on the fast-switching, red light-activated Chrimson variants, because red light has lower light scattering and marginal phototoxicity in tissues. We show paradigmatically for neurons of the cerebral cortex and the auditory nerve that the fast Chrimson mutants enable neural stimulation with firing frequencies of several hundred Hz. They drive spiking at high rates and temporal fidelity with low thresholds for stimulus intensity and duration. Optical cochlear implants restore auditory nerve activity in deaf mice. This demonstrates that the mutants facilitate neuroscience research and future medical applications such as hearing restoration.
Topologically guided tuning of Zr-MOF pore structures for highly selective separation of C6 alkane isomers
Authors: Wang Hao , Dong Xinglong , Lin Junzhong , Teat Simon J. , Jensen Stephanie , Cure Jeremy , Alexandrov Eugeny V. , Xia Qibin , Tan Kui , Wang Qining , Olson David H. , Proserpio Davide M. , Chabal Yves J. , Thonhauser Timo , Sun Junliang , Han Yu , Li Jing 
Published: April 2018

AbstractAs an alternative technology to energy intensive distillations, adsorptive separation by porous solids offers lower energy cost and higher efficiency. Herein we report a topology-directed design and synthesis of a series of Zr-based metal-organic frameworks with optimized pore structure for efficient separation of C6 alkane isomers, a critical step in the petroleum refining process to produce gasoline with high octane rating. Zr6O4(OH)4(bptc)3 adsorbs a large amount of n-hexane but excluding branched isomers. The n-hexane uptake is ~70% higher than that of a benchmark adsorbent, zeolite-5A. A derivative structure, Zr6O4(OH)8(H2O)4(abtc)2, is capable of discriminating all three C6 isomers and yielding a high separation factor for 3-methylpentane over 2,3-dimethylbutane. This property is critical for producing gasoline with further improved quality. Multicomponent breakthrough experiments provide a quantitative measure of the capability of these materials for separation of C6 alkane isomers. A detailed structural analysis reveals the unique topology, connectivity and relationship of these compounds.
EEG Analytics for Early Detection of Autism Spectrum Disorder: A data-driven approach
Authors: Bosl William J. , Tager-Flusberg Helen , Nelson Charles A. 
Published: April 2018

AbstractAutism spectrum disorder (ASD) is a complex and heterogeneous disorder, diagnosed on the basis of behavioral symptoms during the second year of life or later. Finding scalable biomarkers for early detection is challenging because of the variability in presentation of the disorder and the need for simple measurements that could be implemented routinely during well-baby checkups. EEG is a relatively easy-to-use, low cost brain measurement tool that is being increasingly explored as a potential clinical tool for monitoring atypical brain development. EEG measurements were collected from 99 infants with an older sibling diagnosed with ASD, and 89 low risk controls, beginning at 3 months of age and continuing until 36 months of age. Nonlinear features were computed from EEG signals and used as input to statistical learning methods. Prediction of the clinical diagnostic outcome of ASD or not ASD was highly accurate when using EEG measurements from as early as 3 months of age. Specificity, sensitivity and PPV were high, exceeding 95% at some ages. Prediction of ADOS calibrated severity scores for all infants in the study using only EEG data taken as early as 3 months of age was strongly correlated with the actual measured scores. This suggests that useful digital biomarkers might be extracted from EEG measurements.
Genome-wide Analysis of Large-scale Longitudinal Outcomes using Penalization —GALLOP algorithm
Authors: Sikorska Karolina , Lesaffre Emmanuel , Groenen Patrick J. F. , Rivadeneira Fernando , Eilers Paul H. C. 
Published: April 2018

AbstractGenome-wide association studies (GWAS) with longitudinal phenotypes provide opportunities to identify genetic variations associated with changes in human traits over time. Mixed models are used to correct for the correlated nature of longitudinal data. GWA studies are notorious for their computational challenges, which are considerable when mixed models for thousands of individuals are fitted to millions of SNPs. We present a new algorithm that speeds up a genome-wide analysis of longitudinal data by several orders of magnitude. It solves the equivalent penalized least squares problem efficiently, computing variances in an initial step. Factorizations and transformations are used to avoid inversion of large matrices. Because the system of equations is bordered, we can re-use components, which can be precomputed for the mixed model without a SNP. Two SNP effects (main and its interaction with time) are obtained. Our method completes the analysis a thousand times faster than the R package lme4, providing an almost identical solution for the coefficients and p-values. We provide an R implementation of our algorithm.
The extent of wind-mediated dispersal of small metazoans, focusing nematodes
Authors: Ptatscheck Christoph , Gansfort Birgit , Traunspurger Walter 
Published: April 2018

AbstractWind-mediated transport is an important mechanism in the dispersal of small metazoans. Yet, concrete dispersal rates have hardly been examined. Here we present the results of an one-year field experiment investigating the composition and dispersal rates of aeroplankton. To gain insights into the dynamics of dispersal at the species level, we focused on nematodes, worldwide the most common metazoan taxon. Among the six taxa collected in this study (nematodes, rotifers, collembolans, tardigrades, mites, and thrips), nematodes had the highest dispersal rates (up to >3000 individuals m−2 in 4 weeks, 27 species identified) and represented >44% of aeroplankton. Only living nematodes, and no propagules, were dispersed. All taxa had a higher dispersal potential in environments linked to the source habitat, evidenced by the much higher deposition of organisms in funnels placed on the ground than on the rooftop of a ten-story building. Nematodes under conditions of high humidity and wind speed had the highest dispersal rates, while increasing temperatures and dryness had a significantly positive impact on the wind drift of mites and thrips. The results indicated that wind dispersal over long distances is possible. The notable organismal input by wind dispersal may contribute to biodiversity and ecosystem functions.
In vivo Dynamic Phase-Contrast X-ray Imaging using a Compact Light Source
Authors: Gradl Regine , Dierolf Martin , Günther Benedikt , Hehn Lorenz , Möller Winfried , Kutschke David , Yang Lin , Donnelley Martin , Murrie Rhiannon , Erl Alexander , Stoeger Tobias , Gleich Bernhard , Achterhold Klaus , Schmid Otmar , Pfeiffer Franz , Morgan Kaye Susannah 
Published: April 2018

AbstractWe describe the first dynamic and the first in vivo X-ray imaging studies successfully performed at a laser-undulator-based compact synchrotron light source. The X-ray properties of this source enable time-sequence propagation-based X-ray phase-contrast imaging. We focus here on non-invasive imaging for respiratory treatment development and physiological understanding. In small animals, we capture the regional delivery of respiratory treatment, and two measures of respiratory health that can reveal the effectiveness of a treatment; lung motion and mucociliary clearance. The results demonstrate the ability of this set-up to perform laboratory-based dynamic imaging, specifically in small animal models, and with the possibility of longitudinal studies.
Exploring intrinsically disordered proteins in Chlamydomonas reinhardtii
Authors: Zhang Yizhi , Launay Hélène , Schramm Antoine , Lebrun Régine , Gontero Brigitte 
Published: April 2018

AbstractThe content of intrinsically disordered protein (IDP) is related to organism complexity, evolution, and regulation. In the Plantae, despite their high complexity, experimental investigation of IDP content is lacking. We identified by mass spectrometry 682 heat-resistant proteins from the green alga, Chlamydomonas reinhardtii. Using a phosphoproteome database, we found that 331 of these proteins are targets of phosphorylation. We analyzed the flexibility propensity of the heat-resistant proteins and their specific features as well as those of predicted IDPs from the same organism. Their mean percentage of disorder was about 20%. Most of the IDPs (~70%) were addressed to other compartments than mitochondrion and chloroplast. Their amino acid composition was biased compared to other classic IDPs. Their molecular functions were diverse; the predominant ones were nucleic acid binding and unfolded protein binding and the less abundant one was catalytic activity. The most represented proteins were ribosomal proteins, proteins associated to flagella, chaperones and histones. We also found CP12, the only experimental IDP from C. reinhardtii that is referenced in disordered protein database. This is the first experimental investigation of IDPs in C. reinhardtii that also combines in silico analysis.
Genomic analysis and immune response in a murine mastitis model of vB_EcoM-UFV13, a potential biocontrol agent for use in dairy cows
Authors: da Silva Duarte Vinícius , Dias Roberto Sousa , Kropinski Andrew M. , Campanaro Stefano , Treu Laura , Siqueira Carolina , Vieira Marcella Silva , da Silva Paes Isabela , Santana Gabriele Rocha , Martins Franciele , Crispim Josicelli Souza , da Silva Xavier André , Ferro Camila Geovana , Vidigal Pedro M. P. , da Silva Cynthia Canêdo , de Paula Sérgio Oliveira 
Published: April 2018

AbstractBovine mastitis remains the main cause of economic losses for dairy farmers. Mammary pathogenic Escherichia coli (MPEC) is related to an acute mastitis and its treatment is still based on the use of antibiotics. In the era of antimicrobial resistance (AMR), bacterial viruses (bacteriophages) present as an efficient treatment or prophylactic option. However, this makes it essential that its genetic structure, stability and interaction with the host immune system be thoroughly characterized. The present study analyzed a novel, broad host-range anti-mastitis agent, the T4virus vB_EcoM-UFV13 in genomic terms, and its activity against a MPEC strain in an experimental E. coli-induced mastitis mouse model. 4,975 Single Nucleotide Polymorphisms (SNPs) were assigned between vB_EcoM-UFV13 and E. coli phage T4 genomes with high impact on coding sequences (CDS) (37.60%) for virion proteins. Phylogenetic trees and genome analysis supported a recent infection mix between vB_EcoM-UFV13 and Shigella phage Shfl2. After a viral stability evaluation (e.g pH and temperature), intramammary administration (MOI 10) resulted in a 10-fold reduction in bacterial load. Furthermore, pro-inflammatory cytokines, such as IL-6 and TNF-α, were observed after viral treatment. This work brings the whole characterization and immune response to vB_EcoM-UFV13, a biocontrol candidate for bovine mastitis.
Effect of in-situ aged and fresh biochar on soil hydraulic conditions and microbial C use under drought conditions
Authors: Paetsch Lydia , Mueller Carsten W. , Kögel-Knabner Ingrid , von Lützow Margit , Girardin Cyril , Rumpel Cornelia 
Published: April 2018

AbstractBiochar (BC) amendments may be suitable to increase the ecosystems resistance to drought due to their positive effects on soil water retention and availability. We investigated the effect of BC in situ ageing on water availability and microbial parameters of a grassland soil. We used soil containing 13C labeled BC and determined its water holding capacity, microbial biomass and activity during a 3 months incubation under optimum and drought conditions. Our incubation experiment comprised three treatments: soil without BC (Control), soil containing aged BC (BCaged) and soil containing fresh BC (BCfresh), under optimum soil water (pF 1.8) and drought conditions (pF 3.5). Under optimum water as well as drought conditions, soils containing BC showed higher soil organic carbon (SOC) mineralization as compared to control soil. Moreover, BC effects on the soil water regime increase upon in situ aging. Native SOC mineralization increased most for soils containing BCaged. The BCaged led to improved C use under drought as compared to the other treatments. We conclude that BC addition to soils can ameliorate their water regime, especially under drought conditions. This beneficial effect of BC increases upon its aging, which also improved native substrate availability.