bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytoskeleton members, MVBs and the ESCRT-III HvSNF7s are putative key players for protein sorting into protein bodies during barley endosperm development
Authors: Roustan Valentin , Hilscher Julia , Weidinger Marieluise , Reipert Siegfried , Shabrangy Azita , Gebert Claudia , Dietrich Bianca , Dermendjiev Georgi , Roustan Pierre-Jean , Stoger Eva , Ibl Verena 
Published: April 2019

AbstractCereal endosperm is a short-lived tissue adapted for nutrient storage, containing specialized organelles, such as protein bodies (PBs) and protein storage vacuoles (PSVs), for the accumulation of storage proteins. PBs can be used as efficient biotechnological systems to produce high yields of stable recombinant proteins. During development, protein trafficking and storage require an extensive reorganization of the endomembrane system. Consequently, endomembrane-modifying proteins will influence the final grain quality, yield and recombinant protein production. Barley, a cereal crop of worldwide importance for the brewing industry, animal feed and to a lesser extent, human nutrition, has been identified as promising candidate for recombinant protein production. However, little is known about the molecular mechanism underlying endomembrane system remodeling during barley grain development. By usingin vivolabel-free quantitative proteomics profiling, we quantified 1,822 proteins across developing barley grains. Based on proteome annotation and a homology search, 95 proteins associated with the endomembrane system were identified, and 83 of these exhibited significant changes in abundance during grain development. Clustering analysis allowed characterization of three different development stages; notably, integration of proteomics data within situsubcellular microscopic analyses showed a high abundance of cytoskeleton proteins associated with acidified protein bodies at the early development stages. Endosomal sorting complex required for transport (ESCRT)-related proteins and their transcripts are most abundant at early and mid-development. Specifically, multivesicular bodies (MVBs), and the ESCRT-III HvSNF7 proteins are associated with protein bodies (PBs) during barley endosperm development. Taken together, our proteomics results specifically identified members of the cytoskeleton, MVBs, and ESCRT as putative key players for protein sorting into PBs during barley endosperm development. These results present a comprehensive overview of proteins involved in the rearrangement of the endomembrane system during barley early grain development and will provide the basis for future work on engineering the endomembrane system to optimize nutrient content and to produce high yields of recombinant proteins.
Biomolecular Contrast Agents for Optical Coherence Tomography
Authors: Lu George J. , Chou Li-dek , Malounda Dina , Patel Amit K. , Welsbie Derek S. , Chao Daniel L. , Ramalingam Tirunelveli , Shapiro Mikhail G. 
Published: April 2019

ABSTRACTOptical coherence tomography (OCT) has gained wide adoption in biological and medical imaging due to its exceptional tissue penetration, 3D imaging speed and rich contrast. However, OCT plays a relatively small role in molecular and cellular imaging due to the lack of suitable biomolecular contrast agents. In particular, while the green fluorescent protein has provided revolutionary capabilities to fluorescence microscopy by connecting it to cellular functions such as gene expression, no equivalent reporter gene is currently available for OCT. Here we introduce gas vesicles, a unique class of naturally evolved gas-filled protein nanostructures, as the first genetically encodable OCT contrast agents. The differential refractive index of their gas compartments relative to surrounding aqueous tissue and their nanoscale motion enables gas vesicles to be detected by static and dynamic OCT at picomolar concentrations. Furthermore, the OCT contrast of gas vesicles can be selectively erasedin situwith ultrasound, allowing unambiguous assignment of their location. In addition, gas vesicle clustering modulates their temporal signal, enabling the design of dynamic biosensors. We demonstrate the use of gas vesicles as reporter genes in bacterial colonies and as purified contrast agentsin vivoin the mouse retina. Our results expand the utility of OCT as a unique photonic modality to image a wider variety of cellular and molecular processes.
Does Antibody Stabilize the Ligand Binding in GP120 of HIV-1 Envelope Protein? Evidence from MD Simulation
Authors: Pandey Vishnudatt , Tiwari Rakesh Kumar , Ojha Rajendra Prasad , Dubey Kshatresh Dutta 
Published: April 2019

AbstractCD4-mimetic HIV-1 entry inhibitors are small sized molecules which imitate similar conformational flexibility in gp120 as CD4 receptor, the mechanism of the conformational flexibility instigated by these small sized inhibitors, however, is little known. Likewise, the effect of the antibody on the function of these inhibitors is also less studied. In this study, we present a thorough inspection of the mechanism of the conformational flexibility induced by a CD4-mimetic inhibitor, NBD-557, using Molecular Dynamics Simulations and free energy calculations. Our result shows a functional importance of Asn239 in substrate instigated conformational dynamics in gp120. The MD simulations of Asn239Gly mutant provide a less dynamic gp120 in the presence of NBD-557 without incapacitating the binding enthalpy of NBD-557. The MD simulations of complex with the antibody clearly shows the enhanced affinity of NBD-557 due to the presence of the antibody which is in good agreement with experimental Isothermal Titration Calorimetry results (Biochemistry2006,45, 10973-10980).
The transcription factor Zt107320 affects the dimorphic switch, growth and virulence of the fungal wheat pathogenZymoseptoria tritici
Authors: Habig Michael , Bahena-Garrido Sharon Marie , Barkmann Friederike , Haueisen Janine , Stukenbrock Eva Holtgrewe 
Published: April 2019

SummaryZymoseptoria triticiis a filamentous fungus causing Septoria tritici blotch in wheat. The pathogen has a narrow host range and infections of grasses other than susceptible wheat are blocked early after stomatal penetration. During these abortive infections the fungus shows a markedly different expression pattern. However, the underlying mechanisms causing differential gene expression during host and non-host interaction are largely unknown, but likely include transcriptional regulators responsible for the onset of an infection program in compatible hosts. In the rice blast pathogenMagnaporthe oryzae, MoCOD1, a member of the fungal Zn(II)2Cys6transcription factor family, has been shown to directly affect pathogenicity. Here, we analyse the role of the putative transcription factor Zt107320, a homolog of MoCOD1, during infection of compatible and incompatible hosts byZ. tritici. We show for the first time thatZt107320is differentially expressed in host versus non-host infections and that lower expression corresponds to an incompatible infection of non-hosts. Applying reverse genetics approaches we further show that Zt107320 regulates the dimorphic switch as well as the growth rate ofZ. triticiand affects fungal cell wall compositionin vitro. Moreover, ΔZt107320mutants showed reduced virulence during compatible infections of wheat. We conclude that Zt107320 directly influences pathogen fitness and propose that Zt107320 regulates growth processes and pathogenicity during infection. Our results suggest that this putative transcription factor is involved in discriminating compatible and non-compatible infections.
A novel approach to localize cortical TMS effects
Authors: Weise Konstantin , Numssen Ole , Thielscher Axel , Hartwigsen Gesa , Knösche Thomas R. 
Published: April 2019

ABSTRACTDespite the widespread use of transcranial magnetic stimulation (TMS), the precise cortical location underlying the physiological and behavioral stimulation effects are still only coarsely known. So far, mapping strategies rely on center of gravity approaches and therefore localize the stimulated cortical site only approximately and indirectly. Focusing on the motor cortex, we present a novel method to reliably determine the effectively stimulated cortical site at the individual subject level. The approach combines measurements of motor evoked potentials (MEPs) at different coil positions and orientations with numerical modeling of induced electric fields. We identify sharply bounded cortical areas around the gyral crowns and rims of the motor hand area as the origin of MEPs and show that the tangential component and the magnitude of the electric field is most relevant for the observed effect. To validate our approach, we determined motor thresholds for coil positions and orientations for the predicted cortical target. Our methods allows for the identification of optimal coil positions and orientations. Moreover, we used extensive uncertainty and sensitivity analyses to verify the robustness of the method and identify the most critical model parameters. Our generic approach improves the localization of the cortex area stimulated by TMS and may be transferred to other modalities such as language mapping.
Strong spatial genetic structure in a Baltic Sea herbivore due to recent range expansion, multiple bottlenecks and low connectivity
Authors: De Wit Pierre , Jonsson Per R. , Pereyra Ricardo T. , Panova Marina , André Carl , Johannesson Kerstin 
Published: April 2019

AbstractIn the Baltic Sea, recent range expansions following the opening of the Danish straits have resulted in a low-diversity ecosystem, both among and within species. However, relatively little is known about population genetic patterns within the basin, except for in a few commercially caught species and some primary producers thought to be ecosystem engineers. Here, we investigate the population genetic structure of the ecologically important crustaceanIdotea balthicathroughout the Baltic Sea using an array of 33,774 genome-wide SNP markers derived from 2b-RAD sequencing. We also generate a biophysical connectivity matrix, with which we compare the genomic data. We find strong population structure on small scales across the Baltic Sea, and that genomic patterns in most cases closely match biophysical connectivity, suggesting that current patterns are important for dispersal of this species. We also find a strong signal of multiple bottlenecks during the initial range expansion, in the form of reduced heterozygosity along the historical expansion front. The lack of gene flow among sampling sites in the Baltic Sea environmental gradient potentiates local adaptation, while at the same time also increasing genetic drift in low-diversity areas.
Ataxin-3 links NOD2 and TLR2 mediated innate immune sensing and metabolism in myeloid cells
Authors: Chapman Thomas , Corridoni Daniele , Shiraishi Seiji , Pandey Sumeet , Aulicino Anna , Wigfield Simon , do Carmo Costa Maria , Thézénas Marie-Laëtitia , Paulson Henry , Fischer Roman , Kessler Benedikt M , Simmons Alison 
Published: April 2019

AbstractThe interplay between NOD2 and TLR2 following recognition of components of the bacterial cell wall peptidoglycan is well established, however their role in redirecting metabolic pathways in myeloid cells to degrade pathogens and mount antigen presentation remains unclear. We show NOD2 and TLR2 mediate phosphorylation of the deubiquitinase ataxin-3 via RIPK2 and TBK1. In myeloid cells ataxin-3 associates with the mitochondrial cristae protein MIC60, and is required for oxidative phosphorylation. Depletion of ataxin-3 leads to impaired induction of mitochondrial reactive oxygen species (mROS) and defective bacterial killing. A mass spectrometry analysis of NOD2/TLR2 triggered ataxin-3 deubiquitination targets revealed immunometabolic regulators, including HIF-1α and LAMTOR1 that may contribute to these effects. Thus, we define how ataxin-3 plays an essential role in NOD2 and TLR2 sensing and effector functions in myeloid cells.Significance StatementIn recent years it has become clear that cross-talk between metabolic and immune pathways is central to the regulation of host defence. This interplay appears of particular importance in myeloid cells including dendritic cells and macrophages, but it is unclear how two of their key bacterial sensors NOD2 and TLR2 influence metabolism. Here, we define how NOD2/TLR2 signal in myeloid cells to drive optimal mitochondrial functioning required for bacterial destruction. We uncover a new role for Ataxin-3, a deubiquitinase required for non-selective autophagy, in this pathway. We provide a non-biased analysis of Ataxin-3 targets generating evidence for a role in deubiquitination of metabolic mediators during myeloid cell differentiation that will provide an important basis for further study.
Tomato Prf requires NLR helpers NRC2 and NRC3 to confer resistance against the bacterial speck pathogen Pseudomonas syringae pv. tomato
Authors: Wu Chih-Hang , Kamoun Sophien 
Published: April 2019

AbstractBacterial speck, caused by the pathogen Pseudomonas syringae pv. tomato, is one of the most common diseases in tomato production. Together with Pto kinase, the NLR (nucleotide-binding domain leucine-rich repeat containing) protein Prf confers resistance against the bacterial speck pathogen by recognizing AvrPto and AvrPtoB, two Type III effector proteins secreted by P. syringae pv. tomato. This Prf/Pto pathway is part of a complex NLR network in solanaceous plants that mediates resistance to diverse pathogens through the helper NLR proteins NRCs (NLR required for cell death). We previously showed that, in Nicotiana benthamiana, the hypersensitive cell death elicited by expression of AvrPto and Pto, which activate immunity through the endogenous Prf ortholog NbPrf, requires functionally redundant NRC2 and NRC3. However, whether tomato (Solanum lycopersicum) Prf (SlPrf) confers resistance to the bacterial speck pathogen through NRC2 and NRC3 has not been determined. In this study, we show that SlPrf requires NRC2 and NRC3 to trigger hypersensitive cell death and disease resistance in both N. benthamiana and tomato. We found that the hypersensitive cell death induced by AvrPtoB/Pto/SlPrf in N. benthamiana is compromised when NRC2 and NRC3 are silenced, indicating that SlPrf is an NRC2/3-dependent NLR. We validated this finding by showing that silencing NRC2 and NRC3 in the bacterial speck resistant tomato ‘Rio Grande 76R’ compromised Prf-mediated resistance. These results indicate that the NRC network extends beyond N. benthamiana to solanaceous crops.
CRISPR-SID: identifying EZH2 as a druggable target for desmoid tumors viain vivodependency mapping
Authors: Naert Thomas , Tulkens Dieter , Van Nieuwenhuysen Tom , Przybyl Joanna , Demuynck Suzan , van de Rijn Matt , Al Jazrawe Mushriq , Alman Benjamin , Coucke Paul J. , De Leeneer Kim , Vanhove Christian , Savvides Savvas N. , Creytens David , Vleminckx Kris 
Published: April 2019

AbstractCancer precision medicine implies identification of tumor-specific vulnerabilities associated with defined oncogenic pathways. Desmoid tumors are soft-tissue neoplasms strictly driven by Wnt signaling network hyperactivation. Despite this clearly defined genetic etiology and the strict and unique implication of the Wnt/β-catenin pathway, no specific molecular targets for these tumors have been identified. To address this caveat, we developed fast and semi-high throughput geneticXenopus tropicalisdesmoid tumor models to identify and characterize novel drug targets. We used multiplexed CRISPR/Cas9 genome editing in these models to simultaneously target a tumor suppressor gene (apc) and candidate dependency genes. Our methodology CRISPR/Cas9 Selection mediated Identification of Dependencies (CRISPR-SID) uses calculated deviations between experimentally observed gene editing outcomes and deep-learning-predicted double strand break repair patterns, to identify genes under negative selection during tumorigenesis. This revealedEZH2andSUZ12, both encoding polycomb repressive complex 2 components, and the transcription factorCREB3L1, as genetic dependencies for desmoid tumors.In vivoEZH2 inhibition by Tazemetostat induced partial regression of established autochthonous tumors.In vitromodels of patient desmoid tumor cells revealed a direct effect of Tazemetostat on Wnt pathway activity. CRISPR-SID represents a potent novel approach forin vivomapping of tumor vulnerabilities and drug target identification.Significance StatementCRISPR-SID was established in the diploid frogXenopus tropicalisforin vivoelucidation of cancer cell vulnerabilities. CRISPR-SID uses deep learning predictions and binomial theory to identify genes under positive or negative selection during autochthonous tumor development. Using CRISPR-SID in a genetic model for desmoid tumors, treatment-recalcitrant mesenchymal tumors driven by hyper-activation of the Wnt signaling pathway, we identifiedEZH2andSUZ12, both encoding critical components of the polycomb repressive complex 2, as dependency genes for desmoid. Finally, we demonstrate the promise of EZH2 inhibition as a novel therapeutic strategy for desmoid tumors. With the simplicity of CRISPR sgRNA multiplexing inXenopusembryos the CRISPR-SID method may be applicable to reveal vulnerabilities in other tumor types.
History of rare diseases and their genetic causes - a data driven approach
Authors: Ehrhart Friederike , Willighagen Egon L. , Kutmon Martina , Hoften Max van , Sangani Nasim Bahram , Curfs Leopold G.M. , Evelo Chris T. 
Published: April 2019

AbstractThis dataset provides information about monogenic, rare diseases with a known genetic cause supplemented with manually extracted provenance of both the disease and the discovery of the underlying genetic cause of the disease.We collected 4166 rare monogenic diseases according to their OMIM identifier, linked them to 3163 causative genes which are annotated with Ensembl identifiers and HGNC symbols. The PubMed identifier of the scientific publication, which for the first time describes the rare disease, and the publication which found the gene causing this disease were added using information from OMIM, Wikipedia, Google Scholar, Whonamedit, and PubMed. The data is available as a spreadsheet and as RDF in a semantic model modified from DisGeNET.This dataset relies on publicly available data and publications with a PubMed IDs but this is to our knowledge the first time this data has been linked and made available for further study under a liberal license. Analysis of this data reveals the timeline of rare disease and causative genes discovery and links them to developments in methods and databases.
Larvicidal evaluation of the Origanum majorana L. Essential Oil against the larvae of the Aedes aegypti mosquito
Authors: Chaves Renata do Socorro Barbosa , Martins Rosany Lopes , Rodrigues Alex Bruno Lobato , Rabelo Érica de Menezes , Farias Ana Luzia Ferreira , Araújo Camila Mendes da Conceição Vieira , Sobral Talita Fernandes , Galardo Allan Kardec Ribeiro , de Almeida Sheylla Susan Moreira da Silva 
Published: April 2019

ABSTRACTThis study evaluated the larvicidal activity of O. majorana essential oil, identified the chemical composition, evaluated the antimicrobial, cytotoxic and antioxidant potential. The larvicidal activity was evaluated against larvae of the third stage of Aedes aegypti, whereas the chemical composition was identified by gas chromatography coupled to mass spectrometer, the antimicrobial activity was carried out against the bacteria Pseudomonas aeruginosa, Escherichia coli and Staphylococcus auereus, the antioxidant activity was evaluated from of 2.2-diphenyl-1-picryl-hydrazila sequestration and Artemia salina cytotoxicity. Regarding to the results, the larvicidal activity showed that O. majorana essential oil caused high mortality in A. aegypti larvae. In the chromatographic analysis, the main component found in O. majorana essential oil was pulegone (57.05%), followed by the other components verbenone (16.92%), trans-p-menthan-2-one (8.57%), iso-menthone (5.58%), piperitone (2.83%), 3-octanol (2.35%) and isopulegol (1.47%). The antimicrobial activity showed that E. coli and P. aeruginosa bacteria were more sensitive to oil than S. aureus, which was resistant at all concentrations. Essential oil did not present antioxidant activity, but it has high cytotoxic activity against A. salina.
The human microbiota is associated with cardiometabolic risk across the epidemiologic transition
Authors: Fei Na , Bernabé Beatriz Peñalver , Lie Louise , Baghdan Danny , Bedu-Addo Kweku , Plange-Rhule Jacob , Forrester Terrence E. , Lambert Estelle V. , Bovet Pascal , Gottel Neil , Riesen Walter , Korte Wolfgang , Luke Amy , Kliethermes Stephanie A. , Layden Brian T. , Gilbert Jack A. , Dugas Lara R. 
Published: April 2019

AbstractOral and fecal microbial biomarkers have previously been associated with cardiometabolic (CM) risk, however, no comprehensive attempt has been made to explore this association in minority populations or across different geographic regions. We characterized gut- and oral-associated microbiota and CM risk in 655 participants of African-origin, aged 25-45, from Ghana, South Africa, Jamaica, and the United States (US). CM risk was classified using the CM risk cut-points for elevated waist circumference, elevated blood pressure and elevated fasted blood glucose, low high-density lipoprotein (HDL), and elevated triglycerides. Gut-associated bacterial alpha diversity negatively correlated with elevated blood pressure and elevated fasted blood glucose. Similarly, gut bacterial beta diversity was also significantly differentiated by waist circumference, blood pressure, triglyceridemia and HDL-cholesterolemia. Notably, differences in inter- and intra-personal gut microbial diversity were geographic-region specific. Participants meeting the cut-points for 3 out of the 5 CM risk factors were significantly more enriched with Lachnospiraceae, and were significantly depleted of Clostridiaceae, Peptostreptococcaceae, andPrevotella. The predicted relative proportions of the genes involved in the pathways for lipopolysaccharides (LPS) and butyrate synthesis were also significantly differentiated by the CM risk phenotype, whereby genes involved in the butyrate synthesis via lysine, glutarate and 4-aminobutyrate/succinate pathways and LPS synthesis pathway were enriched in participants with greater CM risk. Furthermore, inter-individual oral microbiota diversity was also significantly associated with the CM risk factors, and oral-associatedStreptococcus, Prevotella, andVeillonellawere enriched in participants with 3 out of the 5 CM risk factors. We demonstrate that in a diverse cohort of African-origin adults, CM risk is significantly associated with reduced microbial diversity, and the enrichment of specific bacterial taxa and predicted functional traits in both gut and oral environments. As well as providing new insights into the associations between the gut and oral microbiota and CM risk, this study also highlights the potential for novel therapeutic discoveries which target the oral and gut microbiota in CM risk.