bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel transplantable model of lung cancer associated tissue loss and disrupted muscle regeneration
Authors: Arneson Paige C , Ducharme Alexandra M , Doles Jason D 
Published: November 2019

ABSTRACTBackgroundCancer-associated muscle wasting (CAW), a symptom of cancer cachexia, is associated with approximately 20% of lung cancer deaths, and remains poorly characterized on a mechanistic level. Current animal models for lung cancer-associated cachexia are limited in that they: 1) primarily employ flank transplantation methods, 2) have short survival times not reflective of the patient condition, and 3) are typically performed in young mice not representative of mean patient age. This study investigates a new model for lung cancer-associated cachexia that can address these issues and also implicates muscle regeneration as a contributor to CAW.MethodsWe used tail vein injection as a method to introduce tumor cells that seed primarily in the lungs of mice. Body composition of tumor bearing mice was longitudinally tracked using NMR-based, echo magnetic resonance imaging (echoMRI). These data were combined with histological and molecular assessments of skeletal muscle to provide a complete analysis of muscle wasting.ResultsIn this new lung CAW model we observed 1) progressive loss in whole body weight, 2) progressive loss of lean and fat mass, 3) a circulating cytokine/inflammatory profile similar to that seen in other models of CAW, 4) histological changes associated with muscle wasting, and 5) molecular changes in muscle that implicate suppression of muscle repair/regeneration. Finally, we show that survival can be extended without lessening CAW by titrating injected cell number.ConclusionsOverall, this study describes a new model of CAW that could be useful for further studies of lung cancer-associated wasting and accompanying changes in the regenerative capacity of muscle. Additionally, this model addresses many recent concerns with existing models such as immunocompetence, tumor location, and survival time.
Transcranial Direct current stimulation does not modulate performance on a tongue twister task
Authors: Wiltshire Charlotte E. E. , Watkins Kate E. 
Published: November 2019

AbstractBackgroundTDCS modulates cortical excitability in a polarity-specific way. When used in combination with a behavioural task, it can also alter performance. Previously, tDCS modulated the performance of older adults on a complex speech motor learning task, which involved repetition of tongue twisters [1].ObjectiveWe aimed to replicate this finding in healthy young participants and to extend it by measuring tDCS-induced changes in motor excitability using transcranial magnetic stimulation and motor-evoked potentials elicited in the lips.MethodIn a double-blind randomized sham-controlled study, three groups of 20 participants received: 1) anodal tDCS to the left IFG/LipM1 and cathodal tDCS to the right hemisphere homologue; or 2) cathodal tDCS over the left and anodal over the right; or 3) sham stimulation. Participants heard and repeated tongue twisters and matched simple sentences before, during and 10 minutes after the stimulation. Motor excitability was measured before and immediately after the tDCS.ResultsThe improvement in performance of tongue twister repetition from baseline to after stimulation was significantly greater than for the simple sentences but did not differ among the three groups. Motor excitability significantly decreased to a small but similar extent across the three groups.ConclusionsTDCS did not modulate performance on a complex articulation task in healthy young adults. TDCS applied concurrently with task learning also failed to modulate motor excitability in expected ways. TDCS may be most effective in brains where brain function is sub-optimal due to age-related declines or pathology.
Visualizing a protonated RNA state that modulates microRNA-21 maturation
Authors: Baisden Jared T. , Boyer Joshua A. , Zhao Bo , Zhang Qi 
Published: November 2019

AbstractMicroRNAs are evolutionarily conserved small, non-coding RNAs that regulate diverse biological processes. Due to their essential regulatory roles, microRNA biogenesis is tightly regulated, where protein factors are often found to interact with specific primary and precursor microRNAs for regulation. Here, using NMR relaxation dispersion spectroscopy and mutagenesis, we reveal that the precursor of oncogenic microRNA-21 exists as a pH-dependent ensemble that spontaneously reshuffles the secondary structure of the entire apical stem-loop region, including the Dicer cleavage site. We show that the alternative excited conformation transiently sequesters the bulged adenine into a non-canonical protonated A+–G mismatch, conferring a two-fold enhancement in Dicer processing over its ground conformational state. These results indicate that microRNA maturation efficiency may be encoded in the intrinsic dynamic ensemble of primary and precursor microRNAs, providing potential means of regulating microRNA biogenesis in response to environmental and cellular stimuli.
A novel, ultrasensitive approach for quantitative carbohydrate composition and linkage analysis using LC-ESI ion trap tandem mass spectrometry
Authors: Alagesan Kathirvel , Silva Daniel Varon , Seeberger Peter H , Kolarich Daniel 
Published: November 2019

ABSTRACTGlycan identification and characterisation is essential to correlate glycoconjugate structure to biological function. The structural assignment of carbohydrates is often based on MS composition analyses and knowledge on well-studied glycosylation pathways. Nevertheless, many monosaccharide building blocks are indistinguishable by mass alone and detailed linkage information is also not easily obtained by MS/MS analyses, in particular when organisms are studied where the glycosylation pathways are less well defined. Here, we present a novel, simple and sensitive method using Reversed Phase (RP) – Liquid Chromatography Electrospray ionisation tandem mass spectrometry (LC–ESI-MS/MS) for unambiguous identification and linkage determination of monosaccharides including N-acetylneuraminic acids. Sequential permethylation and reductive amination steps are employed prior and after acid hydrolysis to enable separation and differentiation of the various monosaccharides and their respective linkage positions. The well-established, monosaccharide specific methylation patterns allowed for the identification of the various derivatised monosaccharide alditols based on their retention time and tandem mass spectrometry fingerprint. Absolute quantitation can also be accomplished by including a set of internal standards, thus simultaneously providing qualitative and quantitative information on the monosaccharide residues present.
Viscoelastic properties of ECM-rich embryonic microenvironments
Authors: Akos Zsuzsa , Isai Dona G. , Rajasingh Sheeja , Kosa Edina , Ghazvini Saba , Dhar Prajna , Czirok Andras 
Published: November 2019

AbstractThe material properties of tissues and their mechanical state is an important factor during development, disease, regenerative medicine and tissue engineering. Here we describe a microrheological measurement technique utilizing aggregates of microinjected ferromagnetic nickel particles to probe the viscoelastic properties of embryonic tissues. Quail embryos were cultured in a plastic incubator chamber located at the center of two pairs of crossed electromagnets. We estimate the Young’s modulus of the ECM-rich region separating the mesoderm and endoderm in Hamburger Hamilton stage 6-10 quail embryos as 300±100 Pa. We found a pronounced viscoelastic behavior consistent with a Zener (standard generalized solid) model. The viscoelastic response is about 45% of the total response, with a characteristic relaxation time of 1.3 sec.
Microtubule Nucleation by Single Human γTuRC in a Partly Open Asymmetric Conformation
Authors: Consolati Tanja , Locke Julia , Roostalu Johanna , Asthana Jayant , Lim Wei Ming , Gannon Julian , Martino Fabrizio , Costa Alessandro , Surrey Thomas 
Published: November 2019

SUMMARYThe γ-tubulin ring complex (γTuRC) is the major microtubule nucleator in cells. However, the mechanism of its regulation is not understood. Here, we purified human γTuRC and quantitatively characterized its nucleation properties in a TIRF microscopy-based real-time nucleation assay. We find that microtubule nucleation by γTuRC is kinetically inhibited compared to microtubule elongation. Determining the cryo-EM structure of γTuRC at 4 Å resolution reveals an asymmetric conformation with only part of the complex in a ‘closed’ conformation matching the microtubule geometry. Several factors stabilise the closed conformation. One is actin in the core of the complex and others, likely MZT1 or MZT2, line the outer perimeter of the closed part of γTuRC. The opposed side of γTuRC is in an ‘open’, nucleation-incompetent conformation, leading to a structural asymmetry, explaining the kinetic inhibition of nucleation by human γTuRC. Our data suggest possible regulatory mechanisms for microtubule nucleation by γTuRC closure.
Calcium-induced calcium release in noradrenergic neurons of the locus coeruleus
Authors: Kawano Hiroyuki , Mitchell Sara B. , Koh Jin-Young , Goodman Kirsty M. , Harata N. Charles 
Published: November 2019

ABSTRACTThe locus coeruleus (LC) is a nucleus within the brainstem that consists of norepinephrine-releasing neurons. It is involved in broad processes including autonomic regulation, and cognitive and emotional functions such as arousal, attention and anxiety. Understanding the mechanisms that control the excitability of LC neurons is important because they innervate widespread regions of the central nervous system. One of the key regulators is the cytosolic calcium concentration ([Ca2+]c), the increases in which can be amplified by calcium-induced calcium release (CICR) from the intracellular calcium stores. Although the electrical activities of LC neurons are regulated by changes in [Ca2+]c, the extent of CICR involvement in this regulation has remained unclear. Here we show that CICR hyperpolarizes acutely dissociated LC neurons of the rat brain and demonstrate the pathway whereby it does this. When CICR was activated by extracellular application of 10 mM caffeine, LC neurons were hyperpolarized in the current-clamp mode of the patch-clamp recording, and the majority of neurons showed an outward current in the voltage-clamp mode. This outward current was accompanied by an increase in membrane conductance, and its reversal potential was close to the K+ equilibrium potential, indicating that it is mediated by the opening of K+ channels. The outward current was generated in the absence of extracellular calcium and was blocked when the calcium stores were inhibited by applying ryanodine. Pharmacological experiments indicated that the outward current was mediated by Ca2+-activated K+ channels of the non-small conductance type. Finally, the application of caffeine led to an increase in the [Ca2+]c in these neurons, as visualized by fluorescence microscopy. These findings delineate a mechanism whereby CICR suppresses the electrical activity of LC neurons, and indicate that it could play a dynamic role in modulating the LC-mediated noradrenergic tone in the brain.
NERDSS: a non-equilibrium simulator for multibody self-assembly at the cellular scale
Authors: Varga Matthew J. , Loggia Spencer , Fu Yiben , Yogurtcu Osman N , Johnson Margaret E. 
Published: November 2019

AbstractCurrently, a significant barrier to building predictive models of cell-based self-assembly processes is that molecular models cannot capture minutes-long cellular dynamics that couple distinct components with active processes, while reaction-diffusion models lack sufficient detail for capturing assembly structures. Here we introduce the Non-Equilibrium Reaction-Diffusion Self-assembly Simulator (NERDSS), which addresses this gap by integrating a structure-resolved reaction-diffusion algorithm with rule-based model construction. By representing proteins as rigid, multi-site molecules that adopt well-defined orientations upon binding, NERDSS simulates formation of large reversible structures with sites that can be acted on by reaction rules. We show how NERDSS allows for directly comparing and optimizing models of multi-component assembly against time-dependent experimental data. Applying NERDSS to assembly steps in clathrin-mediated endocytosis, we capture how the formation of clathrin caged structures can be driven by modulating the strength of clathrin-clathrin interactions, by adding cooperativity, or by localizing clathrin to the membrane. NERDSS further predicts how clathrin lattice disassembly can be driven by enzymes that irreversibly change lipid populations on the membrane. By modeling viral lattice assembly and recapitulating oscillations in protein expression levels for a circadian clock model, we illustrate the wide usability and adaptability of NERDSS. NERDSS simulates user-defined assembly models that were previously inaccessible to existing software tools, with broad applications to predicting self-assembly in vivo and designing high-yield assemblies in vitro.
Melanoma-secreted Amyloid Beta Suppresses Neuroinflammation and Promotes Brain Metastasis
Authors: Kleffman Kevin , Levinson Grace , Wong Eitan , Galán-Echevarría Francisco , Von-Itter Richard , Rose Indigo , Blumenberg Lili , Floristán Alfredo , Tranos James , Argibay Diana , Chen Jenny , Dhabaria Avantika , de Miera Sainz de Vega Eleazar , Rogers Robert , Zaim-Wadghiri Youssef , Mathews Paul , Osman Iman , Ruggles Kelly , Ueberheide Beatrix , Liddelow Shane A. , DeMattos Ronald , Li Yue Ming , Schneider Robert J. , Hernando Eva 
Published: November 2019

SummaryBrain metastasis is a significant cause of morbidity and mortality in multiple cancer types and represents an unmet clinical need. The mechanisms that mediate metastatic cancer growth in the brain parenchyma are largely unknown. Melanoma, which has the highest rate of brain metastasis among common cancer types, is an ideal model to study how cancer cells adapt to the brain parenchyma. We performed unbiased proteomics analysis of melanoma short-term cultures, a novel model for the study of brain metastasis. Intriguingly, we found that proteins implicated in neurodegenerative pathologies are differentially expressed in melanoma cells explanted from brain metastases compared to those derived from extracranial metastases. This raised the exciting hypothesis that molecular pathways implicated in neurodegenerative disorders are critical for metastatic adaptation to the brain.Here, we show that melanoma cells require amyloid beta (Aβ), a polypeptide heavily implicated in Alzheimer’s disease, for growth and survival in the brain parenchyma. Melanoma cells produce and secrete Aβ, which activates surrounding astrocytes to a pro-metastatic, anti-inflammatory phenotype. Furthermore, we show that pharmacological inhibition of Aβ decreases brain metastatic burden.Our results reveal a mechanistic connection between brain metastasis and Alzheimer’s disease – two previously unrelated pathologies, establish Aβ as a promising therapeutic target for brain metastasis, and demonstrate suppression of neuroinflammation as a critical feature of metastatic adaptation to the brain parenchyma.
3DGV: Immersive Exploration of 3D Genome Structures using Virtual Reality
Authors: Zhang Éric , Drogaris Chrisostomos , Gédon Antoine , Sossin Aaron , Faraj Rajae , Chen Haifen , Cyr Yan , Majewski Jacek , Blanchette Mathieu , Waldispühl Jérôme 
Published: November 2019

The analysis of 3D genomic data is expected to revolutionize our understanding of genome organization and regulatory mechanisms. Yet, the complex spatial organization of this information can be difficult to interpret with 2D viewers. Virtual Reality (VR) technologies offer an opportunity to rethink our methods to visualize and navigate 3D objects. In this paper, we introduce the Virtual Reality 3D Genome Viewer (3DGV), an open platform to experiment and develop VR solutions to explore 3D genome structures.Availabilityhttp://3dgv.cs.mcgill.ca/
Lysates ofMethylococcus capsulatusBath induce a lean-like microbiota, intestinal FoxP3+RORγt+IL-17+Tregs and improve metabolism
Authors: Jensen Benjamin. A. H. , Holm Jacob B. , Larsen Ida S. , von Burg Nicole , Derer Stefanie , Rivollier Aymeric , Agrinier Anne Laure , Sulek Karolina , Indrelid Stine A. , Arnoldussen Yke J. , Sonne Si B. , Fjære Even , Damgaard Mads T. F. , Pærregaard Simone I. , Angell Inga L. , Rudi Knut , Marette André , Treebak Jonas T. , Madsen Lise , Åkesson Caroline Piercey , Agace William , Sina Christian , Kleiveland Charlotte R. , Kristiansen Karsten , Lea Tor E. 
Published: November 2019

AbstractInteractions between host and gut microbial communities may be modulated by diets and play pivotal roles in securing immunological homeostasis and health. Here we show that intake of feed based on whole-cell lysates of the non-commensal bacteriumMethylococcus capsulatusBath (McB) as protein source reversed high fat high sucrose-induced changes in the gut microbiota to a state resembling that of lean, low fat diet-fed mice, both under mild thermal stress (T22°C) and at thermoneutrality (T30°C). McB feeding selectively upregulated triple positive (Foxp3+RORγt+IL-17+) regulatory T cells in the small intestine and colon, and enhanced mucus production and glycosylation status suggesting improved gut health. Mice receiving McB lysates further exhibited improved glucose regulation, reduced body and liver fat along with diminished hepatic immune infiltration. Collectively, these data points towards profound whole-body effects elicited by the McB lysate suggesting that it may serve as a potent modulator of immunometabolic homeostasis.
Inoculation with a microbe isolated from the Negev Desert enhances corn growth
Authors: Khan Noor , Martínez-Hidalgo Pilar , Humm Ethan A. , Maymon Maskit , Kaplan Drora , Hirsch Ann M. 
Published: November 2019

AbstractCorn (Zea mays L.) is not only an important food source, but also has numerous uses, including for biofuels, fillers for cosmetics, glues, and so on. The amount of corn grown in the U.S. has significantly increased since the 1960s and with it, the demand for synthetic fertilizers and pesticides/fungicides to enhance its production. However, the downside of the continuous use of these products, especially N and P fertilizers, has been an increase in N2O emissions and other greenhouse gases into the atmosphere as well as run-off into waterways that fuel pollution and algal blooms. These approaches to agriculture, especially if exacerbated by climate change, will result in decreased soil health as well as human health. We searched for microbes from arid, native environments that are not being used for agriculture because we reasoned that indigenous microbes from such soils could promote plant growth and help restore degraded soils. Employing cultivation-dependent methods to isolate bacteria from the Negev Desert in Israel, we tested the effects of several microbial isolates on corn in both greenhouse and small field studies. One strain, Dietzia cinnamea 55, originally identified as Planomicrobium chinensis, significantly enhanced corn growth over the uninoculated control in both greenhouse and outside garden experiments. We sequenced and analyzed the genome of this bacterial species to elucidate some of the mechanisms whereby D. cinnamea 55 promoted plant growth. In addition, to ensure the biosafety of this previously unknown plant growth promoting bacterial (PGPB) strain as a potential bioinoculant, we tested the survival and growth of Caenorhabditis elegans (a test for virulence) in response to D. cinnamea 55. We also looked for genes for potential virulence determinants as well as for growth promotion.
Expansion of a subset within C2 clade of Escherichia coli sequence type 131 (ST131) is driving the increasing rates of Aminoglycoside resistance: a molecular epidemiology report from Iran
Authors: Hojabri Zoya , Darabi Narges , Mirmohammadkhani Majid , Hemmati Romina , saeedi Zahra , Roustaee Kiarash , Pajand Omid 
Published: November 2019

AbstractThe most important lineage of Escherichia coli, named sequence type 131 (ST131) is a pandemic clone which drives the increasing rates of antibiotic resistance. While the pervasiveness of ST131 clade C, especially subclades C2 and C1-M27 has been demonstrated in numerous global surveys, no report about the ST131 clades and its virotypes has been published from Iran, so far. So, in this study we investigated and compared the virotypes, antibiotic susceptibility patterns, resistance/virulence determinants and clonality of ST131 clades collected during one-year surveillance study.Most of isolates belonged to clade C2 (34/76 [44.7%]), with the highest virulence factor (VF) scores and resistance rates. The distinctive profiles of clade C2 virulence genes were revealed by “principle coordinates analysis” (PcoA) test. The distribution of hlyA/cnf1virulence genes among clade C2 was not uniform, so that positive strains showed significantly higher rates of resistance markers (blaCTX-M-15, blaOXA-1, aac6Ib/Ib-cr and aac3IIa) and ampicillin- sulbactam/gentamicin/tobramycin resistance. Virotype C as the most common virotype (48.7%) was predominant among clade C1 population, while almost all of virotypes E and F [(22/23), 95.6%] strains belonged to clade C2, with the highest VF scores and aminoglycoside resistance rates. “Multi locus variable Number tandem repeats analysis” (MLVA) clustered clades C1 and C2 together, while clades A and B strains were mostly identified as singletons.Appearance of virotypes E and F among clade C2 strains with higher rates of aminoglycoside resistance/virulence genes content demonstrate the shifting dynamics of this pandemic clone in response to antibiotic selection pressure by establishing the newly-emerged subsets.
Primate-restricted KRAB zinc finger proteins and target retrotransposons control gene expression in human neurons
Authors: Turelli Priscilla , Playfoot Christopher , Grun Dephine , Raclot Charlène , Pontis Julien , Coudray Alexandre , Thorball Christian , Duc Julien , Pankevich Eugenia , Deplancke Bart , Busskamp Volker , Trono Didier 
Published: November 2019

AbstractIn the first days of embryogenesis, transposable element-embedded regulatory sequences (TEeRS) are silenced by Kruppel-associated box (KRAB)-zinc finger proteins (KZFPs). Many TEeRS are subsequently coopted in transcription networks, but how KZFPs influence this process is largely unknown. We identify ZNF417 and ZNF587 as primate-specific KZFPs repressing HERVK (human endogenous retrovirus K) and SVA (SINE-VNTR-Alu) integrants in human embryonic stem cells (ESC). Expressed in specific regions of the human developing and adult brain, ZNF417/587 keep controlling TEeRS in ESC-derived neurons and brain organoids, secondarily influencing the differentiation and neurotransmission profile of neurons and preventing the induction of neurotoxic retroviral proteins and an interferon-like response. Thus, evolutionarily recent KZFPs and their TE targets partner up to influence human neuronal differentiation and physiology.One Sentence SummaryYoung transposable elements and their protein controllers team up to regulate the differentiation and function of human neurons.