bluuebunny/crossref_metadata_2025_split huggingface dataset:
Runx3 prevents spontaneous colitis by directing differentiation of anti-inflammatory mononuclear phagocytes
Authors: Hantisteanu Shay , Dicken Joseph , Negreanu Varda , Goldenberg Dalia , Brenner Ori , Leshkowitz Dena , Lotem Joseph , Levanon Ditsa , Groner Yoram 
Published: August 2019

ABSTRACTRUNX3 is one of three mammalian Runt-domain transcription factors (TFs) that regulate gene expression in several types of immune cells. Runx3-deficiency in mice is associated with a multitude of defects in the adaptive and innate immunity systems, including the development of early onset colitis. Our study reveals that conditional deletion of Runx3 specifically in mononuclear phagocytes (MNP) (MNPRunx3−/−) but not in T cells, recapitulates the early onset spontaneous colitis seen in Runx3−/− mice.We show that Runx3 is expressed in colonic MNP, including resident macrophages (RM) and the dendritic cell cDC2 subsets and its loss results in impaired differentiation/maturation of both cell types. At the transcriptome level, loss of Runx3 in RM and cDC2 was associated with upregulation of pro-inflammatory genes similar to those in the early onset IBD murine model of RMIl10r−/−. The impaired RM maturation in the absence of Runx3 was associated with a marked decrease in expression of anti-inflammatory and TGFβ-regulated genes. Similarly, the decreased expression of β-catenin signaling associated genes in Runx3-deficient cDC2 indicates their impaired differentiation/maturation. Analysis of ChIP-seq data suggests that in both MNP cell types a significant fraction of these differentially expressed genes are high confidence Runx3 directly regulated genes. Interestingly, several of these putative Runx3 target genes harbor SNPs associated with IBD susceptibility in humans. Remarkably, the impaired maturation and pro-inflammatory phenotype of MNP lacking Runx3 was associated with a substantial reduction in the prevalence of colonic lamina propria Foxp3+ regulatory T cells and an increase in IFNγ-producing CD4+ T cells, underscoring Runx3 critical role in establishing tolerogenic MNP.Together, these data emphasize the dual role of Runx3 in colonic MNP, as a transcriptional repressor of pro-inflammatory genes and an activator of maturation-associated genes including anti-inflammatory genes. Our study highlights the significance of the current MNPRunx3−/− model for understanding of human MNP-associated colitis. It provides new insights into the crucial involvement of Runx3 in intestinal immune tolerance by regulating colonic MNP maturation through TGFβR signaling and anti-inflammatory functions by Il10R signaling, befitting the identification of RUNX3 as a genome-wide associated risk gene for various immune-related diseases in humans including gastrointestinal tract diseases such as celiac and Crohn’s disease.
Megakaryocytes Display Innate Immune Cell Functions and Respond during Sepsis
Authors: Frydman Galit H. , Ellett Felix , Jorgensen Julianne , Marand Anika L. , Zukerberg Lawrence , Selig Martin , Tessier Shannon , Wong Keith H. K. , Olaleye David , Vanderburg Charles R. , Fox James G. , Tompkins Ronald G. , Irimia Daniel 
Published: August 2019

AbstractMegakaryocytes (MKs) are precursors to platelets, the second most abundant cells in the peripheral circulation. However, while platelets are known participate in immune responses and play significant roles during infections, the role of MKs within the immune system has not been explored. Here we utilizein vitrotechniques to show that both cord blood-derived MKs (CB MKs) and MKs from a human megakaryoblastic leukemia cell line (Meg-01) chemotax towards pathogenic stimuli, phagocytose bacteria, and release chromatin webs in response to bacteria. Moreover, in patients with sepsis, we found that MK counts were significantly higher in the peripheral blood, and CD61+staining was increased in the kidneys and lungs, correlated with the development of organ dysfunction. Overall, our study suggests that MK cells display basic innate immune cell functions and respond during infections and sepsis.
Analysing complex metagenomic data with MicroWineBar
Authors: Klincke Franziska , Abel-Kistrup Martin , Saerens Sofie Maria Gilberte , Rasmussen Simon 
Published: August 2019

AbstractAn important step in metagenomics studies is to identify which species are present in a sample as well as to compare samples from different environments. Here we introduce MicroWineBar, a graphical tool for analyzing and comparing metagenomics samples. MicroWineBar can visualize the abundances of metagenomics samples in line and bar graphs, as well as analyse the richness and diversity. For a PCA as well as a differential abundance analysis, the abundance data is treated as compositional data and center log-ratio transformed. We use MicroWineBar to analyse two different years of wine fermentation as well as data from a human microbiome study of colorectal cancer. Importantly, MicroWineBar does not require any programming skills, is intuitive and user friendly. MicroWineBar is available athttps://github.com/klincke/MicroWineBarand as a python package from the Python Package Index.
Metal-Assisted and Microwave-Accelerated Germination
Authors: Aslan Kadir , Stevenson Monet , Guy Janelle , Bonyi Enock , Mohammed Muzaffer , Ozturk Birol , Drake Kyle , McLean Freeman , Souffrant Ashley , Bigio Amber 
Published: August 2019

ABSTRACTWe report the proof-of-principle demonstration of a methodology, called Metal-Assisted and Microwave-Accelerated Germination, to modulate the germination of plant seeds and growth of plants using gold nanoparticles (Au NPs) and microwave heating. As a model plant seed, basil seeds were heated in a solution of 20 nm Au NPs using a microwave waveguide fiber connected to a solid-state microwave operating at 8 GHz at 20 W, which resulted in the development of longer basil gum as observed by optical microscopy. In control experiments, Au NPs or microwave heating was omitted to establish a baseline growth level under standard experimental conditions (no microwave heating or no Au NPs). Our results also show that hydroponic growth and soil growth of basil plants can be delayed with the use of 20 nm Au NPs at room temperature without microwave heating. The combined use of 20 nm Au NPs and microwave heating at 10 W for 6 minutes results in accelerated growth prolonged life of basil plants.
Reconstruction of the phase dynamics of the somitogenesis clock oscillator
Authors: Moya Lucas J. Morales , Dale J. Kim , Murray Philip J. 
Published: August 2019

AbstractIn this study we develop a computational framework for the reconstruction of the phase dynamics of the somitogenesis clock oscillator. Our understanding of the somitogenesis clock, a developmental oscillator found in the vertebrate embryo, has been revolutionised by the development of real time reporters of clock gene expression. However, the signals obtained from the real time reporters are typically noisy, nonstationary and spatiotemporally dynamic and there are open questions with regard to how post-processing can be used to both improve the insight gained from a given experiment and to constrain theoretical models. In this study we present a methodology, which is a variant of empirical mode decomposition, that reconstructs the phase dynamics of the somitogenesis clock. After validating the methodology using synthetic datasets, we define a set of metrics that use the reconstructed phase profiles to infer biologically meaningful quantities. We perform experiments in which the signal from a real time reporter of the somitogenesis clock is recorded and reconstruct the phase dynamics. Application of the defined metrics yields results that are consistent with previous experimental observations. Moreover, we extend previous work by developing a gradient descent method for defining automated kymographs and showing that boundary conditions are non-homogeneous. By studying phase dynamics along phase gradient descent trajectories, we show that, consistent with a previous theoretical model, the oscillation frequency is inversely correlated with the phase gradient but that the coefficient is not constant in time. The proposed methodology provides a tool kit for that can be used in the analysis of future experiments and the quantitative observations can be used to guide the development of future mathematical models.
Theory of microtubule length regulation in antiparallel overlaps
Authors: Kuan Hui-Shun , Betterton Meredith D. 
Published: August 2019

AbstractDuring cell division, microtubules in the mitotic spindle form antiparallel overlaps near the center of the spindle. Kinesin motor proteins alter microtubule polymerization dynamics to regulate the length of these overlaps to maintain spindle integrity. Length regulation of antiparallel overlaps has been reconstituted with purified microtubules, crosslinkers, and motors. Here we develop a theory of steady-state overlap length which depends on the filament plus-end motor concentration, determined by a balance between motor arrival (motor binding and stepping in the overlap) and motor departure (motor unbinding from filament tips during depolymerization) in the absence of motor-driven sliding. Assuming that motors processively depolymerize and exhibit altered binding kinetics near MT plus-ends improves the agreement between theory and experiment. Our theory explains the origin of the experimentally observed critical concentration, a minimum motor concentration to observe a steady-state overlap length.
Rapidly Computing the Phylogenetic Transfer Index
Authors: Truszkowski Jakub , Gascuel Olivier , Swenson Krister M. 
Published: August 2019

AbstractGiven trees T and T* on the same taxon set, the transfer index ϕ(b, T*) is the number of taxa that need to be ignored so that the bipartition induced by branch b in T is equal to some bipartition in T*. Recently, Lemoine et al. [14] used the transfer index to design a novel bootstrap analysis technique that improves on Felsenstein’s bootstrap on large, noisy data sets. In this work, we propose an algorithm that computes the transfer index for all branches b ∈ T in O(n log3n) time, which improves upon the current O(n2)-time algorithm by Lin, Rajan and Moret [15]. Our implementation is able to process pairs of trees with hundreds of thousands of taxa in minutes and considerably speeds up the method of Lemoine et al. on large data sets. We believe our algorithm can be useful for comparing large phylogenies, especially when some taxa are misplaced (e.g. due to horizontal gene transfer, recombination, or reconstruction errors).
Phase variable glycosylation in non-typeableHaemophilus influenzae
Authors: Elango Danila , Schulz Benjamin L. 
Published: August 2019

AbstractNon-typeableHaemophilus influenzae(NTHi) is a leading cause of respiratory tract infections worldwide and continues to be a global health burden. Adhesion and colonisation of host cells are crucial steps in bacterial pathogenesis, and in many strains of NTHi interaction with the host is mediated by the high molecular weight adhesins HMW1A and HMW2A. These adhesins areN-glycoproteins which are modified by cytoplasmic glycosyltransferases HMW1C and HMW2C. Phase variation in the number of short sequence repeats in the promoters ofhmw1Aandhmw2Adirectly affects their expression. Here, we report the presence of similar variable repeat elements in the promoters ofhmw1Candhmw2Cin diverse NTHi isolates. In anex vivoassay, we systematically altered substrate and glycosyltransferase expression and showed that both of these factors affected the site-specific efficiency of glycosylation on HMW-A. Glycosylation occupancy was incomplete at many sites, variable between sites, and generally lower close to the C-terminus of HMW-A. We investigated the causes of this variability. As HMW-C glycosylates HMW-A in the cytoplasm, we tested how secretion affected glycosylation on HMW-A and showed that retaining HMW-A in the cytoplasm indeed increased glycosylation occupancy across the full length of the protein. Site-directed mutagenesis showed that HMW-C had no inherent preference for glycosylating asparagines in NxS or NxT sequons. This work provides key insights into factors contributing to the heterogenous modifications of NTHi HMW-A adhesins, expands knowledge of NTHi population diversity and pathogenic capability, and is relevant to vaccine design for NTHi and related pathogens.
Dissecting the Roles of Kalirin-7/PSD95/GluN2B Interactions in Different Forms of Synaptic Plasticity
Authors: Yeh Mason L. , Yasko Jessica R. , Levine Eric S. , Eipper Betty A. , Mains Richard E. 
Published: August 2019

AbstractKalirin-7 (Kal7) is a Rac1/RhoG GEF and multidomain scaffold localized to the postsynaptic density which plays an important role in synaptic plasticity. Behavioral and physiological phenotypes observed in the Kal7 knockout mouse are quite specific: genetics of breeding, growth, strength and coordination are normal; Kal7 knockout animals self-administer cocaine far more than normal mice, show exaggerated locomotor responses to cocaine, but lack changes in dendritic spine morphology seen in wildtype mice; Kal7 knockout mice have depressed surface expression of GluN2B receptor subunits and exhibit marked suppression of long-term potentiation and depression in hippocampus, cerebral cortex, and spinal cord; and Kal7 knockout mice have dramatically blunted perception of pain. To address the underlying cellular and molecular mechanisms which are deranged by loss of Kal7, we administered intracellular blocking peptides to acutely change Kal7 function at the synapse, to determine if plasticity deficits in Kal7-/-mice are the product of developmental processes since conception, or could be detected on a much shorter time scale. We found that specific disruption of the interactions of Kal7 with PSD-95 or GluN2B resulted in significant suppression of long-term potentiation and long-term depression. Biochemical approaches indicated that Kal7 interacted with PSD-95 at multiple sites within Kal7.Graphical Table of ContentsThe postsynaptic density is an integral player in receiving, interpreting and storing signals transmitted by presynaptic terminals. The correct molecular composition is crucial for successful expression of synaptic plasticity. Key components of the postsynaptic density include ligand-gated ion channels, structural and binding proteins, and multidomain scaffolding plus enzymatic proteins. These studies address whether the multiple components of the synaptic density bind together in a static or slowly adapting molecular complex, or whether critical interactions are fluid on a minute-to-minute basis.
Antibody-induced crosslinking and cholesterol-sensitive, anomalous diffusion of nicotinic acetylcholine receptors
Authors: Mosqueira Alejo , Camino Pablo A. , Barrantes Francisco J. 
Published: August 2019

AbstractSynaptic strength depends on the number of cell-surface neurotransmitter receptors in dynamic equilibrium with intracellular pools. Dysregulation of this homeostatic balance occurs e.g. in myasthenia gravis, an autoimmune disease characterized by a decrease in the number of postsynaptic nicotinic acetylcholine receptors (nAChRs). Monoclonal antibody mAb35 mimics this effect. Here we use STORM nanoscopy to characterize the individual and ensemble dynamics of mAb35-crosslinked receptors in the clonal cell line CHO-K1/A5, which robustly expresses adult muscle-type nAChRs. Antibody labeling of live cells results in 80% receptor immobilization. The remaining mobile fraction exhibits a heterogeneous combination of Brownian and anomalous diffusion. Single-molecule trajectories exhibit a two-state switching behavior between free Brownian walks and anticorrelated walks within confinement areas. The latter act as permeable fences (∼34 nm radius, ∼400 ms lifetime). Dynamic clustering, trapping and immobilization also occur in larger nanocluster zones (120-180 nm radius) with longer lifetimes (11 ± 1 s), in a strongly cholesterol-sensitive manner. Cholesterol depletion increases the size and average duration of the clustering phenomenon; cholesterol enrichment has the opposite effect. The disclosed high proportion of mAb35-crosslinked immobile receptors, together with their anomalous, cholesterol-sensitive diffusion and clustering, provides new insights into the antibody-enhanced antigenic modulation that leads to physiopathological internalization and degradation of receptors in myasthenia.A preliminary version of this work has appeared in the biorXiv repository: https://www.biorxiv.org/content/10.1101/744664v1. The study was not pre-registered.
Interdimer “zipping” in the chemoreceptor signaling domain revealed by molecular dynamics simulations
Authors: Petukh Marharyta G. , Ortega Davi R. , Baudry Jerome , Zhulin Igor B. 
Published: August 2019

ABSTRACTChemoreceptors are principal components of the bacterial sensory system that modulates cellular motility. They detect changes in the environment and transmit information to CheA histidine kinase, which ultimately controls cellular flagellar motors. The prototypical Tsr chemoreceptor in E. coli is a homodimer containing two principal functional modules: (i) a periplasmic ligand-binding domain and (ii) a cytoplasmic signaling domain. Chemoreceptor dimers are arranged into a trimer of dimers at the tip of the signaling domain comprising a minimal physical unit essential for enhancing the CheA activity several hundredfold. Trimers of dimers are arranged into highly ordered hexagon arrays at the cell pole; however, the mechanism underlying the trimer-of-dimer and higher order array formation remains unclear. Furthermore, molecular mechanisms of signal transduction that are likely to involve inter-dimer interactions are not fully understood. Here we apply all-atom, microsecond-time scale molecular dynamics simulations of the Tsr trimer of dimers atomic model in order to obtain further insight into potential interactions within the chemoreceptor signaling unit. We show extensive interactions between homodimers at the hairpin tip of the signaling domain, where strong hydrophobic interactions maintain binding. A subsequent zipping of homodimers is facilitated by electrostatic interactions, in particular by polar solvation energy and salt bridges that stabilize the final compact structure, which extends beyond the kinase interacting subdomain. Our study provides evidence that interdimer interactions within the chemoreceptor signaling domain are more complex than previously thought.
Crystal structure of the N-terminal domain of the major virulence factor BB0323 from the Lyme disease agent Borrelia burgdorferi
Authors: Brangulis Kalvis , Akopjana Inara , Kazaks Andris , Tars Kaspars 
Published: August 2019

Lyme disease is an infection caused by the spirochete Borrelia burgdorferi after it is transmitted to a mammalian organism during a tick blood meal. B. burgdorferi encodes at least 140 lipoproteins located on the outer or inner membrane, thus facing the surroundings or the periplasmic space, respectively. However, most of the predicted lipoproteins are of unknown function, and only a few proteins are known to be essential for the persistence and virulence of the pathogen. One such protein is the periplasmic BB0323, which is indispensable for B. burgdorferi to cause Lyme disease and the function of which is associated with cell fission and outer membrane integrity. After expression and transport to the periplasm, BB0323 is cleaved into C-terminal and N-terminal domains by the periplasmic serine protease BB0104. The resulting N-terminal domain is sufficient to ensure the survival of B. burgdorferi throughout the mouse–tick infection cycle. The crystal structure of the N-terminal domain of BB0323 was determined at 2.35 Å resolution. The overall fold of the protein belongs to the spectrin superfamily, with the characteristic interconnected triple-helical bundles known as spectrin repeats that function as linkers between different cell components in other organisms. Overall, the reported three-dimensional structure of the N-terminal domain of BB0323 not only reveals the molecular details of a protein that is essential for B. burgdorferi membrane integrity, cell fission and infectivity, but also suggests that spectrin repeats in bacteria are not limited to the EzrA proteins.
“Same same, but different”
Authors: Davis Jarrett D. , Miles Glenn Michael , Quinley III John H. 
Published: August 2019

Purpose
This paper is a part of a series of papers seeking insight into a holistic perspective into the lives, experiences and vulnerabilities of male-to-female transgender persons (from here on referred to as “transgender persons”/“Ladyboys”) within the sex industry in Southeast Asia. “Ladyboy” in Thai context specifically refers to the cultural subgroup, rather than the person’s gender identity and is not seen as an offensive term. Among the minimal studies that have been conducted, the majority have focused on sexual health and the likelihood of contracting or spreading HIV/AIDS, while often ignoring the possibility of other vulnerabilities. The paper aims to discuss this issue.

Design/methodology/approach
The study interviews 60 transgender persons working within red light areas of Bangkok. The final research instrument was a questionnaire of 11 sub-themes, containing both multiple choice and open-ended questions.

Findings
This study found that 81 percent of participants had entered the sex industry due to financial necessity. There was also a high vulnerability among transgender sex workers to physical and sexual violence. This includes nearly a quarter (24 percent) who cite being forced to have sex and 26 percent who cite physical assault within the last 12 months.

Social implications
These findings can aid the development of programs and social services that address the needs of ladyboys, looking beyond gender expression and social identity to meet needs and vulnerabilities that often go overlooked.

Originality/value
This survey provides deeper understanding of the vulnerability of transgender sex workers, including their trajectory into sex work and potential alternatives.
Exploring the relationships of the culture of competitiveness and knowledge development to sustainable supply chain management and organizational performance
Authors: Fantazy Kamel , Tipu Syed Awais Ahmad 
Published: August 2019

PurposeThe purpose of this paper is to draw upon the resource-based view of the firm to explore how a firm’s resources (assets and capabilities) such as culture of competitiveness (CC) and knowledge development (KD) relate to sustainable supply chain management (SSCM) and organizational performance (OP).Design/methodology/approachData were collected from 242 supply chain and logistics managers in Pakistan and a structured equation modeling approach was used.FindingsThe results of the study provide support for the proposed hypotheses and indicate that CC and KD are positively related to SSCM and OP. This points out that the organizations in Pakistan are likely to emphasize CC and KD to achieve OP. However, the positive but weak association of CC and KD with SSCM highlights that the organizations in Pakistan show less concern for SSCM.Originality/valueThe literature did not reveal any study which examined the relationships of the CC and KD to SSCM and OP in developing countries. The present study aims to address this gap in the literature.