bluuebunny/crossref_metadata_2025_split huggingface dataset:
Golgi-localized GALT7 and GALT8 participate in cellulose biosynthesis
Authors: Nibbering Pieter , Castilleux Romain , Wingsle Gunnar , Niittylä Totte 
Published: April 2021

AbstractArabinogalactan protein (AGP) glycan biosynthesis in the Golgi apparatus contributes to plant cell wall assembly, but the mechanisms underlying this process are largely unknown. Here, we show that two putative galactosyltransferases -named GALT7 and GALT8 -from the glycosyltransferase family 31 (GT31) ofArabidopsis thalianaparticipate in cellulose biosynthesis.galt7galt8mutants show primary cell wall defects manifesting as impaired growth and cell expansion in seedlings and etiolated hypocotyls, along with secondary cell wall defects, apparent as collapsed xylem vessels and reduced xylem wall thickness in the inflorescence stem. These phenotypes were associated with a ∼30% reduction in cellulose content, a ∼50% reduction in secondary cell wall CELLULOSE SYNTHASE (CESA) protein levels and reduced cellulose biosynthesis rate.CESAtranscript levels were not significantly altered ingalt7galt8mutants, suggesting that the reduction in CESA levels was caused by a post-transcriptional mechanism. We provide evidence that both GALT7 and GALT8 localise to the Golgi apparatus, while quantitative proteomics experiments revealed reduced levels of the entire FLA subgroup B in thegalt7galt8mutants. This leads us to hypothesize that a defect in FLA subgroup B glycan biosynthesis reduces cellulose biosynthesis rate ingalt7galt8mutants.
InterARTIC:an interactive web application for whole-genome nanopore sequencing analysis of SARS-CoV-2 and other viruses
Authors: Ferguson James M. , Gamaarachchi Hasindu , Nguyen Thanh , Gollon Alyne , Tong Stephanie , Aquilina-Reid Chiara , Bowen-James Rachel , Deveson Ira W. 
Published: April 2021

ABSTRACTMotivationInterARTICis an interactive web application for the analysis of viral whole-genome sequencing (WGS) data generated on Oxford Nanopore Technologies (ONT) devices. A graphical interface enables users with no bioinformatics expertise to analyse WGS experiments and reconstruct consensus genome sequences from individual isolates of viruses, such as SARS-CoV-2.InterARTICis intended to facilitate widespread adoption and standardisation of ONT sequencing for viral surveillance and molecular epidemiology.Worked exampleWe demonstrate the use ofInterARTICfor the analysis of ONT viral WGS data from SARS-CoV-2 and Ebola virus, using a laptop computer or the internal computer on an ONT GridION sequencing device. We showcase the intuitive graphical interface, workflow customisation capabilities and job-scheduling system that facilitate execution of small- and large-scale WGS projects on any common virus.ImplementationInterARTICis a free, open-source web application implemented in Python. The application can be downloaded as a set of pre-compiled binaries that are compatible with all common Ubuntu distributions, or built from source. For further details please visit:https://github.com/Psy-Fer/interARTIC/.
Spatial aggregation choice in the era of digital and administrative surveillance data
Authors: Lee Elizabeth C. , Arab Ali , Colizza Vittoria , Bansal Shweta 
Published: April 2021

AbstractBackgroundTraditional disease surveillance is increasingly being complemented by data from non-traditional sources like medical claims, electronic health records, and participatory syndromic data platforms. As non-traditional data are often collected at the individual-level and are convenience samples from a population, choices must be made on the aggregation of these data for epidemiological inference. Our study seeks to understand the influence of spatial aggregation choice on our understanding of disease spread with a case study of influenza-like illness in the United States.MethodsUsing U.S. medical claims data from 2002 to 2009, we examined the epidemic source location, onset and peak season timing, and epidemic duration of influenza seasons for data aggregated to the county and state scales. We also compared spatial autocorrelation and tested the relative magnitude of spatial aggregation differences between onset and peak measures of disease burden.ResultsWe found discrepancies in the inferred epidemic source locations and estimated influenza season onsets and peaks when comparing county and state-level data. Spatial autocorrelation was detected across more expansive geographic ranges during the peak season as compared to the early flu season, and there were greater spatial aggregation differences in early season measures as well.ConclusionsEpidemiological inferences are more sensitive to spatial scale early on during U.S. influenza seasons, when there is greater heterogeneity in timing, intensity, and geographic spread of the epidemics. Users of non-traditional disease surveillance should carefully consider how to extract accurate disease signals from finer-scaled data for early use in disease outbreaks.
Public Service Quality under Permanent and Fixed-term Employment Contracts: Evidence from Physician Supply of Primary Care
Authors: Sylvia Sean , Yi Hongmei , Xue Hao , Liu Gordon 
Published: April 2021

AbstractA key feature of public sector employment in many countries is rigid civil service rules that effectively limit manager autonomy over hiring, firing, promotion, and compensation decisions. We study the effect of these rules by comparing the quality of healthcare provided by physicians employed as civil servants with physicians hired in the same facilities on fixed-term contracts that give managers more autonomy over personnel decisions. Using data from interactions with unannounced standardized patients, we find that fixed-term contracts motivate greater diagnostic effort without increasing unnecessary treatments. Lower effort among civil servants appears due to both weaker career and wage incentives.
Flies getting filthy: The precopulatory mating behaviours of three mud-dwelling species of AustralianLispe(Diptera: Muscidae)
Authors: Butterworth Nathan J. , Wallman James F. 
Published: April 2021

AbstractLispe(Diptera: Muscidae) is a cosmopolitan genus of predatory flies that inhabit the muddy and sandy surrounds of water bodies. There are more than 163 described species worldwide, many of which are known to exhibit cursorial courtship displays which involve complex visual and vibratory signals. Despite the widespread distribution of these flies and their remarkable courtship displays, the biology and behaviour of most species are entirely unknown. Here, for the first time, we describe the pre-copulatory mating behaviours of three widespread and common Australian species:Lispe sydneyensis, Lispe albimaculataandLispe xenochaeta. We demonstrate that all three species exhibit entirely unique courtship displays, consisting of complex behavioural repertoires. Importantly, we highlight intrasexual competition inL. sydneyensis, where males engage in competitive dances and combat. We also report female-male aggression inL. albimaculataandL. xenochaetawhere females charge and display towards males. These novel mating systems provide unique opportunities to test ecological and evolutionary hypotheses.
Vertical Sleeve Gastrectomy Induces Enteroendocrine Cell Differentiation of Intestinal Stem Cells Through Farnesoid X Receptor Activation
Authors: Kim Ki-Suk , Peck Bailey C. E. , Hung Yu-Han , Koch-Laskowski Kieran , Wood Landon , Dedhia Priya H. , Spence Jason R. , Seeley Randy J. , Sethupathy Praveen , Sandoval Darleen A. 
Published: April 2021

AbstractVertical sleeve gastrectomy (VSG) is one of several bariatric procedures that substantially improves glycemia and energy homeostasis. Increased secretion of multiple gut peptides has been hypothesized to be a critical contributor to VSG’s potent effects to reduce body weight and improve glucose regulation. VSG results in an increase in the number of hormone-secreting enteroendocrine cells (EECs) in the intestinal epithelium, but whether this increase is via proliferation or differentiation of EECs and their subtypes remains unclear. Notably, the beneficial effects of VSG are lost in a mouse model lacking the bile acid nuclear receptor, farnesoid X receptor (FXR). FXR is a nuclear transcription factor that has been shown to regulate intestinal stem cell (ISC) function in cancer models, but whether it plays a role specifically in normal intestinal differentiation remains unknown. Therefore, we hypothesized that the VSG-induced increase in EECs is due to changes in intestinal differentiation driven by an increase in bile acid signaling through FXR. To test this, we performed VSG in mice that express eGFP in ISC/progenitor cells and performed RNAseq on GFP-positive cells sorted from the intestinal epithelia. We also assessed changes in EEC number (marked by GLP-1) in mouse intestinal organoids following treatment with bile acids and/or an FXR antagonist. RNA-seq revealed that FXR is expressed in ISCs and that VSG explicitly alters ISC expression of several genes that regulate intestinal secretory cell development, including EEC differentiation. Mouse intestinal organoids treated with bile acids increased GLP-1-positive cell numbers, whereas a potent FXR antagonist blocked this effect. Taken together, these data indicate that VSG drives ISC fate towards EEC differentiation through FXR signaling.
Rev-erb-α controls skeletal muscle calcium homeostasis through myoregulin repression: implications in Duchenne Muscular Dystrophy
Authors: Boulinguiez Alexis , Duhem Christian , Mayeuf-Louchart Alicia , Pourcet Benoit , Sebti Yasmine , Kondratska Kateryna , Montel Valérie , Delhaye Stéphane , Thorel Quentin , Beauchamp Justine , Hebras Aurore , Gimenez Marion , Couvelaere Marie , Zecchin Mathilde , Ferri Lise , Prevarskaya Natalia , Forand Anne , Gentil Christel , Piétri-Rouxel France , Bastide Bruno , Staels Bart , Duez Helene , Lancel Steve 
Published: April 2021

AbstractThe sarcoplasmic reticulum (SR) plays an important role in calcium homeostasis. SR calcium mishandling is described in pathological conditions such as myopathies. Here, we investigated whether the nuclear receptor Rev-erb-α regulates skeletal muscle SR calcium homeostasis. Our data demonstrate that Rev-erbα invalidation in mice impairs SERCA-dependent SR calcium uptake. Rev-erb-α acts on calcium homeostasis by repressing the SERCA inhibitor Myoregulin, through direct binding to its promoter. Restoration of Myoregulin counteracts the effects of REV-ERB-α overexpression on SR calcium content. Interestingly, myoblasts from Duchenne myopathy patients display downregulated REV-ERBα expression, whereas pharmacological Rev-erb activation ameliorates SR calcium homeostasis, and improves muscle structure and function in dystrophicmdx/Utr+/-mice. Our findings demonstrate that Rev-erb-α regulates muscle SR calcium homeostasis, pointing to its therapeutic interest for mitigating myopathy.
KMT2D haploinsufficiency in Kabuki syndrome disrupts neuronal function through transcriptional and chromatin rewiring independent of H3K4-monomethylation
Authors: Gabriele Michele , Vitriolo Alessandro , Cuvertino Sara , Pereira Marlene F , Franconi Celeste , Germain Pierre-Luc , Capocefalo Daniele , Castaldi Davide , Tenderini Erika , Bèchet Nicholas Burdon , Millar Catherine , Koemans Tom , Sabherwal Nitin , Stumpel Connie , Frega Monica , Palumbo Orazio , Carella Massimo , Malerba Natascia , Squeo Gabriella Maria , Kleefstra Tjitske , van Bokhoven Hans , Kimber Susan J. , Banka Siddharth , Merla Giuseppe , Nael Nadif Kasri , Testa Giuseppe 
Published: April 2021

AbstractKabuki syndrome (KS) is a rare multisystem disorder, characterized by intellectual disability, growth delay, and distinctive craniofacial features. It is mostly caused byde novomutations ofKMT2D, which is responsible for histone H3lysine 4 mono-methylation (H3K4me1) that marks active and poised enhancers. We assessed the impact of KMT2D mutations on chromatin and transcriptional regulation in a cohort of multiple KS1 tissues, including primary patient samples and disease-relevant lineages, namely cortical neurons (iN), neural crest stem cells (NCSC), and mesenchymal cells (MC). In parallel, we generated an isogenic line derived from human embryonic stem cells (hESC) for the stepwise characterization of neural precursors and mature neurons. We found that transcriptional dysregulation was particularly pronounced in cortical neurons and widely affected synapse activity pathways. This was consistent with highly specific alterations of spontaneous network-bursts patterns evidenced by Micro-electrode-array (MEA)-based neural network. Profiling of H3K4me1 unveiled the almost complete uncoupling between this chromatin mark and the effects on transcription, which is instead reflected by defects in H3K27ac. Finally, we identified the direct targets of KMT2D in mature cortical neurons, uncovering TEAD2 as the main mediator of KMT2D haploinsufficiency. Our results uncover the multi-tissue architecture of KS1 dysregulation and define a unique electrical phenotype and its molecular underpinnings for the cortical neuronal lineage.
Arginine multivalency stabilizes protein/RNA condensates
Authors: Paloni Matteo , Bussi Giovanni , Barducci Alessandro 
Published: April 2021

AbstractBiomolecular condensates assembled through liquid-liquid phase separation (LLPS) of proteins and RNAs are currently recognized to play an important role in cellular organization. Their assembly depends on the formation of a network of transient, multivalent interactions between flexible scaffold biomolecules. Understanding how protein and RNA sequences determine these interactions and ultimately regulate the phase separation is an open key challenge. Recentin vitrostudies have revealed that arginine and lysine residues, which are enriched in most cellular condensates, have markedly distinct propensities to drive the LLPS of protein/RNA mixtures. Here, we employ explicit-solvent atomistic Molecular Dynamics (MD) simulations to shed light on the microscopic origin of this difference by investigating mixtures of polyU oligonucleotides with either polyR/polyK peptides. In agreement with experiments, our simulations indicate that arginine has a higher affinity for polyU than lysine both in highly diluted conditions and in concentrated solutions with a biomolecular density comparable to cellular condensate. The analysis of intermolecular contacts suggests that this differential behavior is due to the propensity of arginine side chains to simultaneously form a higher number of specific interactions with oligonucleotides, including hydrogen bonds and stacking interactions. Our results provide a molecular description of how the multivalency of the guanidinium group enables the coordination of multiple RNA groups by a single arginine residue, thus ultimately stabilizing protein/RNA condensates.
A continuum membrane model predicts curvature sensing by helix insertion
Authors: Fu Yiben , Zeno Wade F. , Stachowiak Jeanne C. , Johnson Margaret E. 
Published: April 2021

AbstractProtein domains, such as ENTH (Epsin N-terminal homology) and BAR (bin/amphiphysin/rvs), contain amphipathic helices that drive preferential binding to curved membranes. However, predicting how the physical parameters of these domains control this ‘curvature sensing’ behavior is challenging due to the local membrane deformations generated by the nanoscopic helix on the surface of a large sphere. To overcome this challenge, we here use a deformable continuum model that accounts for the physical properties of the membrane and the helix insertion to predict curvature sensing behavior and is in good agreement with existing experimental data. Specifically, we show that the insertion can be modeled as a local change to the membrane’s spontaneous curvature,. Using physically reasonable ranges of the membrane bending modulus к, and aof ∼0.2-0.3 nm-1, this approach provides excellent agreement with the energetics extracted from experiment. For small vesicles with high curvature, the insertion lowers the membrane energy by relieving strain on a membrane that is far from its preferred curvature of zero. For larger vesicles with low curvature, however, the insertion has the inverse effect, de-stabilizing the membrane by introducing more strain. The membrane energy cannot be directly predicted analytically, due to shape changes from surface relaxation around the anisotropic insertion. We formulate here an empirical expression that captures numerically calculated membrane energies as a function of both basic membrane properties (bending modulus к and radiusR) as well as stresses applied by the inserted helix (and areaAins). We show that the shape relaxation energy has a similar magnitude to the insertion energy, with a strong nonlinear dependence on. We therefore predict how these physical parameters will alter the energetics of helix binding to curved vesicles, which is an essential step in understanding their localization dynamics during membrane remodeling processes.
Capturing Membrane Trafficking Events During 3D Angiogenic Development in Vitro
Authors: Francis Caitlin R. , Kushner Erich J. 
Published: April 2021

ABSTRACTObjectivesMechanisms that govern angiogenesis are paramount to our understanding of how blood vessels are formed embryonically, maintained in adulthood and manifest disease. Akin to transcriptional regulation of endothelial-specific genes, vesicular trafficking events dictate protein localization, functional activity, and half-life, providing a critically important regulatory step. However, there is little information detailing endothelial-specific trafficking signatures. This is due, in part, by limitations in visualizing trafficking events in endothelial tissues. Our aim in this investigation was to explore the use of a 3-dimensional (3D)in vitrosprouting model to image and evaluate membrane trafficking events compared to the conventional 2-dimensional (2D)-based culture method.MethodsPrimary Human endothelial cells were challenged to make multicellular sprouts using a fibrin-bead assay. An assortment of cell polarity and Rab proteins were quantified via immunocytochemistry and live-imaging to compare their localization between 3D sprouts and 2D culture.ResultsOur results show that sprouts generated from the fibrin-bead assay grow close to the imaging plane allowing for an orthogonal view of apical and basal membrane domains. Compared with 2D culture in which the apical and basal domains are in the axial orientation, limiting resolution, 3D sprouts are acquired in the X-Y plane providing high-resolution for viewing trafficking events. Second, we demonstrate that fibrin-bead generated sprouts have a strong apicobasal polarity axis. Third, we directly compare imaging of trafficking mediators podocalyxin and Rab35 between 3D sprouts and 2D culture. Here, we show that 3D sprouting structures are well-suited to capture trafficking events that are not present in 2D culture due to the lack of a defined apical domain. Lastly, we compared exocytic events of von Willebrand Factor between 3D sprouting and 2D culture. Our results demonstrate a distinct imaging advantage for monitoring these trafficking programs in 3D sprouts as compared with conventional 2D culture.ConclusionsIn general, our results establish that the fibrin-bead sprouting assay is well-suited for sub-cellular imaging of trafficking events during angiogenic growth. Additionally, the 2D endothelial culture does not enforce the formation of an apicobasal polarity axis.
Sesamol and its derivative investigated as antiandrogen - A potential prevention to prostate cancer in rats
Authors: Shah Abhishek , Shah Aarti Abhishek , Rekunge Deelip S. , Pai Aravinda , Chaturbhuj Ganesh U. , Nandakumar K , Lobo Richard 
Published: April 2021

AbstractAndrogen signaling is essential for the development of prostate cancer (PCa) initiated from prostatic basal cells with collocation of androgen receptor gene mutations. Phytoestrogens, the naturally occurring compounds are AR antagonist. These compounds downregulate prostate-specific antigen (PSA) expression and cell proliferation. Thus, this gives a track to research these compounds as a possible treatment for PCa. In this work, STITCH and molecular docking predict the conformation of ligands inside the suitable target binding site. Therefore, a study was planned to know the interactions among SM and its derivatives with AR. It was further, evaluated forin vitroevaluation on LNCaP, PC-3, and DU-145 using MTT studies. The two lead compounds shortlisted from MTT studies were further analyzed for androgen-regulated genes by using RT-PCR, western blot studies and an animal model of prostate cancer. We found that SM and its derivative (3’-MA) may prevent the development of PCa by androgen pathway.
Back to the Wild: Polluted Site Remediation and Biosphere Resilience
Authors: Ramos Débora Toledo , Corseuil Henry Xavier , Vogel Timothy M. 
Published: April 2021

ABSTRACTWorldwide efforts to depollute environments altered by human industrial activity have begun to produce an ever-increasing number of “clean” sites. “Clean” is defined by local regulatory processes and often responds to low compound concentrations or risk evaluations. Yet, these sites have been critically derailed from their historical biological activity by both the pollution event and the clean-up technology. This work explored the impact of contaminated (and remediated) sites on local microbial ecosystems. Different parcels of the same field site with the same relatively uniform microbial ecology were polluted and cleaned-up over the last 15 years. The statistical evaluation of the perturbation described changes to the local ecosystem that went back to the original baseline microbial composition although the pollution sources and the clean-up technologies affected the rate of return to the pre-disturbed condition. This rate reflected the intensity of the clean-up treatments. The role played by microbial communities on ecosystem maintenance and mitigation of pollution events lays the groundwork for predicting the microbial community responses to perturbations and the ability to reassert themselves. Predictions of ecosystem response to anthropogenic impacts could support decision-making on environmental management strategies for contaminated sites clean-up, depending on the ecosystem services desired to maintain or the risk posed to sensitive receptors.
Computational Roles of Intrinsic Synaptic Dynamics
Authors: Shimizu Genki , Yoshida Kensuke , Kasai Haruo , Toyoizumi Taro 
Published: April 2021

AbstractConventional theories assume that long-term information storage in the brain is implemented by modifying synaptic efficacy. Recent experimental findings challenge this view by demonstrating that dendritic spine sizes, or their corresponding synaptic weights, are highly volatile even in the absence of neural activity. Here we review previous computational works on the roles of these intrinsic synaptic dynamics. We first present the possibility for neuronal networks to sustain stable performance in their presence and we then hypothesize that intrinsic dynamics could be more than mere noise to withstand, but they may improve information processing in the brain.Highlights- Synapses exhibit changes due to intrinsic as well as extrinsic dynamics- Computational frameworks suggest stable network performance despite intrinsic changes- Intrinsic dynamics might be beneficial to information processing