bluuebunny/crossref_metadata_2025_split huggingface dataset:
Robustness and the evolution of length control strategies in the type III secretion system and flagellar hook
Authors: Nariya Maulik K. , Mallela Abhishek , Shi Jack J. , Deeds Eric J. 
Published: September 2019

AbstractBacteria construct many structures, like the flagellar hook and the type III secretion system, that aid in crucial processes such as locomotion and pathogenesis. Experimental work has suggested two competing mechanisms bacteria could use to regulate length in these structures: the “ruler” mechanism and the “substrate switching” mechanism. In this work, we constructed a mathematical model of length control based on the ruler mechanism, and found that the predictions of this model are consistent with experimental data not just for the scaling of the average length with the ruler protein length, but also the variance. Interestingly, we found that the ruler mechanism allows for the evolution of needles with large average lengths without the concomitant large increase in variance that occurs in the substrate switching mechanism. These findings shed new light on the trade-offs that may have lead to the evolution of different length control mechanisms in different bacterial species.
Deviations from dynamic equilibrium in ecological communities worldwide
Authors: Kalyuzhny Michael , Flather Curtis H. , Shnerb Nadav M. , Kadmon Ronen 
Published: September 2019

AbstractEcological communities are assembled by colonization and extinction events, that may be regulated by ecological niches1–5. The most parsimonious explanation of local community assembly is the Dynamic Equilibrium (DE) model, which assumes that community dynamics is shaped by random colonization and extinctions events, effectively ignoring the effects of niches1, 6. Despite its empirical success in explaining diversity patterns1, 5, 7, it is unknown to what extent the assembly dynamics of communities around the globe are consistent with this model. Using a newly developed methodology, we show that in 4989 communities from 49 different datasets, representing multiple taxa, biomes and locations, changes in richness and composition are larger than expected by DE. All the fundamental assumptions of DE are violated, but the large changes in species richness and composition primarily stem from the synchrony in the dynamics of different species. These results indicate that temporal changes in communities are predominantly driven by shared responses of co-occurring species to environmental changes, rather than by inter-specific competition. This finding is in sharp contrast to the long-term recognition of competition as a primary driver of species assembly8–12. While ecological niches are often thought to stabilize species diversity and composition4, 13, 14, we found that they promote large changes in ecological communities.
Methylome-Wide Association Study of Central Adiposity Implicate Genes Involved in Immune and Endocrine Systems
Authors: Justice Anne E , Chittoor Geetha , Gondalia Rahul , Melton Phillip E , Lim Elise , Grove Megan L. , Whitsel Eric A. , Liu Ching-Ti , Cupples L. Adrienne , Fernandez-Rhodes Lindsay , Guan Weihua , Bressler Jan , Fornage Myriam , Boerwinkle Eric , Li Yun , Demerath Ellen , Heard-Costa Nancy , Levy Dan , Stewart James D , Baccarelli Andrea , Hou Lifang , Conneely Karen , Mori Trevor , Beilin Lawrence J. , Huang Rae-Chi , Gordon-Larsen Penny , Howard Annie Green , North Kari E 
Published: September 2019

ABSTRACTWe conducted a methylome-wide association study to examine associations between DNA methylation in whole blood and central adiposity and body fat distribution, measured as waist circumference, waist- to-hip ratio, and waist-to-height ratio adjusted for body mass index, in 2684 African American adults in the Atherosclerosis Risk in Communities study. We validated significantly associated Cytosine-phosphate-Guanine methylation sites (CpGs) among adults using the Women’s Health Initiative and Framingham Heart Study participants (combined N=5743) and generalized associations in adolescents from The Raine Study (N=820). We identified 11 CpGs that were robustly associated with one or more central adiposity trait in adults and 2 in adolescents, including CpG site associations nearTXNIP, ADCY7, SREBF1, andRAP1GAP2that had not previously been associated with obesity-related traits.
Mechanisms that allow cortical preparatory activity without inappropriate movement
Authors: Darlington Timothy R. , Lisberger Stephen G. 
Published: September 2019

AbstractWe reveal a novel mechanism that explains how preparatory activity can evolve in motor-related cortical areas without prematurely inducing movement. The smooth eye movement region of the frontal eye fields (FEFSEM) is a critical node in the neural circuit controlling smooth pursuit eye movement. Preparatory activity evolves in FEFSEM during fixation in parallel with an objective measure of visual-motor gain. We propose that the use of FEFSEM output as a gain signal allows for preparation to progress in the pursuit system without causing movement. We also show that preparatory modulation of firing rate in FEFSEM progresses in a way that predicts movement, providing evidence against the “movement-null” space hypothesis of how preparatory activity can progress without movement. Finally, there is partial reorganization of FEFSEM population activity between preparation and movement. We propose that this reorganization allows for a directionally non-specific component of preparatory visual-motor gain enhancement in the pursuit system.
A diet-dependent enzyme from the human gut microbiome promotes Th17 cell accumulation and colitis
Authors: Alexander Margaret , Ang Qi Yan , Nayak Renuka R. , Bustion Annamarie E. , Upadhyay Vaibhav , Pollard Katherine S. , Turnbaugh Peter J. 
Published: September 2019

AbstractAberrant activation of Th17 cells by the gut microbiota contributes to autoimmunity; however, the mechanisms responsible and their diet-dependence remain unclear. Here, we show that the autoimmune disease-associated gut ActinobacteriumEggerthella lentaincreases intestinal Th17 cells and worsens colitis in aRorc-dependent and strain-variable manner. A single genomic locus predicted Th17 accumulation. A gene within this locus, encoding the Cgr2 enzyme, was sufficient to increase Th17 cells. Levels ofcgr2were increased in stool from patients with rheumatoid arthritis compared to healthy controls. Dietary arginine blockedE. lenta-induced Th17 cells and colitis. These results expand the mechanisms through which bacteria shape mucosal immunity and demonstrate the feasibility of dissecting the complex interactions between diet, the gut microbiota, and autoimmune disease.One Sentence SummaryAn autoimmune disease-associated bacterium triggers disease due to a diet-dependent enzyme that regulates mucosal immunity.
Diet alters micronutrient pathways in the gut and placenta that regulate fetal growth and development in pregnant mice
Authors: Palladino Elia , Van Mieghem Tim , Connor Kristin L. 
Published: September 2019

AbstractMaternal malnutrition and micronutrient deficiencies can alter fetal development. However, the mechanisms underlying these relationships are poorly understood. We used a systems-physiology approach to investigate diet-induced effects on maternal gut microbes and folate/inositol transport in the maternal/fetal gut and placenta. Female mice were fed a control diet (CON) diet, undernourished (UN, restricted by 30% of CON intake) or a high fat diet (HF, 60% kcals fat) during pregnancy to model normal pregnancy, fetal growth restriction, or maternal metabolic dysfunction, respectively. At gestational day 18.5 we assessed circulating folate levels by microbiological assay, relative abundance of gut lactobacilli by G3PhyloChip™, and folate/inositol transporters in placenta and maternal/fetal gut by qPCR/immunohistochemistry. UN and HF-fed mothers had lower plasma folate concentrations vs. CON. Relative abundance of three lactobacilli taxa were higher in HF vs. UN and CON. HF-fed mothers had higher gut proton coupled folate transporter (Pcft) and reduced folate carrier 1 (Rfc1), and lower sodium myo-inositol co-transporter 2 (Smit2), mRNA expression vs. UN and CON. HF placentae had increased folate receptor beta (Frβ) expression vs. UN. mRNA expression of Pcft, folate receptor alpha (Frα) and Smit2 was higher in gut of HF fetuses vs. UN and CON. Transporter protein expression was not different between groups. Maternal malnutrition alters abundance of select gut microbes and folate/inositol transporters, which may influence maternal micronutrient status and delivery to the fetus, impacting pregnancy/fetal outcomes.
Learning Divisive Normalization in Primary Visual Cortex
Authors: Burg Max F. , Cadena Santiago A. , Denfield George H. , Walker Edgar Y. , Tolias Andreas S. , Bethge Matthias , Ecker Alexander S. 
Published: September 2019

AbstractDivisive normalization (DN) is a prominent computational building block in the brain that has been proposed as a canonical cortical operation. Numerous experimental studies have verified its importance for capturing nonlinear neural response properties to simple, artificial stimuli, and computational studies suggest that DN is also an important component for processing natural stimuli. However, we lack quantitative models of DN that are directly informed by measurements of spiking responses in the brain and applicable to arbitrary stimuli. Here, we propose a DN model that is applicable to arbitrary input images. We test its ability to predict how neurons in macaque primary visual cortex (V1) respond to natural images, with a focus on nonlinear response properties within the classical receptive field. Our model consists of one layer of subunits followed by learned orientation-specific DN. It outperforms linear-nonlinear and wavelet-based feature representations and makes a significant step towards the performance of state-of-the-art convolutional neural network (CNN) models. Unlike deep CNNs, our compact DN model offers a direct interpretation of the nature of normalization. By inspecting the learned normalization pool of our model, we gained insights into a long-standing question about the tuning properties of DN that update the current textbook description: we found that within the receptive field oriented features were normalized preferentially by features with similar orientation rather than non-specifically as currently assumed.Author summaryDivisive normalization (DN) is a computational building block throughout sensory processing in the brain. We currently lack an understanding of what role this normalization mechanism plays when processing complex stimuli like natural images. Here, we use modern machine learning methods to build a general DN model that is directly informed by data from primary visual cortex (V1). Contrary to high-predictive deep learning models, our DN-based model’s parameters offer a straightforward interpretation of the nature of normalization. Within the receptive field, we found that neurons responding strongly to a specific orientation are preferentially normalized by other neurons that are highly active for similar orientations, rather than being normalized by all neurons as it is currently assumed by textbook models.
Beyond the word and image: III. Neurodynamic properties of the semantic network
Authors: Jouen Anne-Lise , Cazin Nicolas , Hidot Sullivan , Madden-Lombardi Carol , Ventre-Dominey Jocelyne , Dominey Peter Ford 
Published: September 2019

AbstractUnderstanding the neural process underlying the comprehension of visual images and sentences remains a major open challenge in cognitive neuroscience. We previously demonstrated with fMRI and DTI that comprehension of visual images and sentences describing human activities recruits a common semantic system. The current research tests the hypothesis that this common semantic system will display similar neural dynamics during processing in these two modalities. To investigate these neural dynamics we recorded EEG from naïve subjects as they saw simple narratives made up of a first visual image depicting a human event, followed by a second that was either a sequentially coherent narrative follow-up, or not, of the first image. In separate blocks of trials the same protocol was presented using sentences. Analysis of the EEG signal revealed common neural dynamics for semantic processing across image and sentence modalities. Late positive ERPs were observed in response to sequential incoherence for sentences and images, consistent with previous studies that examined coherence in these two modalities separately. Analysis of oscillatory power revealed increased gamma-band activity for sequential coherence, again consistent with previous studies showing gamma increases for coherence and matching in sentence and image processing. Multivariate analysis demonstrated that training a classifier on data from one modality (images or sentences) allowed reliable decoding of the sequential coherence of data from trials in the untrained modality, providing further support for a common underlying semantic system for images and sentences. Processing sequential coherence of successive stimuli is associated with neural dynamics that are common to sentence and visual image modalities and that can be decoded across modalities. These results are discussed in the context of EEG signatures of narrative processing and meaning, and more general neural mechanisms for structure processing.
Interleukin (IL)-17/IL-36 axis participates to the crosstalk between endothelial cells and keratinocytes during inflammatory skin responses
Authors: Failla Cristina M. , Capriotti Lorena , Scarponi Claudia , Mercurio Laura , Facchiano Francesco , Morelli Martina , Rossi Stefania , Pagnanelli Gianluca , Albanesi Cristina , Cavani Andrea , Madonna Stefania 
Published: September 2019

AbstractIn inflammatory skin conditions, such as psoriasis, vascular enlargement is associated with endothelial cell proliferation, release of cytokines and adhesion molecule expression. Interleukin (IL)-17A is a pro-inflammatory cytokine mainly secreted by T helper-17 cells that is critically involved in psoriasis pathogenesis. IL-36α, IL-36β and IL-36γ are also inflammatory cytokines up-regulated in psoriasis and induced by various stimuli, including IL-17A. In this study, we found that human keratinocytes are the main source of IL-36, in particular of IL-36γ. This cytokine was strongly induced by IL-17A and efficiently activated human dermal microvascular endothelial cells (HDMECs), which expressed both IL-17 and IL-36 receptors, by inducing a molecular signaling, such as phosphorylation of ERK1/2 and NF-κB P65 subunit. We highlighted the intense IL-17A- and IL-36γ-dependent interplay between keratinocytes and HDMECs, likely active in the psoriatic lesions and leading to the establishment of a cytokine network responsible for the development and maintenance of the inflamed state. On HDMECs, IL-17A or IL-36γ showed a synergic activity with TNF-α, potently inducing inflammatory cytokine/chemokine release and ICAM-1 expression. We also investigated the involvement of IL-36γ and VEGF-A, substantially reduced in lesional skin of psoriatic patients pharmacologically treated with the anti-IL-17A antibody Secukinumab. Importantly, keratinocyte-derived IL-36γ represented an additional pro-angiogenic mediator of IL-17A. We observed that keratinocyte-derived VEGF-A influenced proliferation but not reduced inflammatory responses of HDMECs. On the other hand, inhibition of IL-36γ released by IL-17A-treated keratinocytes impaired ICAM-1 expression in HDMECs. Taken together, our data demonstrated that IL-17A and IL-36γ are highly involved in endothelial cells/keratinocytes crosstalk in inflammatory skin conditions.
Intra-Specific variability in fluctuating environments - mechanisms of impact on species diversity
Authors: Steinmetz Bnaya , Kalyuzhny Michael , Shnerb Nadav M. 
Published: September 2019

AbstractRecent studies have found considerable trait variations within species. The effect of such intra-specific trait variability (ITV) on the stability, coexistence and diversity of ecological communities received considerable attention and in many models it was shown to impede coexistence and decrease species diversity. Here we present a numerical study of the effect of genetically inherited ITV on species persistence and diversity in a temporally fluctuating environment. Two mechanisms are identified. First, ITV buffers populations against varying environmental conditions (portfolio effect) and reduces abundance variations. Second, the interplay between ITV and environmental variations tends to increase the mean fitness of diverse populations. The first mechanism promotes persistence and tends to increase species richness, while the second reduces the chance of a rare species population (which is usually homogenous) to invade and decreases species richness. We show that for large communities the portfolio effect is dominant, leading to ITV promoting species persistence and richness.
ISGylation drives basal breast tumour progression by promoting EGFR recycling and Akt signalling
Authors: Bolado-Carrancio Alfonso , Muir Morwenna , Ewing Ailith , Macleod Kenneth , Gallagher William , Nguyen Lan , Carragher Neil , Semple Colin , Brunton Valerie G , Caswell Patrick , Kriegsheim Alex von 
Published: September 2019

ABSTRACTISG15 is an ubiquitin-like modifier that is associated with reduced survival rates in breast cancer patients. However, the mechanism by which ISG15 achieves this remains elusive. We demonstrate that modification of Rab GDP-Dissociation Inhibitor Beta (GDI2) by ISG15 (ISGylation) alters endocytic recycling of the EGF receptor (EGFR). By regulating EGFR trafficking, ISGylation sustains Akt-signallingin vitroandin vivo. Persistent and enhanced Akt activation explains the more aggressive tumour behaviour observed in animal models and human breast cancers. We show that ISGylation can act as driver of tumour progression rather than merely being a marker of it.
High-resolution synchrotron imaging studies of intact fresh roots reveal soil bacteria promoted bioremediation and bio-fortification
Authors: Help Hanna , Lusa Merja , Honkanen Ari-Pekka , Diaz Ana , Holler Mirko , Salomé Murielle , Cloetens Peter , Mäkinen Henrik , Huotari Simo , Suhonen Heikki 
Published: September 2019

ABSTRACTPlant-microbe interactions can be utilized in bio-based processes such as bioremediation and biofortification, either to remove hazardous radionuclides and heavy metals from the soil, or to increase the accumulation of desired elements into crops to improve their quality. Optimizing such elegant plant-microbe interactions requires detailed understanding of the chemical element compositions of fresh plant tissues at cellular organelle resolution. However, such analyses remain challenging because conventional methods lack the required spatial resolution, contrast or sensitivity. Using a novel combination of nanoscaleresolution 3D cryogenic synchrotron-light ptychography, holotomography and fluorescence tomography, we show how soil bacteria interact with Arabidopsis thaliana and promote the uptake of various metals. Co-cultivation with Pseudomonas sp. strain T5-6-I alters root anatomy and increases levels of selenium (Se), iron (Fe) and other micronutrients in roots. Our approach highlights the interaction of plants and microbes in bioremediation and biofortification on the subcellular level.
An Erwinia amylovora inducible promoter for improvement of apple fire blight resistance
Authors: Matthieu Gaucher , Laura Righetti , Sébastien Aubourg , de Bernonville Thomas Dugé , Marie-Noёlle Brisset , Elisabeth Chevreau , Emilie Vergne 
Published: September 2019

AbstractIntragenesis is an important alternative to transgenesis to produce modified plants containing native DNA only. A key point to develop such a strategy is the availability of regulatory sequences controlling the expression of the gene of interest. With the aim of finding apple gene promoters either inducible by the fire blight pathogen Erwinia amylovora (Ea) or moderately constitutive, we focused on polyphenoloxidase genes (PPO). These genes encode oxidative enzymes involved in many physiological processes and have been previously shown to be up-regulated during the Ea infection process. We found ten PPO and two PPO-like sequences in the apple genome and characterized the promoters of MdPPO16 (pPPO16) and MdKFDV02 PPO-like (pKFDV02) for their potential as Ea-inducible and low-constitutive regulatory sequences respectively. Expression levels of reporter genes fused to these promoters and transiently or stably expressed in apple were quantified after various treatments. Unlike pKFDV02 which displayed a variable activity, pPPO16 allowed a fast and strong expression of transgenes in apple following Ea infection in a Type 3 Secretion System dependent manner. Altogether our results indicate that pKFDV02 did not keep its promises as a constitutive and weak promoter whereas pPPO16, the first Ea-inducible promoter cloned from apple, can be a useful component of intragenic strategies to create fire blight resistant apple genotypes.Key messagepPPO16, the first Ea-inducible promoter cloned from apple, can be a useful component of intragenic strategies to create fire blight resistant apple genotypes.
Crumbs organizes the transport machinery by regulating apical levels of PI(4,5)P2inDrosophila
Authors: Lattner Johanna , Leng Weihua , Knust Elisabeth , Brankatschk Marko , Flores-Benitez David 
Published: September 2019

AbstractAn efficient vectorial intracellular transport machinery depends on a well-established apico-basal polarity and is a prerequisite for the function of secretory epithelia. Despite extensive knowledge on individual trafficking pathways, little is known about the mechanisms coordinating their temporal and spatial regulation. Here, we report that the polarity protein Crumbs is essential for apical plasma membrane phospholipid-homeostasis and efficient apical secretion. Through recruitingβHeavy-Spectrin and MyosinV to the apical membrane, Crumbs maintains the Rab6-, Rab11- and Rab30-dependent trafficking and regulates the lipid phosphatases Pten and Ocrl. Crumbs knock-down results in increased apical levels of PI(4,5)P2and formation of a novel, Moesin- and PI(4,5)P2-enriched apical membrane sac containing microvilli-like structures. Our results identify Crumbs as an essential hub required to maintain the organization of the apical membrane and the physiological activity of the larval salivary gland.