bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inference of deformation mechanisms and constitutive response of soft material surrogates of biological tissue by full-field characterization and data-driven variational system identification
Authors: Wang Z. , Estrada J.B. , Arruda E.M. , Garikipati K. 
Published: October 2020

AbstractWe present a novel, fully three-dimensional approach to soft material characterization and constitutive modeling with relevance to soft biological tissue. Our approach leverages recent advances in experimental techniques and data-driven computation. The experimental component of this approach involvesin situmechanical loading in a magnetic field (using MRI), yielding the entire deformation tensor field throughout the specimen regardless of the possible irregularities in its three-dimensional shape. Characterization can therefore be accomplished with data at a reduced number of deformation states. We refer to this experimental technique as MR-u. Its combination with powerful approaches to inverse modelling, specifically methods of model inference, would open the door to insightful mechanical characterization for soft materials. In recent computational advances that answer this need, we have developed new, data-driven inverse techniques to infer the model that best explains the physics governing observed phenomena from a spectrum of admissible ones, while maintaining parsimony of representation. This approach is referred to as Variational System Identification (VSI). In this communication, we apply the MR–uapproach to characterize soft polymers regarding them as surrogates of soft biological tissue, and using VSI, we infer the physically best-suited and parsimonious mathematical models of their mechanical response. We demonstrate the performance of our methods in the face of noisy data with physical constraints that challenge the identification of mathematical models, while attaining high accuracy in the predicted response of the inferred models.
SWOTein: A structure-based approach to predict stability Strengths and Weaknesses of prOTEINs
Authors: Hou Q. , Pucci F. , Ancien F. , Kwasigroch J.M. , Bourgeas R. , Rooman M. 
Published: October 2020

AbstractMotivationAlthough structured proteins adopt their lowest free energy conformation in physiological conditions, the individual residues are generally not in their lowest free energy conformation. Residues that are stability weaknesses are often involved in functional regions, whereas stability strengths ensure local structural stability. The detection of strengths and weaknesses provides key information to guide protein engineering experiments aiming to modulate folding and various functional processes.ResultsWe developed the SWOTein predictor which identifies strong and weak residues in proteins on the basis of three types of statistical energy functions describing local interactions along the chain, hydrophobic forces and tertiary interactions. The large-scale comparison of the different types of strengths and weaknesses showed their complementarity and the enhancement of the information they provide. We applied SWOTein to apocytochrome b562and found good agreement between predicted strengths and weaknesses and native hydrogen exchange data. Its application to an amino acid-binding protein identified the hinge at the basis of the conformational change. SWOTein is both fast and accurate and can be applied at small and large scale to analyze and modulate folding and molecular recognition processes.AvailabilityThe SWOTein webserver provides the list of predicted strengths and weaknesses and a protein structure visualization tool that facilitates the interpretation of the predictions. It is freely available for academic use athttp://babylone.ulb.ac.be/SWOTein.
Tasting Pictures: Viewing Images of Foods Evokes Taste-Quality-Specific Activity in Gustatory Insular Cortex
Authors: Avery Jason A. , Liu Alexander G. , Ingeholm John E. , Gotts Stephen J. , Martin Alex 
Published: October 2020

AbstractPrevious studies have shown that the conceptual representation of food involves brain regions associated with taste perception. The specificity of this response, however, is unknown. Does viewing pictures of food produce a general, non-specific response in taste-sensitive regions of the brain? Or, is the response specific for how a particular food tastes? Building on recent findings that specific tastes can be decoded from taste-sensitive regions of insular cortex, we asked whether viewing pictures of foods associated with a specific taste (e.g., sweet, salty, sour) can also be decoded from these same regions and if so, are the patterns of neural activity elicited by the pictures and their associated tastes similar? Using ultra-high resolution functional magnetic resonance imaging at high magnetic field strength (7-Tesla), we were able to decode specific tastes delivered during scanning, as well as the specific taste category associated with food pictures within the dorsal mid-insula, a primary taste responsive region of brain. Thus, merely viewing food pictures triggers an automatic retrieval of specific taste quality information associated with the depicted foods, within gustatory cortex. However, the patterns of activity elicited by pictures and their associated tastes were unrelated, thus suggesting a clear neural distinction between inferred and directly experienced sensory events. These data show how higher-order inferences derived from stimuli in one modality (i.e. vision) can be represented in brain regions typically thought to represent only low-level information about a different modality (i.e. taste).Significance StatementDoes a picture of an apple taste sweet? Previous studies have shown that viewing food pictures activates brain regions involved in taste perception. However, it’s unclear if this response is actually specific to the taste of depicted foods. Using ultra-high resolution functional magnetic resonance imaging and multi-voxel pattern analysis, we decoded specific tastes delivered during scanning, as well as the dominant tastes associated with food pictures within primary taste cortex. Thus, merely viewing pictures of food evokes an automatic retrieval of information about the taste of those foods. These results show how higher-order information from one sensory modality (i.e. vision) can be represented in brain regions thought to represent only low-level information from a different modality (i.e. taste).
Asymmetrical pegs in square holes? Functional and phylogenetic determinants of plant community assembly in temperate forest understories
Authors: Beck Jared J. , Li Daijiang , Johnson Sarah E. , Rogers David , Cameron Kenneth M. , Sytsma Kenneth J. , Givnish Thomas J. , Waller Donald M. 
Published: October 2020

ABSTRACTDespite advances in community assembly theory, uncertainties remain regarding how ecological and evolutionary processes shape species distributions and communities. We analyzed patterns of occurrence for 139 herbaceous plant species across 257 forest stands in Wisconsin (USA) to test predictions from community assembly theory. Specifically, we applied Bayesian phylogenetic linear mixed effects models (PGLMMs) to examine how functional traits and phylogenetic relationships influence plant distributions along environmental gradients and how functional similarity and phylogenetic relatedness affect local species co-occurrence. Leaf height, specific leaf area, and seed mass mediate species distributions along edaphic, climatic, and light gradients. In contrast, functional trait similarity and phylogenetic relationships only weakly affect patterns of local co-occurrence. These results confirm that broad-scale plant distributions are largely shaped by ecological sorting along environmental gradients but suggest deterministic assembly rules based on niche differentiation and complementary resource use may not govern local species co-occurrence in homogeneous environments.Statement of authorshipJB conceived the idea for the study. DL, SJ, and DR collected the vegetation and functional trait data. JB analyzed the data with assistance from DL. KC, KS, TG, and DW secured funding for research and oversaw data collection. JB wrote the first draft of the manuscript, all authors contributed to manuscript revisions.Data accessibility statementUpon acceptance, data will be archived at Figshare (https://figshare.com/) and scripts used to analyze the data will be shared on Github (https://github.com/jaredjbeck/).
Toxoplasma gondii GRA28is required for placenta-specific induction of the regulatory chemokine CCL22 in human and mouse
Authors: Rudzki Elizabeth N. , Ander Stephanie E. , Coombs Rachel S. , Alrubaye Hisham S. , Cabo Leah F. , Blank Matthew L. , Gutierrez-Melo Nicolas , Dubey JP , Coyne Carolyn B. , Boyle Jon P. 
Published: October 2020

ABSTRACTToxoplasma gondiiis an intracellular protozoan pathogen of humans that can cross the placenta and result in adverse pregnancy outcomes and long-term birth defects. The mechanism used byT. gondiito cross the placenta are unknown but complex interactions with the host immune response are likely to play a role in dictating infection outcomes during pregnancy. Prior work showed thatT. gondiiinfection dramatically and specifically increases the secretion of the immunomodulatory chemokine CCL22 in human placental cells during infection.. Given the important role of this chemokine during pregnancy, we hypothesized that CCL22 induction was driven by a specificT. gondii-secreted effector. Using a combination of bioinformatics and molecular genetics, we have now identifiedT. gondiiGRA28 as the gene product required for CCL22 induction. GRA28 is secreted into the host cell where it localizes to the nucleus, and deletion of this gene results in reduced CCL22 placental cells as well as a human monocyte cell line. The impact of GRA28 on CCL22 production is also conserved in mouse immune and placental cells bothin vitroandin vivo. Moreover, parasites lacking GRA28 are impaired in their ability to disseminate throughout the animal, suggesting a link between CCL22 induction and the ability of the parasite to cause disease. Overall these data demonstrate a clear function for GRA28 in altering the immunomodulatory landscape during infection of both placental and peripheral immune cells, and show a clear impact of this immunomodulation on infection outcome.AUTHOR SUMMARYToxoplasma gondiiis a globally ubiquitous pathogen that can cause severe disease in HIV/AIDS patients and can also cross the placenta and infect the developing fetus. We have found that placental and immune cells infected withT. gondiisecrete significant amounts of a chemokine (called “CCL22”) that is critical for immune tolerance during pregnancy. In order to better understand whether this is a response by the host or a process that is driven by the parasite, we have identified aT. gondiigene that is absolutely required to induce CCL22 production in human cells, indicating that CCL22 production is a process driven almost entirely by the parasite rather than the host. Consistent with its role in immune tolerance, we also found thatT. gondiiparasites lacking this gene are less able to proliferate and disseminate throughout the host. Taken together these data illustrate a direct relationship between CCL22 levels in the infected host and a key parasite effector, and provide an interesting example of howT. gondiican directly modulate host signaling pathways in order to facilitate its growth and dissemination.
Co-infection of influenza A virus enhances SARS-CoV-2 infectivity
Authors: Bai Lei , Zhao Yongliang , Dong Jiazhen , Liang Simeng , Guo Ming , Liu Xinjin , Wang Xin , Huang Zhixiang , Sun Xiaoyi , Zhang Zhen , Dong Lianghui , Liu Qianyun , Zheng Yucheng , Niu Danping , Xiang Min , Song Kun , Ye Jiajie , Zheng Wenchao , Tang Zhidong , Tang Mingliang , Zhou Yu , Shen Chao , Dai Ming , Zhou Li , Chen Yu , Yan Huan , Lan Ke , Xu Ke 
Published: October 2020

AbstractThe upcoming flu season in the northern hemisphere merging with the current COVID-19 pandemic raises a potentially severe threat to public health. Through experimental co-infection of IAV with either pseudotyped or SARS-CoV-2 live virus, we found that IAV pre-infection significantly promoted the infectivity of SARS-CoV-2 in a broad range of cell types. Remarkably, increased SARS-CoV-2 viral load and more severe lung damage were observed in mice co-infected with IAVin vivo. Moreover, such enhancement of SARS-CoV-2 infectivity was not seen with several other viruses probably due to a unique IAV segment as an inducer to elevate ACE2 expression. This study illustrates that IAV has a special nature to aggravate SARS-CoV-2 infection, and prevention of IAV is of great significance during the COVID-19 pandemic.
Immunogenicity of novel mRNA COVID-19 vaccine MRT5500 in mice and non-human primates
Authors: Kalnin Kirill V. , Plitnik Timothy , Kishko Michael , Zhang Jinrong , Zhang Donghui , Beauvais Adrien , Anosova Natalie G. , Tibbitts Timothy , DiNapoli Joshua M. , Huang Po-Wei D. , Huleatt James , Vincent Deanne , Fries Katherine , Karve Shrirang , Goldman Rebecca , Gopani Hardip , Dias Anusha , Tran Khang , Zacharia Minnie , Gu Xiaobo , Boeglin Lianne , Chivukula Sudha , Swearingen Ron , Landolfi Victoria , Fu Tong-Ming , DeRosa Frank , Casimiro Danilo 
Published: October 2020

SummaryAn effective vaccine to address the global pandemic of coronavirus disease 2019 (COVID-19) is an urgent public health priority1. Novel synthetic mRNA and vector-based vaccine technologies offer an expeditious development path alternative to traditional vaccine approaches. Here we describe the efforts to utilize an mRNA platform for rational design and evaluations of mRNA vaccine candidates based on Spike (S) glycoprotein of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus causing COVID-19. Several mRNA constructs expressing various structural conformations of S-protein, including wild type (WT), a pre-fusion stabilized mutant (2P), a furin cleavage-site mutant (GSAS) and a double mutant form (2P/GSAS), were tested in a preclinical animal model for their capacity to elicit neutralizing antibodies (nAbs). The lead 2P/GSAS candidate was further assessed in dose-ranging studies in mice andCynomolgusmacaques. The selected 2P/GSAS vaccine formulation, now designated MRT5500, elicited potent nAbs as measured in two types of neutralization assays. In addition, MRT5500 elicited TH1-biased responses in both mouse and non-human primate species, a result that helps to address a hypothetical concern regarding potential vaccine-associated enhanced respiratory diseases associated with TH2-biased responses. These data position MRT5500 as a viable vaccine candidate for clinical development against COVID-19.
IL-13 deficiency exacerbates lung damage and impairs epithelial-derived type 2 molecules during nematode infection
Authors: Chenery AL , Rosini S , Parkinson JE , Herrera JA , Lawless Craig , Chan BHK , Loke P , MacDonald AS , Kadler KE , Sutherland TE , Allen JE 
Published: October 2020

AbstractIL-13 plays a key role during protective type 2 immune responses at mucosal sites, such as during infection with nematodes. However, dysregulation of IL-13 can also contribute to the pathogenesis of atopic and fibrotic diseases such as allergic asthma. Matrix remodelling is an important component of repair processes in the lung but also a hallmark of chronic conditions involving fibrosis. Hence, understanding the role of IL-13 in tissue remodelling has important clinical implications. Since IL-13 shares receptors and signalling pathways with IL-4, disentangling the relative contributions of these type 2 cytokines has been challenging. Additionally, little is known about the singular role of IL-13 following acute tissue injury. In this study, we usedNippostrongylus brasiliensisinfection as a model of acute lung tissue damage comparing responses between WT and IL-13-deficient mice, in which IL-4 signalling is intact. Importantly, we found that IL-13 played a critical role in limiting tissue injury and haemorrhaging in the lung following infection. Through proteomic and transcriptomic profiling, we identified IL-13-dependent changes in matrix and associated regulators. We further showed that IL-13 is required for the induction of epithelial-derived type 2 effector molecules such as RELM-α and surfactant protein D. Pathway analyses predicted that IL-13 was heavily involved in the induction of cellular stress responses and regulation of lung epithelial cell differentiation by suppression of Foxa2 pathways. Thus, we propose that IL-13 has tissue-protective functions during lung injury and regulates epithelial cell responses during type 2 immunity in this acute setting.
Identification of a recently dominate sublineage inSalmonella4,[5],12:i:- sequence type 34 isolated from food animals in Japan
Authors: Arai Nobuo , Sekizuka Tsuyoshi , Tamamura-Andoh Yukino , Barco Lisa , Hinenoya Atsushi , Yamasaki Shinji , Iwata Taketoshi , Watanabe-Yanai Ayako , Kuroda Makoto , Akiba Masato , Kusumoto Masahiro 
Published: October 2020

AbstractSalmonellaTyphimurium and its monophasic variant (Salmonella4,[5],12:i:-) are classified into nine clades. Clade 9 is composed of ST34 strains, including theSalmonella4,[5],12:i:-European clone, which has rapidly disseminated in humans and animals worldwide since the 2000s. To reveal the microevolution of ST34/clade 9, we analyzed the whole-genome-based phylogenetic relationships of 230SalmonellaTyphimurium andSalmonella4,[5],12:i:-strains isolated between 1998 and 2017 in Japan and other countries. We identified clade 9-2, a novel sublineage derived from the conventionalSalmonella4,[5],12:i:-clade 9 that exclusively consists of Japanese isolates. Clade 9-2 was generated by mobile genetic element-mediated stepwise genome reductions caused by IS26and prophages. Furthermore, the recently identified strains developed further resistance to antimicrobials via the acquisition of resistance genes. During this microevolution,Salmonella4,[5],12:i:-clade 9-2 has dominated among recent isolates from food animals in Japan via the emergence of clonally expanding and/or multiple host-adapted subclades.
Ecological specialisation and evolutionary reticulation in extant Hyaenidae
Authors: Westbury M V , Le Duc Diana , Duchêne David A. , Krishnan Arunkumar , Prost Stefan , Rutschmann Sereina , Grau Jose H. , Dalen Love , Weyrich Alexandra , Norén Karin , Werdelin Lars , Dalerum Fredrik , Schöneberg Torsten , Hofreiter Michael 
Published: October 2020

AbstractDuring the Miocene, Hyaenidae was a highly diverse family of Carnivora that has since been severely reduced to four extant genera, each of which contains only a single species. These species include the bone-cracking spotted, striped, and brown hyenas, and the specialised insectivorous aardwolf. Previous genome studies have analysed the evolutionary histories of the spotted and brown hyenas, but little is known about the remaining two species. Moreover, the genomic underpinnings of scavenging and insectivory, defining traits of the extant species, remain elusive. To tackle these questions, we generated an aardwolf genome and analysed it together with those from the other three species. We provide new insights into the evolutionary relationships between the species, the genomic underpinnings of their scavenging and insectivorous lifestyles, and their respective genetic diversities and demographic histories. High levels of phylogenetic discordance within the family suggest gene flow between the aardwolf lineage and the ancestral brown/striped hyena lineage. Genes related to immunity and digestion in the bone-cracking hyenas and craniofacial development in the aardwolf showed the strongest signals of selection in their respective lineages, suggesting putative key adaptations to carrion or termite feeding. We also found a family-wide expansion in olfactory receptor genes suggesting that an acute sense of smell was a key early adaptation for the Hyaenidae family. Finally, we report very low levels of genetic diversity within the brown and striped hyenas despite no signs of inbreeding, which we putatively link to their similarly slow decline in Neover the last ∼2 million years. We found much higher levels of genetic diversity in both the spotted hyena and aardwolf and more stable population sizes through time. Taken together, these findings highlight how ecological specialisation can impact the evolutionary history, demographics, and adaptive genetic changes of a lineage.
Structural analysis of rice Os4BGlu18 monolignol β-glucosidase
Authors: Baiya Supaporn , Pengthaisong Salila , Cairns James R. Ketudat 
Published: October 2020

AbstractMonolignol glucosides are storage forms of monolignols, which are polymerized to lignin to strengthen plant cell walls. The conversion of monolignol glucosides to monolignols is catalyzed by monolignol β-glucosidases. Rice Os4BGlu18 β-glucosidase catalyzes hydrolysis of the monolignol glucosides, coniferin, syringin, andp-coumaryl alcohol glucoside more efficiently than other natural substrates. To understand more clearly the basis for substrate specificity of a monolignol β-glucosidase, the structure of Os4BGlu18 was determined by X-ray crystallography. Crystals of Os4BGlu18 and its complex with δ-gluconolactone diffracted to 1.7 and 2.1 Å resolution, respectively. Two protein molecules were found in the asymmetric unit of theP212121space group of their isomorphous crystals. The Os4BGlu18 structure exhibited the typical (β/α)8TIM barrel of glycoside hydrolase family 1 (GH1), but the four variable loops and two disulfide bonds appeared significantly different from other known structures of GH1 β-glucosidases. Molecular docking studies of the Os4BGlu18 structure with monolignol substrate ligands placed the glycone in a similar position to the δ-gluconolactone in the complex structure and revealed the interactions between protein and ligands. Molecular docking, multiple sequence alignment, and homology modeling identified amino acid residues at the aglycone-binding site involved in substrate specificity for monolignol β-glucosides. Thus, the structural basis of substrate recognition and hydrolysis by monolignol β-glucosidases was elucidated.