bluuebunny/crossref_metadata_2025_split huggingface dataset:
The mechanical and morphological properties of systemic and pulmonary arteries differ in the earth boa, a snake without ventricular pressure separation
Authors: van Soldt Benjamin J. , Wang Tobias , Filogonio Renato , Danielsen Carl Christian 
Published: October 2021

AbstractThe walls of the mammalian aorta and pulmonary artery are characterized by diverging morphologies and mechanical properties, which has been correlated with high systemic and low pulmonary blood pressures, as a result of intraventricular pressure separation in the mammalian ventricle. However, the relation between intraventricular pressure separation and diverging aortic and pulmonary artery wall morphologies and mechanical characteristics is not understood. The snake cardiovascular system poses a unique model for the study of this question, since representatives both with and without intraventricular pressure separation exist. In this study we perform uniaxial tensile testing on vessel samples taken from the aortas and pulmonary arteries of the earth boa, Acrantophis madagascariensis, a species without intraventricular pressure separation. We then compare these morphological and mechanical characteristics with samples from the ball python, Python regius, and the yellow anaconda, Eunectes notaeus, species with and without intraventricular pressure separation, respectively. Strikingly, we find that although the aortas and pulmonary arteries of A. madagascariensis respond similarly to the same intramural blood pressures, they diverge strongly in morphology, and that this is a common attribute among species without intraventricular pressure separation in this study. In contrast, P. regius aortas and pulmonary arteries diverge both morphologically and in terms of their mechanical properties. Altogether our data indicate that intraventricular pressure separation does not explain diverging aortic and pulmonary artery morphologies. Following the Law of Laplace, we propose that thin pulmonary arteries represent a mechanism to protect the fragile pulmonary vascular bed by reducing the blood volume that passes through, to which genetic factors may contribute more strongly than physiological parameters.
Low-dimensional encoding of decisions in parietal cortex reflects long-term training history
Authors: Latimer Kenneth W. , Freedman David J. 
Published: October 2021

AbstractNeurons in parietal cortex exhibit task-related activity during decision-making tasks. However, it remains unclear how long-term training to perform different tasks over months or even years shapes neural computations and representations. We examine lateral intraparietal area (LIP) responses during a visual motion delayed-match-to-category (DMC) task. We consider two pairs of monkeys with different training histories: one trained only on the DMC task, and another first trained to perform fine motion-direction discrimination. We introduce generalized multilinear models to quantify low-dimensional, task-relevant components in population activity. During the DMC task, we found stronger cosine-like motion-direction tuning in the pretrained monkeys than in the DMC-only monkeys, and that the pretrained monkeys’ performance depended more heavily on sample-test stimulus similarity. These results suggest that sensory representations in LIP depend on the sequence of tasks that the animals have learned, underscoring the importance of training history in studies with complex behavioral tasks.
General structure-free energy relationships of hERG blocker binding under native cellular conditions
Authors: Wan Hongbin , Spiru Kristina , Williams Sarah , Pearlstein Robert A. 
Published: October 2021

AbstractWe proposed previously that aqueous non-covalent barriers arise from solute-induced perturbation of the H-bond network of solvating water (“the solvation field”) relative to bulk solvent, where the association barrier equates to enthalpic losses incurred from incomplete replacement of the H-bonds of expelled H-bond enriched solvation by inter-partner H-bonds, and the dissociation barrier equates to enthalpic + entropic losses incurred during dissociation-induced resolvation of H-bond depleted positions of the free partners (where dynamic occupancy is powered largely by the expulsion of such solvation to bulk solvent during association). We went on to analyze blockade of the human ether-a-go-go-related gene potassium channel (hERG) based on these principles, the results of which suggest that blockers: 1) project a single rod-shaped R-group (denoted as “BP”) into the pore at a rate proportional to the desolvation cost of BP, with the largely solvated remainder (denoted as “BC”) occupying the cytoplasmic “antechamber” of hERG; and 2) undergo second-order entry to the antechamber, followed byfirst-orderassociation of BP to the pore. In this work, we used WATMD to qualitatively survey the solvation fields of the pore and a representative set of 16 blockers sampled from the Redfern dataset of marketed drugs spanning a range of pro-arrhythmicity. We show that the highly non-polarporeis solvated principally by H-bond depleted and bulk-like water (incurring zero desolvation cost), whereasblocker BP moietiesare solvated by variable combinations of H-bond enriched and depleted water. With a few explainable exceptions, theblockersolvation fields (and implied desolvation/resolvation costs) are qualitatively well-correlated with both blocker potency and Redfern safety classification.
CCR5 closes the temporal window for memory linking
Authors: Shen Yang , Zhou Miou , Cai Denise , Filho Daniel Almeida , Fernandes Giselle , Cai Ying , Kim Nury , Necula Deanna , Zhou Chengbin , Liu Andy , Kang Xiaoman , Kamata Masakazu , Lavi Ayal , Huang Shan , Silva Tawnie , Heo Won Do , Silva Alcino J. 
Published: October 2021

SummaryReal world memories are formed in a particular context and are not acquired or recalled in isolation 1-5. Time is a key variable in the organization of memories, since events experienced close in time are more likely to be meaningfully associated, while those experienced with a longer interval are not1-4. How does the brain segregate events that are temporally distinct? Here, we report that a delayed (12-24h) increase in the expression of the C-C chemokine receptor type 5 (CCR5), an immune receptor well known as a co-receptor for HIV infection6,7, following the formation of a contextual memory, determines the duration of the temporal window for associating or linking that memory with subsequent memories. This delayed CCR5 expression in mouse dorsal CA1 (dCA1) neurons results in a decrease in neuronal excitability, which in turn negatively regulates neuronal memory allocation, thus reducing the overlap between dCA1 memory ensembles. Lowering this overlap affects the ability of one memory to trigger the recall of the other, thus closing the temporal window for memory linking. Remarkably, our findings also show that an age-related increase in CCL5/CCR5 expression leads to impairments in memory linking in aged mice, which could be reversed with a CCR5 knockout and an FDA approved drug that inhibits this receptor, a result with significant clinical implications. All together the findings reported here provide the first insights into the molecular and cellular mechanisms that shape the temporal window for memory linking.
Persistent Immunogenicity of Integrase Defective Lentiviral Vectors delivering membrane tethered Native-Like HIV-1 Envelope Trimers
Authors: Gallinaro Alessandra , Pirillo Maria Franca , Aldon Yoann , Cecchetti Serena , Michelini Zuleika , Tinari Antonella , Borghi Martina , Canitano Andrea , McKay Paul F. , Bona Roberta , Vescio Maria Fenicia , Grasso Felicia , Blasi Maria , Baroncelli Silvia , Scarlatti Gabriella , LaBranche Celia , Montefiori David , Klotman Mary E. , Sanders Rogier W. , Shattock Robin J. , Negri Donatella , Cara Andrea 
Published: October 2021

ABSTRACTIntegrase Defective Lentiviral Vectors (IDLVs) represent an attractive vaccine platform for delivering HIV-1 antigens, given their ability to induce specific and persistent immune responses in both mice and non-human primates (NHPs). Recent advances in HIV-1 immunogen design demonstrated that native-like HIV-1 Envelope (Env) trimers that mimic the structure of virion-associated Env induce neutralization breadth in rabbits and macaques. Here, we describe the development of an IDLV-based HIV-1 vaccine expressing either soluble ConSOSL.UFO.664 or membrane-tethered ConSOSL.UFO.750 native-like Env immunogens with enhanced bNAb epitopes exposure. We show that IDLV can be pseudotyped with properly folded membrane-tethered native-like UFO.750 trimers. After a single IDLV injection in BALB/c mice, IDLV-UFO.750 induced a faster humoral kinetic as well as higher levels of anti-Env IgG compared to IDLV-UFO.664. IDLV-UFO.750 vaccinated cynomolgus macaques developed unusually long-lasting anti-Env IgG antibodies, as underlined by their remarkable half-life both after priming and boost with IDLV. After boosting with recombinant ConM SOSIP.v7 protein, two animals developed neutralization activity against the autologous tier 1B ConS virus mediated by V1/V2 and V3 glycan sites responses. By combining the possibility to display stabilized trimeric Env on the vector particles with the ability to induce sustained humoral responses, IDLVs represent an appropriate strategy for delivering rationally designed antigens to progress towards an effective HIV-1 vaccine.
Live cell imaging of metabolic heterogeneity by quantitative fluorescent ATP indicator protein, QUEEN-37C
Authors: Yaginuma Hideyuki , Okada Yasushi 
Published: October 2021

AbstractAdenosine triphosphate (ATP) is often referred as the energy currency of the cell. Yet, non-invasive, real-time, and quantitative measurement of its concentration in living mammalian cells has been difficult. Here we report an improved fluorescent ATP indicator protein, QUEEN-37C, which is optimized for measuring ATP concentration in living mammalian cells. Absolute value of the ATP concentration can be estimated from the ratiometric fluorescence imaging, and its accuracy was verified by the luciferase assay. Since QUEEN-37C enables the single-cell measurement of ATP concentration, we can not only measure its mean but its distribution in the cell population, which revealed that the ATP concentration is tightly regulated in most cells. We also noted the positive correlations in the ATP concentration among adjacent cells in epithelial cell sheet and mouse embryonic stem cell colonies. Thus, QUEEN-37C would serve as a new tool for the investigation of the single cell heterogeneity of metabolic states.
Nanchangmycin regulates FYN, FAK and ERK to control the fibrotic activity of hepatic stellate cells
Authors: Li Wenyang , Chen Jennifer Y. , Sun Cheng , Sparks Robert P. , Pantano Lorena , Rahman Raza-Ur , Moran Sean P. , Pondick Joshua V. , Kirchner Rory , Wrobel David , Bieler Michael , Ho Sui Shannan J. , Doerner Julia F. , Rippmann Jörg F. , Mullen Alan C. 
Published: October 2021

AbstractChronic liver injury causes fibrosis, characterized by the formation of scar tissue resulting from excessive accumulation of extracellular matrix (ECM) proteins. Hepatic stellate cell (HSC) myofibroblasts are the primary cell type responsible for liver fibrosis, yet there are currently no therapies directed at inhibiting the activity of HSC myofibroblasts. To search for potential anti-fibrotic drugs, we performed a high-throughput compound screen in primary human HSC myofibroblasts and identified 19 small molecules that induce HSC inactivation, including the polyether ionophore nanchangmycin (NCMC). NCMC induces lipid re-accumulation while reducing collagen expression, deposition of collagen in the extracellular matrix, cell proliferation, and migration. We find that NCMC increases cytosolic Ca2+ and reduces the phosphorylated protein levels of FYN, FAK, ERK1/2, HSP27 and STAT5B. Further, depletion of each of these kinases suppress COL1A1 expression. These studies reveal a signaling network triggered by NCMC to inactivate HSC myofibroblasts and reduce expression of proteins that compose the fibrotic scar. The identification of the antifibrotic effects of NCMC and the pathways by which NCMC inhibits fibrosis provides new tools and therapeutic targets to combat the development and progression of liver fibrosis.
Can floral nectars reduce transmission ofLeishmania?
Authors: Palmer-Young Evan C , Schwarz Ryan S , Chen Yanping , Evans Jay D 
Published: October 2021

ABSTRACTInsect-vectoredLeishmaniaare the second-most debilitating of human parasites worldwide. Elucidation of the environmental factors that affect parasite transmission by vectors is essential to develop sustainable methods of parasite control that do not have off-target effects on beneficial insects or environmental health. Many phytochemicals that inhibit growth of sand fly-vectoredLeishmania—which have been exhaustively studied in the search for phytochemical-based drugs—are abundant in nectar, which provide sugar-based meals to infected sand flies. In a quantitative meta-analysis, we compare inhibitory phytochemical concentrations forLeishmaniato concentrations present in floral nectar and pollen. We show that nectar concentrations of several flowering plant species exceed those that inhibit growth ofLeishmaniacell cultures, suggesting an unexplored, landscape ecology-based approach to reduceLeishmaniatransmission. Strategic planting of antiparasitic phytochemical-rich floral resources or phytochemically enriched baits could reduceLeishmanialoads in vectors, providing an environmentally friendly complement to existing means of disease control.
Targeting a central feature of asthma using a cell type-selective IL-13-responsive enhancer
Authors: Koh Kyung Duk , Bonser Luke R. , Eckalbar Walter L. , Shen Jiangshan , Yizhar-Barnea Ofer , Zeng Xiaoning , Sun Dingyuan I. , Zlock Lorna T. , Finkbeiner Walter E. , Ahituv Nadav , Erle David J. 
Published: October 2021

AbstractIL-13 is a central mediator of asthma1–3. Here, we used genome-wide approaches to characterize genes and regulatory elements modulated by IL-13 and other asthma-associated cytokines in airway epithelial cells and showed how they can be used for therapeutic purposes. Using bulk and single cell RNA-seq, we found distinctive responses to IL-13, IL-17, and interferons in human bronchial epithelial basal, ciliated, and secretory cells. H3K27ac ChIP-seq revealed that IL-13 had widespread effects on regulatory elements. Detailed characterization of an enhancer of SPDEF, a transcription factor required for pathologic mucin production, revealed that STAT6 and KLF5 binding sites cooperate to drive IL-13-dependent transcription selectively in secretory cells. Using this enhancer to drive CRISPRi and knockdown either SPDEF or the mucin MUC5AC showed the potential use of this approach for asthma therapeutics. This work identifies numerous genes and regulatory elements involved in cell type-selective cytokine responses and showcases their use for therapeutic purposes.
Molecular dynamics simulations of hydrophobic peptides that form β-hairpin structures in solution
Authors: Moharana Tushar Ranjan , Nagaraj Ramakrishnan 
Published: October 2021

AbstractPeptides designed with residues that have high propensity to occur in β-turns, form β-hairpin structures in apolar solvents as well in polar organic solvents such as dimethyl sulfoxide (DMSO), methanol and varying percentages of DMSO in chloroform (CHCl3). Presumably due to limited solubility, their conformations have not been investigated by experimental methods in water. We have examined the conformations of such designed peptides that fold into well-defined β-hairpin structures facilitated by β-turns, in the crystalline state and in solution, by Molecular Dynamics Simulations (MDS). The peptides fold into β-hairpin structures in water, starting from extended conformation. In DMSO, folding into β-hairpin structures was not observed, starting from extended conformation. However, when the starting structure is in β-hairpin conformation, unfolding is not observed during MDS in DMSO. Water clearly favours folding of short, hydrophobic peptides into β-turn and β-hairpin conformations from extended structures. DMSO does not have a denaturing effect on short, hydrophobic peptides.
Genomic architecture of three newly isolated unclassified Butyrivibrio species elucidate their potential role in the rumen ecosystem
Authors: Sengupta Kriti , Hivarkar Sai Suresh , Palevich Nikola , Chaudhary Prem Prashant , Dhakephalkar Prashant K. , Dagar Sumit Singh 
Published: October 2021

AbstractOne cellulose-degrading strain CB08 and two xylan-degrading strains XB500-5 and X503 were isolated from buffalo rumen. All the strains were designated as putative novel species of Butyrivibrio based on phylogeny, phylogenomy, digital DNA-DNA hybridization, and average nucleotide identity with their closest type strains. The draft genome length of CB08 was ∼3.54 Mb, while X503 and XB500-5 genome sizes were ∼3.24 Mb and ∼3.27 Mb, respectively. Only 68.28% of total orthologous clusters were shared among three genomes, and 40-44% of genes were identified as hypothetical proteins. The presence of genes encoding diverse carbohydrate-active enzymes (CAZymes) exhibited the lignocellulolytic potential of these strains. Further, the genome annotations revealed the metabolic pathways for monosaccharide fermentation to acetate, butyrate, lactate, ethanol, and hydrogen. The presence of genes for chemotaxis, antibiotic resistance, antimicrobial activity, synthesis of vitamins, and essential fatty acid suggested the versatile metabolic nature of these Butyrivibrio strains in the rumen environment.
Self-organized tissue mechanics underlie embryonic regulation
Authors: Caldarelli Paolo , Chamolly Alexander , Alegria-Prévot Olinda , Gros Jerome , Corson Francis 
Published: October 2021

AbstractEarly amniote development is a highly regulative and self-organized process, capable to adapt to interference through cell-cell interactions, which are widely believed to be mediated by molecules. Analyzing intact and mechanically perturbed avian embryos, we show that the mechanical forces that drive embryogenesis self-organize in an analog of Turing’s molecular reaction-diffusion model, with contractility locally self-activating and the ensuing tension acting as a long-range inhibitor. This mechanical feedback governs the persistent pattern of tissue flows that shape the embryo and steers the concomitant emergence of embryonic territories by modulating gene expression, ensuring the formation of a single embryo under normal conditions, yet allowing the emergence of multiple, well-proportioned embryos upon perturbations. Thus, mechanical forces are a central signal in embryonic self-organization, feeding back onto gene expression to canalize both patterning and morphogenesis.
NOD1 is super-activated through spatially-selective ubiquitination by the Salmonella effector SspH2
Authors: Delyea Cole , Luo Shu Y. , Dubrule Bradley E. , Julien Olivier , Bhavsar Amit P. 
Published: October 2021

ABSTRACTAs part of its pathogenesis, Salmonella enterica serovar Typhimurium delivers effector proteins into host cells. One effector is SspH2, a member of the novel E3 ubiquitin ligase family, interacts with, and enhances, NOD1 pro-inflammatory signaling, though the underlying mechanisms are unclear. Here, we report the novel discovery that SspH2 interacts with multiple members of the NLRC family to enhance pro-inflammatory signaling that results from targeted ubiquitination. We show that SspH2 modulates host innate immunity by interacting with both NOD1 and NOD2 in mammalian epithelial cell culture. We also show that SspH2 specifically interacts with the NBD and LRR domains of NOD1 and super-activates NOD1- and NOD2-mediated cytokine secretion via the NF-κB pathway. Mass spectrometry analyses identified lysine residues in NOD1 that were ubiquitinated after interaction with SspH2. Through NOD1 mutational analyses, we identified four key lysine residues that are required for NOD1 super-activation by SspH2, but not its basal activity. These critical lysine residues are positioned in the same region of NOD1 and define a surface on NOD1 that is targeted by SspH2. Overall, this work provides evidence for post-translational modification of NOD1 by ubiquitin, and uncovers a unique mechanism of spatially-selective ubiquitination to enhance the activation of an archetypal NLR.SYNOPSISSspH2 is an E3 ubiquitin ligase injected by Salmonella Typhimurium into host cells that induces pro-inflammatory signaling. The immune receptor, NOD1, is ubiquitinated in the presence of SspH2, resulting in increased pro-inflammatory cytokine secretion.SspH2 super-activates NOD1 and NOD2 to increase pro-inflammatory cytokine secretion, in part, through the NF-κB pathwayUbiquitin modification of NOD1 were identified by mass spectrometryA specific region of NOD1 is targeted by SspH2 to enhance NOD1 activity.
Stimulus-specific processing of the plasma membrane receptor-like kinase FERONIA inArabidopsis thaliana
Authors: Cornblatt Cassidy S. , Shih Han-Wei , Monshausen Gabriele B. 
Published: October 2021

ABSTRACTFERONIA (FER), a receptor-like kinase involved in plant immunity, cell expansion, and mechanical signal transduction, is known to be endocytosed and degraded in response to treatment with its peptide ligand RAPID ALKALINIZATION FACTOR 1 (RALF1). Using confocal fluorescence microscopy and biochemical assays, we have found that full length FER-eGFP abundance at the plasma membrane is also regulated by mechanical stimulation, but through a separate, cysteine protease-dependent pathway. Like RALF1 treatment, both mechanical bending and mechanical wounding trigger a reduction in plasma membrane-localized, native promoter-driven FER-eGFP in Arabidopsis roots, hypocotyls, and cotyledons. However, pharmacological inhibition of protein trafficking and degradation suggests that while RALF1 induces clathrin-mediated endocytosis and subsequent degradation of FER-eGFP, mechanical stimulation triggers cleavage and/or degradation of FER-eGFP in a cysteine protease-dependent, clathrin-independent manner. Despite the stimulus-dependent differences in these two pathways, we found that both require early FER signaling components, including Ca2+signaling, FER kinase activity, and the presence of LLG1, a FER-interacting protein with an essential role in FER-dependent signal transduction.
TSCDA: A novel greedy approach for community discovery in networks
Authors: Ferdowsi Arman , Khanteymoori Alireza , Chenary Maryam Dehghan 
Published: October 2021

AbstractIn this paper, we introduce a new approach for detecting community structures in networks. The approach is subject to modifying one of the connectivity-based community quality functions based on considering the impact that each community’s most influential node has on the other vertices. Utilizing the proposed quality measure, we devise an algorithm that aims to detect high-quality communities of a given network based on two stages: finding a promising initial solution using greedy methods and then refining the solutions in a local search manner.The performance of our algorithm has been evaluated on some standard real-world networks as well as on some artificial networks. The experimental results of the algorithm are reported and compared with several state-of-the-art algorithms. The experiments show that our approach is competitive with the other well-known techniques in the literature and even outperforms them. This approach can be used as a new community detection method in network analysis.