bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simultaneous and sequential multi-species coronavirus vaccination
Authors: Peng Lei , Fang Zhenhao , Renauer Paul A. , McNamara Andrew , Park Jonathan J. , Lin Qianqian , Zhou Xiaoyu , Dong Matthew B. , Zhu Biqing , Zhao Hongyu , Wilen Craig B. , Chen Sidi 
Published: May 2022

AbstractAlthough successful COVID-19 vaccines have been developed, multiple pathogenic coronavirus species exist, urging for development of multi-species coronavirus vaccines. Here we developed prototype LNP-mRNA vaccine candidates against SARS-CoV-2 (Delta variant), SARS-CoV and MERS-CoV, and test how multiplexing of these LNP-mRNAs can induce effective immune responses in animal models. A triplex scheme of LNP-mRNA vaccination induced antigen-specific antibody responses against SARS-CoV-2, SARS-CoV and MERS-CoV, with a relatively weaker MERS-CoV response in this setting. Single cell RNA-seq profiled the global systemic immune repertoires and the respective transcriptome signatures of multiplexed vaccinated animals, which revealed a systemic increase in activated B cells, as well as differential gene expression signatures across major adaptive immune cells. Sequential vaccination showed potent antibody responses against all three species, significantly stronger than simultaneous vaccination in mixture. These data demonstrated the feasibility, antibody responses and single cell immune profiles of multi-species coronavirus vaccination. The direct comparison between simultaneous and sequential vaccination offers insights on optimization of vaccination schedules to provide broad and potent antibody immunity against three major pathogenic coronavirus species.One sentence summaryMultiplexed mRNA vaccination in simultaneous and sequential modes provide broad and potent immunity against pathogenic coronavirus species.
Multi-level force-dependent allosteric enhancement of αE-catenin binding to F-actin by vinculin
Authors: Bax Nicolas A. , Wang Amy , Huang Derek L. , Pokutta Sabine , Weis William I. , Dunn Alexander R. 
Published: May 2022

AbstractClassical cadherins are transmembrane proteins whose extracellular domains link neighboring cells, and whose intracellular domains connect to the actin cytoskeleton via β-catenin, α- catenin. The cadherin-catenin complex transmits forces that drive tissue morphogenesis and wound healing. In addition, tension-dependent changes in αE-catenin conformation enables it to recruit the actin-binding protein vinculin to cell-cell junctions, where it contributes to junctional strengthening. How and whether multiple cadherin-complexes cooperate to reinforce cell-cell junctions in response to load remains poorly understood. Here, we used single-molecule optical trap measurements to examine how multiple cadherin-catenin complexes interact with F-actin under load, and how this interaction is influenced by the presence of vinculin. We show that force oriented toward the (-) end of the actin filament results in mean lifetimes 3-fold longer than when force was applied towards the barbed (+) end. Further, load is distributed asymmetrically among complexes, such that only one bears the majority of applied load. We also measured force-dependent actin binding by a quaternary complex comprising the cadherin-catenin complex and the vinculin head region, which cannot itself bind actin. Binding lifetimes of this quaternary complex increased as additional complexes bound F-actin, but only when load was oriented toward the (-) end. In contrast, the cadherin-catenin complex alone did not show this form of cooperativity. These findings reveal multi-level, force-dependent regulation that enhances the strength of the association of multiple cadherin/catenin complexes with F-actin, conferring positive feedback that may strengthen the junction and polarize F-actin to facilitate the emergence of higher-order cytoskeletal organization.
Responses of Agricultural plants to Lithium pollution: Trends, Meta-Analysis, and Perspectives
Authors: Shakoor Noman , Adeel Muhammad , Azeem Imran , Ahmad Muhammad Arslan , Zain Muhammad , Abbas Aown , Zhou Pingfan , Li Yuanbo , Ming Xu , Rui Yukui 
Published: May 2022

AbstractLithium (Li) is gaining attention due to rapid rise of modern industries but their ultimate fingerprints on plants are not well established. Herein, we executed a meta-analysis of the existing recent literature investigating the impact of Li sources and levels on plant species under different growth conditions to understand the existing state of knowledge. Toxic effects of Li exposure in plants varies as a function of medium and interestingly, more negative responses are reported in hydroponic media as compared to soil and foliar application. Additionally, toxic effects of Li vary with Li source materials and LiCl more negatively affected plant development parameters such as plant germination (n=48) and root biomass (n=57) and recorded highly uptake in plants (n=78), while LiNO3 has more negative effects on shoot biomass. The Li at <50 mg L-1 concentrations significantly influenced the plant physiological indicators including plant germination and root biomass, while 50-500 mg L-1 Li concentration influence the biochemical parameters. The uptake potential of Li is dose dependent and their translocation/bioaccumulation remains unknown. Future work should include complete lifespan studies of the crop to elucidate the bioaccumulation of Li in edible tissues and to investigate possible trophic transfer of Li.Environmental significanceAccumulation of Li sources is increasing in ecosystem compartments, and this might be vulnerable to plants.
Spatial cumulant models enable spatially informed treatment strategies and analysis of local interactions in cancer systems
Authors: Hamis Sara , Somervuo Panu , Ågren J. Arvid , Tadele Dagim Shiferaw , Kesseli Juha , Scott Jacob G. , Nykter Matti , Gerlee Philip , Finkelshtein Dmitri , Ovaskainen Otso 
Published: May 2022

AbstractTheoretical and applied cancer studies that use individual-based models (IBMs) have been limited by the lack of a mathematical formulation that enables rigorous analysis of these models. However, spatial cumulant models (SCMs), which have arisen from theoretical ecology, describe population dynamics generated by a specific family of IBMs, namely spatio-temporal point processes (STPPs). SCMs are spatially resolved population models formulated by a system of differential equations that approximate the dynamics of two STPP-generated summary statistics: first-order spatial cumulants (densities), and second-order spatial cumulants (spatial covariances).We exemplify how SCMs can be used in mathematical oncology by modelling theoretical cancer cell populations comprising interacting growth factor-producing and non-producing cells. To formulate model equations, we use computational tools that enable the generation of STPPs, SCMs and mean-field population models (MFPMs) from user-defined model descriptions (Cornell et al., 2019). To calculate and compare STPP, SCM and MFPM-generated summary statistics, we develop an application-agnostic computational pipeline. Our results demonstrate that SCMs can capture STPP-generated population density dynamics, even when MFPMs fail to do so. From both MFPM and SCM equations, we derive treatment-induced death rates required to achieve non-growing cell populations. When testing these treatment strategies in STPP-generated cell populations, our results demonstrate that SCM-informed strategies outperform MFPM-informed strategies in terms of inhibiting population growths. We thus demonstrate that SCMs provide a new framework in which to study cell-cell interactions, and can be used to describe and perturb STPP-generated cell population dynamics. We, therefore, argue that SCMs can be used to increase IBMs’ applicability in cancer research.Statements and DeclarationsThe authors have no competing interests to declare that are relevant to the content of this article.
Cardiac patch treatment alleviates ischemic cardiomyopathy correlated with reverting Piezo1/2 expression by unloading left ventricular myocardium
Authors: Zhu Yang , Lu Yuwen , Jiang Sibo , Shen Ting , He Chengbin , Gao Yun , Shen Liyin , Jin Qiao , Zhao Yuting , Hu Hongjie , Ling Jun , He Jin , Zhuang Lenan 
Published: May 2022

AbstractPathologically elevated mechanical load promotes the adverse remodeling of left ventricle (LV) post myocardial infarction, which results in the progression from ischemic cardiomyopathy to heart failure. Cardiac patches could attenuate adverse LV remodeling by providing mechanical support to infarcted myocardium and border zone tissue. However, the mechanism of the translation from mechanical effects to favorable therapeutic outcome is still not clear. By transcriptome analysis, we found that the myocardial transcription levels of mechanosensitive ion channel proteins Piezo1 and Piezo2 significantly increased in patients with ischemic cardiomyopathy. In vitro tensile tests with local tissue information revealed a significant decrease in local strain and mechanical load in rat infarct. Cardiac function and geometry were preserved compared to non-treated control. Further, in LV myocardium of the patch-treated group, MI induced expression levels of Piezo1/2 were significantly reverted to the similar levels of the Sham group, indicating that cardiac patch beneficial effects were correlated with suppressing mechanosensitive genes, particularly Piezo1/2. These findings demonstrated the potential of cardiac patches in treating ICM patients with remodeling risks, and could provide guidance for improvement in next generation of patch devices.
Molecular determinants of TRAF6 binding specificity suggest that native interaction partners are not optimized for affinity
Authors: Halpin Jackson C. , Whitney Dustin , Rigoldi Federica , Sivaraman Venkat , Singer Avinoam , Keating Amy E. 
Published: May 2022

ABSTRACTTRAF6 is an adapter protein and E3 ubiquitin ligase involved in signaling downstream of cell receptors essential for development and the immune system. TRAF6 participates in many protein-protein interactions, some of which are mediated by a C-terminal MATH domain that recruits TRAF6 to cell-surface receptors and associated proteins. The TRAF6 MATH domain binds to short peptide segments containing the motif PxExx[FYWHDE], where x is any amino acid. Blocking TRAF6 interactions is associated with favorable effects in various disease models. To better define the TRAF6 MATH domain binding preferences, we generated a bacterial cell-surface peptide display library to sample the TRAF6 motif sequence space. We performed sorting experiments and identified 236 of the best TRAF6-interacting peptides and a set of 1,200 peptides that match the sequence PxE but do not bind TRAF6. Selected binders, tested by single-clone bacterial display titrations and bio-layer interferometry, bound TRAF6 tighter than previously measured native peptides. To elucidate the structural basis for TRAF6 interaction preferences, we built all-atom structural models of the TRAF6 MATH domain in complex with high-affinity binders and motif-matching nonbinders that were identified in the screen. We identified motif features that favor binding to TRAF6 as well as negative design elements distributed across the motif that can disfavor or preclude binding. Searching the human proteome for matches to the library screening-defined binding motif revealed that most known, biologically relevant TRAF6 motif matches occupy a different sequence space from the most enriched hits discovered in combinatorial library screening. Our experimentally determined binding preferences and structural models can support the design of peptide-based interaction inhibitors with higher affinities than endogenous TRAF6 ligands.
A Drosophila larvae-inspired vacuum-actuated soft robot
Authors: Sun Xiyang , Nose Akinao , Kohsaka Hiroshi 
Published: May 2022

AbstractPeristalsis is one of the most common locomotion patterns in limbless animals. This motion is generated by propagating muscular contraction and relaxation along the body axis. While the kinematics of peristalsis has been examined intensively, the kinetics and mechanical control of peristalsis remain unclear, partially due to the lack of suitable physical models to analyse the force and temporal control in soft-bodied animals’ locomotion. Here, based on a soft-bodied animal, Drosophila larvae, we proposed a vacuum-actuated soft robot replicating their crawling behaviour. The soft structure, made with hyperelastic silicon rubber, was designed to mimic the larval hydrostatic structure. To estimate the adequate range of pressures and time scales for control of the soft robots, a numerical simulation by the finite element method was conducted. Pulse-Width-Modulation (PWM) was used to generate time-series signals to control the vacuum pressure in each segment. Based on this control system, the soft robots could exhibit the peristaltic pattern resembling fly larval crawling. The soft robots reproduced two previous experimental results on fly larvae: slower crawling speed in backward crawling than in forward crawling, and the involvement of segmental contraction duration and intersegmental delay in crawling speed. Furthermore, the soft robot provided a novel prediction that the larger the contraction force, the faster the crawling speed. These observations indicate that the use of soft robots could serve to examine the kinetics and mechanical regulation of crawling behaviour in soft-bodied animals.
Mosaic patterns of selection in genomic regions associated with diverse human traits
Authors: Abraham Abin , LaBella Abigail L. , Capra John A. , Rokas Antonis 
Published: May 2022

AbstractNatural selection shapes the genetic architecture of many human traits. However, the prevalence of different modes of selection on genomic regions associated with variation in traits remains poorly understood. To address this, we developed an efficient computational framework to calculate enrichment of different evolutionary measures among regions associated with complex traits. We applied the framework to summary statistics from >900 genome-wide association studies (GWASs) and 11 evolutionary measures of sequence constraint, population differentiation, and allele age while accounting for linkage disequilibrium, allele frequency, and other potential confounders. We demonstrate that this framework yields consistent results across GWASs with variable sample sizes, numbers of trait-associated SNPs, and analytical approaches. The resulting evolutionary atlas maps diverse signatures of selection on genomic regions associated with complex human traits on an unprecedented scale. We detected positive enrichment for sequence conservation among trait-associated regions for the majority of traits (>77% of 290 high power GWASs), which was most dominant in reproductive traits. Many traits also exhibited substantial enrichment for population differentiation and recent positive selection, especially among hair, skin, and pigmentation traits. In contrast, we detected widespread negative enrichment for balancing selection (51% GWASs) and no evidence of enrichment for selection signals in regions associated with late-onset Alzheimer’s disease. These results support a pervasive role for negative selection on regions of the human genome that contribute to variation in complex traits, but also demonstrate where diverse modes of selection have shaped trait-associated loci. This atlas of signatures of different modes of natural selection across the diversity of available GWASs will enable exploration of the relationship between the genetic architecture and selection in the human genome.
Effects of larval and adult crowding on fitness components in Drosophila populations adapted to larval crowding experienced under different combinations of food amount and egg number
Authors: Pandey Neha , Malhotra Rishabh , Joshi Amitabh 
Published: May 2022

AbstractSince the realization in the 1970s that simple discrete-time population growth models can show complex unstable dynamics of population size, many explanations were proposed for the evolution of enhanced population stability. The most plausible of these was density-dependent selection, suggested to favour greater stability due to r-K trade-offs. However, the first experiment aimed at testing this prediction revealed that Drosophila melanogaster populations adapted to larval crowding did not evolve greater constancy stability than their ancestral controls. A subsequent study showed that D. ananassae populations adapted to larval crowding had evolved greater constancy and persistence than ancestral controls. These D. ananassae populations had experienced chronic larval crowding in conditions of very low amounts of food, whereas the earlier studied D. melanogaster populations had experienced chronic larval crowding at fairly high food amounts. Further theoretical work also suggested that populations adapting to crowding could evolve greater stability even in the absence of r-K trade-offs. Most recently, studies in our laboratory showed that two sets of crowding adapted D. melanogaster populations, derived from a common ancestral lineage, which differed in the food amounts at which they experienced larval crowding, evolved different patterns of constancy and persistence stability. These two sets of populations also differed in the traits, e.g. larval feeding rate, that evolved as they became more competitive. Here, we examine the response of key fitness components to larval and adult densities in these two sets of populations, to see whether differences in their stability attributes can be explained by variation in how their life-histories respond to crowding at different life stages. Of all traits examined, only pre-adult survivorship responded differently to larval density across the two sets of populations. The populations that adapted to larval crowding at low food amounts showed reduced sensitivity of pre-adult survivorship to larval density, compared to those that adapted to larval crowding at high food amounts. We discuss our results in the context of different ways in which density-dependent selection may facilitate the evolution of greater constancy or persistence, depending on the ecological details of how crowding was experienced.
A data-driven approach to quantifying meal characteristics influencing energy intake
Authors: Fazzino Tera L. , Courville Amber B. , Guo Juen , Hall Kevin D. 
Published: May 2022

AbstractWe used a data-driven approach to determine the influence of energy density, hyper-palatability, protein content, and eating rate on ad libitum non-beverage energy intake during 2733 meals consumed by 35 inpatient adults who participated in two 28-day feeding studies. All four meal characteristics significantly contributed to energy intake, but their relative importance varied by the prevailing dietary pattern according to macronutrient composition and degree of processing.
Searching for mates may shape the immune response and parental investments
Authors: Sevgili Hasan 
Published: May 2022

AbstractIn the sexual reproduction model, a wide variety of strategies have emerged in different animal species for individuals to pursue the opposite sex for mating purposes. Many ways (such as chemical signals and calling songs) are utilized to stimulate or invite the other sex. This may lead to differential evolution of sexes in a species. For example, the limitations in signal production or perception of one of the sexes can make this sex sedentary, therefore strategies in pursuing mates evolve diversely among sexes. In this context, McCartney et al. (2012) proposed a theory to explain the differentiation of the mate-searching system in some species of Poecilimon bushcrickets and the reasons for the change in the sexual roles in the search. The aim of the present study was the testing of this theory proposed by McCartney et al. (2012) for Poecilimon species on spermatophore investment, with two species (P. sureyanus-female searching and P. inflatus- male searching), which have different strategies in terms of females’ response to male calling songs. Reproductive effort and physiological activities are both costly for the organism, and these traits belie a trade-off due to the limited energetic resources. Therefore, some immune parameters (Phenoloxidase and lytic activities) of these two species were compared within the context of the allocation of resources resulting from the trade-off between reproductive functions and immune defence. Immune activities are much more plastic in nature than the differentiation of reproductive traits among sexes. The results of this study showed that a mate searching strategy difference, based on the female’s ability to respond to male call sounds -which must acoustically communicate for reproduction-may play a decisive role in both spermatophore and immune activities. On the other hand, the findings also indicated that there may be trade-offs between the costs related to reproduction and the immune system. In addition, it has been revealed that there may be a trade-off between the immune activities and the differences between sexes. On the other hand, our data indicated that the duration of morphogenesis did not have a decisive role on spermatophore and sperm allocation in bushcrickets.
Characterization of a nanobody-epitope tag interaction and its application for receptor engineering
Authors: Cabalteja Chino C. , Sachdev Shivani , Cheloha Ross W. 
Published: May 2022

AbstractPeptide epitope tags offer a valuable means for detection and manipulation of protein targets for which high quality detection reagents are not available. Most commonly used epitope tags are bound by conventional, full-size antibodies (Abs). The complex architecture of Abs complicates their application in protein engineering and intracellular applications. To address these shortcomings, single domain antibodies (nanobodies, Nbs) that recognize short peptide epitopes have become increasingly prized. Here we characterize the interaction between a Nb (Nb6E) and a 14-mer peptide epitope. We identify residues in the peptide epitope essential for high affinity binding. Using this information in combination with computational modeling we propose a mode of interaction between Nb6E and this epitope. We apply this nanobody-epitope pair to augment the potency of a ligand at an engineered adenosine A2A receptor. This characterization of the nanobody-epitope pair opens the door to diverse applications including mechanistic studies of G protein-coupled receptor function.
Secreted cytokines provide local immune tolerance for human stem cell-derived islets
Authors: Gerace Dario , Zhou Quan , Kenty Jennifer Hyoje-Ryu , Sintov Elad , Wang Xi , Boulanger Kyle R , Li Hongfei , Melton Douglas A 
Published: May 2022

SummaryImmunological protection of transplanted stem cell-derived islet (SC-islet) cells is yet to be achieved without chronic immunosuppression or encapsulation. Existing genetic engineering approaches to produce hypoimmunogenic SC-islet cells have so far shown variable results. Here, we show that targeting the human leukocyte antigens (HLAs) and PD-L1 alone do not sufficiently protect SC-islet cells from xeno- or allo-rejection. As an addition to these approaches, we genetically engineered SC-islet cells to secrete the cytokines IL-10, TGF-β and modified IL-2 such that they promote a tolerogenic local microenvironment by activating and expanding regulatory T cells (Tregs). These cytokine-secreting human SC-islet cells prevented xeno-rejection for up to 9 weeks post-transplantation in B6/albino mice. Thus, hESCs engineered to induce a tolerogenic local microenvironment may represent a source of replacement SC-islet cells that do not require encapsulation or immunosuppression for diabetes cell replacement therapy.