bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stiffness Regulates Intestinal Stem Cell Fate
Authors: He Shijie , Lei Peng , Kang Wenying , Cheung Priscilla , Xu Tao , Mana Miyeko , Park Chan Young , Wang Hongyan , Imada Shinya , Russell Jacquelyn O. , Wang Jianxun , Wang Ruizhi , Zhou Ziheng , Chetal Kashish , Stas Eric , Mohad Vidisha , Halasi Marianna , Bruun-Rasmussen Peter , Sadreyev Ruslan I. , Adini Irit , Hodin Richard A. , Zhang Yanhang , Breault David T. , Camargo Fernando D. , Yilmaz Ömer H. , Fredberg Jeffrey J. , Saeidi Nima 
Published: March 2021

SummaryDoes fibrotic gut stiffening caused by inflammatory bowel diseases (IBD) direct the fate of intestinal stem cells (ISCs)? To address this question we first developed a novel long-term culture of quasi-3D gut organoids plated on hydrogel matrix of varying stiffness. Stiffening from 0.6kPa to 9.6kPa significantly reduces Lgr5highISCs and Ki67+progenitor cells while promoting their differentiation towards goblet cells. These stiffness-driven events are attributable to YAP nuclear translocation. Matrix stiffening also extends the expression of the stemness marker Olfactomedin 4 (Olfm4) into villus-like regions, mediated by cytoplasmic YAP. We next used single-cell RNA sequencing to generate for the first time the stiffness-regulated transcriptional signatures of ISCs and their differentiated counterparts. These signatures confirm the impact of stiffening on ISC fate and additionally suggest a stiffening-induced switch in metabolic phenotype, from oxidative phosphorylation to glycolysis. Finally, we used colon samples from IBD patients as well as chronic colitis murine models to confirm thein vivostiffening-induced epithelial deterioration similar to that observedin vitro. Together, these results demonstrate stiffness-dependent ISC reprograming wherein YAP nuclear translocation diminishes ISCs and Ki67+progenitors and drives their differentiation towards goblet cells, suggesting stiffening as potential target to mitigate gut epithelial deterioration during IBD.
Improving localization precision via restricting biomolecule confined stochastic motion in SMLM
Authors: Ni Jielei , Cao Bo , Niu Gang , Xia Tingying , Chen Danni , Zhang Wanlong , Zhang Yilin , Yuan Xiaocong , Ni Yanxiang 
Published: March 2021

AbstractSingle-molecule localization microscopy (SMLM) boosts its applications when combined with the studies of cells, in which nanometer-sized biomolecules are irresolvable due to diffraction limit unless being subjected to SMLM. Although being well immobilized, given the nanometer sizes of biological molecules, they are still capable of movement stochastically around their immobilized sites. The influence of such motion on image quality and possible improvements have not yet been systematically investigated. Here, we accessed the biomolecule stochastic motion in SMLM by calculating the displacements between different localizations from the same molecule in single-molecule samples of Alexa Fluor-647-conjugated oligonucleotides. We found that, for most molecules, localization displacements at random frame intervals are remarkably larger than those between temporally neighbouring frames despite of drift correction, showing that biomolecule stochastic motion is involved in SMLM. Furthermore, the localization displacements were observed to increase with frame intervals and then saturate, suggesting biomolecule stochastic motion is confined within a finite area. Moreover, we showed that the localization precision is deteriorated by enlarging molecule sizes and improved by sample post-fixation. This study reveals confined stochastic motion of biomolecules increase localization uncertainty in SMLM, and improved localization precision can be achieved via restricting biomolecule stochastic motion.
Circular RNA Vaccines against SARS-CoV-2 and Emerging Variants
Authors: Qu Liang , Yi Zongyi , Shen Yong , Lin Liangru , Chen Feng , Xu Yiyuan , Wu Zeguang , Tang Huixian , Zhang Xiaoxue , Tian Feng , Wang Chunhui , Xiao Xia , Dong Xiaojing , Guo Li , Lu Shuaiyao , Yang Chengyun , Tang Cong , Yang Yun , Yu Wenhai , Wang Junbin , Zhou Yanan , Huang Qing , Yisimayi Ayijiang , Cao Yunlong , Wang Youchun , Zhou Zhuo , Peng Xiaozhong , Wang Jianwei , Xie Xiaoliang Sunney , Wei Wensheng 
Published: March 2021

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its emerging variants of concern (VOC), such as Delta (B.1.617.2) and Omicron (B.1.1.529), has continued to drive the worldwide pandemic. Therefore, there is a high demand for vaccines with enhanced efficacy, high thermostability, superior design flexibility, and fast manufacturing speed. Here, we report a circular RNA (circRNA) vaccine that encodes the trimeric RBD of SARS-CoV-2 Spike protein. Without the need of nucleotide modification, 5’-capping or 3’-polyadenylation, circRNA could be rapidly produced viain vitrotranscription and is highly thermostable whether stored in naked or lipid-nanoparticle (LNP)-encapsulated format. LNP-encapsulated circRNARBDelicited potent neutralizing antibodies and T cell responses, providing robust protection against Beta (B.1.351) and native viruses in mice and rhesus macaques, respectively. Notably, circRNA vaccine enabled higher and more durable antigen production than 1mΨ-modified mRNA vaccine, eliciting a higher proportion of neutralizing antibodies and stronger Th1-biased immune responses. Importantly, we found that circRNARBD-Omicronvaccine induced effective neutralizing antibodies against only Omicron but not Delta variant. By contrast, circRNARBD-Deltacould elicit high level of neutralizing antibodies against both Delta and Omicron. Following two doses of either native- or Delta-specific vaccination, circRNARBD-Delta, but not Omicron or Beta vaccines, could effectively boost the neutralizing antibodies against both Delta and Omicron variants. These results suggest that circRNARBD-Deltais a favorable choice for vaccination to provide a broad-spectrum protection against the current variants of concern of SARS-CoV-2.
Size and shape regional differentiation during the development of the spine in the nine-banded armadillo (Dasypus novemcinctus)
Authors: Oliver Jillian D. , Jones Katrina E. , Pierce Stephanie E. , Hautier Lionel 
Published: March 2021

AbstractXenarthrans (armadillos, anteaters, sloths and their extinct relatives) are unique among mammals in displaying a distinctive specialization of the posterior trunk vertebrae - supernumerary vertebral xenarthrous articulations. This study seeks to understand how xenarthry develops through ontogeny and if it may be constrained to appear within pre-existing vertebral regions. Using 3D geometric morphometrics on the neural arches of vertebrae, we explore phenotypic, allometric, and disparity patterns of the different axial morphotypes during ontogeny of nine-banded armadillos. Shape-based regionalisation analyses showed that adult thoracolumbar column is divided into three regions according to the presence or absence of ribs and the presence or absence of xenarthrous articulations. A three-region-division was retrieved in almost all specimens through development, although younger stages (e.g. foetuses, neonates) have more region boundary variability. In size-based regionalisation analyses, thoracolumbar vertebrae are separated into two regions: a pre-diaphragmatic, pre-xenarthrous region, and a post-diaphragmatic xenarthrous region. We show that posterior thoracic vertebrae grow at a slower rate, while anterior thoracics and lumbar grow at a faster rate relatively, with rates decreasing anteroposterioly in the former and increasing anteroposterioly in the latter. We propose that different proportions between vertebrae and vertebral regions might result from differences in growth pattern and timing of ossification.
Manganese toxicity disrupts indole acetic acid homeostasis and suppresses CO2assimilation reaction in rice plants
Authors: Takagi Daisuke , Ishiyama Keiki , Suganami Mao , Ushijima Tomokazu , Fujii Takeshi , Tazoe Youshi , Kawasaki Michio , Noguchi Ko , Makino Amane 
Published: March 2021

ABSTRACTDespite the essentiality of Mn in terrestrial plants, its excessive accumulation in plant tissues causes growth defects, known as Mn toxicity. Mn toxicity can be divided into apoplastic and symplastic types depending on its onset. For growth defects, symplastic rather than apoplastic Mn toxicity is hypothesised to be more critical. However, details of the relationship between growth defects and symplastic Mn toxicity remains elusive. In this study, we aimed to elucidate the molecular mechanisms of symplastic Mn toxicity in rice plants. We found that under excess Mn conditions, CO2assimilation was inhibited by stomatal closure, and both carbon anabolic and catabolic activities were decreased. In addition to stomatal dysfunction, stomatal and leaf anatomical development were also altered by excess Mn accumulation. Furthermore, the indole acetic acid (IAA) concentration was decreased, and auxin-responsive gene expression analyses showed IAA-deficient symptoms in leaves due to excess Mn accumulation. These results suggest that excessive Mn accumulation causes IAA deficiency, and low IAA concentrations suppress plant growth by suppressing stomatal opening and leaf anatomical development for efficient CO2assimilation in leaves.HIGHLIGHTIncreased Mn concentration lowers auxin concentrations in rice leaves, which suppresses photosynthesis by changing stomatal function and development.
Phylotranscriptomics points to multiple independent origins of multicellularity and cellular differentiation in the volvocine algae
Authors: Lindsey Charles Ross , Rosenzweig Frank , Herron Matthew D 
Published: March 2021

AbstractThe volvocine algae, which include the single-celled speciesChlamydomonas reinhardtiiand the colonial speciesVolvox carteri, serve as a model in which to study the evolution of multicellularity and cellular differentiation. Studies reconstructing the evolutionary history of this group have often relied on datasets of one to a few genes for phylogenetic inference and ancestral character state reconstruction. These studies suggest that multicellularity evolved only once in the volvocine algae, that each of its three colonial families is monophyletic, and that there have been at least three independent origins of cellular differentiation in the group. We performed RNA-Seq on 55 strains representing 47 volvocine algal species and obtained similar data from curated databases on 13 additional strains. We compiled a dataset consisting of transcripts for 40 single-copy, protein-coding, nuclear genes, then subjected the predicted amino acid sequences of these genes to maximum likelihood, Bayesian inference, and coalescent-based analyses. These analyses show that multicellularity independently evolved at least twice in the volvocine algae and that the colonial family Goniaceae is not monophyletic. Our data further indicate that cellular differentiation independently arose at least four and possibly as many as six times within the group. Altogether, these results show how multicellularity and cellular differentiation are evolutionarily labile in the volvocine algae, affirming their importance for the study of major transitions in the history of life.
GABAergic neuronal IL-4R mediates T cell effect on memory
Authors: Fu Zhongxiao , Dykstra Taitea , Wall Morgan , Li Huiping , Salvador Andrea Francesca , Zou Bende , Yan Ni , Andrews Patrick H. , Goldman Dylan H. , Papadopoulos Zachary , Smirnov Igor , Xie Xinmin S. , Herz Jasmin , Kipnis Jonathan 
Published: March 2021

SummaryMechanisms governing how immune cells and their derived molecules impact homeostatic brain function are still poorly understood. Here, we elucidate neuronal mechanisms underlying effects of T cells on synaptic function and episodic memory. Depletion of CD4 T cells led to memory deficits and impaired long term potentiation. Severe combined immune-deficient (SCID) mice exhibited amnesia, which was reversible by repopulation with T cells from wild-type but not from IL-4-knockout mice. This rescue was mediated via IL-4 receptors (IL-4R) expressed on neurons. Exploration of snRNAseq of neurons participating in memory processing provided insights into synaptic organization and plasticity-associated pathways and genes regulated by immune cells and molecules. IL-4Rα knockout in inhibitory neurons impaired contextual fear memory, suggesting participation of an IL-4-associated switch in regulating synaptic function and promoting contextual fear memory. These findings provide insights into neuroimmune interactions at the transcriptional and functional levels in neurons.
What’s under the Christmas tree? Soil acidification alters fir tree rhizosphere bacterial and eukaryotic communities, their interactions, and functional traits
Authors: Steven Blaire , La Reau Jacquelyn C. , Taerum Stephen J. , Zuverza-Mena Nubia , Cowles Richard S. 
Published: March 2021

ABSTRACTpH has been identified as a master regulator of the soil environment, controlling the solubility and availability of nutrients. As such, soil pH exerts a strong influence on indigenous microbial communities. In this study we describe a soil acidification experiment and the resulting effects on the rhizosphere communities of fir trees on a Christmas tree plantation. The acidification treatment reduced the pH of bulk soil by ∼1.4 pH units and was associated with reduced Ca, Mg, and organic matter content. Similarly, root chemistry differed due to soil acidification with roots in acidified soils showing significantly higher Al, Mn, and Zn content and reduced levels of B and Ca. 16S rRNA and 18S rRNA gene sequencing was pursued to characterize the bacterial/archaeal and eukaryotic communities in the rhizosphere soils. The acidification treatment induced dramatic and significant changes in the microbial populations, with thousands of 16S RNA gene sequence variants and hundreds of 18S rRNA gene variants being significantly different in relative abundance between the treatments. Additionally, co-occurrence networks showed that bacterial and eukaryotic interactions, network topology, and hub taxa were significantly different when constructed from the control and acidified soil rRNA gene amplicon libraries. Finally, metagenome sequencing showed that the taxonomic shifts in the community resulted in alterations to the functional traits of the dominant community members. Several biochemical pathways related to sulfur and nitrogen cycling distinguished the metagenomes generated from the control and acidified soils, demonstrating the myriad of effects soils acidification induces to rhizosphere microbes.IMPORTANCESoil pH has been identified as the property that exerts the largest influence on soil microbial populations. We employed a soil acidification experiment to investigate the effect of lowering soil pH on the bacterial and eukaryotic populations in the rhizosphere of Christmas trees. Acidification of the soils drove alterations of fir tree root chemistry and large shifts in the taxonomic and functional composition of the communities, involving pathways in sulfur and nitrogen cycling. These data demonstrate that soil pH influences are manifest across all organisms inhabiting the soil, from the host plant to the microorganisms inhabiting the rhizosphere soils. Thus, pH is an important factor that needs to be considered when investigating soil and plant health, the status of the soil microbiome, and terrestrial nutrient cycling.
The Burden Borne by Protein Methyltransferases: Rates and Equilibria of Nonenzymatic Methylation of Amino Acid Side-Chains by SAM in Water
Authors: Lewis Charles A. , Wolfenden Richard 
Published: March 2021

ABSTRACTSAM is a powerful methylating agent, with a methyl group transfer potential matching the phosphoryl group transfer potential of ATP. SAM-dependent N-methyltransferases have evolved to catalyze the modification of specific lysine residues in histones and transcription factors, in addition to generating epinephrine, N-methylnicotinamide, and a quaternary amine (betaine) that is used to maintain osmotic pressure in plants and halophilic bacteria. To assess the catalytic power of these enzymes and their potential susceptibility to transition state and multisubstrate analogue inhibitors, we determined the rates and positions of equilibrium of methyl transfer from the trimethylsulfonium ion to model amines in the absence of a catalyst. Unlike the methyl group transfer potential of SAM, which becomes more negative with increasing pH throughout the normal pH range, equilibrium constants for the hydrolytic demethylation of secondary, tertiary and quaternary amines are found to be insensitive to changing pH and resemble to each other in magnitude, with an average ΔG value of ∼ -0.7 kcal/mol at pH 7. Thus, each of the three steps in the mono- di- and trimethylation of lysine by SAM is accompanied by a free energy change of -7.5 kcal/mol in neutral solution. Arrhenius analysis of the uncatalyzed reactions shows that the unprotonated form of glycine attacks the trimethylsulfonium ion (TMS++) with a second order rates constant of 1.8 × 10−7M-1s-1at 25 °C (ΔH‡= 22 kcal/mol and TΔS‡= -6 kcal/mol). Comparable values are observed for the methylation of secondary and tertiary amines, with k25= 1.1 × 10−7M-1s-1for sarcosine and 4.3 × 10−8M-1s-1for dimethylglycine. The nonenzymatic methylation of imidazole and methionine by TMS++, benchmarks for the methylation of histidine and methionine residues by SETD3, exhibit k25values of 3.3 × 10−9and 1.2 × 10−9M-1s-1respectively. Lysine methylation by SAM, although slow under physiological conditions (t1/27 weeks at 25 °C), is accelerated 1.1 × 1012-fold at the active site of a SET domain methyltransferase.
Geopolitical risk, economic policy uncertainty and asset returns in Chinese financial markets
Authors: Chiang Thomas C. 
Published: March 2021

PurposeThis paper investigates the impact of a change in economic policy uncertainty (ΔEPUt) and the absolute value of a change in geopolitical risk (|ΔGPRt|) on the returns of stocks, bonds and gold in the Chinese market.Design/methodology/approachThe paper uses Engle's (2009) dynamic conditional correlation (DCC) model and Chiang's (1988) rolling correlation model to generate correlations of asset returns over time and analyzes their responses to (ΔEPUt) and |ΔGPRt|.FindingsEvidence shows that stock-bond return correlations are negatively correlated to ΔEPUt, whereas stock-gold return correlations are positively related to the |ΔGPRt|, but negatively correlated with ΔEPUt. This study finds evidence that stock returns are adversely related to the risk/uncertainty measured by downside risk, ΔEPUt and |ΔGPRt|, whereas the bond return is positively related to a rise in ΔEPUt; the gold return is positively correlated with a heightened |ΔGPRt|.Research limitations/implicationsThe findings are based entirely on the data for China's asset markets; further research may expand this analysis to other emerging markets, depending on the availability of GPR indices.Practical implicationsEvidence suggests that the performance of the Chinese market differs from advanced markets. This study shows that gold is a safe haven and can be viewed as an asset to hedge against policy uncertainty and geopolitical risk in Chinese financial markets.Social implicationsThis study identify the special role for the gold prices in response to the economic policy uncertainty and the geopolitical risk. Evidence shows that stock and bond return correlation is negatively related to the ΔEPU and support the flight-to-quality hypothesis. However, the stock-gold return correlation is positively related to |ΔGPR|, resulting from the income or wealth effect.Originality/valueThe presence of a dynamic correlations between stock-bond and stock-gold relations in response to ΔEPUt and |ΔGPRt| has not previously been tested in the literature. Moreover, this study finds evidence that bond-gold correlations are negatively correlated to both ΔEPUt and |ΔGPRt|.
Time-cost optimization in repetitive project scheduling with limited resources
Authors: Zou Xin , Zhang Lihui , Zhang Qian 
Published: March 2021

PurposeThe purpose of this research is to develop a time-cost optimization model to schedule repetitive projects while considering limited resource availability.Design/methodology/approachThe model is based on the constraint programming (CP) framework; it integrates multiple scheduling characteristics of repetitive activities such as continuous or fragmented execution, atypical activities and coexistence of different modes in an activity. To improve project performance while avoiding inefficient hiring and firing conditions, the strategy of bidirectional acceleration is presented and implemented, which requires keeping regular changes in the execution modes between successive subactivities in the same activity.FindingsTwo case studies involving a real residential building construction project and a hotel refurbishing project are used to demonstrate the application of the proposed model based on four different scenarios. The results show that (1) the CP model has great advantages in terms of solving speed and solution quality than its equivalent mathematical model, (2) higher project performance can be obtained compared to using previously developed models and (3) the model can be easily replicated or even modified to enable multicrew implementation.Originality/valueThe original contribution of this research is presenting a novel CP-based repetitive scheduling optimization model to solve the multimode resource-constrained time-cost tradeoff problem of repetitive projects. The model has the capability of minimizing the project total cost that is composed of direct costs, indirect costs, early completion incentives and late completion penalties.
Sustainable strategy to create multisector or unisector smart economic hubs
Authors: Rasmy Mohammed Osama , Abu Atta Tarek Abdel Latif , Mohamed Ibrahim Asmaa Abdelaty 
Published: March 2021

PurposeThis study explores the best strategies for regional economic development to attract highly skilled populations, regardless of whether the region is a multisector or unisector economic hub. It also determines the development variables affecting the success of integrated regional economic hubs to achieve spatial equality, enhance economic productivity and attain environmental sustainability.Design/methodology/approachIn addition to a qualitative analysis, this study employed quantitative techniques using SPSS software. This allowed amplification of the most significant explanatory variables affecting the weaknesses and strengths of economic hubs.FindingsThe results highlight approaches that can be used to achieve socio-economic sustainability in regional hubs. These include multisectors or main centralised hubs (smart economic regional capital), which provide new services to regions and act as a unidevelopment sector or as a regional, economic capital.Research limitations/implicationsThe study analyses the effect of economic strategies and integration of natural resources and the required core services in regional economic development.Practical implicationsCase studies of successful economic hubs are discussed. The most important services proposed in such hubs promote human development and increase the standard of living.Social implicationsIntegration between the hubs in a region is fundamental to attracting direct investments that can benefit the local population.Originality/valueThe results could help governments, economists and planners implement multisector developmental hubs to achieve sustainable development.