bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a diarylpentanoid-producing polyketide synthase revealing an unusual biosynthetic pathway of 2-(2-phenylethyl)chromones in agarwood
Authors: Wang Xiao-Hui , Gao Bo-Wen , Nakashima Yu , Mori Takahiro , Zhang Zhong-Xiu , Kodama Takeshi , Lee Yuan-E , Zhang Ze-Kun , Wong Chin-Piow , Liu Qian-Qian , Qi Bo-Wen , Wang Juan , Li Jun , Liu Xiao , Abe Ikuro , Morita Hiroyuki , Tu Peng-Fei , Shi She-Po 
Published: January 2022

Abstract2-(2-Phenylethyl)chromones (PECs) are the principal constituents contributing to the distinctive fragrance of agarwood. How PECs are biosynthesized is currently unknown. In this work, we describe a diarylpentanoid-producing polyketide synthase (PECPS) identified fromAquilaria sinensis. Through biotransformation experiments using fluorine-labeled substrate, transient expression of PECPS inNicotiana benthamiana, and knockdown ofPECPSexpression inA. sinensiscalli, we demonstrate that the C6–C5–C6scaffold of diarylpentanoid is the common precursor of PECs, and PECPS plays a crucial role in PECs biosynthesis. Crystal structure (1.98 Å) analyses and site-directed mutagenesis reveal that, due to its small active site cavity (247 Å3), PECPS employs a one-pot formation mechanism including a “diketide-CoA intermediate-released” step for the formation of the C6–C5–C6scaffold. The identification of PECPS, the pivotal enzyme of PECs biosynthesis, provides insight into not only the feasibility of overproduction of pharmaceutically important PECs using metabolic engineering approaches, but also further exploration of how agarwood is formed.
Stratification constrains future heat and carbon uptake in the Southern Ocean between 30°S and 55°S
Authors: Bourgeois Timothée , Goris Nadine , Schwinger Jörg , Tjiputra Jerry F. 
Published: January 2022

AbstractThe Southern Ocean between 30°S and 55°S is a major sink of excess heat and anthropogenic carbon, but model projections of these sinks remain highly uncertain. Reducing such uncertainties is required to effectively guide the development of climate mitigation policies for meeting the ambitious climate targets of the Paris Agreement. Here, we show that the large spread in the projections of future excess heat uptake efficiency and cumulative anthropogenic carbon uptake in this region are strongly linked to the models’ contemporary stratification. This relationship is robust across two generations of Earth system models and is used to reduce the uncertainty of future estimates of the cumulative anthropogenic carbon uptake by up to 53% and the excess heat uptake efficiency by 28%. Our results highlight that, for this region, an improved representation of stratification in Earth system models is key to constrain future carbon budgets and climate change projections.
Pantothenate biosynthesis is critical for chronic infection by the neurotropic parasite Toxoplasma gondii
Authors: Lunghi Matteo , Kloehn Joachim , Krishnan Aarti , Varesio Emmanuel , Vadas Oscar , Soldati-Favre Dominique 
Published: January 2022

AbstractCoenzyme A (CoA) is an essential molecule acting in metabolism, post-translational modification, and regulation of gene expression. While all organisms synthesize CoA, many, including humans, are unable to produce its precursor, pantothenate. Intriguingly, like most plants, fungi and bacteria, parasites of the coccidian subgroup of Apicomplexa, including the human pathogen Toxoplasma gondii, possess all the enzymes required for de novo synthesis of pantothenate. Here, the importance of CoA and pantothenate biosynthesis for the acute and chronic stages of T. gondii infection is dissected through genetic, biochemical and metabolomic approaches, revealing that CoA synthesis is essential for T. gondii tachyzoites, due to the parasite’s inability to salvage CoA or intermediates of the pathway. In contrast, pantothenate synthesis is only partially active in T. gondii tachyzoites, making the parasite reliant on its uptake. However, pantothenate synthesis is crucial for the establishment of chronic infection, offering a promising target for intervention against the persistent stage of T. gondii.
Nanobubbles explain the large slip observed on lubricant-infused surfaces
Authors: Vega-Sánchez Christopher , Peppou-Chapman Sam , Zhu Liwen , Neto Chiara 
Published: January 2022

AbstractLubricant-infused surfaces hold promise to reduce the huge frictional drag that slows down the flow of fluids at microscales. We show that infused Teflon wrinkled surfaces induce an effective slip length 50 times larger than expected based on the presence of the lubricant alone. This effect is particularly striking as it occurs even when the infused lubricant’s viscosity is several times higher than that of the flowing liquid. Crucially, the slip length increases with increasing air content in the water but is much higher than expected even in degassed and plain Milli-Q water. Imaging directly the immersed interface using a mapping technique based on atomic force microscopy meniscus force measurements reveals that the mechanism responsible for this huge slip is the nucleation of surface nanobubbles. Using a numerical model and the height and distribution of these surface nanobubbles, we can quantitatively explain the large fluid slip observed in these surfaces.
Pre-configuring chromatin architecture with histone modifications guides hematopoietic stem cell formation in mouse embryos
Authors: Li Chen C. , Zhang Guangyu , Du Junjie , Liu Di , Li Zongcheng , Ni Yanli , Zhou Jie , Li Yunqiao , Hou Siyuan , Zheng Xiaona , Lan Yu , Liu Bing , He Aibin 
Published: January 2022

AbstractThe gene activity underlying cell differentiation is regulated by a diverse set of transcription factors (TFs), histone modifications, chromatin structures and more. Although definitive hematopoietic stem cells (HSCs) are known to emerge via endothelial-to-hematopoietic transition (EHT), how the multi-layered epigenome is sequentially unfolded in a small portion of endothelial cells (ECs) transitioning into the hematopoietic fate remains elusive. With optimized low-input itChIP-seq and Hi-C assays, we performed multi-omics dissection of the HSC ontogeny trajectory across early arterial ECs (eAECs), hemogenic endothelial cells (HECs), pre-HSCs and long-term HSCs (LT-HSCs) in mouse embryos. Interestingly, HSC regulatory regions are already pre-configurated with active histone modifications as early as eAECs, preceding chromatin looping dynamics within topologically associating domains. Chromatin looping structures between enhancers and promoters only become gradually strengthened over time. Notably, RUNX1, a master TF for hematopoiesis, enriched at half of these loops is observed early from eAECs through pre-HSCs but its enrichment further increases in HSCs. RUNX1 and co-TFs together constitute a central, progressively intensified enhancer-promoter interactions. Thus, our study provides a framework to decipher how temporal epigenomic configurations fulfill cell lineage specification during development.
Contribution of the medial eye field network to the voluntary deployment of visuospatial attention
Authors: Herbet Guillaume , Duffau Hugues 
Published: January 2022

AbstractHistorically, the study of patients with spatial neglect has provided fundamental insights into the neural basis of spatial attention. However, lesion mapping studies have been unsuccessful in establishing the potential role of associative networks spreading on the dorsal-medial axis, mainly because they are uncommonly targeted by vascular injuries. Here we combine machine learning-based lesion-symptom mapping, disconnection analyses and the longitudinal behavioral data of 128 patients with well-delineated surgical resections. The analyses show that surgical resections in a location compatible with both the supplementary and the cingulate eye fields, and disrupting the dorsal-medial fiber network, are specifically associated with severely diminished performance on a visual search task (i.e., visuo-motor exploratory neglect) with intact performance on a task probing the perceptual component of neglect. This general finding provides causal evidence for a role of the frontal-medial network in the voluntary deployment of visuo-spatial attention.
Fibroblast-mediated uncaging of cancer cells and dynamic evolution of the physical microenvironment
Authors: Liu Chang , Mak Michael 
Published: January 2022

AbstractStromal cells are prominent in solid tumor microenvironments and contribute to tumor progression. In particular, fibroblasts are common cell types in the tumor stroma that play important roles in remodeling the extracellular matrix (ECM). Here, we perform co-culture experiments with tumor cells and fibroblasts embedded in 3D collagen I matrices. We investigate the impact of fibroblasts on the migratory behavior of neighboring tumor cells and on the evolution of the surrounding ECM. We find that fibroblasts increase tumor cell motility and facilitate the transition from confined to diffusive tumor cell motions, indicative of an uncaging effect. Furthermore, the ECM is globally and locally remodeled substantially with the presence of fibroblasts. Moreover, these fibroblast-mediated phenomena are in part dependent on matrix metalloproteinases.
Extracting phylogenetic dimensions of coevolution reveals hidden functional signals
Authors: Colavin Alexandre , Atolia Esha , Bitbol Anne-Florence , Huang Kerwyn Casey 
Published: January 2022

AbstractDespite the structural and functional information contained in the statistical coupling between pairs of residues in a protein, coevolution associated with function is often obscured by artifactual signals such as genetic drift, which shapes a protein’s phylogenetic history and gives rise to concurrent variation between protein sequences that is not driven by selection for function. Here, we introduce a background model for phylogenetic contributions of statistical coupling that separates the coevolution signal due to inter-clade and intra-clade sequence comparisons and demonstrate that coevolution can be measured on multiple phylogenetic timescales within a single protein. Our method, nested coevolution (NC), can be applied as an extension to any coevolution metric. We use NC to demonstrate that poorly conserved residues can nonetheless have important roles in protein function. Moreover, NC improved the structural-contact predictions of several coevolution-based methods, particularly in subsampled alignments with fewer sequences. NC also lowered the noise in detecting functional sectors of collectively coevolving residues. Sectors of coevolving residues identified after application of NC were more spatially compact and phylogenetically distinct from the rest of the protein, and strongly enriched for mutations that disrupt protein activity. Thus, our conceptualization of the phylogenetic separation of coevolution provides the potential to further elucidate relationships among protein evolution, function, and genetic diseases.
Intestinal ion regulation exhibits a daily rhythm in Gymnocypris przewalskii exposed to high saline and alkaline water
Authors: Wang Fei , Zhu Lin , Wei Yuxing , Gao Pengcheng , Liu Yimeng , Zhou Kai , Sun Zhen , Lai Qifang , Yao Zongli 
Published: January 2022

AbstractNaked carp (Gymnocypris przewalskii), endemic to the saline-alkaline Lake Qinghai, have the capacity to tolerate combinations of high salinity and alkalinity, but migrate to spawn in freshwater rivers each year. In this study, we measured the drinking rate over a 24 h period for naked carp exposed to saline-alkaline lake waters with salinities of 15 (L15) and 17 (L17). We also assessed the daily feed intakes of naked carp exposed to L15 and fresh water (FW). Additionally, we studied the daily expression of acid–base regulation and osmoregulation related genes and proteins in the intestine of naked carp exposed to saline-alkaline lake waters. Our results revealed that the drinking rate at night was significantly higher than in daytime when exposed to either L15 or L17, while feed intakes in daytime were significantly higher than at night. The relative expression of Na+/K+-ATPase α (NKA-α), solute carrier family members 26A6 (SLC26A6) and 4A4 (SLC4A4) in the intestine of naked carp exposed to L17 at night was higher than in daytime. Specifically, NKA-α mRNA expression at 4:00 was 7.22-fold and 5.63-fold higher than that at 10:00 and 16:00, respectively, and the expression at 22:00 was 11.29-fold and 8.80-fold higher than that at 10:00 and 16:00, respectively. Similarly, SLC26A6 mRNA expression was greatest at 22:00, exceeding that observed at 4:00, 10:00 and 16:00 by 3.59, 4.44 and 11.14-fold, respectively. Finally, the expression of NKA-α and SLC26A6 protein at the single cell level was also higher at night than during the day, which was 1.65-fold and 1.37-fold higher at 22:00 respectively compared to 16:00. Overall, the present findings revealed that naked carp drinks at night and feeds during the day, demonstrating that intestinal ion regulation exhibits a daily rhythm when exposed to high saline and alkaline lake water.
Multi-objective optimization of water resources allocation in Han River basin (China) integrating efficiency, equity and sustainability
Authors: Deng Lele , Guo Shenglian , Yin Jiabo , Zeng Yujie , Chen Kebing 
Published: January 2022

AbstractThe hydrological cycle, affected by climate change and rapid urbanization in recent decades, has been altered to some extent and further poses great challenges to three key factors of water resources allocation (i.e., efficiency, equity and sustainability). However, previous studies usually focused on one or two aspects without considering their underlying interconnections, which are insufficient for interaction cognition between hydrology and social systems. This study aims at reinforcing water management by considering all factors simultaneously. The efficiency represents the total economic interests of domesticity, industry and agriculture sectors, and the Gini coefficient is introduced to measure the allocation equity. A multi-objective water resources allocation model was developed for efficiency and equity optimization, with sustainability (the river ecological flow) as a constraint. The Non-dominated sorting genetic algorithm II (NSGA-II) was employed to derive the Pareto front of such a water resources allocation system, which enabled decision-makers to make a scientific and practical policy in water resources planning and management. The proposed model was demonstrated in the middle and lower Han River basin, China. The results indicate that the Pareto front can reflect the conflicting relationship of efficiency and equity in water resources allocation, and the best alternative chosen by cost performance method may provide rich information as references in integrated water resources planning and management.
Construction of a potential microRNA and messenger RNA regulatory network of acute lung injury in mice
Authors: Zhang Yufeng , Jiang Weilong , Xia Qingqing , Lin Jinfeng , Xu Junxian , Zhang Suyan , Tian Lijun , Han Xudong 
Published: January 2022

AbstractAcute lung injury (ALI) is a life-threatening clinical condition associated with critically ill patients, and the construction of potential microRNA (miRNA) and messenger RNA (mRNA) regulatory networks will help to fully elucidate its underlying molecular mechanisms. First, we screened fifteen upregulated differentially expressed miRNAs (DE-miRNAs) and six downregulated DE-miRNAs from the Gene Expression Omnibus (GEO) database. Then, the predicted target genes of the upregulated and downregulated DE-miRNAs were identified from the miRNet database. Subsequently, differentially expressed mRNAs (DE-mRNAs) were identified from the GEO database and subjected to combined analysis with the predicted DE-miRNA target genes. Eleven target genes of the upregulated DE-miRNAs and one target gene of the downregulated DE-miRNAs were screened out. To further validate the prediction results, we randomly selected a dataset for subsequent analysis and found some accurate potential miRNA-mRNA regulatory axes, including mmu-mir-7b-5p-Gria1, mmu-mir-486a-5p-Shc4 and mmu-mir-486b-5p-Shc4 pairs. Finally, mir-7b and its target gene Gria1 and mir-486b and its target gene Shc4 were further validated in a bleomycin-induced ALI mouse model. We established a potential miRNA-mRNA regulatory network of ALI in mice, which may provide a basis for basic and clinical research on ALI and advance the available treatment options.
A role for community-level socioeconomic indicators in targeting tuberculosis screening interventions
Authors: Brooks Meredith B. , Jenkins Helen E. , Puma Daniela , Tzelios Christine , Millones Ana Karina , Jimenez Judith , Galea Jerome T. , Lecca Leonid , Becerra Mercedes C. , Keshavjee Salmaan , Yuen Courtney M. 
Published: January 2022

AbstractTuberculosis screening programs commonly target areas with high case notification rates. However, this may exacerbate disparities by excluding areas that already face barriers to accessing diagnostic services. We compared historic case notification rates, demographic, and socioeconomic indicators as predictors of neighborhood-level tuberculosis screening yield during a mobile screening program in 74 neighborhoods in Lima, Peru. We used logistic regression and Classification and Regression Tree (CART) analysis to identify predictors of screening yield. During February 7, 2019–February 6, 2020, the program screened 29,619 people and diagnosed 147 tuberculosis cases. Historic case notification rate was not associated with screening yield in any analysis. In regression analysis, screening yield decreased as the percent of vehicle ownership increased (odds ratio [OR]: 0.76 per 10% increase in vehicle ownership; 95% confidence interval [CI]: 0.58–0.99). CART analysis identified the percent of blender ownership (≤ 83.1% vs > 83.1%; OR: 1.7; 95% CI: 1.2–2.6) and the percent of TB patients with a prior tuberculosis episode (> 10.6% vs ≤ 10.6%; OR: 3.6; 95% CI: 1.0–12.7) as optimal predictors of screening yield. Overall, socioeconomic indicators were better predictors of tuberculosis screening yield than historic case notification rates. Considering community-level socioeconomic characteristics could help identify high-yield locations for screening interventions.
Biomechanical comparison of lag screw and non-spiral blade fixation of a novel femoral trochanteric nail in an osteoporotic bone model
Authors: Fuse Yoshifumi , Zenke Yukichi , Okimoto Nobukazu , Yoshioka Toru , Yamanaka Yoshiaki , Kawasaki Makoto , Terayama Hiroshi , Sakai Akinori 
Published: January 2022

AbstractThere is no consensus regarding the advantages of the lag screw type over the blade type for treating femoral trochanteric fractures. We aimed to investigate whether non-spiral blade (Conventional-Blade, Fid-Blade) nails provide better biomechanical fixation than lag screws in a severe osteoporotic bone model. Different severities of osteoporotic cancellous bone were modelled using polyurethane foam blocks of three densities (0.24, 0.16, and 0.08 g/cm3). Three torsional tests were performed using each component for each density of the polyurethane block, and the maximum torque was recorded; subsequently, the energy required to achieve 30° rotation was calculated. Using a push-in test, the maximum force was recorded, and the energy required to achieve 4-mm displacement was calculated. For 0.08-g/cm3 density, the peak torques to achieve 30° rotation, energy required to achieve 30° rotation, peak force to achieve 4-mm displacement, and energy required to achieve 4-mm displacement were significantly greater for Conventional-Blade and Fid-Blade than those for Lag Screw. The fixation stability of the blade-type Magnum nail component is better than that of the lag screw type under any test condition. The blade-type nail component may have better fixation stability than the lag screw type in a severe osteoporotic bone model.
Increasing the performance of cucumber (Cucumis sativus L.) seedlings by LED illumination
Authors: Hamedalla Ali Mohamed , Ali Muhammad Moaaz , Ali Waleed M. , Ahmed Mohamed A. A. , Kaseb Mohamed Omar , Kalaji Hazem M. , Gajc-Wolska Janina , Yousef Ahmed Fathy 
Published: January 2022

AbstractLight is one of the most important limiting factors for photosynthesis and the production of plants, especially in the regions where natural environmental conditions do not provide sufficient sunlight, and there is a great dependence on artificial lighting to grow plants and produce food. The influence of light intensity, quality, and photoperiod on photosynthetic pigments content and some biochemical and growth traits of cucumber seedlings grown under controlled conditions was investigated. An orthogonal design based on a combination of different light irradiances, ratio of LEDs and photoperiods was used. Treaments consisted of three light irradiance regimes (80, 100, and 150 µmol m−2 s−1) provided by light-emitting diodes (LEDs) of different ratios of red and blue (R:B) (30:70, 50:50, and 70:30) and three different photoperiods (10/14, 12/12, and 14/10 h). The white light was used as a control/reference. Plant height, hypocotyl length, stem diameter, leaf area, and soluble sugar content were highest when exposed to LM9 (150 µmol m−2 s−1; R70:B30; 12/12 h) light mode, while the lowest values for the above parameters were obtained under LM1 (80 µmol m−2 s−1; R30:B70; 10/14 h). Higher pigments contents (chlorophyll a, chlorophyll b, and carotenoid) were obtained when light regime LM9 (150 µmol m−2 s−1; R70:B30; 12/12 h) was applied. In general, cucumber seedlings grown under the LM9 regime showed a significant increase in growth as well as photosynthetic capacity. It seems that the content of photosynthetic pigments is the key factor responsible for the performance of cucumber seedlings grown under different lighting modes, compared to other traits studied. We recommend monitoring the content of chlorophyll a, b, and their ratio value when studying the light requirement of cucumber plants.
A computational analysis of atrial fibrillation effects on coronary perfusion across the different myocardial layers
Authors: Saglietto Andrea , Fois Matteo , Ridolfi Luca , De Ferrari Gaetano Maria , Anselmino Matteo , Scarsoglio Stefania 
Published: January 2022

AbstractPatients with atrial fibrillation (AF) may present ischemic chest pain in the absence of classical obstructive coronary disease. Among the possible causes, the direct hemodynamic effect exerted by the irregular arrhythmia has not been studied in detail. We performed a computational fluid dynamics analysis by means of a 1D-0D multiscale model of the entire human cardiovascular system, enriched by a detailed mathematical modeling of the coronary arteries and their downstream distal microcirculatory districts (subepicardial, midwall and subendocardial layers). Three mean ventricular rates were simulated (75, 100, 125 bpm) in both sinus rhythm (SR) and atrial fibrillation, and an inter-layer and inter-frequency analysis was conducted focusing on the ratio between mean beat-to-beat blood flow in AF compared to SR. Our results show that AF exerts direct hemodynamic consequences on the coronary microcirculation, causing a reduction in microvascular coronary flow particularly at higher ventricular rates; the most prominent reduction was seen in the subendocardial layers perfused by left coronary arteries (left anterior descending and left circumflex arteries).