bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complex small-world regulatory networks emerge from the 3D organisation of the human genome
Authors: Brackley Chris , Gilbert Nick , Michieletto Davide , Papantonis Argyris , Pereira Maria , Cook Peter , Marenduzzo Davide 
Published: June 2021

Abstract
The discovery that overexpressing one or a few critical transcription factors can switch cell state suggests that gene regulatory networks are relatively simple. In contrast, genome-wide association studies (GWAS) point to complex phenotypes being determined by hundreds of loci that rarely encode transcription factors and which in- dividually have small effects. Here, we use computer simulations and a simple fitting-free polymer model of chromosomes to show that spatial correlations arising from 3D genome organisation naturally lead to stochastic and bursty transcription as well as complex small-world regulatory networks (where the transcriptional activity of each genomic region subtly affects almost all others). These effects require factors to be present at sub-saturating levels; increasing levels dramatically simplifiies networks as more transcription units are pressed into use. Consequently, results from GWAS can be reconciled with those involving overexpression. We apply this pan-genomic model to predict patterns of transcriptional activity in whole human chromosomes, and, as an example, the effects of the deletion causing the diGeorge syndrome.
The Bird Community in a Coastal Wetland in East China and Its Spatial Responses to a Wind Farm
Authors: Cheng Yinrui , Zha Yong , Zhang Wenmin , Wei Geng , Tong Chuan , Du Dandan 
Published: June 2021

Abstract
Coastal wetlands in East China are essential stopover places for birds along the East Asian-Australian Flyway. However, numerous wind turbines have been built in or near these wetlands in recent years, which might disturb the bird community in the area. Therefore, investigating the bird community and its responses to wind farms in coastal wetlands of East China is of great significance for bird conservation. In the spring and autumn of 2019 and 2020, we investigated the bird community in the Rudong coastal wetland in East China using point counts. We determined 4 geographical factors at each census point, i.e., distance to the wind farm boundary (DW), distance to the suburbs, distance to the sea, and vegetation area, and analysed the relationship between bird number and DW through partial correlation analysis. A total of 11 orders and 103 species of birds, including 4 endangered species, were observed during our survey. Charadriiformes was the dominant taxon in the wetland, and Calidris alpina was the most common species in both spring and autumn. Passeriformes exhibited high species richness but low numbers. The results of partial correlation analysis indicated that birds’ responses to the wind farm varied depending on their dominance and category: dominant and subdominant birds tended to avoid the wind farm, whereas rare birds tended to approach them; aquatic birds were alert to the wind farm, whereas terrestrial birds better adapted to them. We concluded that the dominant aquatic birds, including the endangered species Calidris tenuirostris, were most negatively impacted by the wind farm; the occasional birds and rare aquatic birds might be disturbed by wind farm but not significantly so; and the rare terrestrial birds were least disturbed by or even benefited from the wind farm.
Tissue Accumulation of Neutrophil Extracellular Traps Mediates Muscle Hyperalgesia in a Mouse Model
Authors: Suzuki Kazuaki , Tsuchiya Masahiro , Yoshida Shinichiro , Ogawa Kazumi , Chen Weijian , Kanzaki Makoto , Takahashi Tadahisa , Fujita Ryo , Li Yuqing , Yabe Yutaka , Aizawa Toshimi , Hagiwara Yoshihiro 
Published: June 2021

Abstract
Background: Accumulation of uric acid during muscular trauma is potentially a causative factor of damage-associated molecular patterns (DAMPs) involved in the development of muscle hyperalgesia. Neutrophil extracellular traps (NETs), DNA-based reticular structures to capture DAMPs, play a central role in the onset of pain in gout attacks associated with hyperuricemia; however, their association with muscle hyperalgesia due to overuse injuries remains unknown. Therefore, the aim of this study was to investigate the involvement of NETs via the elevation of local uric acid level in muscle nociception.Methods: The triceps surae muscles (TSMs) in the unilateral hindlimb of mice were repeatedly stimulated with electrical pulses to induce excessive muscle contraction, and the contralateral TSM was used as a control. In addition to mechanical nociceptive thresholds, tissue uric acid levels, neutrophil recruitment, protein amount, and histological distribution of citrullinated histone 3 (citH3), a major marker of NETs, were investigated. Furthermore, whether neutrophil depletion, extracellular DNA cleavage (deoxyribonuclease I), and administration of the urate-lowering agent febuxostat, a xanthine oxidase inhibitor, improved muscle hyperalgesia due to NET accumulation was examined. Using a combination of multiphoton imaging analysis and intravital fluorescence staining, we also evaluated the intramuscular distribution of NET accumulation in stimulated TSMs.Results: CitH3 expression upon neutrophil recruitment significantly increased in the stimulated TSMs tissues with an increase in tissue uric acid levels. However, neutrophil depletion and extracellular DNA cleavage prevented the increase in uric acid levels in damaged muscle tissues. Furthermore, febuxostat administration significantly improved muscle hyperalgesia, with decreases not only in citH3 and tissue uric acid levels, but also in neutrophil recruitment. Interestingly, the intramuscular distribution of NETs in the stimulated TSM was predominantly observed in the myofascial region.Conclusions: Our findings suggest that NET accumulation caused by excessive muscle contraction was strongly associated with the pathogenesis of muscle hyperalgesia. Further, the mechanism underlying induction of locally recruited neutrophils forming NETs was increased tissue uric acid levels, which potentially plays a significant role in creating a vicious circle of muscle pain.
In Search of Traces of the Mandrake Myth – The Etymological, Historical, and Ethnobotanical Roots of Its Vernacular Names
Authors: Dafni Amots , Blanché Cesar , Khatib Salekh Aqil , Petanidou Theodora , Aytaç Bedrettin , Pacini Ettore , Kohazurova Ekaterina , Geva-Kleinberger Aharon , Shahvar Soli , Dajic Zora , Klug Helmut W. , Benítez Guillermo 
Published: June 2021

Abstract
Background: Mandrake (Mandragora spp.) is perhaps the most famous medicinal plant in western cultures since Biblical times and throughout written history. In many cultures, mandrake is related to magic and witchcraft, which and is said to have a psychosomatic effect (especially when mandrake contains narcotic compounds) in addition to the pharmacological influence, as occurs with other narcotic magical plants. Due to its unique properties and related myths, it is not surprising that this plant has many names in many languages.Methods: This paper presents an attempt to reconstruct the etymological, ethnobotanical, and historical and folkloristic roots of 296 vernacular names of Mandragora sp. in forty-two languages. We used the plant’s morphological data, philology, myths and legends, medicinal properties and uses, as well as historical evidence and folkloric data, to explain meaning, origin, migration, and history of the plant’s names.Results: The names were classified into the following main categories: Derivatives of mandragora (20 languages), alraun (7) and of yabroukh (5). The salient groups of the plant’s vernacular names are related to: Anthropomorphism (33 names in 13 languages); Similarity to other plants (29/9); Supernatural agents (28/9); Narcotic effects (21/8); Leaves, fruits, and seeds (21/8); Aphrodisiac properties (17/10); Use of a dog (15/9); Gallows (14/5); Black magic, sorcery, witchcraft (13/8), and Medicinal use (11/7). Conclusions: This frequency distribution of the mandrake’s vernacular names reflects its widespread reputation as related to the Doctrine of Signatures, beliefs in its supernatural, natural, and mythic powers, and to a lesser extent, its uses in magic and medicine. A spatiotemporal analysis of the mandrake’s names supports the old idea that the pulling ceremonies for this plant originated in the Near East and that various other myths related to this plant may have originated in different places and periods.
High-Accuracy Parameter Estimation for Damped Signal via Three Weighted DFT Samples
Authors: Xu Haitao , Du Ying , Zhou Shengxi , Fan Hongwei , Zhang Xuhui 
Published: June 2021

Abstract
Recently, accurate parameter estimation of the damped complex exponential plays an increasingly important role in the field of precise measurement. However, the estimation variance of interpolation-based algorithms for the parameter estimation cannot be asymptotic to the Crámer-Rao lower bound (CRLB). This paper originally proposes a generalized, fast, and the accurate two-iteration estimator (TIE) based on the discrete Fourier transform (DFT). It can be operated by an arbitrary window (symmetric or asymmetric window). Theoretical estimation variances of the frequency and the damping factor for arbitrary windows are derived, respectively. Furthermore, extensive computer simulations are performed to compare the performance of the TIE with other state-of-the-art algorithms in the literature. The results support the theoretical findings and verify that high-accuracy parameter estimation can be ensured by the proposed algorithm. More importantly, the estimation variances returned by the TIE with the rectangle window exactly track the CRLB for a damped single tone.
Temporal and spatial topography of cell proliferation in cancer
Authors: Gaglia Giorgio , Kabraji Sheheryar , Argyropoulou Danae , Dai Yang , Wang Shu , Bergholz Johann , Coy Shannon , Lin Jia-Ren , Jeselsohn Rinath , Metzger Otto , Winer Eric , Dillon Deborah , Zhao Jean , Sorger Peter , Santagata Sandro 
Published: June 2021

Abstract
Proliferation is a fundamental trait of cancer cells but is poorly characterized in tumors by classical histologic methods. We use multiplexed tissue imaging to quantify the abundance of multiple cell cycle regulating proteins at single-cell level and develop robust multivariate proliferation metrics. Across cancers, the proliferative architecture is organized at two distinct spatial scales: large domains, and local niches enriched for specific immune lineages. A subset of tumor cells express cell cycle regulators in canonical patterns consistent with unrestrained proliferation, a phenomenon we refer to as “cell cycle coherence”. By contrast, the cell cycles of other tumor cell populations are skewed toward a specific phase or characterized by non-canonical (incoherent) marker combinations. Coherence varies across space, with changes in oncogene activity, and with therapeutic intervention, and is associated with aggressive behavior. Multivariate measures capture clinically significant features of cancer proliferation, a fundamental step in enabling more precise use of anti-cancer therapies.
Accurate Prediction of Acute Pancreatitis Severity based on Genome-Wide Cell free DNA Methylation Profiles
Authors: Sun Hong-Wei , Dai Sheng-Jie , Kong Hong-Ru , Yang Fang-Yuan , Dai Ju-Qing , Jin Yue-Peng , Shi Keqing 
Published: June 2021

Abstract
BackgroundPatients with severe acute pancreatitis (SAP) have a high mortality, thus early diagnosis and interventions are critical for improving survival. However, conventional tests are limited in acute pancreatitis (AP) stratification. We aimed to assess AP severity by integrating the informative clinical measurements with cell free DNA (cfDNA) methylation markers.MethodsOne hundred and seventy-five blood samples were collected from 61 AP patients at multiple time points, plus 24 samples from healthy individuals. Genome-wide cfDNA methylation profiles of all samples were characterized with reduced representative bisulfite sequencing. Clinical blood tests covering 93 biomarkers were performed on AP patients within 24 hours. SAP predication models were built based on cfDNA methylation and conventional blood biomarkers separately and in combination. ResultsWe identified 565 and 59 cfDNA methylation markers informative for acute pancreatitis and its severity. These markers were used to develop prediction models for AP and SAP with area under the receiver operating characteristic of 0.92 and 0.81, respectively. Twelve blood biomarkers were systematically screened for a predictor of SAP with a sensitivity of 87.5% for SAP, and a specificity of 100% in mild acute pancreatitis, significantly higher than existing blood tests. An expanded model integrating 12 conventional blood biomarkers with 59 cfDNA methylation markers further improved the SAP prediction sensitivity to 92.2%.ConclusionsWe have demonstrated accurate prediction of SAP by the integration of conventional and novel blood molecular markers, paving the way for early and effective SAP intervention through a non-invasive rapid diagnostic test.
Natural mineral modulated single atom catalyst for effective water treatment
Authors: Dong Xiongbo , Chen Zitong , Tang Aidong , Dionysiou Dionysios , Huaming Yang 
Published: June 2021

Abstract
Single atom catalysts (SACs) have been growing as an emerging “hot” topic in environmental remediation. Their performance can be rationally optimized via modulating spatial coordination configuration and porous structure of SACs, which is still challenging. Herein, a novel Si, N co-coordinated cobalt SACs (p-CoSi1N3@D) with 3D freestanding architecture was tailored via employing natural mineral (diatomite) as Si source and porous template. Theoretical calculations and experimental analysis reveal that Si substitution dramatically decreases electronegativity of CoN4 moieties and thus accelerates interaction and electron transfer between peroxymonosulfate and Co single atom center. Moreover, p-CoSi1N3@D inherits hierarchically porous architecture of diatomite, providing more accessible cobalt sites and open diffusion channels for peroxymonosulfate and contaminants in water treatment applications. Thanks to optimal coordination structure and porous architecture, p-CoSi1N3@D can serve as highly active catalyst toward peroxymonosulfate activation, with a turn-over frequency of 299.8 min− 1 for bisphenol A degradation, surpassing those of catalysts with transition metal SACs or oxides in disclosed literature. This work provides a novel vision for development of SACs towards wastewater reclamation.
Hunting alters viral transmission and evolution
Authors: Fountain-Jones Nicholas , Kraberger Simona , Gagne Roderick , Gilbertson Marie , Trumbo Daryl , Charleston Michael , Salerno Patricia , Funk W. Chris , Crooks Kevin , Logan Ken , Alldredge Mat , Dellicour Simon , Baele Guy , Didelot Xavier , Vandewoude Sue , Carver Scott , Craft Meggan 
Published: June 2021

Abstract
Hunting can fundamentally alter wildlife population dynamics, but the consequences of hunting on pathogen transmission and evolution remain poorly understood. Here we present a study that leverages a unique landscape-scale experiment coupled with pathogen transmission tracing, network simulation and phylodynamics to provide insights into how hunting shapes viral dynamics in puma (Puma concolor). We show that removing hunting pressure enhances the role of males in transmission, increases the viral population growth rate and the role of evolutionary forces on the pathogen compared to when hunting was reinstated. Changes in transmission could be linked to short term social changes while the male population increased. These findings are supported through comparison with a region with stable hunting management over the same time period. This study shows that routine wildlife management can have impacts on pathogen transmission and evolution not previously considered.
The Impact of Traditional Conservation Practices on Species Composition and Diversity Patterns of Sacred Swamps in the Central Western Ghats, India
Authors: Hegde Narasimha , Gunaga Shrikanth Vasudev , Joosten Hans 
Published: June 2021

Abstract
Sacred forests are of immense value for their ecosystem functions. Traditional indigenous conservation practices have helped maintaining biological diversity over centuries and have resulted in the preservation of some of the best patches of natural vegetation.
Exclusive taxa find refuge in the micro-climatic conditions of sacred groves and many rare species are found here. Ten sacred swamps and ten non-sacred swamps in the central Western Ghats region, India, with a similar distance from roads, village settlements, or commercial orchards and with nearly the same size, were compared with regard to their species composition, floristic structure, diversity, occurrence of amphibians, odonates and birds.
In the sacred swamps, 122 plant species from 99 genera and 58 families occur against 83 species from 72 genera and 47 families in the non-sacred swamps. Tree stem density was 277 individuals/ha in sacred swamps against 158.4 in non-sacred swamps. Average basal area was 47.57 m 2 /ha in sacred swamps and only 14.60 m 2 /ha in non-sacred swamps. Sacred swamps have higher number of endemic species (28%) when compared to non-sacred swamps. We conclude that the traditional belief system of treating the swamps as sacred has helped to protect these ecologically important forests.
LINC00659 Regulates Colorectal Cancer Migration and Invasion by Targeting miR-485-5p/HOXC13 Axis
Authors: Yang Haojie , Fu Jihong , Jiao Guangyang , Zhu Yilian , Han Yilin , Yang Yiheng , Xia Yubin , Han Changpeng , Wang Zhenyi 
Published: June 2021

Abstract
BackgroundLong noncoding RNA LINC00659 has been reported to be involved in the carcinogenesis and progression of colorectal cancer. However, the molecular mechanism remains ambiguous.MethodsIn this study, we found that HOXC13 expression was closely related with colorectal cancer and positively correlated with LINC00659 via bioinformatics analysis and clinical validation experiment. Meanwhile, miR-485-5p was identified as an overlapped target miRNA. To further dissect whether miR-485-5p and HOXC13 were involved in LINC00659 mediated colorectal cancer progression, we first established human in vitro models and demonstrated that LINC00659 could directly bind with miR-485-5p and knockdown of LINC00659 upregulated the expression of miR-485-5p. In addition, knockdown of LINC00659 inhibited the expression of HOXC13 by targeting miR-485-5p. Finally, we analyzed the effect of LINC00659/miR-485-5p/HOXC13 axis on tumor growth. Both animal model and in vitro model confirmed the anti-tumor effect of knockdown of LINC00659, which could suppress the colorectal cancer cell viability, migration and invasion by targeting miR-485-5p/HOXC13 axis. Results1. LINC00659 and HOXC13 are highly expressed in colorectal cancer cells.2. miRNA-485-5p is lowly expressed in colorectal cancer cells.3. LINC00659/miR-485-5p/HOXC13 axis is important for colorectal cancer cells.4. LINC00659 promotes tumor growth by sponging miR-485-5p.ConclusionsOur study uncovered a novel mechanism of LINC00659 in the progression of colorectal cancer and provided a potential strategy for the treatment and diagnose of colorectal cancer.
Long Noncoding RNA LINC00958 Suppresses Apoptosis and Radiosensitivity of Colorectal Cancer Through Targeting miR-422a
Authors: Liang Hong , Zhao Qiuyan , Zhu Zhonglin , Zhang Chao , Zhang Hui 
Published: June 2021

Abstract
Background: Long non-coding RNAs (lncRNAs) have been elucidated to participate in the development and progression of various cancers. In this study, we aim to explore the underlying functions and mechanisms of LINC00958 in colorectal cancer. Methods: LINC00958 expression in colorectal cancer tissues was examined by qRT-PCR. The associations between LINC00958 expression with clinical characteristics and prognosis were evaluated. The biological functions of LINC00958 were detected by CCK-8, MTT, colony formation and Flow cytometric analyses. RNA-pull down, RIP and luciferase reporter assays were used to confirm the regulation of LINC00958 on miR-422a. Rescue experiments were performed to detect the effects of miR-422a on the roles of LINC00958. Results: LINC00958 was upregulated in colorectal cancer tissues and cell lines; high LINC00958 level was significantly associated with tumor differentiation, T stage and TNM stage, and also predicted poor prognosis. Cell experiments showed that LINC00958 promoted cell proliferation and suppressed apoptosis and the sensitivity of radiotherapy in vitro, and promoted cell growth in vivo. Bioinformatics analysis predicted the binding site of miR-422a on LINC00958. Mechanistically, RNA-pull down, RIP and luciferase reporter assays demonstrated that LINC00958 specially targeted miR-422a. In addition, we provided evidence that miR-422a suppressed MAPK1 expression through directly binding to the 3’-UTR of MAPK1, thereby inhibiting cell proliferation and enhancing apoptosis and the radiosensitivity. Furthermore, miR-422a rescued the roles of LINC00958 on promoting MAPK1 expression and cell proliferation and decreasing apoptosis and the radiosensitivity. Conclusions: LINC00958 promoted MAPK1 expression and cell proliferation and suppressed apoptosis and the radiosensitivity through targeting miR-422a, highlighting a potential biomarker for the prognosis and treatment of colorectal cancer.
Quadruple Recombination Events Discovered in Hepatitis E Virus
Authors: Shen Hao , Liu Shuning , Ding Min , Gu Haixia , Chang Ming , Li Yanshuang , Wang Hua , Shen Hongxing 
Published: June 2021

Abstract
Hepatitis E virus (HEV) can infect humans, pigs, and many other animals, but the recombination of HEV has rarely been reported. In the present study, phylogenetic and recombination analyses were performed on 557 complete HEV genomes in GenBank. A potentially significant quadruple recombination event was identified by recombination detection analysis. The recombinant progeny virus HEV_32_Manchester_301214 was produced by recombination between the major parent HEPAC-44 and the minor parent HE-JA15-1335, thereby reflecting inter-genotype recombination. HEV_32_Manchester_301214 and HEPAC-44 belong to genotype 3, while HE-JA15-1335 belongs to genotype 1, and these three strains have all been separated from humans. Three breakpoints of the four recombination events occurred in the ORF2 region, while another occurred in the ORF1 region. This quadruple recombination event was confirmed by phylogenetic analysis. The genotype, host and the recombination regions of the three strains were analyzed. These results of the analyses provide valuable suggestions for future research on HEV diversity.