bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNF141 interacts with KRAS to promote colorectal cancer progression
Authors: Zhang Jiuna , Jiang Xiaoyu , Yin Jie , Dou Shiying , Xie Xiaoli , Liu Ting , Wang Yijun , Wang Shuling , Zhou Xue , Zhang Dongxuan , Jiang Huiqing 
Published: August 2021

AbstractRING finger proteins (RNFs) play a critical role in cancer initiation and progression. RNF141 is a member of RNFs family; however, its clinical significance, roles, and mechanism in colorectal cancer (CRC) remain poorly understood. Here, we examined the expression of RNF141 in 64 pairs of CRC and adjacent normal tissues by real-time PCR, Western blot, and immunohistochemical analysis. We found that there was more expression of RNF141 in CRC tissue compared with its adjacent normal tissue and high RNF141 expression associated with T stage. In vivo and in vitro functional experiments were conducted and revealed the oncogenic role of RNF141 in CRC. RNF141 knockdown suppressed proliferation, arrested the cell cycle in the G1 phase, inhibited migration, invasion and HUVEC tube formation but promoted apoptosis, whereas RNF141 overexpression exerted the opposite effects in CRC cells. The subcutaneous xenograft models showed that RNF141 knockdown reduced tumor growth, but its overexpression promoted tumor growth. Mechanistically, liquid chromatography-tandem mass spectrometry indicated RNF141 interacted with KRAS, which was confirmed by Co-immunoprecipitation, Immunofluorescence assay. Further analysis with bimolecular fluorescence complementation (BiFC) and Glutathione-S-transferase (GST) pull-down assays showed that RNF141 could directly bind to KRAS. Importantly, the upregulation of RNF141 increased GTP-bound KRAS, but its knockdown resulted in a reduction accordingly. Next, we demonstrated that RNF141 induced KRAS activation via increasing its enrichment on the plasma membrane not altering total KRAS expression, which was facilitated by the interaction with LYPLA1. Moreover, KRAS silencing partially abolished the effect of RNF141 on cell proliferation and apoptosis. In addition, our findings presented that RNF141 functioned as an oncogene by upregulating KRAS activity in a manner of promoting KRAS enrichment on the plasma membrane in CRC.
Selective inhibition of HDAC6 regulates expression of the oncogenic driver EWSR1-FLI1 through the EWSR1 promoter in Ewing sarcoma
Authors: García-Domínguez Daniel J. , Hajji Nabil , Sánchez-Molina Sara , Figuerola-Bou Elisabet , de Pablos Rocío M. , Espinosa-Oliva Ana M. , Andrés-León Eduardo , Terrón-Camero Laura Carmen , Flores-Campos Rocío , Pascual-Pasto Guillem , Robles María José , Machado Isidro , Llombart-Bosch Antonio , Magagnoli Giovanna , Scotlandi Katia , Carcaboso Ángel M. , Mora Jaume , de Álava Enrique , Hontecillas-Prieto Lourdes 
Published: August 2021

AbstractEwing sarcoma (EWS) is an aggressive bone and soft tissue tumor of children and young adults in which the principal driver is a fusion gene, EWSR1-FLI1. Although the essential role of EWSR1-FLI1 protein in the regulation of oncogenesis, survival, and tumor progression processes has been described in-depth, little is known about the regulation of chimeric fusion-gene expression. Here, we demonstrate that the active nuclear HDAC6 in EWS modulates the acetylation status of specificity protein 1 (SP1), consequently regulating the SP1/P300 activator complex binding to EWSR1 and EWSR1-FLI1 promoters. Selective inhibition of HDAC6 impairs binding of the activator complex SP1/P300, thereby inducing EWSR1-FLI1 downregulation and significantly reducing its oncogenic functions. In addition, sensitivity of EWS cell lines to HDAC6 inhibition is higher than other tumor or non-tumor cell lines. High expression of HDAC6 in primary EWS tumor samples from patients correlates with a poor prognosis in two independent series accounting 279 patients. Notably, a combination treatment of a selective HDAC6 and doxorubicin (a DNA damage agent used as a standard therapy of EWS patients) dramatically inhibits tumor growth in two EWS murine xenograft models. These results could lead to suitable and promising therapeutic alternatives for patients with EWS.
NSUN2-mediated RNA 5-methylcytosine promotes esophageal squamous cell carcinoma progression via LIN28B-dependent GRB2 mRNA stabilization
Authors: Su Jiachun , Wu Guandi , Ye Ying , Zhang Jialiang , Zeng Lingxing , Huang Xudong , Zheng Yanfen , Bai Ruihong , Zhuang Lisha , Li Mei , Pan Ling , Deng Junge , Li Rui , Deng Shuang , Zhang Shaoping , Zuo Zhixiang , Liu Zexian , Lin Junzhong , Lin Dongxin , Zheng Jian 
Published: August 2021

Abstract5-Methylcytosine (m5C) is a posttranscriptional RNA modification participating in many critical bioprocesses, but its functions in human cancer remain unclear. Here, by detecting the transcriptome-wide m5C profiling in esophageal squamous cell carcinoma (ESCC), we showed increased m5C methylation in ESCC tumors due to the overexpressed m5C methyltransferase NSUN2. Aberrant expression of NSUN2 was positively regulated by E2F Transcription Factor 1 (E2F1). High NSUN2 levels predicted poor survival of ESCC patients. Moreover, silencing NSUN2 suppressed ESCC tumorigenesis and progression in Nsun2 knockout mouse models. Mechanistically, NSUN2 induced m5C modification of growth factor receptor-bound protein 2 (GRB2) and stabilized its mRNA, which was mediated by a novel m5C mediator, protein lin-28 homolog B (LIN28B). Elevated GRB2 levels increased the activation of PI3K/AKT and ERK/MAPK signalling. These results demonstrate that NSUN2 enhances the initiation and progression of ESCC via m5C-LIN28B dependent stabilization of GRB2 transcript, providing a promising epitranscriptomic-targeted therapeutic strategy for ESCC.
Variants in PAX6, PITX3 and HSF4 causing autosomal dominant congenital cataracts
Authors: Berry Vanita , Ionides Alex , Pontikos Nikolas , Moore Anthony T. , Quinlan Roy A. , Michaelides Michel 
Published: August 2021

Abstract
Background
Lens development is orchestrated by transcription factors. Disease-causing variants in transcription factors and their developmental target genes are associated with congenital cataracts and other eye anomalies.

Methods
Using whole exome sequencing, we identified disease-causing variants in two large British families and one isolated case with autosomal dominant congenital cataract. Bioinformatics analysis confirmed these disease-causing mutations as rare or novel variants, with a moderate to damaging pathogenicity score, with testing for segregation within the families using direct Sanger sequencing.

Results
Family A had a missense variant (c.184 G>A; p.V62M) in PAX6 and affected individuals presented with nuclear cataract. Family B had a frameshift variant (c.470–477dup; p.A160R*) in PITX3 that was also associated with nuclear cataract. A recurrent missense variant in HSF4 (c.341 T>C; p.L114P) was associated with congenital cataract in a single isolated case.

Conclusions
We have therefore identified novel variants in PAX6 and PITX3 that cause autosomal dominant congenital cataract.
PSG-Audio, a scored polysomnography dataset with simultaneous audio recordings for sleep apnea studies
Authors: Korompili Georgia , Amfilochiou Anastasia , Kokkalas Lampros , Mitilineos Stelios A. , Tatlas Nicolas- Alexander , Kouvaras Marios , Kastanakis Emmanouil , Maniou Chrysoula , Potirakis Stelios M. 
Published: August 2021

AbstractThe sleep apnea syndrome is a chronic condition that affects the quality of life and increases the risk of severe health conditions such as cardiovascular diseases. However, the prevalence of the syndrome in the general population is considered to be heavily underestimated due to the restricted number of people seeking diagnosis, with the leading cause for this being the inconvenience of the current reference standard for apnea diagnosis: Polysomnography. To enhance patients’ awareness of the syndrome, a great endeavour is conducted in the literature. Various home-based apnea detection systems are being developed, profiting from information in a restricted set of polysomnography signals. In particular, breathing sound has been proven highly effective in detecting apneic events during sleep. The development of accurate systems requires multitudinous datasets of audio recordings and polysomnograms. In this work, we provide the first open access dataset, comprising 212 polysomnograms along with synchronized high-quality tracheal and ambient microphone recordings. We envision this dataset to be widely used for the development of home-based apnea detection techniques and frameworks.
Probing an Ixodes ricinus salivary gland yeast surface display with tick-exposed human sera to identify novel candidates for an anti-tick vaccine
Authors: Trentelman Jos J. A. , Tomás-Cortázar Julen , Knorr Sarah , Barriales Diego , Hajdusek Ondrej , Sima Radek , Ersoz Jasmin I. , Narasimhan Sukanya , Fikrig Erol , Nijhof Ard M. , Anguita Juan , Hovius Joppe W. 
Published: August 2021

AbstractIn Europe, Ixodes ricinus is the most important vector of human infectious diseases, most notably Lyme borreliosis and tick-borne encephalitis virus. Multiple non-natural hosts of I. ricinus have shown to develop immunity after repeated tick bites. Tick immunity has also been shown to impair B. burgdorferi transmission. Most interestingly, multiple tick bites reduced the likelihood of contracting Lyme borreliosis in humans. A vaccine that mimics tick immunity could therefore potentially prevent Lyme borreliosis in humans. A yeast surface display library (YSD) of nymphal I. ricinus salivary gland genes expressed at 24, 48 and 72 h into tick feeding was constructed and probed with antibodies from humans repeatedly bitten by ticks, identifying twelve immunoreactive tick salivary gland proteins (TSGPs). From these, three proteins were selected for vaccination studies. An exploratory vaccination study in cattle showed an anti-tick effect when all three antigens were combined. However, immunization of rabbits did not provide equivalent levels of protection. Our results show that YSD is a powerful tool to identify immunodominant antigens in humans exposed to tick bites, yet vaccination with the three selected TSGPs did not provide protection in the present form. Future efforts will focus on exploring the biological functions of these proteins, consider alternative systems for recombinant protein generation and vaccination platforms and assess the potential of the other identified immunogenic TSGPs.
Transcriptomic landscape of blood platelets in healthy donors
Authors: Supernat Anna , Popęda Marta , Pastuszak Krzysztof , Best Myron G. , Grešner Peter , Veld Sjors In ’t , Siek Bartłomiej , Bednarz-Knoll Natalia , Rondina Matthew T. , Stokowy Tomasz , Wurdinger Thomas , Jassem Jacek , Żaczek Anna J. 
Published: August 2021

AbstractBlood platelet RNA-sequencing is increasingly used among the scientific community. Aberrant platelet transcriptome is common in cancer or cardiovascular disease, but reference data on platelet RNA content in healthy individuals are scarce and merit complex investigation. We sought to explore the dynamics of platelet transcriptome. Datasets from 204 healthy donors were used for the analysis of splice variants, particularly with regard to age, sex, blood storage time, unit of collection or library size. GenesB2M, PPBP, TMSB4X, ACTB, FTL, CLU, PF4, F13A1, GNAS, SPARC, PTMA, TAGLN2, OAZ1andOST4demonstrated the highest expression in the analysed cohort, remaining substantial transcription consistency.CSF3Rgene was found upregulated in males (fold change 2.10, FDR q < 0.05). Cohort dichotomisation according to the median age, showed upregulatedKSR1in the older donors (fold change 2.11, FDR q < 0.05). Unsupervised hierarchical clustering revealed two clusters which were irrespective of age, sex, storage time, collecting unit or library size. However, when donors are analysed globally (as vectors), sex, storage time, library size, the unit of blood collection as well as age impose a certain degree of between- and/or within-group variability. Healthy donor platelet transcriptome retains general consistency, with very few splice variants deviating from the landscape. Although multidimensional analysis reveals statistically significant variability between and within the analysed groups, biologically, these changes are minor and irrelevant while considering disease classification. Our work provides a reference for studies working both on healthy platelets and pathological conditions affecting platelet transcriptome.
Tracking oxidation-induced alterations in fibrin clot formation by NMR-based methods
Authors: Lau Wai-Hoe , White Nathan J. , Yeo Tsin-Wen , Gruen Russell L. , Pervushin Konstantin 
Published: August 2021

AbstractPlasma fibrinogen is an important coagulation factor and susceptible to post-translational modification by oxidants. We have reported impairment of fibrin polymerization after exposure to hypochlorous acid (HOCl) and increased methionine oxidation of fibrinogen in severely injured trauma patients. Molecular dynamics suggests that methionine oxidation poses a mechanistic link between oxidative stress and coagulation through protofibril lateral aggregation by disruption of AαC domain structures. However, experimental evidence explaining how HOCl oxidation impairs fibrinogen structure and function has not been demonstrated. We utilized polymerization studies and two dimensional-nuclear magnetic resonance spectrometry (2D-NMR) to investigate the hypothesis that HOCl oxidation alters fibrinogen conformation and T2 relaxation time of water protons in the fibrin gels. We have demonstrated that both HOCl oxidation of purified fibrinogen and addition of HOCl-oxidized fibrinogen to plasma fibrinogen solution disrupted lateral aggregation of protofibrils similarly to competitive inhibition of fibrin polymerization using a recombinant AαC fragment (AαC 419–502). DOSY NMR measurement of fibrinogen protons demonstrated that the diffusion coefficient of fibrinogen increased by 17.4%, suggesting the oxidized fibrinogen was more compact and fast motion in the prefibrillar state. 2D-NMR analysis reflected that water protons existed as bulk water (T2) and intermediate water (T2i) in the control plasma fibrin. Bulk water T2 relaxation time was increased twofold and correlated positively with the level of HOCl oxidation. However, T2 relaxation of the oxidized plasma fibrin gels was dominated by intermediate water. Oxidation induced thinner fibers, in which less water is released into the bulk and water fraction in the hydration shell was increased. We have confirmed that T2 relaxation is affected by the self-assembly of fibers and stiffness of the plasma fibrin gel. We propose that water protons can serve as an NMR signature to probe oxidative rearrangement of the fibrin clot.
Macroscale patterns of oceanic zooplankton composition and size structure
Authors: Brandão Manoela C. , Benedetti Fabio , Martini Séverine , Soviadan Yawouvi Dodji , Irisson Jean-Olivier , Romagnan Jean-Baptiste , Elineau Amanda , Desnos Corinne , Jalabert Laëtitia , Freire Andrea S. , Picheral Marc , Guidi Lionel , Gorsky Gabriel , Bowler Chris , Karp-Boss Lee , Henry Nicolas , de Vargas Colomban , Sullivan Matthew B. ,   Tara Oceans Consortium Coordinators, Acinas Silvia G. , Babin Marcel , Bork Peer , Boss Emmanuel , Bowler Chris , Cochrane Guy , de Vargas Colomban , Gorsky Gabriel , Guidi Lionel , Grimsley Nigel , Hingamp Pascal , Iudicone Daniele , Jaillon Olivier , Kandels Stefanie , Karp-Boss Lee , Karsenti Eric , Not Fabrice , Ogata Hiroyuki , Poulton Nicole , Pesant Stephane , Raes Jeroen , Sardet Christian , Speich Sabrina , Stemmann Lars , Sullivan Matthew B. , Sunagawa Shinichi , Wincker Patrick , Stemmann Lars , Lombard Fabien 
Published: August 2021

AbstractOcean plankton comprise organisms from viruses to fish larvae that are fundamental to ecosystem functioning and the provision of marine services such as fisheries and CO2 sequestration. The latter services are partly governed by variations in plankton community composition and the expression of traits such as body size at community-level. While community assembly has been thoroughly studied for the smaller end of the plankton size spectrum, the larger end comprises ectotherms that are often studied at the species, or group-level, rather than as communities. The body size of marine ectotherms decreases with temperature, but controls on community-level traits remain elusive, hindering the predictability of marine services provision. Here, we leverage Tara Oceans datasets to determine how zooplankton community composition and size structure varies with latitude, temperature and productivity-related covariates in the global surface ocean. Zooplankton abundance and median size decreased towards warmer and less productive environments, as a result of changes in copepod composition. However, some clades displayed the opposite relationships, which may be ascribed to alternative feeding strategies. Given that climate models predict increasingly warmed and stratified oceans, our findings suggest that zooplankton communities will shift towards smaller organisms which might weaken their contribution to the biological carbon pump.
A new image encryption scheme based on fractional-order hyperchaotic system and multiple image fusion
Authors: Gao Xinyu , Yu Jiawu , Banerjee Santo , Yan Huizhen , Mou Jun 
Published: August 2021

AbstractA multi-image encryption scheme based on the fractional-order hyperchaotic system is designed in this paper. The chaotic characteristics of this system are analyzed by the phase diagram, Lyapunov exponent and bifurcation diagram. According to the analyses results, an interesting image encryption algorithm is proposed. Multiple grayscale images are fused into a color image using different channels. Then, the color image is scrambled and diffused in order to obtain a more secure cipher image. The pixel confusion operation and diffusion operation are assisted by fractional hyperchaotic system. Experimental simulation and test results indicate that the devised multi-image encryption scheme can effectively encrypt multiple images, which increase the efficiency of image encryption and transmission, and have good security performance.
Cortical representation of experimental periodontal pain: a functional magnetic resonance imaging study
Authors: Maurer Angelika , Verma Damian , Reddehase Annika , Scheef Lukas , Radbruch Alexander , Attenberger Ulrike , Jäger Andreas , Boecker Henning 
Published: August 2021

AbstractThe aim of this study was to investigate central pain representations during loading of the periodontium induced by orthodontic and occlusal stress. Nineteen healthy male volunteers (25.7 ± 2.8 years) were tested on two consecutive days: after phenotyping (questionnaires) and determination of warmth (WPT) and heat (HPT) pain thresholds, functional magnetic resonance imaging was performed as event-related paradigm including 36 tooth clenchings of 3 s duration, alternating with rest periods varying between 20–30 s. The task was performed in absence (T1) and 24 h after placement of an elastic separator between the second bicuspid and the first molar on the right side of the lower jaw (T2). No significant changes in WPT and HPT were observed but pain ratings were significantly elevated at T2. Significantly elevated activation at T2, as compared to T1, was found in bilateral sensorimotor cortex, bilateral secondary sensory cortex, supplementary motor area, right rolandic operculum, and bilateral insula. Our data show for the first time in humans that periodontal stimulation, as tested by tooth clenching in the presence of an elastic separator, goes along with specific expressions of pain at behavioral and neuronal network levels. Findings supplement the existing neuroimaging literature on odontogenic pain.
The COL-4A1 polypeptide destroy endothelial cells through the TGF-β/PI3K/AKT pathway
Authors: Li Ting , Ling Zhonghui , Xie Kaipeng , Wang Yixiao , Miao Zhijing , Ji Xiaohong , Li Jingyun , Hou Wenwen , Tang Qiuqin , Yuan Xiaojie , Li Nan , Li Chanjuan , Ding Hongjuan 
Published: August 2021

AbstractPreeclampsia (PE) is commonly considered as a placental disorder in pregnancy. Until now, the etiology and pathological mechanism of PE have remained ambiguous. Although PE can lead to a variety of maternal and infant complications, there are still no effective treatments. This study aimed to explore the correlation between the novel polypeptide COL-4A1 and PE, and to identify the underlying mechanism by which this polypeptide may function and to explore new therapeutic targets for PE. A rat model of PE was established and used to verify the function of the polypeptide COL-4A1 in vivo. Additionally, human umbilical vascular endothelial cells (HUVECs) were cultured with or without COL-4A1 and TNF-α (20 ng/ml). Cell Counting Kit-8 (CCK-8), wound-healing, Transwell and tube formation assays were used to evaluate cell proliferation, migration and angiopoiesis. RNA sequencing and mass spectrometry were conducted to explore the underlying downstream mechanism of COL-4A1. In vivo, COL-4A1 increased blood pressure and elevated the risk of fetal growth restriction (FGR) which was induced by lipopolysaccharide (LPS) in the rat model. In vitro, COL-4A1 significantly inhibited the proliferation and migration of HUVECs. After culture with COL-4A1, compared to control group the adhesive ability and level of reactive oxygen species (ROS) were enhanced and tube formation ability was decreased. Furthermore, Western blotting (WB) and pull-down assays were conducted to explore the underlying mechanism by which COL-4A1 functions, and the TGF-β/PI3K/AKT pathway was identified as the potential pathway involved in its effects. In summary, these results revealed that the polypeptide COL-4A1 caused PE-like symptoms in cells and a rat model. Through the TGF-β/PI3K/AKT pathway, COL-4A1 interferes with the pathogenesis of PE. Thus COL-4A1 is expected to become a potential target of PE, providing a basis for exploring the treatment of PE.
TrendyGenes, a computational pipeline for the detection of literature trends in academia and drug discovery
Authors: Serrano Nájera Guillermo , Narganes Carlón David , Crowther Daniel J. 
Published: August 2021

AbstractTarget identification and prioritisation are prominent first steps in modern drug discovery. Traditionally, individual scientists have used their expertise to manually interpret scientific literature and prioritise opportunities. However, increasing publication rates and the wider routine coverage of human genes by omic-scale research make it difficult to maintain meaningful overviews from which to identify promising new trends. Here we propose an automated yet flexible pipeline that identifies trends in the scientific corpus which align with the specific interests of a researcher and facilitate an initial prioritisation of opportunities. Using a procedure based on co-citation networks and machine learning, genes and diseases are first parsed from PubMed articles using a novel named entity recognition system together with publication date and supporting information. Then recurrent neural networks are trained to predict the publication dynamics of all human genes. For a user-defined therapeutic focus, genes generating more publications or citations are identified as high-interest targets. We also used topic detection routines to help understand why a gene is trendy and implement a system to propose the most prominent review articles for a potential target. This TrendyGenes pipeline detects emerging targets and pathways and provides a new way to explore the literature for individual researchers, pharmaceutical companies and funding agencies.