bluuebunny/crossref_metadata_2025_split huggingface dataset:
Persistent Eastward EEJ Enhancement During the Geomagnetic Storm Recovery Phases
Authors: Li Qiaoling , Zhang Ruilong , Liu Libo , Kuai Jiawei , Yang Na , Zhong Jiahao , Wan Xin , Liu Jing 
Published: April 2022

AbstractRecent case studies disclosed that sometimes the dayside ionospheric equatorial electric field underwent persistent long‐duration (>4 hr) eastward enhancements during geomagnetic storm recovery phases, rather than anticipated decrease or reversal. However, it is still unknown the occurrence and morphology of the persistent enhancement as well as its impact on the low‐latitude ionospheric plasma distribution. For the first time, we examined the issue with superposed epoch analyses of equatorial electrojet (EEJ) and GNSS total electron content (TEC) responses in the American (49°W) and Indian (78°E) sectors. The occurrence rates of the persistent enhancement during storm recovery phases are more than 30%, with higher occurrence rates in second to fourth days of the recovery phase, equinoxes, and American sector. The corresponding averaged EEJ and TEC responses were disclosed and compared with those storm samples without the persistent enhancement. On the first day of recovery phase, the dayside equatorial ionosphere was dominated by the prevalent westward electric field and causative inhibited equatorial fountain. In contrast, after the first day, the dayside morphologies showed different patterns: (a) for the persistent cases, the large eastward EEJ and TEC enhancement indicated the enhanced eastward electric field at forenoon and causative intensified equatorial fountain. (b) For the storms without the persistent cases, the general westward EEJ and equatorial TEC enhancements were dominated. Our study indicates that dayside eastward enhancement is an important disturbed pattern of equatorial ionospheric electric field during the late recovery phases, and the enhancement generally causes the intensification of equatorial ionization anomaly.
PINK1-mediated Drp1S616 phosphorylation modulates synaptic development and plasticity via promoting mitochondrial fission
Authors: Gao Qingtao , Tian Runyi , Han Hailong , Slone Jesse , Wang Caifang , Ke Xiao , Zhang Tongmei , Li Xiangyu , He Yuhong , Liao Panlin , Wang Fang , Chen Ye , Fu Shiqing , Zhang Kexuan , Zeng Fangfang , Yang Yingxuan , Li Zhuo , Tan Jieqiong , Li Jiada , Lu Youming , Huang Taosheng , Hu Zhonghua , Zhang Zhuohua 
Published: April 2022

AbstractDynamic change of mitochondrial morphology and distribution along neuronal branches are essential for neural circuitry formation and synaptic efficacy. However, the underlying mechanism remains elusive. We show here thatPink1knockout (KO) mice display defective dendritic spine maturation, reduced axonal synaptic vesicles, abnormal synaptic connection, and attenuated long-term synaptic potentiation (LTP). Drp1 activation via S616 phosphorylation rescues deficits of spine maturation inPink1KO neurons. Notably, mice harboring a knockin (KI) phosphor-nullDrp1S616Arecapitulate spine immaturity and synaptic abnormality identified inPink1KO mice. Chemical LTP (cLTP) induces Drp1S616phosphorylation in a PINK1-dependent manner. Moreover, phosphor-mimetic Drp1S616Drestores reduced dendritic spine localization of mitochondria inPink1KO neurons. Together, this study provides the first in vivo evidence of functional regulation of Drp1 by phosphorylation and suggests that PINK1-Drp1S616phosphorylation coupling is essential for convergence between mitochondrial dynamics and neural circuitry formation and refinement.
RNF8 up-regulates AR/ARV7 action to contribute to advanced prostate cancer progression
Authors: Zhou Tingting , Wang Shengli , Song Xiaoyu , Liu Wensu , Dong Fang , Huo Yunlong , Zou Renlong , Wang Chunyu , Zhang Siyi , Liu Wei , Sun Ge , Lin Lin , Zeng Kai , Dong Xiang , Guo Qiqiang , Yi Fei , Wang Zhuo , Li Xiaoman , Jiang Bo , Cao Liu , Zhao Yue 
Published: April 2022

AbstractAndrogen receptor (AR) signaling drives prostate cancer (PC) progression. Androgen deprivation therapy (ADT) is temporally effective, whereas drug resistance inevitably develops. Abnormal expression of AR/ARV7 (the most common AR splicing variant) is critical for endocrine resistance, while the detailed mechanism is still elusive. In this study, bioinformatics and immunohistochemical analyses demonstrate that RNF8 is high expressed in PC and castration-resistant PC (CRPC) samples and the expression of RNF8 is positively correlated with the Gleason score. The high expression of RNF8 in PCs predicts a poor prognosis. These results provide a potential function of RNF8 in PC progression. Furthermore, the mRNA expression of RNF8 is positively correlated with that of AR in PC. Mechanistically, we find that RNF8 upregulates c-Myc-induced AR transcription via altering histone modifications at the c-Myc binding site within the AR gene. RNF8 also acts as a co-activator of AR, promoting the recruitment of AR/ARV7 to the KLK3 (PSA) promoter, where RNF8 modulates histone modifications. These functions of RNF8 are dependent on its E3 ligase activity. RNF8 knockdown further reduces AR transactivation and PSA expression in CRPC cells with enzalutamide treatment. RNF8 depletion restrains cell proliferation and alleviates enzalutamide resistance in CRPC cells. Our findings indicate that RNF8 may be a potential therapeutic target for endocrine resistance in PC.
KDM5B promotes tumorigenesis of Ewing sarcoma via FBXW7/CCNE1 axis
Authors: Chen Binbin , Chen Huimou , Lu Suying , Zhu Xiaoqin , Que Yi , Zhang Yu , Huang Junting , Zhang Li , Zhang Yu , Sun Feifei , Wang Juan , Zhu Jia , Zhen Zijun , Zhang Yizhuo 
Published: April 2022

AbstractEwing sarcoma (EwS) is an aggressive tumor that affects children and young adults. Patients with relapsed/refractory diseases have limited treatment options. Targeting the driver fusion oncoproteins of EwS remains a technical problem. Epigenetic mechanisms have been pointed out as key players and alternative therapeutic targets in EwS. Here, we reported that lysine demethylase 5B (KDM5B), a histone demethylase that specifically demethylates tri- and di-methylated H3 Lys-4 (H3K4), was upregulated in EwS and overexpressed KDM5B was correlated with poor outcomes of patients. KDM5B knockdown and KDM5B inhibitor AS-8351 suppressed EwS cell proliferation and induced cell cycle arrest. Bioinformatics analysis revealed that KDM5B mainly influenced the cell cycle pathways in EwS. In mechanistic studies, we found that overexpression of KDM5B resulted in increased CCNE1 protein level, but did not affect the mRNA level of CCNE1. KDM5B upregulation blocked the degradation pathway of CCNE1 by reducing the expression of FBXW7. KDM5B downregulated FBXW7 gene by demethylation of H3K4me3 at promoter region. Moreover, AS-8351 could inhibit tumor growth in nude mice models, indicating the antitumor effect of targeting KDM5B in EwS. Our study uncovered that KDM5B in EwS attenuated FBXW7 transcription and accumulated CCNE1 protein, leading to malignant proliferation of EwS. Epigenetic drug targeting KDM5B could be a potential treatment for EwS.
SIRT1 restoration enhances chondrocyte autophagy in osteoarthritis through PTEN-mediated EGFR ubiquitination
Authors: Lu Qunshan , Liu Peilai , Miao Zhuang , Luo Desu , Li Songlin , Lu Mei 
Published: April 2022

AbstractThe pharmacological interventions aimed at activating pathways inducing chondrocyte autophagy or reversing extracellular matrix degradation may be promising approaches for the management of osteoarthritis (OA). Evidence exists suggesting that sirtuin 1 (SIRT1) is involved in the pathogenesis of OA. The present study aimed to explore the regulatory role and downstream mechanisms of SIRT1 in OA. Bioinformatics predictions identified downstream factors phosphatase and tensin homolog (PTEN) and epidermal growth factor receptor (EGFR) in OA. We validated poorly expressed SIRT1 and EGFR and highly expressed PTEN in cartilage tissues of OA patients. OA was induced in vitro by exposing human primary chondrocytes to IL-1β and in vivo by destabilization of the medial meniscus (DMM) in a mouse model. SIRT1 knockdown was found to augment IL-1β-stimulated inflammation and chondrocyte metabolic imbalance. Knockdown of SIRT1 diminished PTEN acetylation and then enhanced PTEN expression. PTEN inactivation decreased EGFR ubiquitination and promoted EGFR expression by destabilizing the EGFR-Cbl complex, which in turn inhibited extracellular matrix degradation in cartilage tissues and activated chondrocyte autophagy. In the DMM mouse model, knockdown of SIRT1 inhibited chondrocyte autophagy, promoted metabolic imbalance, thus accelerating osteoarthritic process. In conclusion, SIRT1 represses the ubiquitination of EGFR by down-regulating PTEN, inhibits extracellular matrix degradation and activates chondrocyte autophagy, thereby performing an OA-alleviating role.
Rhesus negative males have an enhanced IFNγ-mediated immune response to influenza A virus
Authors: Sugrue Jamie A. , Smith Megan , Posseme Celine , Charbit Bruno ,   Milieu Interieur Consortium, Abel Laurent , Alcover Andres , Aschard Hugues , Bousso Philippe , Bourke Nollaig , Brodin Petter , Bruhns Pierre , Cerf-Bensussan Nadine , Cumano Ana , D’Enfert Christophe , Deriano Ludovic , Dillies Marie-Agnès , Santo James Di , Dromer Françoise , Eberl Gérard , Enninga Jost , Fellay Jacques , Gomperts-Boneca Ivo , Hasan Milena , Hedestam Gunilla Karlsson , Hercberg Serge , Ingersoll Molly A. , Lantz Olivier , Kenny Rose Anne , Ménager Mickaël , Mouquet Hugo , O’Farrelly Cliona , Patin Etienne , Pellegrini Sandra , Rausell Antonio , Rieux-Laucat Frédéric , Rogge Lars , Fontes Magnus , Sakuntabhai Anavaj , Schwartz Olivier , Schwikowski Benno , Shorte Spencer , Tangy Frédéric , Toubert Antoine , Touvier Mathilde , Ungeheuer Marie-Noëlle , Zimmer Christophe , Albert Matthew L. , Duffy Darragh , Quintana-Murci Lluis , Bourke Nollaig M. , Duffy Darragh , O’Farrelly Cliona 
Published: April 2022

AbstractThe Rhesus D antigen (RhD) has been associated with susceptibility to several viral infections. Reports suggest that RhD-negative individuals are better protected against infectious diseases and have overall better health. However, potential mechanisms contributing to these associations have not yet been defined. Here, we used transcriptomic and genomic data from the Milieu Interieur cohort of 1000 healthy individuals to explore the effect of Rhesus status on the immune response. We used the rs590787 SNP in the RHD gene to classify the 1000 donors as either RhD-positive or -negative. Whole blood was stimulated with LPS, polyIC, and the live influenza A virus and the NanoString human immunology panel of 560 genes used to assess donor immune response and to investigate sex-specific effects. Using regression analysis, we observed no significant differences in responses to polyIC or LPS between RhD-positive and -negative individuals. However, upon sex-specific analysis, we observed over 40 differentially expressed genes (DEGs) between RhD-positive (n = 384) and RhD-negative males (n = 75) after influenza virus stimulation. Interestingly these Rhesus-associated differences were not seen in females. Further investigation, using gene set enrichment analysis, revealed enhanced IFNγ signalling in RhD-negative males. This amplified IFNγ signalling axis may explain the increased viral resistance previously described in RhD-negative individuals.
Validation of accelerometry as a digital phenotyping measure of negative symptoms in schizophrenia
Authors: Strauss Gregory P. , Raugh Ian M. , Zhang Luyu , Luther Lauren , Chapman Hannah C. , Allen Daniel N. , Kirkpatrick Brian , Cohen Alex S. 
Published: April 2022

AbstractNegative symptoms are commonly assessed via clinical rating scales; however, these measures have several inherent limitations that impact validity and utility for their use in clinical trials. Objective digital phenotyping measures that overcome some of these limitations are now available. The current study evaluated the validity of accelerometry (ACL), a passive digital phenotyping method that involves collecting data on the presence, vigor, and variability of movement. Outpatients with schizophrenia (SZ: n = 50) and demographically matched healthy controls (CN: n = 70) had ACL continuously recorded from a smartphone and smartband for 6 days. Active digital phenotyping assessments, including surveys related to activity context, were also collected via 8 daily surveys throughout the 6 day period. SZ participants had lower scores on phone ACL variables reflecting vigor and variability of movement compared to CN. ACL variables demonstrated convergent validity as indicated by significant correlations with active digital phenotyping self-reports of time spent in goal-directed activities and clinical ratings of negative symptoms. The discriminant validity of ACL was demonstrated by low correlations with clinical rating scale measures of positive, disorganized, and total symptoms. Collectively, findings suggest that ACL is a valid objective measure of negative symptoms that may complement traditional approaches to assessing the construct using clinical rating scales.
Study on partial discharge characteristics of C6F12O mixed gas
Authors: Rao Xiajin , Li Dajian , Zhang Xiaoxing , Xia Xiaofei , Su Yi , Lu Yufeng , Peng Boya 
Published: April 2022

AbstractThe greenhouse effect of SF6 increasingly limits its application in various gas insulated equipment. C6F12O combines the advantages of insulation resistance, safety and environmental protection. When mixed with buffer gas, C6F12O is considered to have potential application prospects in medium and low voltage equipment. In this paper, about the partial discharge characteristics of the mixed gas, an experimental study was carried out. The partial discharge initiation voltage and discharge extinction voltage of mixed gas under power frequency voltage are measured and compared with the breakdown voltage. The results show that the breakdown voltage is greatly improved after adding C6F12O, with the increase of mixing ratio, the partial discharge initiation voltage and extinction voltage of mixed gas gradually increase, and the effect of gas pressure on high mixing ratio is obvious. The difference between the partial discharge inception voltage and the breakdown voltage is larger than that of pure N2. The research in this paper can provide an important reference for the application, operation and protection of C6F12O mixed gas in medium and low voltage equipment.
Misfolding-induced chronic pancreatitis in CPA1 N256K mutant mice is unaffected by global deletion of Ddit3/Chop
Authors: Németh Balázs Csaba , Demcsák Alexandra , Geisz Andrea , Sahin-Tóth Miklós 
Published: April 2022

AbstractGenetic mutations in pancreatic digestive enzymes may cause protein misfolding, endoplasmic reticulum (ER) stress and chronic pancreatitis. The CPA1 N256K mouse model carries the human p.N256K carboxypeptidase A1 (CPA1) mutation, a classic example of a pancreatitis-associated misfolding variant. CPA1 N256K mice develop spontaneous, progressive chronic pancreatitis with moderate acinar atrophy, acinar-to-ductal metaplasia, fibrosis, and macrophage infiltration. Upregulation of the ER-stress associated pro-apoptotic transcription factor Ddit3/Chop mRNA was observed in the pancreas of CPA1 N256K mice suggesting that acinar cell death might be mediated through this mechanism. Here, we crossed the CPA1 N256K strain with mice containing a global deletion of the Ddit3/Chop gene (Ddit3-KO mice) and evaluated the effect of DDIT3/CHOP deficiency on the course of chronic pancreatitis. Surprisingly, CPA1 N256K x Ddit3-KO mice developed chronic pancreatitis with a similar time course and features as the CPA1 N256K parent strain. In contrast, Ddit3-KO mice showed no pancreas pathology. The observations indicate that DDIT3/CHOP plays no significant role in the development of misfolding-induced chronic pancreatitis in CPA1 N256K mice and this transcription factor is not a viable target for therapeutic intervention in this disease.
Feasibility of circulating tumor DNA analysis in dogs with naturally occurring malignant and benign splenic lesions
Authors: Favaro Patricia Filippsen , Stewart Samuel D. , McDonald Bradon R. , Cawley Jacob , Contente-Cuomo Tania , Wong Shukmei , Hendricks William P. D. , Trent Jeffrey M. , Khanna Chand , Murtaza Muhammed 
Published: April 2022

AbstractComparative studies of naturally occurring canine cancers have provided new insight into many areas of cancer research. Development and validation of circulating tumor DNA (ctDNA) analysis in pet dogs can help address diagnostic needs in veterinary as well as human oncology. Dogs have high incidence of naturally occurring spontaneous cancers, demonstrate molecular heterogeneity and clonal evolution during therapy, allow serial sampling of blood from the same individuals during the course of disease progression, and have relatively compressed intervals for disease progression amenable to longitudinal studies. Here, we present a feasibility study of ctDNA analysis performed in 48 dogs including healthy dogs and dogs with either benign splenic lesions or malignant splenic tumors (hemangiosarcoma) using shallow whole genome sequencing (sWGS) of cell-free DNA. To enable detection and quantification of ctDNA using sWGS, we adapted two informatic approaches and compared their performance for the canine genome. At the time of initial clinical presentation, mean ctDNA fraction in dogs with malignant splenic tumors was 11.2%, significantly higher than dogs with benign lesions (3.2%; p = 0.001). ctDNA fraction was 14.3% and 9.0% in dogs with metastatic and localized disease, respectively (p = 0.227). In dogs treated with surgical resection of malignant tumors, mean ctDNA fraction decreased from 11.0% prior to resection to 7.9% post-resection (p = 0.047 for comparison of paired samples). Our results demonstrate that ctDNA analysis is feasible in dogs with hemangiosarcoma using a cost-effective approach such as sWGS. Additional studies are needed to validate these findings, and determine the role of ctDNA to assess burden of disease and treatment response in dogs with cancer.
An integrated systems-level model of ochratoxin A toxicity in the zebrafish (Danio rerio) embryo based on NMR metabolic profiling
Authors: Eeza Muhamed N. H. , Bashirova Narmin , Zuberi Zain , Matysik Jörg , Berry John P. , Alia A. 
Published: April 2022

AbstractOchratoxin A (OTA) is one of the most widespreadmycotoxincontaminants of agricultural crops. Despite being associated with a range of adverse health effects, a comprehensive systems-level mechanistic understanding of the toxicity of OTA remains elusive. In the present study, metabolic profiling by high-resolution magic angle spinning (HRMAS) NMR, coupled to intact zebrafish embryos, was employed to identify metabolic pathways in relation to a systems-level model of OTA toxicity. Embryotoxicity was observed at sub-micromolar exposure concentrations of OTA. Localization of OTA, based on intrinsic fluorescence, as well as a co-localization of increased reactive oxygen species production, was observed in the liver kidney, brain and intestine of embryos. Moreover, HRMAS NMR showed significant alteration of metabolites related to targeting of the liver (i.e., hepatotoxicity), and pathways associated with detoxification and oxidative stress, and mitochondrial energy metabolism. Based on metabolic profiles, and complementary assays, an integrated model of OTA toxicity is, thus, proposed. Our model suggests that OTA hepatotoxicity compromises detoxification and antioxidant pathways, leading to mitochondrial membrane dysfunction manifested by crosstalk between pathways of energy metabolism. Interestingly, our data additionally aligns with a possible role of mitochondrial fusion as a “passive mechanism” to rescue mitochondrial integrity during OTA toxicity.
Thermo-mechanical properties of 3D printed photocurable shape memory resin for clear aligners
Authors: Lee Se Yeon , Kim Hoon , Kim Hyun-Joong , Chung Chooryung J. , Choi Yoon Jeong , Kim Su-Jung , Cha Jung-Yul 
Published: April 2022

AbstractTo overcome the limitations of the conventional vacuum thermoforming manufacturing method, direct 3D printing of clear aligners has been developed. The present study investigated the thermo-mechanical and viscoelastic properties of a photocurable resin TC-85, which is a new material for the direct 3D printed clear aligners, comparing to a conventional thermoplastic material polyethylene terephthalate glycol. Dynamic mechanical analysis was performed to analyse the mechanical behaviours of the two materials at 37 °C and 80 °C, respectively. Furthermore, the shape memory property of the two materials was evaluated using a U-shape bending test, and the shape recovery ratio for 60 min at 37 °C was calculated. The results indicate that TC-85 can constantly apply a light force to the teeth when used for the 3D printed clear aligners, owing to its flexibility and viscoelastic properties. In addition, it is expected that the force decay induced by repeated insertion of the clear aligners will be reduced and a constant orthodontic force will be maintained. Furthermore, its geometric stability at high temperatures and the shape memory properties provide advantages for the clinical application.
Development of a paper printed colorimetric sensor based on Cu-Curcumin nanoparticles for evolving point-of-care clinical diagnosis of sodium
Authors: Chandran Neeli , Janardhanan Prajit , Bayal Manikanta , Pilankatta Rajendra , Nair Swapna S. 
Published: April 2022

AbstractThe homeostatic control of Sodium (Na+) ion in the human body assumes paramount relevance owing to its physiological importance. Any deviation from the normal level causes serious health problems like hypernatremia, hyponatremia, stroke, kidney problems etc. Therefore, quantification of Na+ levels in body fluids has significant diagnostic and prognostic importance. However, interfering ions like Potassium ion (K+) is the major hurdle in sodium detection. In this work, we synthesized the clusters of 3–9 nm-sized highly stable and pure Copper nanoparticles surface functionalised with curcumin, through chemical reduction method. Each cluster of particles is encapsulated in a curcumin layer which is clearly visible in TEM images. The results show that these curcumin functionalized Cu NPs (CuC) are highly selective to the colorimetric detection of Na+. The ions like K+, Mg2+ and Zn2+ did not interfere with the Na+ in this sensing technique. Low-cost paper-based sensor strips are fabricated and calibrated for the sensing of sodium in the physiological range and shade cards were developed as a calorimetric guide for estimation of Na+ which makes them ideal point of care diagnostic platform. We demonstrate that the proposed CuC paper strip can be used for detecting Na+ concentration within the whole physiological range in both blood serum and urine.