bluuebunny/crossref_metadata_2025_split huggingface dataset:
PCBP2 maintains antiviral signaling homeostasis by regulating cGAS enzymatic activity via antagonizing its condensation
Authors: Gu Haiyan , Yang Jing , Zhang Jiayu , Zhang Pengfei , Li Lin , Chen Dahua , Sun Qinmiao 
Published: January 2021

Abstract
Cyclic GMP-AMP synthase (cGAS) plays a major role in detecting pathogenic DNA. It produces cyclic dinucleotide cGAMP, which subsequently binds to the adaptor protein STING and further triggers antiviral innate immune responses. However, the molecular mechanisms regulating cGAS enzyme activity remain largely unknown. Here, we characterize the cGAS-interacting protein Poly(rC)-binding protein 2 (PCBP2), which plays an important role in controlling cGAS enzyme activity, thereby mediating appropriate cGAS-STING signaling transduction. We found that PCBP2 overexpression reduced cGAS-STING antiviral signaling, whereas loss of PCBP2 significantly increased cGAS activity. Mechanistically, we showed that PCBP2 negatively regulated anti-DNA viral signaling by specifically interacting with cGAS but not other components. Moreover, PCBP2 inhibited cGAS enzyme activity by antagonizing cGAS condensation, thus ensuring the normal production of cGAMP and balancing cGAS-STING signal transduction. Collectively, our findings provide novel insight into mechanisms regulating cGAS-mediated antiviral innate immune signaling.
Mutation analysis of the ATP7B gene and genotype-phenotype correlation in Chinese patients with Wilson disease
Authors: Li Mingming , Ma Jing , Wang Wenlong , Yang Xu , Luo Kaizhong 
Published: January 2021

Abstract
AIM To discover the novel ATP7B mutations in 103 southern Chinese patients with Wilson disease (WD), and to determine the spectrum and frequency of mutations in the ATP7B gene and genotype-phenotype correlation in a large-scale sample of Chinese WD patients. Methods One hundred three WD patients from 101 unrelated families in southern China were enrolled in this study. Genomic DNA was extracted from the peripheral blood. Direct sequencing of all 21 exons within ATP7B was performed. Subsequently, an extensive study of the overall spectrum and frequency of ATP7B mutations and genotype-phenotype correlation was performed in all Chinese patients eligible from the literature, combined with the current southern group.Results In 103 patients with WD, we identified 48 different mutations (42 missense mutations, 4 nonsense mutations and 2 frameshifts). Of these, 7 mutations had not been previously reported: 1510_1511insA, 2075T>C (Leu692Pro), 2233C>A (Leu745Met), 3209C>G (Pro1070Arg),3677C>T (Thr1226Ile), 3793G>T (Val1265Leu) and 3824T>C (Leu1275Ser). The 2333G>T (Arg778 Leu) at exon 8, was the most common mutation with an allelic frequency of 18.8%, followed by 2975C>T (Pro992Leu) at exon 13, with an allelic frequency of 13.4%. In the comprehensive study, 233 distinct mutations were identified, including 154 missense mutations, 23 nonsense mutations and 56 frameshifts. Eighty-five variants were identified as novel mutations. The 2333G>T (Arg778 Leu) and 2975C>T (Pro992Leu) were the most common mutations, with allelic frequencies of 28.6% and 13.0%, respectively. Exons 8, 12, 13, 16 and 18 were recognised as hot spot exons. Phenotype-genotype correlation analysis suggested that 2333G>T (Arg778 Leu) was significantly associated with lower levels of serum ceruloplasmin (P=0.034). 2975C>T (Pro992Leu) was correlated with earlier age of disease onset (P=0.002). Additionally, we found that the 3809A>G (Asn1270Ser) mutation significantly indicated younger onset age (P=0.012), and the 3884C>T (Ala1295Val) mutation at exon 18 was significantly associated with hepatic presentation (P=0.048). Moreover, the patients with mixed presentation displayed the initial WD features at an older onset age than the groups with either liver disease or neurological presentation (P=0.039, P=0.015, respectively). No significant difference was observed in the presence of KF rings among the three groups with different clinical manifestations. Conclusion In this study, we identified seven novel mutations in 103 WD patients from the southern part of China, which could enrich the previously established mutational spectrum of the ATP7B gene. Moreover, we tapped into a large-scale study of a Chinese WD cohort to characterise the overall phenotypic and genotypic spectra and assess the association between genotype and phenotype, which enhances the current knowledge about the population genetics of WD in China.
Evidence for New Enantiospecific Interaction Force in Chiral Biomolecules
Authors: Kapon Yael , Saha Abhijit , Duanias-Assaf Tal , Stuyver Thijs , Ziv Amir , Metzger Tzuriel , Yochelis Shira , Shaik Sason , Naaman Ron , Reches Meital , Paltiel Yossi 
Published: January 2021

Abstract
Enantiospecific biorecognition interactions are key to many biological events. Commonly, bio-affinity values, measured in these processes, are higher than those calculated by available methods. We report here the first direct measurement of the interaction force between right and left handed helical polyalanine peptides using atomic force microscope (AFM) and calculations based on a simple theoretical model. A force difference of 60pN between same and opposite enantiomer interactions is measured. Additional measurements show spin dependency and fast decay of the interaction term, consistent with spin exchange interactions. This short range enantiospecific interaction term is especially relevant in crowded biological systems. The results shed light on the importance of spin and exchange interactions in biological processes, providing explanation to the discrepancies between past calculations and experiments.
Dentistry Faculty Members’ Lived Experiences of Obstacles in Institutionalizing Performance Assessments to Implement Professional Competency-Based Evaluation: A Qualitative Study
Authors: Bilan Nemat , Moghaddam Saeid Foroughi , Hazrati Hakimeh , Negahdari Ramin 
Published: January 2021

Abstract
Background Evaluation is one of the main components of the learning and teaching process, which indicates the achievement rate of educational goals and also quality of education. The objective of this study was to evaluate dentistry faculty members’ lived experiences of obstacles in institutionalizing performance assessments to implement professional competency-based evaluation as a qualitative study.Methods This study was conducted with a qualitative approach by using a semi-structured interview in a focus group discussion, in which the experiences of clinical dentistry faculty members regarding obstacles of using performance assessments and faculty members’ approaches to conducting professional competency-based evaluation were analyzed. The participants of the study were faculty members of the dentistry and medical education faculties. The purposive sampling technique was used and continued until reaching saturation. Five focus group discussions were conducted with 14 dentistry faculty members and three medical education faculty members. The data was analyzed by using thematic analysis.Results Analysis of interviews yielded 450 codes which were placed in three general categories of “current condition of clinical education”, “obstacles of implementing new evaluation methods”, and “requirements for effective evaluation of clinical skills”.Conclusions Based on the analysis of dentistry faculty members’ responses, creating changes by the faculty members appeared to be necessary. They are in fact moving towards creating changes in traditional evaluation methods. This change of paradigm requires support from the department and provision of infrastructures is deemed necessary. Also, in order to enhance motivation, spiritual support of the active faculty members should be taken into consideration and educational innovation should find its place in the promotion of faculty members.
Dual targeting of FGFR3 and the ERBB receptor family or AXL enhances the efficacy of FGFR inhibitors in FGFR3 fusion-driven bladder cancer
Authors: Lau David , Hodgson-Garms Margeaux , Lavis Austen , Luk Ian , Jenkins Laura , Vukelic Natalia , Ioannidis Paul , Mariadason John , Weickhardt Andrew 
Published: January 2021

Abstract
BackgroundMutations and fusions in Fibroblast Growth Factor Receptor 3 (FGFR3) occur in 10-20% of metastatic urothelial carcinomas, and can confer sensitivity to FGFR inhibitors such as BGJ398 and erdafitinib. However, responses to these agents are often short-lived due to the development of acquired resistance. The objective of this study was to identify mechanisms of acquired resistance to FGFR inhibitors in two previously uncharacterized bladder cancer cell lines harbouring FGFR3 fusions, and assess rational combination therapies to enhance their activity. MethodsAcquired resistance to FGFR inhibitors was generated in two FGFR3 fusion harbouring cell lines, SW780 (FGFR3-BAIAP2L1 fusion) and RT4 (FGFR3-TACC3 fusion), by either long-term exposure to increasing concentrations of BGJ398 or sustained exposure to high concentrations of drug. Alterations in levels of key cell signalling regulators was assessed in resistant lines by phospho-RTK arrays and immunoblotting. Synergy between BGJ398 and alternate targeted therapies was explored using cell viability and apoptosis assays.ResultsAcquired resistance to BGJ398 in SW780 and RT4 cells was associated with increased expression of members of ERBB family of receptor tyrosine kinases and pAXL. Combination treatment of resistant cells with an FGFR inhibitor and either a pan-ERBB or an AXL inhibitor overcame this resistance. We also noted rapid reactivation of pERK in parental FGFR3 fusion-driven lines within 4-72 hours of BGJ398 treatment, with concomitant increase in pERBB3. Up-front combination treatment with BGJ398 and the pan-ERBB inhibitor AZD8931 delayed the reactivation of pERK, and induced a synergistic inhibition of cell viability and a concomitant increase in apoptosis.ConclusionsWe identify increased activation of AXL and ERBB family receptors as mechanisms of resistance to FGFR inhibition. Our findings suggest that upfront combination treatment with FGFR and pan-ERBB inhibitors warrants further investigation for FGFR3-fusion harbouring bladder cancers.
Tropical Drivers of Interannual Vegetation Variability in Eastern Africa
Authors: Kim In-Won , Stuecker Malte , Timmermann Axel , Kug Jong-Seong , Park So-Won , Kim Jin-Soo 
Published: January 2021

Abstract
Mechanisms by which tropical Pacific and Indian Ocean sea surface temperatures influence vegetation in Eastern Africa and which role drought-induced fires play have not been fully explored. Here, we use a suite of idealized Earth system model simulations to elucidate the governing processes for eastern African interannual vegetation changes. Our analysis focuses on Tanzania. In the absence of ENSO-induced sea surface temperature (SST) anomalies in the Tropical Indian Ocean (TIO), El Niño causes during its peak phase negative precipitation anomalies over Tanzania due to a weakening of the tropical-wide Walker circulation and anomalous descending motion over the Indian Ocean and southeastern Africa. Resulting drought conditions increase the occurrence of wildfires, which leads to a marked decrease in vegetation cover. Subsequent wetter La Niña conditions in boreal winter reverse the trend in vegetation, causing a gradual 1-year-long recovery phase. The 2-year-long vegetation response in Tanzania can be explained as a double-integration of the local rainfall anomalies, which originate from the seasonally-modulated ENSO Pacific-SST forcing (Combination mode). In the presence of interannual TIO SST forcing, the southeast African precipitation and vegetation responses to ENSO are muted due to Indian Ocean warming and the resulting anomalous upward motion in the atmosphere.
On-field Phenotypic Evaluation of Sunflower Germplasm: Breeding for Broad-spectrum Resistance to Verticillium Leaf Mottle and Wilt
Authors: Montecchia Juan , Fass Mónica , Cerrudo Ignacio , Quiroz Facundo , Nicosia Salvador , Maringolo Carla , Rienzo Julio Di , Troglia Carolina , Hopp H. , Escande Alberto , González Julio , Álvarez Daniel , Heinz Ruth , Lia Verónica , Paniego Norma 
Published: January 2021

Abstract
Sunflower Verticillium Wilt and Leaf Mottle (SVW), caused by Verticillium dahliae (Kleb.; Vd), is a soil-borne disease affecting sunflower worldwide. A single dominant locus, known as V1, was formerly effective in controlling North-American Vd races, whereas races from Argentina, Europe and an emerging race from USA overcome its resistance. This emphasizes the need for identifying broad-spectrum genetic resistance (BSR) sources. Here we characterize two sunflower Mapping Populations (MPs) for SVW resistance: a biparental MP and the association MP from the National Institute of Agricultural Technology (INTA), under field growing conditions. Nine field-trials (FTs) were conducted in highly infested fields in the most SVW-affected region of Argentina. Several disease descriptors (DDs), including incidence and severity, were scored across four phenological stages. Generalized linear models were fitted according to the nature of each variable, adjusting mean phenotypes for inbred lines (IL) across and within FTs. Comparison of these responses allowed the identification of novel BSR sources. Furthermore, we present the first report of SVW resistance heritability, with estimates ranging from 35% to 45% for DDs related to disease incidence and severity, respectively. This study constitutes the largest SVW resistance characterization reported to date in sunflower, identifying valuable genetic resources for BSR-breeding to cope with a pathogen of increasing importance worldwide.
Alterations in Lipid Profile Upon Uterine Fibroids and Its Recurrence
Authors: Tonoyan Narine , Chagovets Vitaliy , Starodubtseva Natalia , Tokareva Alisa , Chingin Konstantin , Kozachenko Irena , Adamyan Leyla , Frankevich Vladimir 
Published: January 2021

Abstract
Background. Uterine fibroids (UF) is the most common (about 70% cases) type of gynecological disease, with the recurrence rate varying from 11% to 40%. Because UF has no distinct symptomatology and is often asymptomatic, the specific and sensitive diagnosis of UF as well as the assessment for the probability of UF recurrence pose considerable challenge.Aim. The aim of this study was to characterize alterations in the lipid profile of tissues associated with the first-time diagnosed UF and recurrent uterine fibroids (RUF) and to explore the potential of mass spectrometry (MS) lipidomics analysis of blood plasma samples for the sensitive and specific determination of UF and RUF with low invasiveness of analysis.Materials and methods. MS analysis of lipid levels in the myometrium tissues, fibroids tissues and blood plasma samples was carried out on 66 patients, including35 patients with first-time diagnosed UF and 31 patients with RUF. The control group consisted of 15 patients who underwent surgical treatment for the intrauterine septum. Fibroids and myometrium tissue samples were analyzed using direct MS approach. Blood plasma samples were analyzed using high performance liquid chromatography hyphened with mass spectrometry (HPLC/MS). MS data were processed by discriminant analysis with projection into latent structures (OPLS-DA).Results. Significant differences were found between the first-time UF, RUF and control group in the levels of lipids involved in the metabolism of glycerophospholipids, sphingolipids, lipids with an ether bond, triglycerides and fatty acids. Significant differences between the control group and the groups with UF and RUF were found in the blood plasma levels of cholesterol esters, triacylglycerols, (lyso) phosphatidylcholines and sphingomyelins. Significant differences between the UF and RUF groups were found in the blood plasma levels of cholesterol esters, phosphotidylcholines, sphingomyelins and triacylglycerols. Diagnostic models based on the selected differential lipids using logistic regression showed sensitivity and specificity of 88% and 86% for the diagnosis of first-time UF and 95% and 79% for RUF, accordingly.Conclusion. This study confirms the involvement of lipids in the pathogenesis of uterine fibroids. A diagnostically significant panel of differential lipid species has been identified for the diagnosis of UF and RUF by low-invasive blood plasma analysis. The developed diagnostic models demonstrated high potential for clinical use and further research in this direction.
Tinnitus Assessment : Chinese Version of Tinnitus Primary Function Questionnaire
Authors: XIN YING , Tyler Richard , Yao Zi-ming , Zhou Na , Tao Li-yuan , Ma Fu-rong , Pan Tao 
Published: January 2021

Abstract
OBJECTIVE: The aim of the study was to evaluate the Chinese version of Tinnitus Primary Function Questionnaire (TPFQ).DESIGN: Tinnitus patients were administered the TPFQ, the Tinnitus Handi­cap Inventory (THI), the Beck Anxiety Inventory (BAI), the Beck Depression Inventory (BDI), and the Pittsburgh Sleep Quality Index (PSQI). Additionally, the magnitude estimate of tinnitus loudness, pure tone audiogram and tinnitus matching were obtained. The factor structure was measured by Kaiser-Meyer-Olkin. The internal consistency was examined using Cron­bach coefficient alpha. The relationships between the TPFQ scores and other measurements were compared with Spearman rank correlation coefficient.STUDY SAMPLE：116 patients whose tinnitus lasting longer than 3 months were included in this study.RESULTS: The Cronbach’s α of the 20-item version TPFQ was 0.94, and the 12-item version TPFQ was 0.92. Both the 20-item and 12-item version TPFQ were significantly correlated with magnitude estimation of tinnitus loudness, THI, PSQI, BDI and BAI. The average pure tone hearing thresholds were significantly correlated with the hearing subscale. CONCLUSIONS: The 20-item and 12-item versions of Chinese TPFQ are a reliable and valid measures of tinnitus. The TPFQ can be used in the assessment and management of tinnitus among the Chinese speaking population.
Association of TLR2&nbsp;Haplotypes Encoding Q650 With Reduced Susceptibility to Ovine Johne’s Disease in Turkish Sheep
Authors: YAMAN Yalçın , AYMAZ Ramazan , KELEŞ Murat , BAY Veysel , ÜN Cemal , HEATON Michael P 
Published: January 2021

Abstract
Ovine Johne’s disease (OJD) is caused by Mycobacterium avium subsp. paratuberculosis (MAP) and carries a potential zoonotic risk for humans. Selective breeding strategies for reduced OJD susceptibility would be welcome tools in disease eradication efforts, if available. The Toll-like receptor 2 gene (TLR2) plays an important signaling role in immune response to MAP, and missense variants are associated with mycobacterial infections in mammals. Our aim was to identify and evaluate ovine TLR2 missense variants for association with OJD in Turkish sheep. Eleven TLR2 missense variants and 17 haplotype configurations were identified in genomic sequences of 221 sheep from 61 globally-distributed breeds. The five most frequent haplotypes were tested for OJD association in 102 matched pairs of infected and uninfected ewes identified in 2257 Turkish sheep. Ewes with one or two copies of TLR2 haplotypes encoding glutamine (Q) at position 650 (Q650) in the Tir domain were 6.6-fold more likely to be uninfected compared to ewes with arginine (R650) at that position (CI95 = 2.6 to 16.9, p-value = 3.7x10-6). The protective TLR2 Q650 allele was present in at least 25% of breeds tested and thus may facilitate selective breeding for sheep with reduced susceptibility to OJD.
Which Fracture Pattern Characteristics of Partial Articular Radial Head Fractures Are Associated With Concomitant Injuries of Elbow?
Authors: Zhu Jian , Deng Xiangtian , Cheng Xiaodong , Tan Zhanchao , Hu Hongzhi , Zhang Yingze 
Published: January 2021

Abstract
Background: Radial head fractures are the most common fractures around the elbow and about one third of patients have associated injuries. Identification of these injuries is important, because they often dictate the treatment. While it is not clear whether the fracture pattern characteristics of radial head were correlated with associated injuries. The aim of this study was to identify whether the fracture pattern characteristics of partial articular radial head fractures are correlated with associated elbow injuries.Methods: Patients who had a partial articular radial head fracture from 2015-2019 were retrospective analyzed. A three-dimension radial head model was created with MIMICS software to accurately measure the fracture pattern characteristics, including the size, the arc, and the location of the fragment as well as fracture comminution status and fracture fragment separation. Information of age, gender, side and associated injuries was extracted from clinical data. The patients with and without associated elbow injuries were compared. The multivariant logistic regression was used to examine the correlation between fracture pattern characteristics and associated injuries.Results: Of the 70 patients with partial articular radial head fractures, 41 had concomitant elbow injuries. Significant differences were not found in age，gender as well as affected side and articular surface involved. Patients with associated elbow injuries were more likely to have large fragment located in anteromedial quadrant and large arc of fracture fragment. In addition, they also had more frequently to have comminuted fracture pattern and separated fragments. However, in the multiple logistic regression analysis, large fragment located in anteromedial quadrant, comminuted fracture pattern and separated fragments remained significantly associated.Conclusions: The present study showed a large fragment located in anteromedial quadrant, comminuted fracture pattern and separated fragments are independent risk factors for elbow associated injury after radial head fractures.