bluuebunny/crossref_metadata_2025_split huggingface dataset:
A kinome-wide screen identifies a CDKL5-SOX9 regulatory axis in epithelial cell death and kidney injury
Authors: Kim Ji Young , Bai Yuntao , Jayne Laura A. , Hector Ralph D. , Persaud Avinash K. , Ong Su Sien , Rojesh Shreshtha , Raj Radhika , Feng Mei Ji He Ho , Chung Sangwoon , Cianciolo Rachel E. , Christman John W. , Campbell Moray J. , Gardner David S. , Baker Sharyn D. , Sparreboom Alex , Govindarajan Rajgopal , Singh Harpreet , Chen Taosheng , Poi Ming , Susztak Katalin , Cobb Stuart R. , Pabla Navjot Singh 
Published: April 2020

AbstractRenal tubular epithelial cells (RTECs) perform the essential function of maintaining the constancy of body fluid composition and volume. Toxic, inflammatory, or hypoxic-insults to RTECs can cause systemic fluid imbalance, electrolyte abnormalities and metabolic waste accumulation- manifesting as acute kidney injury (AKI), a common disorder associated with adverse long-term sequelae and high mortality. Here we report the results of a kinome-wide RNAi screen for cellular pathways involved in AKI-associated RTEC-dysfunction and cell death. Our screen and validation studies reveal an essential role of Cdkl5-kinase in RTEC cell death. In mouse models, genetic or pharmacological Cdkl5 inhibition mitigates nephrotoxic and ischemia-associated AKI. We propose that Cdkl5 is a stress-responsive kinase that promotes renal injury in part through phosphorylation-dependent suppression of pro-survival transcription regulator Sox9. These findings reveal a surprising non-neuronal function of Cdkl5, identify a pathogenic Cdkl5-Sox9 axis in epithelial cell-death, and support CDKL5 antagonism as a therapeutic approach for AKI.
Genomic release-recapture experiment in the wild reveals within-generation polygenic selection in stickleback fish
Authors: Laurentino Telma G. , Moser Dario , Roesti Marius , Ammann Matthias , Frey Anja , Ronco Fabrizia , Kueng Benjamin , Berner Daniel 
Published: April 2020

AbstractHow rapidly natural selection sorts genome-wide standing genetic variation during adaptation remains largely unstudied experimentally. Here, we present a genomic release-recapture experiment using paired threespine stickleback fish populations adapted to selectively different lake and stream habitats. First, we use pooled whole-genome sequence data from the original populations to identify hundreds of candidate genome regions likely under divergent selection between these habitats. Next, we generate F2 hybrids from the same lake-stream population pair in the laboratory and release thousands of juveniles into a natural stream habitat. Comparing the individuals surviving one year of stream selection to a reference sample of F2 hybrids allows us to detect frequency shifts across the candidate regions toward the genetic variants typical of the stream population—an experimental outcome consistent with polygenic directional selection. Our study reveals that adaptation in nature can be detected as a genome-wide signal over just a single generation.
Similar prevalence of hepatic steatosis among patients with chronic hepatitis C with and without HIV coinfection
Authors: Fernandez-Fuertes M. , Macías J. , Corma-Gómez A. , Rincón P. , Merchante N. , Gómez-Mateos J. , Pineda J. A. , Real L. M. 
Published: April 2020

AbstractHepatic steatosis (HS) is frequently observed in HIV-infected patients. It is not known whether HIV infection is an independent risk factor for HS development. We aimed to analyze whether HIV coinfection was associated with a higher frequency of HS in patients with chronic hepatitis C. This was a retrospective cross-sectional study. 574 subjects with chronic hepatitis C virus (HCV) infection were included, 246 (43%) of them coinfected with HIV. All of them underwent transient elastography with controlled attenuation parameter (CAP) measurement. HS was defined as CAP ≥ 248 dB/m. 147 individuals (45%) showed HS in the HCV-monoinfected group and 100 (40.7%) in the HIV/HCV-coinfected group (p = 0.318). HS was associated with body mass index (BMI) [<25 Kg/m2 vs. ≥25 Kg/m2, 67 (23.5%) vs. 171 (62.9%); p = 0.001], with plasma HDL-cholesterol [<50 mg/dL vs. ≥50 mg/dL, 122 (48.6%) vs. 95 (37.5%), p = 0.012], with plasma triglycerides [<150 mg/dL vs. ≥150 mg/dL, 168 (40.2%) vs. 65 (52.4%); p = 0.016] and with plasma total cholesterol [<200 mg/dL vs. ≥200 mg/dL, 181 (41%) vs. 53 (52.5%); p = 0.035]. In the multivariate analysis, HS was associated with BMI [adjusted OR (AOR) = 1.264 (1.194–1.339); p = 0.001], age [AOR = 1.029 (1.001–1.058); p = 0.047] and HCV genotype 3 infection [AOR = 1.901 (1.081–2.594); p = 0.026]. HIV coinfection was not associated with HS [AOR = 1.166 (0.719–1.892); p = 0.534]. In conclusion, HIV coinfection is not related with an increased frequency of HS in HCV-infected patients.
Splice modulating antisense oligonucleotides restore some acid-alpha-glucosidase activity in cells derived from patients with late-onset Pompe disease
Authors: Aung-Htut May Thandar , Ham Kristin A. , Tchan Michel , Johnsen Russell , Schnell Frederick J. , Fletcher Sue , Wilton Steve D. 
Published: April 2020

AbstractPompe disease is caused by mutations in the GAA gene, resulting in deficient lysosomal acid-α-glucosidase activity in patients, and a progressive decline in mobility and respiratory function. Enzyme replacement therapy is one therapeutic option, but since not all patients respond to this treatment, alternative interventions should be considered. One GAA mutation, c.-32-13T > G, impacts upon normal exon 2 splicing and is found in two-thirds of late-onset cases. We and others have explored a therapeutic strategy using splice modulating phosphorodiamidate morpholino oligomers to enhance GAA exon 2 inclusion in the mature mRNA of patients with one c.-32-13T > G allele. We designed 20 oligomers and treated fibroblasts derived from five patients to identify an oligomer sequence that maximally increased enzyme activity in all fibroblasts. The most effective splice correcting oligomer was chosen to treat forced-myogenic cells, derived from fibroblasts from nine patients carrying the c.-32-13T > G mutation. After transfection, we show increased levels of the full-length GAA transcript, acid-α-glucosidase protein, and enzyme activity in all patients’ myogenic cells, regardless of the nature of the mutation in the other allele. This data encourages the initiation of clinical trials to assess the therapeutic efficacy of this oligomer for those patients carrying the c.-32-13T > G mutation.
Long-term Changes of Temporomandibular Joint Osteoarthritis on Computed Tomography
Authors: Song Hwanhee , Lee Jeong Yun , Huh Kyung-Hoe , Park Ji Woon 
Published: April 2020

AbstractThis study aimed to understand long-term changes of the osteoarthritic temporomandibular joint (TMJ) condyle using computed tomography (CT) and to verify its correlation with clinical characteristics of temporomandibular disorders. Eighty-nine patients (152 joints; 76 female, 13 male) who had taken follow-up CTs (mean follow-up period: 644.58 ± 325.71 days) at least once in addition to their initial evaluation were selected. Cross-sectional demographic and clinical data and longitudinal CT images were collected. Data were analyzed by analysis of variance and logistic regression. Overall destructive change index (number of TMJ condyle sections in which destructive change was observed) decreased from 1.56 to 0.66. Improvement was seen in 93 joints (61.2%) and 27 joints (17.8%) worsened. In the pain positive group, both initial and final destructive change index were significantly higher compared to the pain negative group (p = 0.04). Occlusal stabilization splint therapy and nonsteroidal anti-inflammatory drug administration showed a significant effect on improving the prognosis of TMJ osteoarthritis (p = 0.015 and 0.011). In conclusion, TMJ osteoarthritis showed long-term improvement in the majority of cases. TMJ osteoarthritis accompanied by pain showed unfavorable prognosis with additional bone destruction. Occlusal stabilization splint and nonsteroidal anti-inflammatory drug administration were beneficial on the prognosis of TMJ osteoarthritis.
Platelet-rich plasma enhances the repair capacity of muscle-derived mesenchymal stem cells to large humeral bone defect in rabbits
Authors: Yin Nuo , Wang Yifei , Ding Liang , Yuan Junjie , Du Li , Zhu Zhongsheng , Pan Mingmang , Xue Feng , Xiao Haijun 
Published: April 2020

AbstractMesenchymal stem cell-based therapy is a highly attractive strategy that promotes bone tissue regeneration. The aim of the present study was to evaluate the combination effect of muscle-derived mesenchymal stem cells (M-MSCs) and platelet-rich plasma (PRP) on bone repair capacity in rabbits with large humeral bone defect. Precise cylindrical bone defects of 10 mm diameter and 5 mm depth were established in rabbit humeral bones, which were unable to be repaired under natural conditions. The rabbits received treatment with M-MSCs/PRP gel, M-MSCs gel, or PRP gel, or no treatment. The bone tissue regeneration was evaluated at day 0–90 after surgery by HE morphological staining, Lane-Sandhu histopathological scoring, tetracycline detection, Gomori staining and micro-computed tomography. Beyond that, Transwell assay, CCK8 assay, Western blot analysis and ALP activity detection were performed in M-MSCs in vitro with or without PRP application to detect the molecular effects of PRP on M-MSCs. We found that the repair effect of M-MSCs group or PRP group was limited and the bone defects were not completely closed at post-operation 90 d. In contrast, M-MSCs/PRP group received obvious filling in the bone defects with a Lane-Sandhu evaluation score of 9. Tetracycline-labeled new bone area in M-MSCs/PRP group and new mineralized bone area were significantly larger than that in other groups. Micro-computed tomography result of M-MSCs/PRP group displayed complete recovery of humeral bone at post-operation 90 d. Further in vitro experiment revealed that PRP significantly induced migration, enhanced the growth, and promoted the expression of Cbfa-1 and Coll I in M-MSCs. In conclusion, PRP application significantly enhanced the regeneration capacity of M-MSCs in large bone defect via promoting the migration and proliferation of M-MSCs, and also inducing the osteogenic differentiation.
Application of a convolutional neural network for predicting the occurrence of ventricular tachyarrhythmia using heart rate variability features
Authors: Taye Getu Tadele , Hwang Han-Jeong , Lim Ki Moo 
Published: April 2020

AbstractPredicting the occurrence of ventricular tachyarrhythmia (VTA) in advance is a matter of utmost importance for saving the lives of cardiac arrhythmia patients. Machine learning algorithms have been used to predict the occurrence of imminent VTA. In this study, we used a one-dimensional convolutional neural network (1-D CNN) to extract features from heart rate variability (HRV), thereby to predict the onset of VTA. We also compared the prediction performance of our CNN with other machine leaning (ML) algorithms such as an artificial neural network (ANN), a support vector machine (SVM), and a k-nearest neighbor (KNN), which used 11 HRV features extracted using traditional methods. The proposed CNN achieved relatively higher prediction accuracy of 84.6%, while the ANN, SVM, and KNN algorithms obtained prediction accuracies of 73.5%, 67.9%, and 65.9% using 11 HRV features, respectively. Our result showed that the proposed 1-D CNN could improve VTA prediction accuracy by integrating the data cleaning, preprocessing, feature extraction, and prediction.
Undifferentiated-type predominant mixed-type early gastric cancer is a significant risk factor for requiring additional surgeries after endoscopic submucosal dissection
Authors: Horiuchi Yusuke , Fujisaki Junko , Yamamoto Noriko , Ishizuka Naoki , Ishiyama Akiyoshi , Yoshio Toshiyuki , Hirasawa Toshiaki , Yamamoto Yorimasa , Nagahama Masatsugu , Takahashi Hiroshi , Tsuchida Tomohiro 
Published: April 2020

AbstractWe aimed to clarify the differences in therapeutic outcomes of patients with pure undifferentiated-type and mixed undifferentiated-type cancers who underwent endoscopic submucosal dissection (ESD), and whether pre-treatment diagnosis of mixed undifferentiated-type cancer is associated with requiring additional surgery after ESD. Patients subjected to ESD as initial treatment between May 2005 and March 2017 were enrolled. There were 277 undifferentiated-type cancers (265 patients). Histologically, 258 lesions were pure-type and 19 were mixed-type. We compared therapeutic outcomes and pre-treatment factors (tumour diameter, tumour depth, ulcerative findings, tumour location, and the macroscopic, and histological type of the biopsy specimen) between pure-type and mixed-type lesions, and between cases not requiring additional surgeries and cases requiring additional surgeries. Tumour diameter >20 mm, submucosal invasion, and the presence of ulcerative findings made pre-treatment diagnosis more difficult for mixed-type than for pure-type lesions. In cases requiring additional surgery, pre-treatment diagnosis of mixed-type lesions was significantly more likely than pre-treatment diagnosis of pure-type lesions. For mixed-type lesions, pre-treatment histological diagnosis and careful consideration are necessary to determine indications for ESD to avoid additional surgery after ESD.
Single-molecule long-read sequencing of the full-length transcriptome of Rhododendron lapponicum L.
Authors: Jia Xinping , Tang Ling , Mei Xueying , Liu Huazhou , Luo Hairong , Deng Yanming , Su Jiale 
Published: April 2020

AbstractRhododendron lapponicum L. is a familiar ornamental plant worldwide with important ornamental and economic value. However, a full-length R. lapponicum transcriptome is still lacking. In the present study, we used the Pacific Biosciences single-molecule real-time sequencing technology to generate the R. lapponicum transcriptome. A total of 346,270 full-length non-chimeric reads were generated, from which we obtained 75,002 high-quality full-length transcripts. We identified 55,255 complete open reading frames, 7,140 alternative splicing events and 2,011 long non-coding RNAs. In gene annotation analyses, 71,155, 33,653, 30,359 and 31,749 transcripts were assigned to the Nr, GO, COG and KEGG databases, respectively. Additionally, 3,150 transcription factors were detected. KEGG pathway analysis showed that 96 transcripts were identified coding for the enzymes associated with anthocyanin synthesis. Furthermore, we identified 64,327 simple sequence repeats from 45,319 sequences, and 150 pairs of primers were randomly selected to develop SSR markers. This study provides a large number of full-length transcripts, which will facilitate the further study of the genetics of R. lapponicum.
Effects of Combined Acid-alkali and Heat Treatment on the Physiochemical Structure of Moso Bamboo
Authors: Gao Jingjing , Qu Lijie , Qian Jing , Wang Zhenyu , Li Yajing , Yi Songlin , He Zhengbin 
Published: April 2020

AbstractTo improve the performance of bamboo and increase its utilization value, this study aimed at investigating the effects of impregnation pretreatment and thermal treatment on the structural changes of bamboo. The samples were pretreated in sodium hydroxide or zinc chloride solution, and then treated at 160 °C. The pretreated and control samples were characterized by X-ray diffraction (XRD), thermogravimetric analysis (TG), and Fourier transform infrared spectroscopy (FTIR). The results showed that the cellulose crystallinity and intensity of samples pretreated by ZnCl2 could be reduced, but the crystal structure remained the same. As for samples pretreated in NaOH, the crystal structure of fiber was destroyed and the crystallinity was increased significantly. High temperature treatment has little effect on the thermal stability of bamboo. However, after treatment with NaOH and ZnCl2, the thermal degradation temperature changed obviously and moved to a lower temperature. ZnCl2 pretreatment had influence on the chemical structure of bamboo, while NaOH pretreatment had greater influence on the chemical structure of bamboo.
Chytrid fungi distribution and co-occurrence with diatoms correlate with sea ice melt in the Arctic Ocean
Authors: Kilias Estelle S. , Junges Leandro , Šupraha Luka , Leonard Guy , Metfies Katja , Richards Thomas A. 
Published: April 2020

AbstractGlobal warming is rapidly altering physicochemical attributes of Arctic waters. These changes are predicted to alter microbial networks, potentially perturbing wider community functions including parasite infections and saprotrophic recycling of biogeochemical compounds. Specifically, the interaction between autotrophic phytoplankton and heterotrophic fungi e.g. chytrids (fungi with swimming tails) requires further analysis. Here, we investigate the diversity and distribution patterns of fungi in relation to abiotic variables during one record sea ice minimum in 2012 and explore co-occurrence of chytrids with diatoms, key primary producers in these changing environments. We show that chytrid fungi are primarily encountered at sites influenced by sea ice melt. Furthermore, chytrid representation positively correlates with sea ice-associated diatoms such as Fragilariopsis or Nitzschia. Our findings identify a potential future scenario where chytrid representation within these communities increases as a consequence of ice retreat, further altering community structure through perturbation of parasitic or saprotrophic interaction networks.
Hydrogen gas represses the progression of lung cancer via down-regulating CD47
Authors: Meng Jinghong , Liu Leyuan , Wang Dongchang , Yan Zhenfeng , Chen Gang 
Published: April 2020

Abstract
Hydrogen gas (H2) has been identified to play an anti-tumor role in several kinds of cancers, but the molecular mechanisms remain largely unknown. In our previous study, our project group found that H2 could decrease the expression of CD47 in lung cancer A549 cells via the next-generation sequencing, indicating that CD47 might be involved in H2-mediated lung cancer repression. Therefore, the present study aimed to explore the effects of CD47 on H2-induced lung cancer repression. Western blotting and real-time PCR (RT-PCR) assays were used to detect the levels of proteins and mRNAs, respectively. Cell proliferation, invasion, migration and apoptosis were detected by using the cell counting kit-8 (CCK-8), Transwell chambers, wound healing and flow cytometry assays, respectively. The results showed that H2 treatment caused decreases in the expression levels of CD47 and cell division control protein 42 (CDC42) in a dose-dependent manner. Up-regulation of CD47 abolished H2 roles in promoting lung cancer cell apoptosis and repressing cell growth, invasion and migration in both A549 and H1975 cell lines. However, knockdown of CD47 enhanced H2 role in lung cancer inhibition. Moreover, we also observed that H2 treatment induced obvious inhibitions in the expression levels of CDC42 and CD47 in mice tumor tissues, as well as reinforced macrophage-mediated phagocytosis in A549 and H1975 cells. In conclusion, the current study reveals that H2 inhibits the progression of lung cancer via down-regulating CD47, which might be a potent method for lung cancer treatment.
VCAM-1-targeted and PPARδ-agonist-loaded nanomicelles enhanced suppressing effects on apoptosis and migration of oxidized low-density lipoprotein-induced vascular smooth muscle cells
Authors: Wei Gang , Hao Liangang , Li Xueli , Xu Wen , Liu Fuxiang , Peng Qian , Lv Shoutian 
Published: April 2020

Abstract
Purpose: Nanomicelles (NMs) have been widely used for various biomedical applications due to its unique physiochemical properties. The present study aims to investigate the effects of vascular cell adhesion molecule-1 (VCAM-1)-targeted and peroxisome proliferator-activated receptor δ (PPARδ) agonist (GW0742)-loaded NMs on apoptosis and migration in oxidized low-density lipoprotein (ox-LDL)-induced human aortic vascular smooth muscle cells (HAVSMCs).
Methods: The GW0742-loaded NMs (M-GW) and VCAM-1-targeted NMs loaded with GW0742 (TM-GW) were prepared, and then the morphologies and the size distribution of M-GM and TM-GM were observed by transmission electron microscopy (TEM) and dynamic light scattering (DLS), respectively. In vitro drug release assay of M-GM and TM-GM were performed as well. Next, HAVSMCs were cultured in medium containing ox-LDL to mimic atherosclerotic environment, and the effects of free GW0742, M-GM and TM-GM on endocytosis, cell migration and apoptosis, as well as the expression of VCAM-1, and proteins associated with migration and apoptosis were measured in HAVSMCs treated with ox-LDL.
Results: M-GM and TM-GM were successfully prepared. VCAM-1 was overexpressed in HAVSMCs treated with ox-LDL, and TM-GM had a strong targeting ability to HAVSMCs treated with ox-LDL compared with M-GM. In addition, compared with free GW0742, both M-GM and TM-GM significantly diminished cell apoptosis and migration in HAVSMCs treated with ox-LDL.
Conclusions: TM-GM had a superior suppressing effect on apoptosis and migration of ox-LDL-induced HAVSMCs.
Identification of PCNA-interacting protein motifs in human DNA polymerase δ
Authors: Khandagale Prashant , Thakur Shweta , Acharya Narottam 
Published: April 2020

Abstract
DNA polymerase δ (Polδ) is a highly processive essential replicative DNA polymerase. In humans, the Polδ holoenzyme consists of p125, p50, p68 and p12 subunits and recently, we showed that the p12 subunit exists as a dimer. Extensive biochemical studies suggest that all the subunits of Polδ interact with the processivity factor proliferating cell nuclear antigen (PCNA) to carry out a pivotal role in genomic DNA replication. While PCNA-interacting protein motif (PIP) motifs in p68, p50 and p12 have been mapped, same in p125, the catalytic subunit of the holoenzyme, remains elusive. Therefore, in the present study by using multiple approaches we have conclusively mapped a non-canonical PIP motif from residues 999VGGLLAFA1008 in p125, which binds to the inter-domain-connecting loop (IDCL) of PCNA with high affinity. Collectively, including previous studies, we conclude that similar to Saccharomyces cerevisiae Polδ, each of the human Polδ subunits possesses motif to interact with PCNA and significantly contributes toward the processive nature of this replicative DNA polymerase.