bluuebunny/crossref_metadata_2025_split huggingface dataset:
NF-kappa B interacting long noncoding RNA enhances the Warburg effect and angiogenesis and is associated with decreased survival of patients with gliomas
Authors: Chen Zheng , Li Shiting , Shen Lin , Wei Xiangyu , Zhu Hanshuo , Wang Xueyi , Yang Min , Zheng Xuesheng 
Published: May 2020

Abstract
In various malignant tumors, NF-kappa B interacting long noncoding RNA (NKILA) displays antitumor activity by inhibiting the NF-kappa B pathway. However, the role of NKILA in gliomas remains unclear. Surprisingly, this study showed that NKILA is significantly upregulated in gliomas, and the increased levels of NKILA were correlated with a decrease in patient survival time. NKILA increased the expression level of hypoxia-inducible factor-1α, and the activity of the hypoxia pathway in gliomas. Furthermore, we demonstrated that NKILA enhances the Warburg effect and angiogenesis in gliomas both in vitro and in vivo. Therefore, NKILA is a potential therapeutic target in gliomas. In addition, we showed that a 20(S)-Rg3 monomer suppresses NKILA accumulation and reverses its stimulation of the Warburg effect and angiogenesis in gliomas, both in vitro and in vivo. Therefore, this study not only identified NKILA as a potential therapeutic target in gliomas, but also demonstrated a practical approach to treatment.
PKCθ-JunB axis via upregulation of VEGFR3 expression mediates hypoxia-induced pathological retinal neovascularization
Authors: Kumar Raj , Mani Arul M. , Singh Nikhlesh K. , Rao Gadiparthi N. 
Published: May 2020

AbstractPathological retinal neovascularization is the most common cause of vision loss. PKCθ has been shown to play a role in type 2 diabetes, which is linked to retinal neovascularization. Based on these clues, we have studied the role of PKCθ and its downstream target genes JunB and VEGFR3 in retinal neovascularization using global and tissue-specific knockout mouse models along with molecular biological approaches. Here, we show that vascular endothelial growth factor A (VEGFA) induces PKCθ phosphorylation in human retinal microvascular endothelial cells (HRMVECs) and downregulation of its levels attenuates VEGFA-induced HRMVECs migration, sprouting and tube formation. Furthermore, the whole body deletion of PKCθ or EC-specific deletion of its target gene JunB inhibited hypoxia-induced retinal EC proliferation, tip cell formation and neovascularization. VEGFA also induced VEGFR3 expression via JunB downstream to PKCθ in the regulation of HRMVEC migration, sprouting, and tube formation in vitro and OIR-induced retinal EC proliferation, tip cell formation and neovascularization in vivo. In addition, VEGFA-induced VEGFR3 expression requires VEGFR2 activation upstream to PKCθ-JunB axis both in vitro and in vivo. Depletion of VEGFR2 or VEGFR3 levels attenuated VEGFA-induced HRMVEC migration, sprouting and tube formation in vitro and retinal neovascularization in vivo and it appears that these events were dependent on STAT3 activation. Furthermore, the observations using soluble VEGFR3 indicate that VEGFR3 mediates its effects on retinal neovascularization in a ligand dependent and independent manner downstream to VEGFR2. Together, these observations suggest that PKCθ-dependent JunB-mediated VEGFR3 expression targeting STAT3 activation is required for VEGFA/VEGFR2-induced retinal neovascularization.
QKI deficiency leads to osteoporosis by promoting RANKL-induced osteoclastogenesis and disrupting bone metabolism
Authors: Du Tianshu , Yan Zhao , Zhu Shu , Chen Guo , Wang Li , Ye Zichen , Wang Wenwen , Zhu Qingsheng , Lu Zifan , Cao Xiaorui 
Published: May 2020

AbstractQuaking (QKI), an RNA-binding protein, has been reported to exhibit numerous biological functions, such as mRNA regulation, cancer suppression, and anti-inflammation. However, little known about the effects of QKI on bone metabolism. In this study, we used a monocyte/macrophage-specific QKI knockout transgenic mouse model to investigate the effects of QKI deficiency on receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis. The loss of QKI promoted the formation of multinucleated tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts (OCs) from bone marrow macrophages, and upregulated the expression of OC-specific markers, including TRAP (Acp5) and cathepsin K (Ctsk). The pro-osteoclastogenesis effect of QKI deficiency was achieved by amplifying the signaling cascades of the NF-κB and mitogen-activated protein kinase (MAPK) pathways; then, signaling upregulated the activation of nuclear factor of activated T cells c1 (NFATc1), which is considered to be the core transcription factor that regulates OC differentiation. In addition, QKI deficiency could inhibit osteoblast (OB) formation through the inflammatory microenvironment. Taken together, our data suggest that QKI deficiency promoted OC differentiation and disrupted bone metabolic balance, and eventually led to osteopenia under physiological conditions and aggravated the degree of osteoporosis under pathological conditions.
NT5DC2 promotes tumor cell proliferation by stabilizing EGFR in hepatocellular carcinoma
Authors: Li Kang-Shuai , Zhu Xiao-Dong , Liu Hong-Da , Zhang Shi-Zhe , Li Xiao-Long , Xiao Nan , Liu Xue-Feng , Xu Bin , Lei Ming , Zhang Yuan-Yuan , Shi Wen-Kai , Cao Man-Qing , Xu Yun-Fei , Tang Zhao-You , Sun Hui-Chuan 
Published: May 2020

AbstractMost hepatocellular carcinoma (HCC) patients are diagnosed at an advanced stage; however, the effect of systemic therapy on advanced HCC remains undetermined. Therefore, new treatment targets must be identified. We analyzed Gene Expression Omnibus datasets from two HCC patient cohorts and found that NT5DC2 was associated with vascular invasion and poor survival. In two hepatoma cell lines, NT5DC2 overexpression promoted HCC cell proliferation and clone formation in vitro and promoted tumor growth in vivo. Coimmunoprecipitation assays and liquid chromatography with tandem mass spectrometry analysis revealed that NT5DC2 bound directly to epidermal growth factor receptor (EGFR). NT5DC2 upregulated EGFR expression by downregulating EGFR ubiquitination and preventing its degradation via the ubiquitin-proteasome pathway but did not upregulate its transcription. EGFR upregulation activated downstream signal transduction, which played a critical role in the protumor effects of NT5DC2. Erlotinib, a small-molecule inhibitor of EGFR, blocked the effect of NT5DC2 in promoting HCC cell proliferation. In a cohort of 79 patients who underwent curative resection for HCC, NT5DC2 expression in the tumors was associated with larger tumors and microvascular invasion. NT5DC2 expression was also independently associated with recurrence-free survival. The present study demonstrated for the first time that NT5DC2 promotes tumor cell proliferation in HCC and may serve as a potential molecular target for treating HCC. EGFR blockage could be used to treat selected patients with NT5DC2 upregulation.
LncRNA SNORD3A specifically sensitizes breast cancer cells to 5-FU by sponging miR-185-5p to enhance UMPS expression
Authors: Luo Liyun , Zhang Jianlei , Tang Hailin , Zhai Dongfeng , Huang Danqing , Ling Li , Wang Xiaorong , Liu Ting , Zhang Qiong , Zhang Zhijie , He Zhimin , Zheng Guopei 
Published: May 2020

AbstractBreast cancer is the most common cancer type in women. Long non-coding RNAs (lncRNAs) have been reported as potential new diagnostic markers, prognostic factors, and therapeutic targets in cancer. However, the specific roles and mechanisms of lncRNAs in breast cancer remain to be elucidated. Here we demonstrated the downregulation of lncRNA SNORD3A in breast cancer cells and tissues and verified its non-protein-coding property. SNORD3A overexpression had no effect on cell proliferation but specifically sensitized breast cancer cells to 5-fluorouracil (5-FU) in vitro and in vivo. Mechanistically, SNORD3A exerts its effect via enhancing uridine monophosphate synthetase (UMPS) protein expression. SNORD3A acts as a competing endogenous RNA for miR-185-5p, leading to UMPS protein upregulation. miR-185-5p overexpression disrupted the effect of SNORD3A on chemosensitization to 5-FU in vitro and in vivo. Moreover, Meis1 overexpression transcriptionally promotes SNORD3A expression, and Meis1 is downregulated in breast cancer cells and tissues. In breast cancer tissues, SNORD3A level positively correlates with Meis1 and UMPS protein levels, whereas miR-185-5p level negatively correlates with UMPS protein level. High SNORD3A transcript and Meis1 and UMPS protein levels predicts a better outcome, but high miR-185-5p level predicts a worse outcome in breast cancer patients receiving 5-FU-based chemotherapy. Our findings indicate that Meis1-regulated SNORD3A specifically sensitizes breast cancer cells to 5-FU via enhancing UMPS expression. The SNORD3A–UMPS axis may serve as a potential biomarker and therapeutic target to improve the efficacy of 5-FU-based chemotherapy for breast cancer patients.
On-demand tuning of charge accumulation and carrier mobility in quantum dot solids for electron transport and energy storage devices
Authors: Septianto Ricky Dwi , Liu Liming , Iskandar Ferry , Matsushita Nobuhiro , Iwasa Yoshihiro , Bisri Satria Zulkarnaen 
Published: May 2020

Abstract
Assemblies of colloidal quantum dots (CQDs) are attractive for a broad range of applications because of the ability to exploit the quantum confinement effect and the large surface-to-volume ratio due to their small dimensions. Each application requires different types of assemblies based on which properties are intended to be utilized. Greater control of assembly formation and optimization of the related carrier transport characteristics are vital to advance the utilization of these materials. Here, we demonstrate on-demand control of the assembly morphology and electrical properties of highly crosslinked CQD solids through the augmentation of various assembly methods. Employment of electric-double-layer (EDL) gating on these assembly structures (i.e., an amorphous assembly, a hierarchical porous assembly, and a compact superlattice assembly) reveals their intrinsic carrier transport and accumulation characteristics. Demonstrations of high electron mobility with a high current modulation ratio reaching 105 in compact QD films and of a record-high areal capacitance of 400 μF/cm2 in an electric-double-layer supercapacitor with very thin (<100 nm) QD hierarchical porous assemblies signify the versatility of CQDs as building blocks for various modern electronic devices.
Early Jurassic dinosaur fetal dental development and its significance for the evolution of sauropod dentition
Authors: Reisz Robert R. , LeBlanc Aaron R. H. , Maddin Hillary C. , Dudgeon Thomas W. , Scott Diane , Huang Timothy , Chen Jun , Chen Chuan-Mu , Zhong Shiming 
Published: May 2020

AbstractRare occurrences of dinosaurian embryos are punctuated by even rarer preservation of their development. Here we report on dental development in multiple embryos of the Early Jurassic Lufengosaurus from China, and compare these to patterns in a hatchling and adults. Histology and CT data show that dental formation and development occurred early in ontogeny, with several cycles of tooth development without root resorption occurring within a common crypt prior to hatching. This differs from the condition in hatchling and adult teeth of Lufengosaurus, and is reminiscent of the complex dentitions of some adult sauropods, suggesting that their derived dental systems likely evolved through paedomorphosis. Ontogenetic changes in successive generations of embryonic teeth of Lufengosaurus suggest that the pencil-like teeth in many sauropods also evolved via paedomorphosis, providing a mechanism for the convergent evolution of small, structurally simple teeth in giant diplodocoids and titanosaurids. Therefore, such developmental perturbations, more commonly associated with small vertebrates, were likely also essential events in sauropod evolution.
Damped circadian oscillation in the absence of KaiA in Synechococcus
Authors: Kawamoto Naohiro , Ito Hiroshi , Tokuda Isao T. , Iwasaki Hideo 
Published: May 2020

AbstractProteins KaiA, KaiB and KaiC constitute a biochemical circadian oscillator in the cyanobacterium Synechococcus elongatus. It has been reported kaiA inactivation completely abolishes circadian oscillations. However, we show here that kaiBC promoter activity exhibits a damped, low-amplitude oscillation with a period of approximately 24 h in kaiA-inactivated strains. The damped rhythm resonates with external cycles with a period of 24–26 h, indicating that its natural frequency is similar to that of the circadian clock. Double-mutation experiments reveal that kaiC, kaiB, and sasA (encoding a KaiC-binding histidine kinase) are all required for the damped oscillation. Further analysis suggests that the kaiA-less damped transcriptional rhythm requires KaiB-KaiC complex formation and the transcription-translation feedback loop, but not the KaiC phosphorylation cycle. Our results provide insights into mechanisms that could potentially underlie the diurnal/circadian behaviors observed in other bacterial species that possess kaiB and kaiC homologues but lack a kaiA homologue.
Evolutionary conserved NSL complex/BRD4 axis controls transcription activation via histone acetylation
Authors: Gaub Aline , Sheikh Bilal N. , Basilicata M. Felicia , Vincent Marie , Nizon Mathilde , Colson Cindy , Bird Matthew J. , Bradner James E. , Thevenon Julien , Boutros Michael , Akhtar Asifa 
Published: May 2020

AbstractCells rely on a diverse repertoire of genes for maintaining homeostasis, but the transcriptional networks underlying their expression remain poorly understood. The MOF acetyltransferase-containing Non-Specific Lethal (NSL) complex is a broad transcription regulator. It is essential in Drosophila, and haploinsufficiency of the human KANSL1 subunit results in the Koolen-de Vries syndrome. Here, we perform a genome-wide RNAi screen and identify the BET protein BRD4 as an evolutionary conserved co-factor of the NSL complex. Using Drosophila and mouse embryonic stem cells, we characterise a recruitment hierarchy, where NSL-deposited histone acetylation enables BRD4 recruitment for transcription of constitutively active genes. Transcriptome analyses in Koolen-de Vries patient-derived fibroblasts reveals perturbations with a cellular homeostasis signature that are evoked by the NSL complex/BRD4 axis. We propose that BRD4 represents a conserved bridge between the NSL complex and transcription activation, and provide a new perspective in the understanding of their functions in healthy and diseased states.
Surface processes forcing on extensional rock melting
Authors: Sternai Pietro 
Published: May 2020

AbstractSurface processes and magmatism condition the structural evolution of continental rifts and passive margins through mechanical and thermal effects on the lithosphere rheology. However, their inter-relationships in extensional settings are largely unknown. Here, I use coupled thermo-mechanical geodynamic and landscape evolution numerical modeling to assess the links between erosion of rift shoulders, sedimentation within the rift basin and extensional rock melting. Results suggest that, when the crust is thinner than ~40 km, the extension rate is slower than ~2 cm/yr and the mantle potential temperature is below ~1230 °C, efficient surface processes may double crustal melting by Moho lowering and inhibit mantle decompression melting by ~50% through sediment loading within the rift basin. It is thus likely that surface processes significantly influenced the magmatic activity of a number of extensional settings worldwide – e.g. the Mediterranean, the Gulf of California, the Iberia-Newfoundland margin, and the South China Sea. Because magmatism and surface processes affect jointly the geological carbon cycle, the surface processes forcing on extensional rock melting investigated here involves an additional means of linkage between plate tectonics and climate changes.
Pregnancy rates after slow-release insemination (SRI) and standard bolus intrauterine insemination (IUI) – A multicentre randomised, controlled trial
Authors: Marschalek Julian , Egarter Christian , Vytiska-Binsdorfer Elisabeth , Obruca Andreas , Campbell Jackie , Harris Philip , van Santen Maarten , Lesoine Bernd , Ott Johannes , Franz Maximilian 
Published: May 2020

AbstractThis multicentre, randomised, controlled cross-over trial was designed to investigate the effect of intra-uterine slow-release insemination (SRI) on pregnancy rates in women with confirmed infertility or the need for semen donation who were eligible for standard bolus intra-uterine insemination (IUI). Data for a total of 182 women were analysed after randomisation to receive IUI (n = 96) or SRI (n = 86) first. The primary outcome was serological pregnancy defined by a positive beta human chorionic gonadotropin test, two weeks after insemination. Patients who did not conceive after the first cycle switched to the alternative technique for the second cycle: 44 women switched to IUI and 58 switched to SRI. In total, there were 284 treatment cycles (IUI: n = 140; SRI: n = 144). Pregnancy rates following SRI and IUI were 13.2% and 10.0%, respectively, which was not statistically significant (p = 0.202). A statistically significant difference in pregnancy rates for SRI versus IUI was detected in women aged under 35 years. In this subgroup, the pregnancy rate with SRI was 17% compared to 7% with IUI (relative risk 2.33; p = 0.032) across both cycles. These results support the hypothesis that the pregnancy rate might be improved with SRI compared to standard bolus IUI, especially in women aged under 35 years.
Deep learning-based decision support system for the diagnosis of neoplastic gallbladder polyps on ultrasonography: Preliminary results
Authors: Jeong Younbeom , Kim Jung Hoon , Chae Hee-Dong , Park Sae-Jin , Bae Jae Seok , Joo Ijin , Han Joon Koo 
Published: May 2020

AbstractUltrasonography (US) has been considered image of choice for gallbladder (GB) polyp, however, it had limitations in differentiating between nonneoplastic polyps and neoplastic polyps. We developed and investigated the usefulness of a deep learning-based decision support system (DL-DSS) for the differential diagnosis of GB polyps on US. We retrospectively collected 535 patients, and they were divided into the development dataset (n = 437) and test dataset (n = 98). The binary classification convolutional neural network model was developed by transfer learning. Using the test dataset, three radiologists with different experience levels retrospectively graded the possibility of a neoplastic polyp using a 5-point confidence scale. The reviewers were requested to re-evaluate their grades using the DL-DSS assistant. The areas under the curve (AUCs) of three reviewers were 0.94, 0.78, and 0.87. The DL-DSS alone showed an AUC of 0.92. With the DL-DSS assistant, the AUCs of the reviewer’s improved to 0.95, 0.91, and 0.91. Also, the specificity of the reviewers was improved (65.1–85.7 to 71.4–93.7). The intraclass correlation coefficient (ICC) improved from 0.87 to 0.93. In conclusion, DL-DSS could be used as an assistant tool to decrease the gap between reviewers and to reduce the false positive rate.
Flying on their own wings: young and adult cuckoos respond similarly to long-distance displacement during migration
Authors: Thorup Kasper , Vega Marta Lomas , Snell Katherine Rachel Scotchburn , Lubkovskaia Regina , Willemoes Mikkel , Sjöberg Sissel , Sokolov Leonid V. , Bulyuk Victor 
Published: May 2020

AbstractCommon cuckoos Cuculus canorus are obligate nest parasites yet young birds reach their distant, species-specific wintering grounds without being able to rely on guidance from experienced conspecifics – in fact they never meet their parents. Naïve marine animals use an inherited navigational map during migration but in inexperienced terrestrial animal migrants unequivocal evidence of navigation is lacking. We present satellite tracking data on common cuckoos experimentally displaced 1,800 km eastward from Rybachy to Kazan. After displacement, both young and adult travelled similarly towards the route of non-displaced control birds. The tracking data demonstrate the potential for young common cuckoos to return to the species-specific migration route after displacement, a response so far reported exclusively in experienced birds. Our results indicate that an inherited map allows first-time migrating cuckoos to locate suitable wintering grounds. This is in contrast to previous studies of solitary terrestrial bird migrants but similar to that reported from the marine environment.
Alterations to neuromuscular properties of skeletal muscle are temporally dissociated from the oxygen uptake slow component
Authors: Gajanand Trishan , Conde Alonso Sonia , Ramos Joyce S. , Antonietti Jean-Philippe , Borrani Fabio 
Published: May 2020

AbstractTo assess if the alteration of neuromuscular properties of knee extensors muscles during heavy exercise co-vary with the SCV ($${\dot{{\rm{V}}}{\rm{O}}}_{2}$$V̇O2 slow component), eleven healthy male participants completed an incremental ramp test to exhaustion and five constant heavy intensity cycling bouts of 2, 6, 10, 20 and 30 minutes. Neuromuscular testing of the knee extensor muscles were completed before and after exercise. Results showed a significant decline in maximal voluntary contraction (MVC) torque only after 30 minutes of exercise (−17.01% ± 13.09%; p < 0.05) while single twitch (PT), 10 Hz (P10), and 100 Hz (P100) doublet peak torque amplitudes were reduced after 20 and 30 minutes (p < 0.05). Voluntary activation (VA) and M-wave were not affected by exercise, but significant correlation was found between the SCV and PT, MVC, VA, P10, P100, and P10/P100 ratio, respectively (p < 0.015). Therefore, because the development of the SCV occurred mainly between 2–10 minutes, during which neuromuscular properties were relatively stable, and because PT, P10 and P100 were significantly reduced only after 20-30 minutes of exercise while SCV is stable, a temporal relationship between them does not appear to exist. These results suggest that the development of fatigue due to alterations of neuromuscular properties is not an essential requirement to elicit the SCV.