bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulating tumor suppressor genes: post-translational modifications
Authors: Chen Ling , Liu Shuang , Tao Yongguang 
Published: June 2020

AbstractTumor suppressor genes cooperate with each other in tumors. Three important tumor suppressor proteins, retinoblastoma (Rb), p53, phosphatase, and tensin homolog deleted on chromosome ten (PTEN) are functionally associated and they regulated by post-translational modification (PTMs) as well. PTMs include phosphorylation, SUMOylation, acetylation, and other novel modifications becoming growing appreciated. Because most of PTMs are reversible, normal cells use them as a switch to control the state of cells being the resting or proliferating, and PTMs also involve in cell survival and cell cycle, which may lead to abnormal proliferation and tumorigenesis. Although a lot of studies focus on the importance of each kind of PTM, further discoveries shows that tumor suppressor genes (TSGs) form a complex “network” by the interaction of modification. Recently, there are several promising strategies for TSGs for they change more frequently than carcinogenic genes in cancers. We here review the necessity, characteristics, and mechanisms of each kind of post-translational modification on Rb, p53, PTEN, and its influence on the precise and selective function. We also discuss the current antitumoral therapies of Rb, p53 and PTEN as predictive, prognostic, and therapeutic target in cancer.
POU4F1 promotes the resistance of melanoma to BRAF inhibitors through MEK/ERK pathway activation and MITF up-regulation
Authors: Liu Lin , Yue Qiao , Ma Jingjing , Liu Yu , Zhao Tao , Guo Weinan , Zhu Guannan , Guo Sen , Wang Shiyu , Gao Tianwen , Li Chunying , Shi Qiong 
Published: June 2020

AbstractBRAF inhibitors (BRAFi) have shown remarkable clinical efficacy in the treatment of melanoma with BRAF mutation. Nevertheless, most patients end up with the development of BRAFi resistance, which strongly limits the clinical application of these agents. POU4F1 is a stem cell-associated transcriptional factor that is highly expressed in melanoma cells and contributes to BRAF-activated malignant transformation. However, whether POU4F1 contributes to the resistance of melanoma to BRAFi remains poorly understood. Here, we report that over-expressed POU4F1 contributed to the acquired resistance of melanoma cells to Vemurafenib. Furthermore, POU4F1 promoted the activation of ERK signaling pathway via transcriptional regulation on MEK expression. In addition, POU4F1 could increase the expression of MITF to retain the resistance of melanoma cells to BRAFi. Collectively, our findings reveal that POU4F1 re-activates the MAPK pathway by transcriptional regulation on MEK expression and promotes MITF expression, which ultimately results in the resistance to BRAFi in melanoma. Our study supports that POU4F1 is a potential combined therapeutic target with BRAFi therapy for melanoma.
Association between BMI, vitamin D, and estrogen levels in postmenopausal women using adjuvant letrozole: a prospective study
Authors: Elliott Mitchell J. , Ennis Marguerite , Pritchard Kathleen I. , Townsley Carol , Warr Dave , Elser Christine , Amir Eitan , Bedard Philippe L. , Rao Lakshmi , Stambolic Vuk , Sridhar Srikala , Goodwin Pamela J. , Cescon David W. 
Published: June 2020

AbstractStudies have suggested that women with elevated BMI or 25-OH vitamin D levels may derive less benefit from AIs versus tamoxifen. We prospectively investigated whether high BMI or 25-OH vitamin D levels were associated with higher estrogen levels in post-menopausal women receiving standard adjuvant letrozole (2.5 mg/day). Furthermore, we evaluated whether an increased dose of letrozole resulted in lower serum estrogens in women with BMI > 25 kg/m2. Correlation between entry BMI and day 29 serum biomarkers (estrogens, 25-OH vitamin D, insulin, CRP, leptin) was assessed in all patients. On day 29, participants with BMI > 25 kg/m2 switched to letrozole 5 mg/day for 4-weeks and blood was drawn upon completion of the study. The change in serum estrogen levels was assessed in these patients (BMI > 25 kg/m2). 112 patients completed days 1–28. The Pearson correlations of estradiol and estrone with BMI or serum 25-OH vitamin D levels were near zero (−0.04 to 0.07, p = 0.48–0.69). Similar results were obtained for correlation with markers of obesity (insulin, CRP, and leptin) with estradiol and estrone (−0.15 to 0.12; p = 0.11–0.82). Thirty-one patients (BMI > 25 kg/m2) completed the interventional component; Increasing the dose of letrozole did not further reduce estradiol or estrone levels (change 0.1 and 0.4 pmol/L respectively; p = 0.74 and 0.36). There was no observed association between markers of obesity (BMI, insulin, leptin, and CRP), serum 25-OH vitamin D levels and estradiol or estrone levels. Additionally, an increased dose of letrozole did not further reduce estradiol or estrone levels compared to the standard dose.
Characterization of amyloid β fibril formation under microgravity conditions
Authors: Yagi-Utsumi Maho , Yanaka Saeko , Song Chihong , Satoh Tadashi , Yamazaki Chiaki , Kasahara Haruo , Shimazu Toru , Murata Kazuyoshi , Kato Koichi 
Published: June 2020

AbstractAmyloid fibrils are self-assembled and ordered proteinaceous supramolecules structurally characterized by the cross-β spine. Amyloid formation is known to be related to various diseases typified by neurogenerative disorders and involved in a variety of functional roles. Whereas common mechanisms for amyloid formation have been postulated across diverse systems, the mesoscopic morphology of the fibrils is significantly affected by the type of solution condition in which it grows. Amyloid formation is also thought to share a phenomenological similarity with protein crystallization. Although many studies have demonstrated the effect of gravity on protein crystallization, its effect on amyloid formation has not been reported. In this study, we conducted an experiment at the International Space Station (ISS) to characterize fibril formation of 40-residue amyloid β (Aβ(1–40)) under microgravity conditions. Our comparative analyses revealed that the Aβ(1–40) fibrilization progresses much more slowly on the ISS than on the ground, similarly to protein crystallization. Furthermore, microgravity promoted the formation of distinct morphologies of Aβ(1–40) fibrils. Our findings demonstrate that the ISS provides an ideal experimental environment for detailed investigations of amyloid formation mechanisms by eliminating the conventionally uncontrollable factors derived from gravity.
The development of β phase Mg–Li alloys for ultralight corrosion resistant applications
Authors: Cain Taylor W. , Labukas Joseph P. 
Published: June 2020

AbstractMagnesium alloys with high lithium concentrations possess a lightweight body centered cubic (BCC) matrix structure with densities in the range of 1.3–1.65 g/cm3. These alloys have shown the ability to provide an excellent combination of strength, ductility, and corrosion resistance. Despite these great properties, the developmental history of Mg–Li alloys has observed widely varying degrees of interest but has regained momentum over the past decade. The intention of this review is to provide an overview of the mechanical properties and available corrosion data from inceptive BCC Mg–Li alloy reports to contemporary works with an emphasis on the chemical and microstructural aspects contributing to corrosion behavior. A discussion on the state of the art of the corrosion mechanism of BCC Mg–Li alloys is provided with an emphasis on hi fidelity characterization techniques that were not available to early researchers working on the Mg–Li system. In the current state, there remains a great potential for further improvement in the mechanical properties and corrosion resistance.
On the generalization of tones: A detailed exploration of non-speech auditory perception stimuli
Authors: Schutz Michael , Gillard Jessica 
Published: June 2020

AbstractThe dynamic changes in natural sounds’ temporal structures convey important event-relevant information. However, prominent researchers have previously expressed concern that non-speech auditory perception research disproportionately uses simplistic stimuli lacking the temporal variation found in natural sounds. A growing body of work now demonstrates that some conclusions and models derived from experiments using simplistic tones fail to generalize, raising important questions about the types of stimuli used to assess the auditory system. To explore the issue empirically, we conducted a novel, large-scale survey of non-speech auditory perception research from four prominent journals. A detailed analysis of 1017 experiments from 443 articles reveals that 89% of stimuli employ amplitude envelopes lacking the dynamic variations characteristic of non-speech sounds heard outside the laboratory. Given differences in task outcomes and even the underlying perceptual strategies evoked by dynamic vs. invariant amplitude envelopes, this raises important questions of broad relevance to psychologists and neuroscientists alike. This lack of exploration of a property increasingly recognized as playing a crucial role in perception suggests future research using stimuli with time-varying amplitude envelopes holds significant potential for furthering our understanding of the auditory system’s basic processing capabilities.
Ultra-Fast High-Precision Metallic Nanoparticle Synthesis using Laser-Accelerated Protons
Authors: Barberio M. , Giusepponi S. , Vallières S. , Scisció M. , Celino M. , Antici P. 
Published: June 2020

AbstractLaser-driven proton acceleration, as produced during the interaction of a high-intensity (I > 1 × 1018 W/cm2), short pulse (<1 ps) laser with a solid target, is a prosperous field of endeavor for manifold applications in different domains, including astrophysics, biomedicine and materials science. These emerging applications benefit from the unique features of the laser-accelerated particles such as short duration, intense flux and energy versatility, which allow obtaining unprecedented temperature and pressure conditions. In this paper, we show that laser-driven protons are perfectly suited for producing, in a single sub-ns laser pulse, metallic nanocrystals with tunable diameter ranging from tens to hundreds of nm and very high precision. Our method relies on the intense and very quick proton energy deposition, which induces in a bulk material an explosive boiling and produces nanocrystals that aggregate in a plasma plume composed by atoms detached from the proton-irradiated surface. The properties of the obtained particles depend on the deposited proton energy and on the duration of the thermodynamical process. Suitably controlling the irradiated dose allows fabricating nanocrystals of a specific size with low polydispersity that can easily be isolated in order to obtain a monodisperse nanocrystal solution. Molecular Dynamics simulations confirm our experimental results.
Remote ischemic conditioning in active ulcerative colitis: An explorative randomized clinical trial
Authors: Godskesen Line E. , Lassen Thomas R. , Jespersen Nichlas R. , Siersbæk Majken , Yan Yan , Nielsen Michael M. , Tjønnfjord Sara K. , Grøntved Lars , Madsen Gunvor , Kjems Jørgen , Bøtker Hans E. , Schmidt Michael R. , Krag Aleksander , Kjeldsen Jens 
Published: June 2020

AbstractRemote ischemic conditioning (RIC) by repetitive brief periods of limb ischemia and reperfusion renders organs more resistant to ischemic injury. The protection is partly through down-regulation of the inflammatory response. Our aim was to investigate the clinical and anti-inflammatory effects of RIC in patients with active ulcerative colitis (UC). We included 22 patients with active UC in this explorative, randomized, sham-controlled clinical trial. The patients were randomly assigned 1:1 to RIC (induced in the arm through four cycles of 5-min inflation and 5-min deflation of a blood-pressure cuff) or sham (incomplete inflation of the blood-pressure cuff) once daily for 10 days. Outcome variables were measured at baseline and on day 11. When compared with sham, RIC did not affect inflammation in the UC patients measured by fecal calprotectin, plasma C-reactive protein, Mayo Score, Mayo Endoscopic Subscore, Nancy Histological Index or inflammatory cytokines involved in UC and RIC. The mRNA and miRNA expression profiles in the UC patients were measured by RNA sequencing and multiplexed hybridization, respectively, but were not significantly affected by RIC. We used the Langendorff heart model to assess activation of the organ protective mechanism induced by RIC, but could not confirm activation of the organ protective mechanism in the UC patients.
Reproduction of sediment deposition and prediction of 137Cs concentration in the major urban rivers of Tokyo
Authors: Mouri Goro 
Published: June 2020

AbstractRadioactive caesium- 137 (137Cs) can be used as a tracer to infer sediment dynamics due not only to its long radioactive half-life but also its affinity for fine sediment. A novel advanced interpolation assessment was conducted to examine radionuclide activity in terraced land covered with volcanic ash soil in Tokyo, Japan, which had a time-dependent input function and incorporated the effects of mixed-sediment particle dynamic behaviour on radioactive decay. In addition, transport parameters derived from Chernobyl measurements were applied as predictors of the long-term contamination of the cardinal urban rivers by the fallout from the Tokyo Electric Power Fukushima Daiichi Nuclear Power Plant (FDNPP) accident in 2011. The behaviour of suspended sediment substances, incorporating the effects of deposition and pickup, was assessed using a mixed-sediment particle dynamics model. The concentrations of 137Cs adsorbed on fine sediment particles of each size fraction were determined. Removal of 137Cs from the cardinal urban river channel had significant effects on both long-term decline, including extreme flash flood events, and the dynamic and time-dependent behaviours of interspersed 137Cs and sediment activity. A novel advanced interpolation assessment method was used to examine radionuclide activity in terraced land covered with volcanic ash soil in Tokyo, Japan. The assessment procedure has a time-dependent input function and incorporates the effects of mixed-sediment particle dynamics on this time dependence. The results indicated that sediment and 137Cs concentrations could decline more rapidly than observed in the Fukushima and Chernobyl regions. This rate of decrease depended on terraces covered with volcanic ash soil, which incorporated the effects of fine sediment behaviour for particle adsorption. In addition, comparatively large impacts were observed during extreme flash flooding events, which were associated with the land cover of the major urban river catchments in Tokyo. This work provides a new perspective for understanding 137Cs behaviour associated with reproduction of sediment deposition and prediction of 137Cs concentration in the major urban rivers of Tokyo, incorporating the effects of baseline 137Cs behaviour with the impact of sediment particle adsorption in a volcanic ash soil-covered terrace.
Molecular evolution and genetic variations of  V and W proteins derived by RNA editing in Avian Paramyxoviruses
Authors: Rao Pachineella Lakshmana , Gandham Ravi Kumar , Subbiah Madhuri 
Published: June 2020

AbstractThe newly assigned subfamily Avulavirinae in the family Paramyxoviridae includes avian paramyxoviruses (APMVs) isolated from a wide variety of avian species across the globe. Till date, 21 species of APMVs are reported and their complete genome sequences are available in GenBank. The APMV genome comprises of a single stranded, negative sense, non-segmented RNA comprising six transcriptional units (except APMV-6 with seven units) each coding for a structural protein. Additionally, by co-transcriptional RNA editing of phosphoprotein (P) gene, two mRNAs coding for accessory viral proteins, V and W, are generated along with unedited P mRNA. However, in APMV-11, the unedited mRNA codes for V protein while +2 edited mRNA translates to P protein, similar to members of subfamily Rubulavirinae in the same family. Such RNA editing in paramyxoviruses enables maximizing the coding capacity of their smaller genome. The three proteins of P gene: P, V and W, share identical N terminal but varied C terminal sequences that contribute to their unique functions. Here, we analyzed the P gene editing site, V and W sequences of all 21 APMV species known so far (55 viruses) by using bioinformatics and report their genetic variations and molecular evolution. The variations observed in the sequence and hexamer phase positions of the P gene editing sites is likely to influence the levels and relative proportions of P, V and W proteins’ expressions which could explain the differences in the pathogenicity of APMVs. The V protein sequences of APMVs had conserved motifs similar to V proteins of other paramyxoviruses including the seven cysteine residues involved in MDA5 interference, STAT1 degradation and interferon antagonism. Conversely, W protein sequences of APMVs were distinct. High sequence homology was observed in both V and W proteins between strains of the same species than between species except in APMV-3 which was the most divergent APMV species. The estimates of synonymous and non-synonymous substitution rates suggested negative selection pressure on the V and W proteins within species indicating their low evolution rate. The molecular clock analysis revealed higher conservation of  V protein sequence compared to W protein indicating the important role played by V protein in viral replication, pathogenesis and immune evasion. However, we speculate the genetic diversity of W proteins could impact the degree of pathogenesis, variable interferon antagonistic activity and the wide host range exhibited by APMV species. Phylogenetically, V proteins of APMVs clustered into three groups similar to the recent classification of APMVs into three new genera while no such pattern could be deciphered in the analysis of W proteins except that strains of same species grouped together. This is the first comprehensive study describing in detail the genetic variations and the molecular evolution of P gene edited, accessory viral proteins of Avian paramyxoviruses.
Direct incorporation of mesenchymal stem cells into a Nanofiber scaffold – in vitro and in vivo analysis
Authors: Schüttler Karl F. , Bauhofer Michael W. , Ketter Vanessa , Giese Katja , Eschbach Daphne A. , Yenigün Mesut , Fuchs-Winkelmann Susanne , Paletta Jürgen R. J. 
Published: June 2020

AbstractBony defects are a common problem in musculoskeletal surgery. Replacement with autologous bone grafts is limited by availability of transplant material. Sterilized cancellous bone, while being osteoconductive, has limited osteoinductivity. Nanofiber scaffolds are currently used for several purposes due to their capability of imitating the extracellular matrix. Furthermore, they allow modification to provide functional properties. Previously we showed that electrospun nanofiber scaffolds can be used for bone tissue regeneration. While aiming to use the osteoinductive capacities of collagen type-I nanofibers we saw reduced scaffold pore sizes that limited cellular migration and thus colonization of the scaffolds. Aim of the present study was the incorporation of mesenchymal stem cells into the electrospinning process of a nanofiber scaffold to produce cell-seeded nanofiber scaffolds for bone replacement. After construction of a suitable spinning apparatus for simultaneous electrospinning and spraying with independently controllable spinning and spraying devices and extensive optimization of the spinning process, in vitro and in vivo evaluation of the resulting scaffolds was conducted. Stem cells isolated from rat femora were incorporated into PLLA (poly-l-lactide acid) and PLLA-collagen type-I nanofiber scaffolds (PLLA Col I Blend) via simultaneous electrospinning and –spraying. Metabolic activity, proliferation and osteoblastic differentiation were assessed in vitro. For in vivo evaluation scaffolds were implanted into critical size defects of the rat scull. After 4 weeks, animals were sacrificed and bone healing was analyzed using CT-scans, histological, immunhistochemical and fluorescence evaluation. Successful integration of mesenchymal stem cells into the scaffolds was achieved by iteration of spinning and spraying conditions regarding polymer solvent, spinning distance, the use of a liquid counter-electrode, electrode voltage and spinning duration. In vivo formation of bone tissue was achieved. Using a PLLA scaffold, comparable results for the cell-free and cell-seeded scaffolds were found, while the cell-seeded PLLA-collagen scaffolds showed significantly better bone formation when compared to the cell-free PLLA-collagen scaffolds. These results provide support for the future use of cell-seeded nanofiber scaffolds for large bony defects.
Automated Retinal Layer Segmentation Using Graph-based Algorithm Incorporating Deep-learning-derived Information
Authors: Mishra Zubin , Ganegoda Anushika , Selicha Jane , Wang Ziyuan , Sadda SriniVas R. , Hu Zhihong 
Published: June 2020

AbstractRegular drusen, an accumulation of material below the retinal pigment epithelium (RPE), have long been established as a hallmark early feature of nonneovascular age-related macular degeneration (AMD). Advances in imaging have expanded the phenotype of AMD to include another extracellular deposit, reticular pseudodrusen (RPD) (also termed subretinal drusenoid deposits, SDD), which are located above the RPE. We developed an approach to automatically segment retinal layers associated with regular drusen and RPD in spectral domain (SD) optical coherence tomography (OCT) images. More specifically, a shortest-path algorithm enhanced with probability maps generated through a fully convolutional neural network was used to segment drusen and RPD, as well as 11 retinal layers in SD-OCT volumes. This algorithm achieves a mean difference that is within the subpixel accuracy range drusen and RPD, alongside the other 11 retinal layers, highlighting the high robustness of this algorithm for this dataset. To the best of our knowledge, this is the first report of a validated algorithm for the automated segmentation of the retinal layers including early AMD features of RPD and regular drusen separately on SD-OCT images.
Biosafety of Non-Return Valves for Infusion Systems in Radiology
Authors: Azevedo Marcela Padilha Facetto , Monteiro Rachel Maciel , Castelani Carla , Bim Felipe Lazarini , Bim Lucas Lazarini , Macedo Ana Paula , Oliveira Viviane de Cássia , Watanabe Evandro 
Published: June 2020

AbstractCross-infection in contrast injectors is still a subject under discussion with little understanding. This study evaluated the biosafety of non-return valves (NRVs). Initially, the maximum pressure during backflow of intact and disrupted flexible diaphragms (FDs) from NRVs, as well as the functionality of connectors with NRVs were verified. The performance of air columns interposed by water in connectors with NRVs was analyzed, and the diffusion distance of crystal violet through connectors with NRVs was measured. The efficacy of NRVs as a barrier to bacterial contamination from backflow was evaluated. Finally, a clinical study of bacteriological contamination from syringes was conducted. There were differences among the maximum tolerated pressure by intact and disrupted FDs. Disrupted FDs showed no failures in the functionality of connectors with NRVs based on the lack of air bubbles released. Air columns could move through connectors with NRVs with intact and disrupted FDs. The longest diffusion distance of crystal violet was 6 cm of connector length, and NRVs showed efficacy as a barrier to bacterial contamination. In the clinical study, there was no bacterial growth in any of the evaluated samples. In conclusion, biosafety depends on the functionality of NRVs as well as proper practical clinical performance.