bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immortalization of human hepatocytes from biliary atresia with CDK4R24C, cyclin D1, and TERT for cytochrome P450 induction testing
Authors: Nishiwaki Manami , Toyoda Masashi , Oishi Yoshie , Ishida Seiichi , Horiuchi Shin-ichiro , Makino-Itou Hatsune , Kimura Tohru , Ohno Shin-ichi , Ohkura Takashi , Enosawa Shin , Akutsu Hidenori , Nakazawa Atsuko , Kasahara Mureo , Kiyono Tohru , Umezawa Akihiro 
Published: October 2020

AbstractHepatocytes are an important tool for in vitro toxicology testing. In addition to primary cultures, a limited number of immortalized cell lines have been developed. We here describe a new cell line, designated as HepaMN, which has been established from a liver associated with biliary atresia. Hepatocytes were isolated from a liver of 4-year-old girl with biliary atresia and immortalized by inoculation with CSII-CMV-TERT, CSII-CMV-Tet-Off, CSII-TRE-Tight-cyclin D1 and CSII-TRE-Tight-CDK4R24C (mutant CDK4: an INK4a-resistant form of CDK4) lentiviruses at the multiplicity of infection of 3 to 10. HepaMN cells exhibited morphological homogeneity, displaying hepatocyte-like phenotypes. Phenotypic studies in vivo and in vitro revealed that HepaMN cells showed polarized and functional hepatocyte features along with a canalicular cell phenotype under defined conditions, and constitutively expressed albumin and carbamoyl phosphate synthetase I in addition to epithelial markers. Since HepaMN cells are immortal and subcloned, kinetics and expression profiles were independent of population doublings. HepaMN cells showed increased CYP3A4 expression after exposure to rifampicin, implying that their close resemblance to normal human hepatocytes makes them suitable for research applications including drug metabolism studies.
Genomic identification and expression analysis of nuclear pore proteins in Malus domestica
Authors: Zhang Chenguang , An Na , Jia Peng , Zhang Wei , Liang Jiayan , Zhang Xu , Zhou Hua , Ma Wenchun , Han Mingyu , Xing Libo , Ren Xiaolin 
Published: October 2020

AbstractThe nuclear pore complex (NPC), comprised of individual nucleoporin (Nup) proteins, controls nucleo-cytoplasmic transport of RNA and protein, and is important for regulating plant growth and development. However, there are no reports on this complex in fruit tree species. In this study, we identified 38 apple Nups and named them based on the known Arabidopsis thaliana homologs. We also completed bioinformatics analyses of the intron and exon structural data for apple Nups. The proteins encoded by the apple Nups lacked a universally conserved domain. Moreover, a phylogenetic analysis separated the apple and A. thaliana Nups into three groups. The phylogenetic tree indicated that MdNup54 and MdNup62 are most closely related to genes in other Rosaceae species. To characterize the 38 candidate Malus domestica Nups, we measured their stage-specific expression levels. Our tests revealed these proteins were differentially expressed among diverse tissues. We analyzed the expression levels of seven apple Nups in response to an indole-3-acetic acid (IAA) treatment. The phytohormone treatment significantly inhibited apple flowering. A qRT-PCR analysis proved that an IAA treatment significantly inhibited the expression of these seven genes. A preliminary study regarding two members of the Nup62 subcomplex, MdNup54 and MdNup62, confirmed these two proteins can interact with each other. A yeast two-hybrid assay verified that MdNup54 can interact with MdKNAT4 and MdKNAT6. On the basis of the study results, we identified apple NPC and predicted its structure and function. The data generated in this investigation provide important reference material for follow-up research.
Different types of agricultural land use drive distinct soil bacterial communities
Authors: Lee Shin Ae , Kim Jeong Myeong , Kim Yiseul , Joa Jae-Ho , Kang Seong-Soo , Ahn Jae-Hyung , Kim Mincheol , Song Jaekyeong , Weon Hang-Yeon 
Published: October 2020

AbstractBiogeographic patterns in soil bacterial communities and their responses to environmental variables are well established, yet little is known about how different types of agricultural land use affect bacterial communities at large spatial scales. We report the variation in bacterial community structures in greenhouse, orchard, paddy, and upland soils collected from 853 sites across the Republic of Korea using 16S rRNA gene pyrosequencing analysis. Bacterial diversities and community structures were significantly differentiated by agricultural land-use types. Paddy soils, which are intentionally flooded for several months during rice cultivation, had the highest bacterial richness and diversity, with low community variation. Soil chemical properties were dependent on agricultural management practices and correlated with variation in bacterial communities in different types of agricultural land use, while the effects of spatial components were little.Firmicutes,Chloroflexi, andAcidobacteriawere enriched in greenhouse, paddy, and orchard soils, respectively. Members of these bacterial phyla are indicator taxa that are relatively abundant in specific agricultural land-use types. A relatively large number of taxa were associated with the microbial network of paddy soils with multiple modules, while the microbial network of orchard and upland soils had fewer taxa with close mutual interactions. These results suggest that anthropogenic agricultural management can create soil disturbances that determine bacterial community structures, specific bacterial taxa, and their relationships with soil chemical parameters. These quantitative changes can be used as potential biological indicators for monitoring the impact of agricultural management on the soil environment.
Coexisting with sharks: a novel, socially acceptable and non-lethal shark mitigation approach
Authors: Adams Kye R. , Gibbs Leah , Knott Nathan A. , Broad Allison , Hing Martin , Taylor Matthew D. , Davis Andrew R. 
Published: October 2020

AbstractConflict between humans and large predators is a longstanding challenge that can present negative consequences for humans and wildlife. Sharks have a global distribution and are considered to pose a potential threat to humans; concurrently many shark species are themselves threatened. Developing strategies for coexistence between humans and this keystone group is imperative. We assess blimp surveillance as a technique to simply and effectively reduce shark encounters at ocean beaches and determine the social acceptance of this technique as compared to an established mitigation strategy—shark meshing. We demonstrate the suitability of blimps for risk mitigation, with detection probabilities of shark analogues by professional lifeguards of 0.93 in ideal swimming conditions. Social surveys indicate strong social acceptance of blimps and preference for non-lethal shark mitigation. We show that continuous aerial surveillance can provide a measurable reduction in risk from sharks, improving beach safety and facilitating coexistence between people and wildlife.
Discovery of a CNS penetrant small molecule SMN2 splicing modulator with improved tolerability for spinal muscular atrophy
Authors: Ando Shiori , Suzuki Shunya , Okubo Shoichi , Ohuchi Kazuki , Takahashi Kei , Nakamura Shinsuke , Shimazawa Masamitsu , Fuji Koji , Hara Hideaki 
Published: October 2020

AbstractSpinal muscular atrophy (SMA) is a motor neuron disease, typically resulting from loss-of-function mutations in the survival motor neuron 1 (SMN1) gene. Nusinersen/SPINRAZA, a splice-switching oligonucleotide that modulates SMN2 (a paralog of SMN1) splicing and consequently increases SMN protein levels, has a therapeutic effect for SMA. Previously reported small-molecule SMN2 splicing modulators such as risdiplam/EVRYSDI and its analog SMN-C3 modulate not only the splicing of SMN2 but also that of secondary splice targets, including forkhead box protein M1 (FOXM1). Through screening SMA patient-derived fibroblasts, a novel small molecule, designated TEC-1, was identified that selectively modulates SMN2 splicing over three secondary splice targets. TEC-1 did not strongly affect the splicing of FOXM1, and unlike risdiplam, did not induce micronucleus formation. In addition, TEC-1 showed higher selectively on galactosylceramidase and huntingtin gene expression compared to previously reported compounds (e.g., SMN-C3) due to off-target effects on cryptic exon inclusion and nonsense-mediated mRNA decay. Moreover, TEC-1 significantly ameliorated the disease phenotype in an SMA murine model in vivo. Thus, TEC-1 may have promising therapeutic potential for SMA, and our study demonstrates the feasibility of RNA-targeting small-molecule drug development with an improved tolerability profile.
Dyke apertures record stress accumulation during sustained volcanism
Authors: Thiele Samuel T. , Cruden Alexander R. , Micklethwaite Steven , Bunger Andrew P. , Köpping Jonas 
Published: October 2020

AbstractThe feedback between dyke and sill intrusions and the evolution of stresses within volcanic systems is poorly understood, despite its importance for magma transport and volcano instability. Long-lived ocean island volcanoes are crosscut by thousands of dykes, which must be accommodated through a combination of flank slip and visco-elastic deformation. Flank slip is dominant in some volcanoes (e.g., Kilauea), but how intrusions are accommodated in other volcanic systems remains unknown. Here we apply digital mapping techniques to collect > 400,000 orientation and aperture measurements from 519 sheet intrusions within Volcán Taburiente (La Palma, Canary Islands, Spain) and investigate their emplacement and accommodation. We show that vertically ascending dykes were deflected to propagate laterally as they approached the surface of the volcano, forming a radial dyke swarm, and propose a visco-elastic model for their accommodation. Our model reproduces the measured dyke-aperture distribution and predicts that stress accumulates within densely intruded regions of the volcano, blocking subsequent dykes and causing eruptive activity to migrate. These results have significant implications for the organisation of magma transport within volcanic edifices, and the evolution and stability of long-lived volcanic systems.
Phosphate clearance in peritoneal dialysis
Authors: Debowska Malgorzata , Gomez Rafael , Pinto Joyce , Waniewski Jacek , Lindholm Bengt 
Published: October 2020

AbstractIn renal failure, hyperphosphatemia is common and correlates with increased mortality making phosphate removal a key priority for dialysis therapy. We investigated phosphate clearance, removal and serum level, and factors associated with phosphate control in patients undergoing continuous ambulatory (CAPD), continuous cyclic (CCPD) and automated (APD) peritoneal dialysis (PD). In 154 prevalent PD patients (mean age 53.2 ± 17.6 year, 59% men, 47% anuric), 196 daily collections of urine and 368 collections of dialysate were evaluated in terms of renal, peritoneal and total (renal plus peritoneal) phosphorus removal (g/week), phosphate and creatinine clearances (L/week) and urea KT/V. Dialytic removal of phosphorus was lower in APD (1.34 ± 0.62 g/week) than in CAPD (1.89 ± 0.73 g/week) and CCPD (1.91 ± 0.63 g/week) patients; concomitantly, serum phosphorus was higher in APD than in CAPD (5.55 ± 1.61 vs. 4.84 ± 1.23 mg/dL; p < 0.05). Peritoneal and total phosphate clearances correlated with peritoneal (rho = 0.93) and total (rho = 0.85) creatinine clearances (p < 0.001) but less with peritoneal and total urea KT/V (rho = 0.60 and rho = 0.65, respectively, p < 0.001). Phosphate removal, clearance and serum levels differed between PD modalities. CAPD was associated with higher peritoneal removal and lower serum level of phosphate than APD.
Oxygen vacancies induced photoluminescence in $$\hbox {SrZnO}_2$$ nanophosphors probed by theoretical and experimental analysis
Authors: Manju  , Jain Megha , Madas Saibabu , Vashishtha Pargam , Rajput Parasmani , Gupta Govind , Kahaly Mousumi Upadhyay , Özdoğan Kemal , Vij Ankush , Thakur Anup 
Published: October 2020

AbstractWe report, for the first time, the influence of oxygen vacancies on band structure and local electronic structure of $$\hbox {SrZnO}_2$$

SrZnO
2

(SZO) nanophosphors by combined first principle calculations based on density functional theory and full multiple scattering theory, correlated with experimental results obtained from X-ray absorption and photoluminescence spectroscopies. The band structure analysis from density functional theory revealed the formation of new energy states in the forbidden gap due to introduction of oxygen vacancies in the system, thereby causing disruption in intrinsic symmetry and altering bond lengths in SZO system. These defect states are anticipated as origin of observed photoluminescence in SZO nanophosphors. The experimental X-ray absorption near edge structure (XANES) at Zn and Sr K-edges were successfully imitated by simulated XANES obtained after removing oxygen atoms around Zn and Sr cores, which affirmed the presence and signature of oxygen vacancies on near edge structure.
Ordered interpersonal synchronisation in ASD children via robots
Authors: Giannopulu Irini , Etournaud Aude , Terada Kazunori , Velonaki Mari , Watanabe Tomio 
Published: October 2020

AbstractChildren with autistic spectrum disorders (ASD) experience persistent disrupted coordination in interpersonal synchronisation that is thought to be associated with deficits in neural connectivity. Robotic interventions have been explored for use with ASD children worldwide revealing that robots encourage one-to-one social and emotional interactions. However, associations between interpersonal synchronisation and emotional empathy have not yet been directly explored in French and Japanese ASD children when they interact with a human or a robot under analogous experimental conditions. Using the paradigm of actor-perceiver, where the child was the actor and the robot or the human the perceiver, we recorded the autonomic heart rate activation and reported emotional feelings of ASD children in both countries. Japanese and French ASD children showed different interpersonal synchronisation when they interacted with the human perceiver, even though the human was the same in both countries. However, they exhibited similar interpersonal synchronisation when the perceiver was the robot. The findings suggest that the mechanism combining interpersonal synchronisation and emotional empathy might be weakened but not absent in ASD children and that both French and Japanese ASD children do spontaneously and unconsciously discern non verbal actions of non human partners through a direct matching process that occurs via automatic mapping.
Incisional hernia after 2498 single-port access (SPA) gynecologic surgery over a 10-year period
Authors: Noh Joseph J. , Kim Tae-Hyun , Kim Chul-Jung , Kim Tae-Joong 
Published: October 2020

AbstractThe present study was conducted to report the perioperative outcomes of single-port access (SPA) laparoscopic gynecologic surgeries with focus on the incidence of postoperative incisional hernia from our cumulative data of 2498 patients. A retrospective review was performed on the women who had received SPA surgeries from 2008 to 2018. Patient characteristics and perioperative outcomes including the incidence of postoperative incisional hernia were analyzed. There were 2498 Korean patients who received SPA surgeries for various gynecologic diseases. The median age of the patients was 40.3 ± 9.2 years, and the mean body mass index (BMI) was 22.6 ± 3.2 kg/m2. A total of 3 postoperative incisional hernia occurred during the study period. Two patients whose fascial layers were closed in running sutures developed hernias 6 and 8 months after their operations. One patient whose fascial layers were closed in interrupted sutures developed hernia 11 months after her operation. The incidence of postoperative incisional hernia following SPA surgery is low in Asian women whose BMI is relatively lower than other patient populations. Interrupted suture technique may reduce postoperative incisional hernia by providing a distinct visualization of fascial layers during closure. Detailed descriptions of our surgical techniques of closing the port incision are provided.
Impacts of parent material on distributions of potentially toxic elements in soils from Pearl River Delta in South China
Authors: Hou Qingye , Yang Zhongfang , Yu Tao , You Yuanhang , Dou Lei , Li Kuo 
Published: October 2020

AbstractAssessing the impacts of parent material on distributions of potentially toxic elements (PTEs) in soils has significant consequences in the apportionment of their sources. In this study, geochemical distributions and sources of PTEs in the soils developed in quaternary sediments and granite plutons of Pearl River Delta (PRD), South China, were investigated. The results indicate that there are systematic differences between the concentrations of oxides and PTEs in the soils developed in these two parent materials. The parent material predominantly determines the element distributions in the soils. The PTEs of the deep soils developed in quaternary sediments originated mainly from mafic, felsic, and carbonate sources materials as well as polymetallic deposits. For the deep soils developed in granite plutons, the element associations are governed mainly by their geochemical affinities and behaviors and the mineral compositions of granite plutons. Anthropogenic activities impact the features of the PTEs in the surface soils of PRD. However, superimposed regional-scale pollution was found to not hide the effect of the parent material on the distribution of PTEs in the surface soils.
Duodenal acidification induces gastric relaxation and alters epithelial barrier function by a mast cell independent mechanism
Authors: Vanheel Hanne , Vicario Maria , Beeckmans Dorien , Cocca Silvia , Wauters Lucas , Accarie Alison , Toth Joran , Rodewald Hans-Reimer , De Hertogh Gert , Matteoli Gianluca , Boeckxstaens Guy , Tack Jan , Farre Ricard , Vanuytsel Tim 
Published: October 2020

AbstractDuodenal hyperpermeability and low-grade inflammation in functional dyspepsia is potentially related to duodenal acid exposure. We aimed to evaluate in healthy volunteers the involvement of mast cell activation on the duodenogastric reflex and epithelial integrity during duodenal acidification. This study consisted of 2 parts: (1) Duodenal infusion of acid or saline during thirty minutes in a randomized, double-blind cross-over manner with measurement of intragastric pressure (IGP) using high resolution manometry and collection of duodenal biopsies to measure epithelial barrier function and the expression of cell-to-cell adhesion proteins. Mast cells and eosinophils were counted and activation and degranulation status were assessed. (2) Oral treatment with placebo or mast cell stabilizer disodiumcromoglycate (DSCG) prior to duodenal perfusion with acid, followed by the procedures described above. Compared with saline, acidification resulted in lower IGP (P < 0.01), increased duodenal permeability (P < 0.01) and lower protein expression of claudin-3 (P < 0.001). Protein expression of tryptase (P < 0.001) was increased after acid perfusion. Nevertheless, an ultrastructural examination did not reveal degranulation of mast cells. DSCG did not modify the drop in IGP and barrier dysfunction induced by acid. Duodenal acidification activates an inhibitory duodenogastric motor reflex and, impairs epithelial integrity in healthy volunteers. However, these acid mediated effects occur independently from mast cell activation.
Implication of a new function of human tDNAs in chromatin organization
Authors: Iwasaki Yuki , Ikemura Toshimichi , Kurokawa Ken , Okada Norihiro 
Published: October 2020

AbstractTransfer RNA genes (tDNAs) are essential genes that encode tRNAs in all species. To understand new functions of tDNAs, other than that of encoding tRNAs, we used ENCODE data to examine binding characteristics of transcription factors (TFs) for all tDNA regions (489 loci) in the human genome. We divided the tDNAs into three groups based on the number of TFs that bound to them. At the two extremes were tDNAs to which many TFs bound (Group 1) and those to which no TFs bound (Group 3). Several TFs involved in chromatin remodeling such as ATF3, EP300 and TBL1XR1 bound to almost all Group 1 tDNAs. Furthermore, almost all Group 1 tDNAs included DNase I hypersensitivity sites and may thus interact with other chromatin regions through their bound TFs, and they showed highly conserved synteny across tetrapods. In contrast, Group 3 tDNAs did not possess these characteristics. These data suggest the presence of a previously uncharacterized function of these tDNAs. We also examined binding of CTCF to tDNAs and their involvement in topologically associating domains (TADs) and lamina-associated domains (LADs), which suggest a new perspective on the evolution and function of tDNAs.
Lung function over the life course of paediatric and adult patients with cystic fibrosis from a large multi-centre registry
Authors: Earnest Arul , Salimi Farhad , Wainwright Claire E. , Bell Scott C. , Ruseckaite Rasa , Ranger Tom , Kotsimbos Tom , Ahern Susannah 
Published: October 2020

AbstractA key measure of lung function in people with Cystic Fibrosis (CF) is Forced Expiratory Volume in the first second FEV1 percent predicted (FEV1pp). This study aimed to address challenges in identifying predictors of FEV1pp, specifically dealing with non-linearity and the censoring effect of death. Data was obtained from a large multi-centre Australian Cystic Fibrosis Data Registry (ACFDR). A linear mixed model was used to study FEV1pp as the endpoint. There were 3655 patients (52.4% male) included in our study. Restricted cubic splines were used to fit the non-linear relationship between age of visit and FEV1pp. The following predictors were found to be significant in the multivariate model: age of patient at visit, BMI z-score, age interaction with lung transplantation, insulin dependent diabetes, cirrhosis/portal hypertension, pancreatic insufficiency, Pseudomonas aeruginosa infection and baseline variability in FEV1pp. Those with P. aeruginosa infection had a lower mean difference in FEV1pp of 4.7 units, p < 0.001 compared to those who did not have the infection. Joint modelling with mortality outcome did not materially affect our findings. These models will prove useful for to study the impact of CFTR modulator therapies on rate of change of lung function among patients with CF.
A C-peptide complex with albumin and Zn2+ increases measurable GLUT1 levels in membranes of human red blood cells
Authors: Geiger M. , Janes T. , Keshavarz H. , Summers S. , Pinger C. , Fletcher D. , Zinn K. , Tennakoon M. , Karunarathne A. , Spence D. 
Published: October 2020

AbstractPeople with type 1 diabetes (T1D) require exogenous administration of insulin, which stimulates the translocation of the GLUT4 glucose transporter to cell membranes. However, most bloodstream cells contain GLUT1 and are not directly affected by insulin. Here, we report that C-peptide, the 31-amino acid peptide secreted in equal amounts with insulin in vivo, is part of a 3-component complex that affects red blood cell (RBC) membranes. Multiple techniques were used to demonstrate saturable and specific C-peptide binding to RBCs when delivered as part of a complex with albumin. Importantly, when the complex also included Zn2+, a significant increase in cell membrane GLUT1 was measured, thus providing a cellular effect similar to insulin, but on a transporter on which insulin has no effect.