bluuebunny/crossref_metadata_2025_split huggingface dataset:
NOD2 agonist murabutide alleviates radiation‐induced injury through DNA damage response pathway mediated by ATR
Authors: Liu Lei , Qu Hongjin , Qin Hongran , Yang Yanyong , Liao Zebin , Cui Jianguo , Gao Fu , Cai Jianming 
Published: May 2019

AbstractInjury‐induced by ionizing radiation (IR) severely reduces the quality of life of victims. The development of radiation protectors is regarded as one of the most resultful strategies to alleviate damages caused by IR exposure. In the present study, we investigated the radioprotective effects of the agonist of nucleotide‐binding‐oligomerization‐domain‐containing proteins 2 called murabutide (MBD) and clarified the potential mechanisms. Our results showed that the pretreatment with MBD effectively protected cultured cells and mice against IR‐induced toxicity and the pretreatment with MBD in vitro and in vitro also inhibited apoptosis caused by IR exposure. The downregulation of γ‐H2AX and the upregulation of ATR signaling pathways by MBD treatment indicated that the radioprotective effects of MBD were due to the stimulation of DNA damage response (DDR) pathway to repair DNA double‐strand breaks caused by IR exposure. As the radioprotective effects of MBD were diminished by the ATR selective inhibitor rather than the ATM inhibitor, ATR pathway was confirmed to be a more crucial checkpoint pathway in mediating the stimulation of DDR pathway by MBD. Taken together, our data provide a novel and effective protector to relieve the injury induced by IR exposure.
PARTICLE − The RNA podium for genomic silencers
Authors: O'Leary Valerie B. , Ovsepian Saak V. , Smida Jan , Atkinson Michael J. 
Published: May 2019

AbstractRadiation exposure can evoke cellular stress responses. Emerging recognition that long non‐coding RNAs (lncRNAs) act as regulators of gene expression has broadened the spectra of molecules controlling the genomic landscape upon alterations in environmental conditions. Knowledge of the mechanisms responding to low dose irradiation (LDR) exposure is very limited yet most likely involve subtle ancillary molecular pathways other than those protecting the cell from direct cellular damage. The discovery that transcription of the lncRNA PARTICLE (promoter of MAT2A‐ antisense radiation‐induced circulating lncRNA; PARTICL) becomes dramatically instigated within a day after LDR exposure introduced a new gene regulator onto the biological landscape. PARTICLE affords an RNA binding platform for genomic silencers such as DNA methyltransferase 1 and histone tri‐methyltransferases to reign in the expression of tumor suppressors such as its neighboring MAT2A in cis as well as WWOX in trans. In silico evidence offers scope to speculate that PARTICLE exploits the abundance of Hoogsten bonds that exist throughout mammalian genomes for triplex formation, presumably a vital feature within this RNA silencer. PARTICLE may provide a buffering riboswitch platform for S‐adenosylmethionine. The correlation of PARTICLE triplex formation sites within tumor suppressor genes and their abundance throughout the genome at cancer‐related hotspots offers an insight into potential avenues worth exploring in future therapeutic endeavors.
Long noncoding RNA FOXD3‐AS1 promotes colon adenocarcinoma progression and functions as a competing endogenous RNA to regulate SIRT1 by sponging miR‐135a‐5p
Authors: Wu Qiong , Shi Min , Meng Wenying , Wang Yugang , Hui Pingping , Ma Jiali 
Published: May 2019

AbstractMore and more documents have proved that the abnormal expression of long noncoding RNAs (lncRNAs) are correlated with the initiation and progression of colorectal cancer (CRC). lncRNA FOXD3‐AS1 has been reported in glioma for its oncogenic property. According to the survival analysis of The Cancer Genome Atlas database, FOXD3‐AS1 upregulation implied lower survival rate of patients with CRC. Quantitative real‐time polymerase chain reaction showed the overexpression of FOXD3‐AS1 in both CRC tissues and cells. The Kaplan–Meier method demonstrated the prognostic value of FOXD3‐AS1 for patients with CRC. To explore the effect of FOXD3‐AS1 on CRC progression, loss‐of‐function experiments were carried out, whose results indicated that knockdown of FOXD3‐AS1 suppressed cell proliferation, migration, and invasion, inhibited cell cycle and promoted cell apoptosis in vitro. In vivo experiments affirmed that FOXD3‐AS1 affected tumor growth. FOXD3‐AS1 expression was enriched in the cytoplasm of CRC cells. Mechanism experiments revealed that FOXD3‐AS1 served as a competing endogenous RNA to upregulate SIRT1 by sponging miR‐135a‐5p. In addition, SIRT1 silencing also restrained cell proliferation and motility. Rescue assays revealed the biological function of FOXD3‐AS1/miR‐135a‐5p/SIRT1 axis in CRC progression. In conclusion, FOXD3‐AS1 promotes CRC progression by regulating miR‐135a‐5p/SIRT1 axis, shedding lights on the way to CRC treatments.
Restoration of p53 acetylation by HDAC inhibition permits the necrosis/apoptosis switch of pancreatic ainar cell during experimental pancreatitis in mice
Authors: Hu Yangyang , Dai Juanjuan , Zong Guanzhao , Xiao Jingbo , Guo Xingya , Dai Yiqi , Lu Zhanjun , Wan Rong 
Published: May 2019

AbstractThe severity of acute pancreatitis (AP) is greatly attributed to the pancreatic acinar cell (PAC) death response. It has been established that the apoptosis‐inducing therapy can protect against experimental pancreatitis and have great clinical therapeutic potential. However, current pharmacologic agents that target apoptosis during AP largely lack specificity. Thus, it remains imperative to reveal the specific mechanisms governing acinar cell death. Death responses of PAC are manifested by the progressive necrosis accompanied by apoptosis silencing during AP in mice. In this study, we found that the transcriptional activity of p53 was impaired and the expressions of its proapoptotic targets Puma and CD95 were significantly decreased, which explains the apoptosis silencing during AP. Furthermore, we found that the functional depression of p53 was resulted from histone deacetylase (HDAC)‐mediated deacetylation of p53 C‐terminal in PAC during AP. Treatment of the HDAC inhibitor trichostatin‐A restored p53 apoptosis pathway, resulted in a necrosis/apoptosis switch and protected mice from cerulein‐ or l‐Arg‐induced AP. Our research identified the HDAC‐dependent regulation of p53 activity as a critical mechanism underlying acinar cell death response, which represents a specific target for the treatment of AP.
microRNA‐25 promotes cardiomyocytes proliferation and migration via targeting Bim
Authors: Qin Xiaofeng , Gao Shufang , Yang Yadong , Wu Leilei , Wang Liming 
Published: May 2019

AbstractmicroRNAs (miRNAs) are pleiotropic players in cardiac development. Recent evidence have suggested miRNAs as promisingly therapeutic targets for cardiac regeneration. This study aimed to reveal the potential effects of miR‐25 on cardiomyocytes proliferation and migration. Sprague‐Dawley rats received left coronary occlusion surgery to induce an in vivo model of myocardial ischemia/reperfusion (I/R) injury. Expression changes of miR‐25 and Bim were tested by quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) and western blot. Besides, primary neonatal and adult cardiomyocytes were transfected by the antisense oligonucleotides or mimic specific for miR‐25, and then 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT), 5‐ethynyl‐2’‐deoxyuridine (EdU), Boyden chamber, and terminal‐deoxynucleotidyl transferase‐mediated nick end labeling (TUNEL) assay were respectively used to determine cardiomyocytes growth and migration. Binding effects of miR‐25 on the 3'‐untranslated region (3’‐UTR) of Bim was assessed by dual‐luciferase reporter assay. We found that miR‐25 was low expressed, whereas Bim was highly expressed in I/R injury model and hypoxia‐stimulated cardiomyocytes. Downregulation of miR‐25 in neonatal and adult cardiomyocytes markedly reduced cell proliferation and migration, but promoted apoptosis. Consistently, downregulation of miR‐25 decreased the expression of cyclin E2, cyclin D1, and CDK4, and increased the expression of p57 (KIP2) in cardiomyocytes. We additionally found that Bim was a target of miR‐25. The inhibitory effects of miR‐25 downregulation on cardiomyocytes survival and migration were all significantly attenuated when Bim was silenced. To sum up, our study demonstrates that miR‐25 downregulation inhibits cardiomyocytes proliferation and migration, but promotes apoptosis. The role of miR‐25 in cardiomyocytes was by targeting Bim.
Three‐dimensional space variable–separated PGD in electrostatic field problems: A comparison between two implementations
Authors: Yan Shuai , Zong Wei , Xu Xiaoyu , Li Yalan , Ren Zhuoxiang 
Published: May 2019

AbstractProper generalized decomposition (PGD) is a promising model order reduction (MOR) technique to solve partial differential equations (PDEs). It usually bases on an explicit variable‐separated formulation of the problems to be solved. However, it can be expensive to derive the separated formulations. Also, the PGD process can become inefficient because of the massive separated terms. Another way of implementing PGD is based on direct integration. In this work, we illustrate this kind of implementation algebraically by introducing tensors to represent the operator and right‐hand side of the problem. The separated formulation–based PGD and tensor‐based PGD are compared in computational complexity and accuracy. The pros and cons of both approaches are discussed. The methods are applied in three‐dimensional (3D) electrostatic field problems.
Simulation of temperature series and small networks from data
Authors: Washington Benjamin , Seymour Lynne , Lund Robert , Willett Kate 
Published: May 2019

AbstractIt is often desirable to simulate a single temperature series or a collection (network) of temperature series. Accurate simulations can enhance our understanding of temperature trends and variabilities. Simulation can also be used to generate data with known specifications, which are useful in assessing climate data processing routines such as quality control and homogenization algorithms. Possessing multiple realistic temperature series is often beneficial as only one natural record of our climate is available. The current popularity of general circulation models (GCMs) demonstrates how important simulation techniques are. However, even with sophisticated downscaling, it is difficult to replicate station temperature data that have realistic seasonal cycles as well as realistic temporal and spatial correlations. This paper reviews and studies statistical time series methods that can replicate a single series or a network of series from data. The methods are purely statistical—no atmospheric dynamics are involved—and attempt to produce replicates of the records under study. The work here develops (a) methods that simulate temperatures from a fixed season (say a particular day or month of the year) that match the distributional characteristics of the observed data; (b) methods for simulating an entire series that matches the series' temporal autocorrelations and seasonal cycle; and (c) methods for simulating a network of series that reproduce the data's observed seasonal cycles and spatial and temporal autocorrelations. Applications are given throughout, including one where a GCM series and local station data are used in tandem to describe long‐term trends and inject realistic station‐level short‐term fluctuations. This paper can be used as a tutorial for the simulation of a single climate observation, an entire climate series, or a network of multiple climate series simultaneously. Extensions of the ideas that involve GCMs are also examined.
Endoscopic palliation of biliary obstruction
Authors: Aadam A. Aziz , Liu Kevin 
Published: May 2019

AbstractAdvanced pancreaticobiliary malignancy tends to be uncurable at presentation and causes significant morbidity for patients. Palliation for malignant biliary obstruction should be minimally invasive, cost‐effective, and aim to improve quality of life of patients. Strategies of endoscopic palliation of malignant biliary obstruction can differ based on sites and degree of biliary obstruction with complex decisions of optimal stent type and placement that involve conscientious planning by a multidisciplinary team.
The Debate About Bait: A Red Herring in Wildlife Research
Authors: Stewart Frances E. C. , Volpe John P. , Fisher Jason T. 
Published: May 2019

ABSTRACTThe use of bait (or attractants) to lure animals to a sampling site is common in wildlife research and important for optimizing species detection rates. The effect of bait on animal movement and space‐use, however, is contested, fueled by concerns bait may affect animal movement and increase residency time. If founded, bait may bias parameter estimates from density, species distribution, resource selection, or behavioral models, produce spurious ecological inferences, and skew resulting management recommendations. To test whether animal movement varies with proximity to bait, we used high‐resolution global positioning system telemetry data of 10 fishers (Pekania pennanti), temporally paired with 64 baited wildlife camera traps, to quantify the effect of bait on individual and population movement metrics. Although bait appeared to have a significant correlative effect on 1‐hour movement segments, landscape characteristics had an effect 1.7 times greater, where the proportion of mixed forest and cultivation explained the majority of variability in animal movements. We contend that maximizing probability of detection and controlling or modeling local‐scale landscape variability that could affect the probability of detection is a more important consideration in wildlife research than the effect of bait, which is eclipsed by differences incurred by natural habitat heterogeneity. Failing to maximize the probability of detection may obscure the modest bias potentially presented by the use of bait, or attractants, on ecological inference. © 2019 The Wildlife Society
Identifying gene mutations of Chinese patients with polycystic kidney disease through targeted next‐generation sequencing technology
Authors: Wang Tao , Li Qinggang , Shang Shunlai , Geng Guangrui , Xie Yuansheng , Cai Guangyan , Chen Xiangmei 
Published: May 2019

AbstractBackgroundPolycystic kidney disease (PKD) is the most common hereditary kidney disease. The main mutational genes causing autosomal dominant polycystic kidney disease (ADPKD) are PKD1 and PKD2 as well as some rare pathogenic genes. Unilateral PKD is rare in clinics, and its association with gene mutations is unclear.MethodsTargeted next‐generation sequencing (NGS) was performed to detect the renal ciliopathy‐associated genes (targeted NGS panel including 63 genes) in PKD patients.ResultsForty‐eight PKD1 and PKD2 mutation sites were detected in 44 bilateral PKD patients, of which 48 were PKD1 mutation sites (87.5%) and six were PKD2 mutation sites (12.5%). All of which exhibited typical ADPKD. Furthermore, we detected HNF1B heterozygous mutations in three families. Although these three patients showed HNF1B heterozygous mutations, their clinical characteristics differed and showed phenotypic heterogeneity.ConclusionsTargeted NGS panel was helpful in detecting typical ADPKD patients and even in non‐typical PKD patients. Macromutation in HNF1B may lead to bilateral PKD. The 16 novel PKD gene mutation sites and two novel PKD2 gene mutation sites discovered in this study have some significance in genetic counseling for ADPKD patients, and increase the number of studied families and expand the mutation database of ADPKD.
PMS2 germline mutation c.943C>T (p.Arg315*)‐induced Lynch syndrome‐associated ovarian cancer
Authors: Guo Xiaoqing , Wu Weimin , Gao Hao , Li Xiaofeng , He Qizhi , Zhu Yong , Liu Na 
Published: May 2019

AbstractBackgroundLynch syndrome (LS) is an autosomal dominant cancer predisposition condition caused by germline heterozygous mutations in mismatch repair (MMR) genes. However, as one of the MMR genes, PMS2 mutation‐induced LS‐associated ovarian cancer (LSAOC) has rarely been reported.MethodsNext‐generation sequencing (NGS) or Sanger sequencing was used to detect the genetic status of one family including four generations with 16 members. Then, quantitative real‐time PCR (qPCR), western blotting, immunohistochemistry (IHC) staining, and Swiss‐Model software were used to identify the function of the PMS2 mutation.ResultsFive individuals [I‐1, II‐1, II‐2, II‐4, and III‐2 (proband)] suffered from LS‐associated cancers, for example, colon cancer, gastric cancer, and ovarian cancer, with the age of onset ranging from 39 to 70 years old. A PMS2 germline heterozygous mutation (c.943C>T) was confirmed in three members [II‐9, III‐2, and IV‐1] by gene sequencing. In addition, this PMS2 mutation was verified by qPCR, western blotting, and IHC, and a dramatic change with partial loss of the C‐terminal domain in an α‐helix might be exhibited.ConclusionCarrying PMS2 germline mutations (c.943C>T) confers an extremely high susceptibility of suffering from LS‐associated cancers. Thus, close clinical monitoring and prophylactic surgery is highly recommended to help reduce the morbidity and mortality of LS‐associated cancers.
The Enamel Phenotype in Homozygous Fam83h Truncation Mice
Authors: Wang Shih‐Kai , Hu Yuanyuan , Smith Charles E. , Yang Jie , Zeng Chunhua , Kim Jung‐Wook , Hu Jan C‐C. , Simmer James P. 
Published: May 2019

AbstractBackgroundTruncation FAM83H mutations cause human autosomal dominant hypocalcified amelogenesis imperfecta (ADHCAI), an inherited disorder characterized by severe hardness defects in dental enamel. No enamel defects were observed in Fam83h null mice suggesting that Fam83h truncation mice would better replicate human mutations.MethodsWe generated and characterized a mouse model (Fam83hTr/Tr) expressing a truncated FAM83H protein (amino acids 1–296), which recapitulated the ADHCAI‐causing human FAM83H p.Tyr297* mutation.ResultsDay 14 and 7‐week Fam83hTr/Tr molars exhibited rough enamel surfaces and slender cusps resulting from hypoplastic enamel defects. The lateral third of the Fam83hTr/Tr incisor enamel layer was thinner, with surface roughness and altered enamel rod orientation, suggesting disturbed enamel matrix secretion. Regular electron density in mandibular incisor enamel indicated normal enamel maturation. Only mildly increased posteruption attrition of Fam83hTr/Tr molar enamel was observed at 7‐weeks. Histologically, the Fam83hTr/Tr enamel organ, including ameloblasts, and enamel matrices at sequential stages of amelogenesis exhibited comparable morphology without overt abnormalities, except irregular and less evident ameloblast Tomes' processes in specific areas.ConclusionsConsidering Fam83h−/− mice showed no enamel phenotype, while Fam83hTr/Tr (p.Tyr297*) mice displayed obvious enamel malformations, we conclude that FAM83H truncation mutations causing ADHCAI in humans disturb amelogenesis through a neomorphic mechanism, rather than haploinsufficiency.
A low‐cost variable polarization reflectarray based on controllable wave‐path difference
Authors: Wang Quan , Shao Zhen Hai , Jin Mou Ping , Zhang Xiao Lin , Fang Jia , Chen Qian , Zou Wen Man 
Published: May 2019

AbstractA variable polarization reflectarray antenna is investigated in this communication. It consists of the dual‐layer three parallel dipole loops (TPDLs) to independently control the reflected spatial compensative phase and the phase difference of two orthogonal LP components. In this case, the proposed variable polarization reflectarray can transform a linear polarization (LP) mode into an arbitrary polarization mode by simply rotating the feeder and adjusting the wave‐path difference between the dual‐layer TPDL. A detailed operating mechanism of the variable polarization is introduced in this work. As an example, a 13 × 13‐element offset reflectarray is designed, fabricated, and measured. Four different polarization states of right‐hand circularly polarized (RHCP), 45°LP, left‐hand CP (LHCP), and 135°LP are measured and validated with a specific incident LP wave. The measured gains of 22 dB and 1.5‐dB gain bandwidths of 11% are achieved for all the states. This new reflectarray antenna is especially useful for low‐cost variable polarization applications.
Technical Note: Sensitive volume effects on ion chamber responses in longitudinal magnetic fields
Authors: Reynolds Michael , Rathee Satyapal , Fallone B. Gino 
Published: May 2019

PurposeIt has been shown that ion chamber dose response Monte Carlo simulations, in transverse magnetic fields, are susceptible to small changes in the scored sensitive volume. Changes in sensitive volumes have been investigated as a surrogate for modeling the true collection volume governed by the electric field. This work has not been fully extended to longitudinal fields. This study investigates the effect of the sensitive volume of ion chambers on magnetic field dose response within longitudinal magnetic fields.MethodsThe egs_chamber application within EGSnrc was used to model the Exradin A19, A28, and A1SL ion chambers within a uniform longitudinal magnetic field. The sensitive volume of the ion chambers was varied by removing portions of the air volume (from 0.2 to 3 mm) closest to the chamber stem from the dose scoring region; the dose to the scoring volume as a function of magnetic fields strength was normalized to 0 T in all cases.ResultsWith the chamber long axis oriented parallel to the radiation and magnetic fields, for every magnetic field strength, all investigated chambers' dose response remained inside statistical variations for all investigated chamber sensitive volumes. When the chamber long axis is oriented perpendicular to the radiation and magnetic fields, the A28 and A1SL show negligible sensitive volume effects, while the A19 under responded by 0.5% for the largest removed volume of 3 mm.ConclusionsWhen the ion chambers' long axis is parallel to the radiation and magnetic fields, the magnetic field dose response is unaffected by small changes in sensitive volume. When oriented perpendicularly, only the A19 exhibits sensitive volume based magnetic field dose response changes, and only with ≥ 1 mm of assumed insensitive volume. We can therefore safely assume complete charge collection in Monte Carlo calculated correction factors involving similar chambers in similar conditions.