bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Cyclin-Dependent Kinase 5 Inhibitor Peptide Inhibits Herpes Simplex Virus Type 1 Replication
Authors: Man Adrian , Slevin Mark , Petcu Eugen , Fraefel Cornel 
Published: February 2019

AbstractIn order to evaluate the influence of CDK5 inhibitory peptide (CIP) on Human alphaherpesvirus 1 (HSV-1) replication, we constructed two recombinant adeno-associated-virus 2 (rAAV2) vectors encoding CIP fused with cyan-fluorescent-protein (CFP), with or without nuclear localization signal. A third vector encoding non-fused CIP and CFP was also constructed. HeLa and HEK 293T cells were infected with the rAAV-CIP vectors at multiplicity of infection (MOI) of 5000, in the absence or presence of a recombinant HSV-1 that encodes a yellow-fluorescent-protein (rHSV48Y; MOI = 1). Cells co-infected with rHSV48Y and rAAV vectors that did not express the CIP gene (rAAV-CFP-Neo) served as controls. At 24 h after infection, the effect of CIP on rHSV48Y replication was assessed by PCR, qRT-PCR, Western-blot, flow-cytometry, epifluorescence and confocal microscopy. We show that in cultures co-infected with rAAV-CFP-Neo, 27% of the CFP-positive cells present rHSV48Y replication compartments. By contrast, in cultures co-infected with CIP-encoding rAAV2 vectors and rHSV48Y only 6–20% of the cells positive for CIP showed rHSV48Y replication compartments, depending on the CIP variant. Flow-cytometry showed that less than 40% of the rHSV48Y/rAAV-CIP, and more than 75% of rHSV48Y/rAAV-CFP-Neo co-infected cells were positive for both transgene products. The microscopy and flow-cytometry data support the hypothesis that CIP is inhibiting HSV-1 replication.
Molecular genetic analysis using targeted NGS analysis of 677 individuals with retinal dystrophy
Authors: Jespersgaard Cathrine , Fang Mingyan , Bertelsen Mette , Dang Xiao , Jensen Hanne , Chen Yulan , Bech Niels , Dai Lanlan , Rosenberg Thomas , Zhang Jianguo , Møller Lisbeth Birk , Tümer Zeynep , Brøndum-Nielsen Karen , Grønskov Karen 
Published: February 2019

AbstractInherited retinal diseases (IRDs) are a common cause of visual impairment. IRD covers a set of genetically highly heterogeneous disorders with more than 150 genes associated with one or more clinical forms of IRD. Molecular genetic diagnosis has become increasingly important especially due to expanding number of gene therapy strategies under development. Next generation sequencing (NGS) of gene panels has proven a valuable diagnostic tool in IRD. We present the molecular findings of 677 individuals, residing in Denmark, with IRD and report 806 variants of which 187 are novel. We found that deletions and duplications spanning one or more exons can explain 3% of the cases, and thus copy number variation (CNV) analysis is important in molecular genetic diagnostics of IRD. Seven percent of the individuals have variants classified as pathogenic or likely-pathogenic in more than one gene. Possible Danish founder variants in EYS and RP1 are reported. A significant number of variants were classified as variants with unknown significance; reporting of these will hopefully contribute to the elucidation of the actual clinical consequence making the classification less troublesome in the future. In conclusion, this study underlines the relevance of performing targeted sequencing of IRD including CNV analysis as well as the importance of interaction with clinical diagnoses.
Clostridium ramosum regulates enterochromaffin cell development and serotonin release
Authors: Mandić Ana D. , Woting Anni , Jaenicke Tina , Sander Anika , Sabrowski Wiebke , Rolle-Kampcyk Ulrike , von Bergen Martin , Blaut Michael 
Published: February 2019

AbstractPeripheral serotonin (5-hydroxytryptamine: 5-HT) synthesized in the intestine by enterochromaffin cells (ECs), plays an important role in the regulation of peristaltic of the gut, epithelial secretion and promotes the development and maintenance of the enteric neurons. Recent studies showed that the indigenous gut microbiota modulates 5-HT signalling and that ECs use sensory receptors to detect dietary and microbiota-derived signals from the lumen to subsequently transduce the information to the nervous system. We hypothesized that Clostridium ramosum by increasing gut 5-HT availability consequently contributes to high-fat diet-induced obesity. Using germ-free mice and mice monoassociated with C. ramosum, intestinal cell lines and mouse organoids, we demonstrated that bacterial cell components stimulate host 5-HT secretion and program the differentiation of colonic intestinal stem progenitors toward the secretory 5-HT-producing lineage. An elevated 5-HT level regulates the expression of major proteins involved in intestinal fatty acid absorption in vitro, suggesting that the presence of C. ramosum in the gut promotes 5-HT secretion and thereby could facilitates intestinal lipid absorption and the development of obesity.
High content screening identifies monensin as an EMT-selective cytotoxic compound
Authors: Vanneste Marion , Huang Qin , Li Mengshi , Moose Devon , Zhao Lei , Stamnes Mark A. , Schultz Michael , Wu Meng , Henry Michael D. 
Published: February 2019

AbstractEpithelial-to-mesenchymal transition (EMT) is implicated in cancer metastasis and drug resistance. Specifically targeting cancer cells in an EMT-like state may have therapeutic value. In this study, we developed a cell imaging-based high-content screening protocol to identify EMT-selective cytotoxic compounds. Among the 2,640 compounds tested, salinomycin and monensin, both monovalent cation ionophores, displayed a potent and selective cytotoxic effect against EMT-like cells. The mechanism of action of monensin was further evaluated. Monensin (10 nM) induced apoptosis, cell cycle arrest, and an increase in reactive oxygen species (ROS) production in TEM 4-18 cells. In addition, monensin rapidly induced swelling of Golgi apparatus and perturbed mitochondrial function. These are previously known effects of monensin, albeit occurring at much higher concentrations in the micromolar range. The cytotoxic effect of monensin was not blocked by inhibitors of ferroptosis. To explore the generality of our findings, we evaluated the toxicity of monensin in 24 human cancer cell lines and classified them as resistant or sensitive based on IC50 cutoff of 100 nM. Gene Set Enrichment Analysis identified EMT as the top enriched gene set in the sensitive group. Importantly, increased monensin sensitivity in EMT-like cells is associated with elevated uptake of 3H-monensin compared to resistant cells.
Caveolin-1α regulates primary cilium length by controlling RhoA GTPase activity
Authors: Rangel Laura , Bernabé-Rubio Miguel , Fernández-Barrera Jaime , Casares-Arias Javier , Millán Jaime , Alonso Miguel A. , Correas Isabel 
Published: February 2019

AbstractThe primary cilium is a single non-motile protrusion of the plasma membrane of most types of mammalian cell. The structure, length and function of the primary cilium must be tightly controlled because their dysfunction is associated with disease. Caveolin 1 (Cav1), which is best known as a component of membrane invaginations called caveolae, is also present in non-caveolar membrane domains whose function is beginning to be understood. We show that silencing of α and β Cav1 isoforms in different cell lines increases ciliary length regardless of the route of primary ciliogenesis. The sole expression of Cav1α, which is distributed at the apical membrane, restores normal cilium size in Cav1 KO MDCK cells. Cells KO for only Cav1α, which also show long cilia, have a disrupted actin cytoskeleton and reduced RhoA GTPase activity at the apical membrane, and a greater accumulation of Rab11 vesicles at the centrosome. Subsequent experiments showed that DIA1 and ROCK help regulate ciliary length. Since MDCK cells lack apical caveolae, our results imply that non-caveolar apical Cav1α is an important regulator of ciliary length, exerting its effect via RhoA and its effectors, ROCK and DIA1.
Multiple roles for Vitamin B6 in plant acclimation to UV-B
Authors: Czégény Gyula , Kőrösi László , Strid Åke , Hideg Éva 
Published: February 2019

AbstractDirect and indirect roles of vitamin B6 in leaf acclimation to supplementary UV-B radiation are shown in vitamin B6 deficient Arabidopsis thaliana mutant rsr4-1 and C24 wild type. Responses to 4 days of 3.9 kJ m−2 d−1 biologically effective UV-B dose were compared in terms of leaf photochemistry, vitamer content, and antioxidant enzyme activities; complemented with a comprehensive study of vitamer ROS scavenging capacities. Under UV-B, rsr4-1 leaves lost more (34%) photochemical yield than C24 plants (24%). In the absence of UV-B, rsr4-1 leaves contained markedly less pyridoxal-5′-phosphate (PLP) than C24 ones, but levels increased up to the C24 contents in response to UV-B. Activities of class-III ascorbate and glutathione peroxidases increased in C24 leaves upon the UV-B treatment but not in the rsr4-1 mutant. SOD activities remained the same in C24 but decreased by more than 50% in rsr4-1 under UV-B. Although PLP was shown to be an excellent antioxidant in vitro, our results suggest that the UV-B protective role of B6 vitamers is realized indirectly, via supporting peroxidase defence rather than by direct ROS scavenging. We hypothesize that the two defence pathways are linked through the PLP-dependent biosynthesis of cystein and heme, affecting peroxidases.
Secondary structures and cell-penetrating abilities of arginine-rich peptide foldamers
Authors: Oba Makoto , Nagano Yu , Kato Takuma , Tanaka Masakazu 
Published: February 2019

AbstractFoldamers, which are folded oligomers with well-defined conformations, have been recently reported to have a good cell-penetrating ability. α,α-Disubstituted α-amino acids are one such promising tool for the design of peptide foldamers. Here, we prepared four types of L-arginine-rich nonapeptides containing L-leucine or α,α-disubstituted α-amino acids, and evaluated their secondary structures and cell-penetrating abilities in order to elucidate a correlation between them. Peptides containing α,α-disubstituted α-amino acids had similar resistance to protease digestion but showed different secondary structures. Intracellular uptake assays revealed that the helicity of peptides was important for their cell-penetrating abilities. These findings suggested that a peptide foldamer with a stable helical structure could be promising for the design of cell-penetrating peptides.
Global meridional eddy heat transport inferred from Argo and altimetry observations
Authors: Sun Bowen , Liu Chuanyu , Wang Fan 
Published: February 2019

AbstractProportion and pathways of the eddy-induced heat transport are critical in maintaining world’s ocean and climate states. However, an observation-based three-dimensional picture of how oceanic eddies contribute to the global heat transport is yet not quantitatively specified, particularly due to insufficiency of data. Here, using refined methods, we have achieved this goal by analyzing millions of high-quality Argo hydrographic profiles and high-resolution satellite altimetric data. We first presented the spatial differences of individual eddies by reconstructing 254 representative eddies all over the ocean, and then calculated heat fluxes associated with eddies in 5° × 5° boxes. It is revealed that all parameters of eddies vary significantly with both latitudes and longitudes, which is crucial in yielding spatially varying heat fluxes and transports. The eddies not only transport heat towards high latitudes (down-gradient), but also towards low latitudes (up-gradient), particularly at subsurface layers of mid-latitude northern Pacific Ocean and low-latitude Atlantic Ocean. The eddy heat transport is mainly confined in the upper 1000 m of the western part and mid-latitudes of the world’s ocean basins, coinciding with maximum meridional temperature gradients. It peaks at 0.8 PW and 0.3 PW (1 PW = 1015 W) at 45°S and 35°N, respectively, stronger than previous estimates based on model results, and accounts for about one half and one third of the estimated total oceanic heat transport at the same latitudes, respectively. In any location except for the areas associated with the Antarctic Circumpolar Current, the eddy stirring component is distinctly (1–10 times) larger than the eddy trapping component.
The role of frailty in predicting mortality and readmission in older adults in acute care wards: a prospective study
Authors: Hao Qiukui , Zhou Lixing , Dong Biao , Yang Ming , Dong Birong , Weil Yuquan 
Published: February 2019

AbstractFew studies have focused on frailty as a predictor of mortality and readmission among inpatients in the acute care setting, especially over long follow-up periods. We conducted this study to determine the impact of the frailty on subsequent mortality and readmission in this setting. This study was a prospective observational study conducted in the acute geriatric wards, with a three-year follow-up duration. We assessed frailty via the 36-item Frailty Index (FI), and a cut-off value of 0.25 was used to identify the presence or absence of frailty. We collected survival and readmission information through telephone interviews at 12, 24, and 36 months. We used the Cox regression model to examine the association between frailty and outcomes interested (death and readmission). The present study included 271 patients (mean age: 81.1 years old; 20.3% females), of whom 21.4% died during the 3-year follow-up period. One hundred and thirty-three patients (49.1%) were identified as being frail. The prevalence of frailty was similar in men and women (46.8% vs.58.2%, P = 0.130). Compared with non-frail patients, death and hospital readmission rates of frail patients were increased. Frailty was an independent predictor of 3-year death (adjusted hazard ratio (HR): 2.09; 95% confidence interval (CI): 1.20 to 3.63) and readmission (adjusted HR: 1.40; 95% CI: 1.04 to 1.88) after adjusting for several potential confounders. Frailty is prevalent among older inpatients and is a valuable predictor of 3-year mortality and hospital readmission in an acute care setting.
2,3-Dihydroxybenzoate meta-Cleavage Pathway is Involved in o-Phthalate Utilization in Pseudomonas sp. strain PTH10
Authors: Kasai Daisuke , Iwasaki Takumi , Nagai Kazuki , Araki Naoto , Nishi Tatsunari , Fukuda Masao 
Published: February 2019

AbstractPseudomonas sp. strain PTH10 can utilize o-phthalate which is a key intermediate in the bacterial degradation of some polycyclic aromatic hydrocarbons. In this strain, o-phthalate is degraded to 2,3-dihydroxybenzoate and further metabolized via the 2,3-dihydroxybenzoate meta-cleavage pathway. Here, the opa genes which are involved in the o-phthalate catabolism were identified. Based on the enzymatic activity of the opa gene products, opaAaAbAcAd, opaB, opaC, and opaD were found to code for o-phthalate 2,3-dioxygenase, dihydrodiol dehydrogenase, 2,3-dihydroxybenzoate 3,4-dioxygenase, and 3-carboxy-2-hydroxymuconate-6-semialdehyde decarboxylase, respectively. Collectively, these enzymes are thought to catalyze the conversion of o-phthalate to 2-hydroxymuconate-6-semialdehyde. Deletion mutants of the above opa genes indicated that their products were required for the utilization of o-phthalate. Transcriptional analysis showed that the opa genes were organized in the same transcriptional unit. Quantitative analysis of opaAa, opaB, opaC, opaD, opaE, and opaN revealed that, except for opaB and opaC, all other genes were transcriptionally induced during growth on o-phthalate. The constitutive expression of opaB and opaC, and the transcriptional induction of opaD located downstream of opaB, suggest several possible internal promoters are existence in the opa cluster. Together, these results strongly suggest that the opa genes are involved in a novel o-phthalate catabolic pathway in strain PTH10.
Analysis of mRNA abundance for histone variants, histone- and DNA-modifiers in bovine in vivo and in vitro oocytes and embryos
Authors: Duan J. , Zhu L. , Dong H. , Zheng X. , Jiang Z. , Chen J. , Tian X. C. 
Published: February 2019

AbstractTranscript abundance of histone variants, modifiers of histone and DNA in bovine in vivo oocytes and embryos were measured as mean transcripts per million (TPM). Six of 14 annotated histone variants, 8 of 52 histone methyl-transferases, 5 of 29 histone de-methylases, 5 of 20 acetyl-transferases, 5 of 19 de-acetylases, 1 of 4 DNA methyl-transferases and 0 of 3 DNA de-methylases were abundant (TPM >50) in at least one stage studied. Overall, oocytes and embryos contained more varieties of mRNAs for histone modification than for DNA. Three expression patterns were identified for histone modifiers: (1) transcription before embryonic genome activation (EGA) and down-regulated thereafter such as PRMT1; (2) low in oocytes but transiently increased for EGA such as EZH2; (3) high in oocytes but decreased by EGA such as SETD3. These expression patterns were altered by in vitro culture. Additionally, the presence of mRNAs for the TET enzymes throughout pre-implantation development suggests persistent de-methylation. Together, although DNA methylation changes are well-recognized, the first and second orders of significance in epigenetic changes by in vivo embryos may be histone variant replacements and modifications of histones.
A universal dimensionality function for the fractal dimensions of Laplacian growth
Authors: Nicolás-Carlock J. R. , Carrillo-Estrada J. L. 
Published: February 2019

AbstractLaplacian growth, associated to the diffusion-limited aggregation (DLA) model or the more general dielectric-breakdown model (DBM), is a fundamental out-of-equilibrium process that generates structures with characteristic fractal/non-fractal morphologies. However, despite diverse numerical and theoretical attempts, a data-consistent description of the fractal dimensions of the mass-distributions of these structures has been missing. Here, an analytical model of the fractal dimensions of the DBM and DLA is provided by means of a recently introduced dimensionality equation for the scaling of clusters undergoing a continuous morphological transition. Particularly, this equation relies on an effective information-function dependent on the Euclidean dimension of the embedding-space and the control parameter of the system. Numerical and theoretical approaches are used in order to determine this information-function for both DLA and DBM. In the latter, a connection to the Rényi entropies and generalized dimensions of the cluster is made, showing that DLA could be considered as the point of maximum information-entropy production along the DBM transition. The results are in good agreement with previous theoretical and numerical estimates for two- and three-dimensional DBM, and high-dimensional DLA. Notably, the DBM dimensions conform to a universal description independently of the initial cluster-configuration and the embedding-space.
One-pot selective synthesis of azoxy compounds and imines via the photoredox reaction of nitroaromatic compounds and amines in water
Authors: Tan Hao , Liu XingChen , Su JiHu , Wang YingXiong , Gu XianMo , Yang DongJiang , Waclawik Eric R. , Zhu HuaiYong , Zheng ZhanFeng 
Published: February 2019

AbstractA facile one-pot two-stage photochemical synthesis of aromatic azoxy compounds and imines has been developed by coupling the selective reduction of nitroaromatic compounds with the selective oxidation of amines in an aqueous solution. In the first stage (light illumination, Ar atmosphere), the light excited nitroaromatic molecule abstract H from amine to form ArNO2H and amine radical, which then form nitrosoaromatic, hydroxylamine and imine compounds. Water acts as a green solvent for the dispersion of the reactants and facilitates the formation of nitrosoaromatic and hydroxylamine intermediate compounds. In the second stage (no light, air atmosphere), the condensation of nitrosoaromatic and hydroxylamine compounds yields aromatic azoxy product with the aid of molecular oxygen in air. This photochemical synthesis achieved both high conversion and high product selectivity (>99%) at room temperature.
Four-dimensional CT as a valid approach to detect and quantify kinematic changes after selective ankle ligament sectioning
Authors: Buzzatti Luca , Keelson Benyameen , Apperloo Jildert , Scheerlinck Thierry , Baeyens Jean-Pierre , Van Gompel Gert , Vandemeulebroucke Jef , de Maeseneer Michel , de Mey Johan , Buls Nico , Cattrysse Erik 
Published: February 2019

AbstractThe objective of the current study was to explore the potential of dynamic computed tomography to detect kinematic changes, induced by sequential sectioning of the lateral collateral ligaments of the ankle, during full motion sequence of the talocrural joint. A custom-made device was used to induce cyclic controlled ankle inversion movement in one fresh frozen cadaver leg. A 256-slice CT scanner was used to investigate four different scenarios. Scenario 1 with all ligaments intact was first investigated followed by sequential section of the anterior talo-fibular ligament (Scenario 2), the calcaneo-fibular ligament (Scenario 3) and posterior talo-fibular ligament (Scenario 4). Off-line image processing based on semi-automatic segmentation and bone rigid registration was performed. Motion parameters such as translation, rotational angles and orientation and position of the axis of rotation were calculated. Differences between scenarios were calculated. Progressive increase of cranio-caudal displacement up to 3.9 mm and flexion up to 10° compared to Scenario 1 were reported. Progressive changes in orientation (up to 20.6°) and position (up to 4.1 mm) of the axis of rotation were also shown. Estimated effective dose of 0.005 mSv (1.9 mGy CTDIvol) was reported. This study demonstrated that kinematic changes due to the absence of ligament integrity can be detected with 4DCT with minimal radiation exposure. Identifying abnormal kinematic patterns could have future application in helping clinicians to choose patients’ optimal treatment. Therefore, further studies with bigger in vitro sample sizes and consequent investigations in vivo are recommended to confirm the current findings.
A High Performance Triboelectric Nanogenerator Using Porous Polyimide Aerogel Film
Authors: Saadatnia Zia , Mosanenzadeh Shahriar Ghaffari , Esmailzadeh Ebrahim , Naguib Hani E. 
Published: February 2019

AbstractThis paper presents a novel aerogel-based Triboelectric Nanogenerator (TENG) which shows a superior performance for energy harvesting and sensing applications. Polyimide-based aerogel film with varying open-cell content level is developed to be used as the main contact material for the TENG. The fabricated aerogel film is fully characterized to reveal the chemical and mechanical properties of the developed material. It is shown the use of Polyimide aerogel film remarkably enhances the performance of the TENG compared to a TENG with fully dense Polyimide layer with no porosity. This enhancement is due to the increase on the effective surface area, charge generation inside the open-cells of the aerogel, and increase on the relative capacitance of the TENG device. The effect of varying porosity from zero to 70% of open-cell content reveals that the aerogel film with 50% shows the highest performance where the peak open-circuit voltage of 40V and peak short-circuit current of 5 μA are obtained. These values are higher than those of the TENG with simple Polyimide layer with an order of magnitude. Finally, the performance of proposed TENG under resistive loads and capacitors are tested. Thus, this work presents an effective method for high performance TENG.