bluuebunny/crossref_metadata_2025_split huggingface dataset:
C/EBPβ regulates Vegf gene expression in granulosa cells undergoing luteinization during ovulation in female rats
Authors: Shinagawa Masahiro , Tamura Isao , Maekawa Ryo , Sato Shun , Shirafuta Yuichiro , Mihara Yumiko , Okada - Matsumoto Maki , Taketani Toshiaki , Asada Hiromi , Tamura Hiroshi , Sugino Norihiro 
Published: January 2019

AbstractThe ovulatory LH-surge increases Vegf gene expression in granulosa cells (GCs) undergoing luteinization during ovulation. To understand the factors involved in this increase, we examined the roles of two transcription factors and epigenetic mechanisms in rat GCs. GCs were obtained from rats treated with eCG before, 4 h, 8 h, 12 h and 24 h after hCG injection. Vegf mRNA levels gradually increased after hCG injection and reached a peak at 12 h. To investigate the mechanism by which Vegf is up-regulated after hCG injection, we focused on C/EBPβ and HIF1α. Their protein expression levels were increased at 12 h. The binding activity of C/EBPβ to the Vegf promoter region increased after hCG injection whereas that of HIF1α did not at this time point. The C/EBPβ binding site had transcriptional activities whereas the HIF1α binding sites did not have transcriptional activities under cAMP stimulation. The levels of H3K9me3 and H3K27me3, which are transcriptional repression markers, decreased in the C/EBPβ binding region after hCG injection. The chromatin structure of this region becomes looser after hCG injection. These results show that C/EBPβ regulates Vegf gene expression with changes in histone modifications and chromatin structure of the promoter region in GCs undergoing luteinization during ovulation.
Spatio-temporal overview of neuroinflammation in an experimental mouse stroke model
Authors: Buscemi Lara , Price Melanie , Bezzi Paola , Hirt Lorenz 
Published: January 2019

AbstractAfter ischemic stroke, in the lesion core as well as in the ischemic penumbra, evolution of tissue damage and repair is strongly affected by neuroinflammatory events that involve activation of local specialized glial cells, release of inflammatory mediators, recruiting of systemic cells and vascular remodelling. To take advantage of this intricate response in the quest to devise new protective therapeutic strategies we need a better understanding of the territorial and temporal interplay between stroke-triggered inflammatory and cell death-inducing processes in both parenchymal and vascular brain cells. Our goal is to describe structural rearrangements and functional modifications occurring in glial and vascular cells early after an acute ischemic stroke. Low and high scale mapping of the glial activation on brain sections of mice subjected to 30 minutes middle cerebral artery occlusion (MCAO) was correlated with that of the neuronal cell death, with markers for microvascular changes and with markers for pro-inflammatory (IL-1β) and reparative (TGFβ1) cytokines. Our results illustrate a time-course of the neuroinflammatory response starting at early time-points (1 h) and up to one week after MCAO injury in mice, with an accurate spatial distribution of the observed phenomena.
Two-Parameter Quasi-Ballistic Transport Model for Nanoscale Transistors
Authors: Lee Ji Ung , Cuduvally Ramya , Dhakras Prathamesh , Nguyen Phung , Hughes Harold L. 
Published: January 2019

AbstractWe show that by adding only two fitting parameters to a purely ballistic transport model, we can accurately characterize the current-voltage characteristics of nanoscale MOSFETs. The model is an extension of Natori’s model and includes transmission probability and drain-channel coupling parameter. The latter parameter gives rise to a theoretical RON that is significantly larger than those predicted previously. To validate our model, we fabricated n-channel MOSFETs with varying channel lengths. We show the length dependence of these parameters to support a quasi-ballistic description of our devices.
The highly GABARAP specific rat monoclonal antibody 8H5 visualizes GABARAP in immunofluorescence imaging at endogenous levels
Authors: Simons Indra M. , Mohrlüder Jeannine , Feederle Regina , Kremmer Elisabeth , Zobel Thomas , Dobner Jochen , Bleffert Nicole , Hoffmann Silke , Willbold Dieter 
Published: January 2019

AbstractThe determination of unique functions of GABARAP (gamma-aminobutyric acid type A receptor-associated protein), a member of the highly conserved protein family of mammalian autophagy-related 8 protein (mATG8), within diverse cellular processes remains challenging. Because available anti-GABARAP antibodies perform inadequate, especially within various microscopy-based applications, we aimed to develop an antibody that targets GABARAP but not its close orthologs. Following the latest recommendations for antibody validation including fluorescence protein tagging, genetic and orthogonal strategies, we characterized the resulting anti-GABARAP (8H5) antibody during confocal immunofluorescence imaging in-depth. We compared the antibody staining pattern with that obtained for fluorescence protein tagged GABARAP, GABARAPL1 or GABARAPL2 each ectopically expressed in GABARAP knockout cells. Furthermore, we imaged cells expressing all mATG8 family members at endogenous levels and checked GABARAP knockout cells for unspecific staining under fed or macroautophagy-inducing conditions. Finally, we simultaneously stained cells for endogenous GABARAP and the common autophagosomal marker LC3B. Summarized, the presented antibody shows high specificity for GABARAP without cross-reactivity to other mATG8 family members in immunofluorescence imaging making it a valuable tool for the identification of unique GABARAP functions.
Epidermal growth factor receptor promotes cerebral and retinal invasion by Toxoplasma gondii
Authors: Corcino Yalitza Lopez , Portillo Jose-Andres C. , Subauste Carlos S. 
Published: January 2019

AbstractLittle is known about strategies used by pathogens to facilitate CNS invasion.Toxoplasma gondiireaches the CNS by circulating in blood within leukocytes or as extracellular tachyzoites.T. gondiiinduces EGFR signalingin vitroduring invasion of mammalian cells. We examined the effects of endothelial cell EGFR on CNS invasion. Transgenic mice whose endothelial cells expressed a dominant negative (DN) EGFR (inhibits EGFR signaling) exhibited diminished parasite load and histopathology in the brain and retina afterT. gondiiinfection. I.V. administration of infected leukocytes or extracellular tachyzoites led to reduced parasite loads in mice with DN EGFR. This was not explained by enhanced immunity or reduced leukocyte recruitment. Endothelial cell infection is key for CNS invasion. Parasite foci in brain endothelial cells were reduced by DN EGFR. DN EGFR in these cells led to recruitment of the autophagy protein LC3 aroundT. gondiiand spontaneous parasite killing dependent on the autophagy protein ULK1 and lysosomal enzymes. The autophagy inhibitor 3-MA prevented DN EGFR mice from exhibiting reduced CNS invasion. Altogether, EGFR is a novel regulator ofT. gondiiinvasion of neural tissue, enhancing invasion likely by promoting survival of the parasite within endothelial cells.
Learning from Longitudinal Data in Electronic Health Record and Genetic Data to Improve Cardiovascular Event Prediction
Authors: Zhao Juan , Feng QiPing , Wu Patrick , Lupu Roxana A. , Wilke Russell A. , Wells Quinn S. , Denny Joshua C. , Wei Wei-Qi 
Published: January 2019

AbstractCurrent approaches to predicting a cardiovascular disease (CVD) event rely on conventional risk factors and cross-sectional data. In this study, we applied machine learning and deep learning models to 10-year CVD event prediction by using longitudinal electronic health record (EHR) and genetic data. Our study cohort included 109, 490 individuals. In the first experiment, we extracted aggregated and longitudinal features from EHR. We applied logistic regression, random forests, gradient boosting trees, convolutional neural networks (CNN) and recurrent neural networks with long short-term memory (LSTM) units. In the second experiment, we applied a late-fusion approach to incorporate genetic features. We compared the performance with approaches currently utilized in routine clinical practice – American College of Cardiology and the American Heart Association (ACC/AHA) Pooled Cohort Risk Equation. Our results indicated that incorporating longitudinal feature lead to better event prediction. Combining genetic features through a late-fusion approach can further improve CVD prediction, underscoring the importance of integrating relevant genetic data whenever available.
Revisiting the Maxillary Teeth in 384 Subjects Reveals A Deviation From the Classical Aesthetic Dimensions
Authors: Melo María , Ata-Ali Fadi , Huertas Julia , Cobo Teresa , Shibli Jamil Awad , Galindo-Moreno Pablo , Ata-Ali Javier 
Published: January 2019

AbstractDental esthetics need to be defined from the scientific perspective in order to obtain predictable treatment outcomes and avoid the effects of subjectivisms on the part of the dental profesional. It can be deduced that the ideal dimensions in the maxillary anterior sector are difficult to establish. Therefore, the primary purpose of this study was to define the dimensions of the maxillary anterior teeth and the relationships between them. In addition, an analysis was made to reinvestigate whether they complied with the Golden proportion, the RED (Recurrent Esthetic Dental) proportion and the Golden percentage. A total of 2304 tooth corresponding to 384 subjects were evaluated. The central incisor presented a mean width of 8.58 mm and a height of 9.35 mm, while the lateral incisor presented a width of 6.69 mm and a height of 7.75 mm. The mean width of the canine was 7.69 mm, with a height of 8.68 mm. The teeth revisited in this study did not comply with the ideal dimensions in the anterior maxillary sector as established by the Golden proportion, Golden percentage and RED. The information obtained from this study can be clinically applied to restore the dimensions during periodontal surgery, restorative dentistry and prosthetic rehabilitation.
Working memory performance in the elderly relates to theta-alpha oscillations and is predicted by parahippocampal and striatal integrity
Authors: Steiger Tineke K. , Herweg Nora A. , Menz Mareike M. , Bunzeck Nico 
Published: January 2019

AbstractThe ability to maintain information for a short period of time (i.e. working memory, WM) tends to decrease across the life span with large inter-individual variability; the underlying neuronal bases, however, remain unclear. To address this issue, we used a multimodal imaging approach (voxel-based morphometry, diffusion-tensor imaging, electroencephalography) to test the contribution of brain structures and neural oscillations in an elderly population. Thirty-one healthy elderly participants performed a change-detection task with different load conditions. As expected, accuracy decreased with increasing WM load, reflected by power modulations in the theta-alpha band (5–12 Hz). Importantly, these power changes were directly related to the tract strength between parahippocampus and parietal cortex. Furthermore, between-subject variance in gray matter volume of the parahippocampus and dorsal striatum predicted WM accuracy. Together, our findings provide new evidence that WM performance critically depends on parahippocampal and striatal integrity, while theta-alpha oscillations may provide a mechanism to bind the nodes within the WM network.
STC1 and PTHrP Modify Carbohydrate and Lipid Metabolism in Liver of a Teleost Fish
Authors: Palma Pedro F. S. , Bock Christian , Silva Tomé S. , Guerreiro Pedro M. , Power Deborah M. , Pörtner Hans-Otto , Canário Adelino V. M. 
Published: January 2019

AbstractStanniocalcin 1 (STC1) and parathyroid hormone-related protein (PTHrP) are calciotropic hormones in vertebrates. Here, a recently hypothesized metabolic role for these hormones is tested on European sea bass treated with: (i) teleost PTHrP(1–34), (ii) PTHrP(1–34) and anti-STC1 serum (pro-PTHrP groups), (iii) a PTHrP antagonist PTHrP(7–34) or (iv) PTHrP(7–34) and STC1 (pro-STC1 groups). Livers were analysed using untargeted metabolic profiling based on proton nuclear magnetic resonance (1H-NMR) spectroscopy. Concentrations of branched-chain amino acid (BCAA), alanine, glutamine and glutamate increased in pro-STC1 groups suggesting their mobilization from the muscle to the liver for degradation and gluconeogenesis from alanine and glutamine. In addition, only STC1 treatment decreased the concentrations of succinate, fumarate and acetate, indicating slowing of the citric acid cycle. In the pro-PTHrP groups the concentrations of glucose, erythritol and lactate decreased, indicative of gluconeogenesis from lactate. Taurine, trimethylamine, trimethylamine N-oxide and carnitine changed in opposite directions in the pro-STC1 versus the pro-PTHrP groups, suggesting opposite effects, with STC1 stimulating lipogenesis and PTHrP activating lipolysis/β-oxidation of fatty acids. These findings suggest a role for STC1 and PTHrP related to strategic energy mechanisms that involve the production of glucose and safeguard of liver glycogen reserves for stressful situations.
Optimization of HER3 expression imaging using affibody molecules: Influence of chelator for labeling with indium-111
Authors: Rinne Sara S. , Leitao Charles Dahlsson , Mitran Bogdan , Bass Tarek Z. , Andersson Ken G. , Tolmachev Vladimir , Ståhl Stefan , Löfblom John , Orlova Anna 
Published: January 2019

AbstractRadionuclide molecular imaging of human epidermal growth factor receptor 3 (HER3) expression using affibody molecules could be used for patient stratification for HER3-targeted cancer therapeutics. We hypothesized that the properties of HER3-targeting affibody molecules might be improved through modification of the radiometal-chelator complex. Macrocyclic chelators NOTA (1,4,7-triazacyclononane-N,N′,N′′-triacetic acid), NODAGA (1-(1,3-carboxypropyl)-4,7-carboxymethyl-1,4,7-triazacyclononane), DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), and DOTAGA (1,4,7,10-tetraazacyclododececane,1-(glutaric acid)−4,7,10-triacetic acid) were conjugated to the C-terminus of anti-HER3 affibody molecule Z08698 and conjugates were labeled with indium-111. All conjugates bound specifically and with picomolar affinity to HER3 in vitro. In mice bearing HER3-expressing xenografts, no significant difference in tumor uptake between the conjugates was observed. Presence of the negatively charged 111In-DOTAGA-complex resulted in the lowest hepatic uptake and the highest tumor-to-liver ratio. In conclusion, the choice of chelator influences the biodistribution of indium-111 labeled anti-HER3 affibody molecules. Hepatic uptake of anti-HER3 affibody molecules could be reduced by the increase of negative charge of the radiometal-chelator complex on the C-terminus without significantly influencing the tumor uptake.
Mutual action by Gγ and Gβ for optimal activation of GIRK channels in a channel subunit-specific manner
Authors: Tabak Galit , Keren-Raifman Tal , Kahanovitch Uri , Dascal Nathan 
Published: January 2019

AbstractThe tetrameric G protein-gated K+ channels (GIRKs) mediate inhibitory effects of neurotransmitters that activate Gi/o-coupled receptors. GIRKs are activated by binding of the Gβγ dimer, via contacts with Gβ. Gγ underlies membrane targeting of Gβγ, but has not been implicated in channel gating. We observed that, in Xenopus oocytes, expression of Gγ alone activated homotetrameric GIRK1* and heterotetrameric GIRK1/3 channels, without affecting the surface expression of GIRK or Gβ. Gγ and Gβ acted interdependently: the effect of Gγ required the presence of ambient Gβ and was enhanced by low doses of coexpressed Gβ, whereas excess of either Gβ or Gγ imparted suboptimal activation, possibly by sequestering the other subunit “away” from the channel. The unique distal C-terminus of GIRK1, G1-dCT, was important but insufficient for Gγ action. Notably, GIRK2 and GIRK1/2 were not activated by Gγ. Our results suggest that Gγ regulates GIRK1* and GIRK1/3 channel’s gating, aiding Gβ to trigger the channel’s opening. We hypothesize that Gγ helps to relax the inhibitory effect of a gating element (“lock”) encompassed, in part, by the G1-dCT; GIRK2 acts to occlude the effect of Gγ, either by setting in motion the same mechanism as Gγ, or by triggering an opposing gating effect.
Search for efficient inhibitors of myotoxic activity induced by ophidian phospholipase A2-like proteins using functional, structural and bioinformatics approaches
Authors: Salvador Guilherme H. M. , Cardoso Fábio Florença , Gomes Antoniel A. , Cavalcante Walter L. G. , Gallacci Márcia , Fontes Marcos R. M. 
Published: January 2019

AbstractOphidian accidents are considered an important neglected tropical disease by the World Health Organization. Particularly in Latin America,Bothropssnakes are responsible for the majority of the snakebite envenomings that are not efficiently treated by conventional serum therapy. Thus, the search for simple and efficient inhibitors to complement this therapy is a promising research area, and a combination of functional and structural assays have been used to test candidate ligands against specific ophidian venom compounds. Herein, we tested a commercial drug (acetylsalicylic acid, ASA) and a plant compound with antiophidian properties (rosmarinic acid, RA) using myographic, crystallographic and bioinformatics experiments with a phospholipase A2-like toxin, MjTX-II. MjTX-II/RA and MjTX-II/ASA crystal structures were solved at high resolution and revealed the presence of ligands bound to different regions of the toxin. However,in vitromyographic assays showed that only RA is able to prevent the myotoxic effects of MjTX-II. In agreement with functional results, molecular dynamics simulations showed that the RA molecule remains tightly bound to the toxin throughout the calculations, whereas ASA molecules tend to dissociate. This approach aids the design of effective inhibitors of PLA2-like toxins and, eventually, may complement serum therapy.
Novel pseudo-aspartic peptidase from the midgut of the tick Rhipicephalus microplus
Authors: Lu S. , Parizi L. F. , Torquato R. J. S. , Vaz Junior I. S. , Tanaka A. S. 
Published: January 2019

AbstractThe characterization of Rhipicephalus microplus tick physiology can support efforts to develop and improve the efficiency of control methods. A sequence containing a domain with similarity to one derived from the aspartic peptidase family was isolated from the midgut of engorged female R. microplus. The lack of the second catalytic aspartic acid residue suggest that it may be a pseudo-aspartic peptidase, and it was named RmPAP. In this work we confirm the lack of proteolytic activity of RmPAP and investigate it’s non-proteolytic interaction with bovine hemoglobin by Surface Plasmon Resonance and phage display. Moreover we carried out RNAi interference and artificial feeding of ticks with anti-RmPAP antibodies to assess it’s possible biological role, although no changes were observed in the biological parameters evaluated. Overall, we hypothesize that RmPAP may act as a carrier of hemoglobin/heme between the tick midgut and the ovaries.
Relationship between ultraviolet index (UVI) and first-, second- and third-degree sunburn using the Probit methodology
Authors: Sánchez-Pérez J. F. , Vicente-Agullo D. , Barberá M. , Castro-Rodríguez E. , Cánovas M. 
Published: January 2019

AbstractIn this paper, a relation between the ultraviolet index (UVI) as a Sun exposure time and its effects in the form of burns according to the skin type has been elaborated. Moreover, we present a new expression that relates the intensity of solar radiation and the UVI, as well as expressions to obtain the percentage of population affected both by first and second degree lllsunburn for every skin-type. The results have been adjusted and validated through experimental results taken from the bibliography. Finally, this paper presents a table where the population can easily interpret the UVI values and calculate the maximum time one can be exposed to solar radiation without getting sunburn. In addition, this article aims to raise awareness of the potential harm caused by solar radiation by indicating the percentage of population affected by different types of sunburn depending on skin-type. Moreover, ultraviolet exposure to sunlight could not just result in sunburn, but also have long-term effects on eyes, or even cause immune system disorders or melanoma. Therefore, managing risk perception with this useful table could familiarize the population with actual harm prevention.
BCR-associated factors driving chronic lymphocytic leukemia cells proliferation ex vivo
Authors: Schleiss Cédric , Ilias Wassila , Tahar Ouria , Güler Yonca , Miguet Laurent , Mayeur-Rousse Caroline , Mauvieux Laurent , Fornecker Luc-Matthieu , Toussaint Elise , Herbrecht Raoul , Bertrand Frédéric , Maumy-Bertrand Myriam , Martin Thierry , Fournel Sylvie , Georgel Philippe , Bahram Seiamak , Vallat Laurent 
Published: January 2019

AbstractA chronic antigenic stimulation is believed to sustain the leukemogenic development of chronic lymphocytic leukemia (CLL) and most of lymphoproliferative malignancies developed from mature B cells. Reproducing a proliferative stimulation ex vivo is critical to decipher the mechanisms of leukemogenesis in these malignancies. However, functional studies of CLL cells remains limited since current ex vivo B cell receptor (BCR) stimulation protocols are not sufficient to induce the proliferation of these cells, pointing out the need of mandatory BCR co-factors in this process. Here, we investigated benefits of several BCR co-stimulatory molecules (IL-2, IL-4, IL-15, IL-21 and CD40 ligand) in multiple culture conditions. Our results demonstrated that BCR engagement (anti-IgM ligation) concomitant to CD40 ligand, IL-4 and IL-21 stimulation allowed CLL cells proliferation ex vivo. In addition, we established a proliferative advantage for ZAP70 positive CLL cells, associated to an increased phosphorylation of ZAP70/SYK and STAT6. Moreover, the use of a tri-dimensional matrix of methylcellulose and the addition of TLR9 agonists further increased this proliferative response. This ex vivo model of BCR stimulation with T-derived cytokines is a relevant and efficient model for functional studies of CLL as well as lymphoproliferative malignancies.
Marine biogenics in sea spray aerosols interact with the mTOR signaling pathway
Authors: Asselman Jana , Van Acker Emmanuel , De Rijcke Maarten , Tilleman Laurentijn , Van Nieuwerburgh Filip , Mees Jan , De Schamphelaere Karel A. C. , Janssen Colin R. 
Published: January 2019

AbstractSea spray aerosols (SSAs) have profound effects on our climate and ecosystems. They also contain microbiota and biogenic molecules which could affect human health. Yet the exposure and effects of SSAs on human health remain poorly studied. Here, we exposed human lung cancer cells to extracts of a natural sea spray aerosol collected at the seashore in Belgium, a laboratory-generated SSA, the marine algal toxin homoyessotoxin and a chemical inhibitor of the mammalian target of rapamycin (mTOR) pathway. We observed significant increased expression of genes related to the mTOR pathway and Proprotein convertase subtilisin/kexin type 9 (PCSK9) after exposure to homoyessotoxin and the laboratory-generated SSA. In contrast, we observed a significant decrease in gene expression in the mTOR pathway and of PCSK9 after exposure to the natural SSA and the mTOR inhibitor, suggesting induction of apoptosis. Our results indicate that marine biogenics in SSAs interact with PCSK9 and the mTOR pathway and can be used in new potential pharmaceutical applications. Overall, our results provide a substantial molecular evidence base for potential beneficial health effects at environmentally relevant concentrations of natural SSAs.