bluuebunny/crossref_metadata_2025_split huggingface dataset:
An African loss-of-function CACNA1C variant p.T1787M associated with a risk of ventricular fibrillation
Authors: Blancard Malorie , Debbiche Amal , Kato Koichi , Cardin Christelle , Sabrina Guichard , Gandjbakhch Estelle , Probst Vincent , Haissaguerre Michel , Extramiana Fabrice , Hocini Mélèze , Olivier Geoffroy , Leenhardt Antoine , Guicheney Pascale , Rougier Jean-Sébastien 
Published: September 2018

AbstractCalcium regulation plays a central role in cardiac function. Several variants in the calcium channel Cav1.2 have been implicated in arrhythmic syndromes. We screened patients with Brugada syndrome, short QT syndrome, early repolarisation syndrome, and idiopathic ventricular fibrillation to determine the frequency and pathogenicity of Cav1.2 variants. Cav1.2 related genes, CACNA1C, CACNB2 and CACNA2D1, were screened in 65 probands. Missense variants were introduced in the Cav1.2 alpha subunit plasmid by mutagenesis to assess their pathogenicity using patch clamp approaches. Six missense variants were identified in CACNA1C in five individuals. Five of them, A1648T, A1689T, G1795R, R1973Q, C1992F, showed no major alterations of the channel function. The sixth C-terminal variant, Cavα1c-T1787M, present mostly in the African population, was identified in two patients with resuscitated cardiac arrest. The first patient originated from Cameroon and the second was an inhabitant of La Reunion Island with idiopathic ventricular fibrillation originating from Purkinje tissues. Patch-clamp analysis revealed that Cavα1c-T1787M reduces the calcium and barium currents by increasing the auto-inhibition mediated by the C-terminal part and increases the voltage-dependent inhibition. We identified a loss-of-function variant, Cavα1c-T1787M, present in 0.8% of the African population, as a new risk factor for ventricular arrhythmia.
The Role of p53 in Determining Mitochondrial Adaptations to Endurance Training in Skeletal Muscle
Authors: Beyfuss Kaitlyn , Erlich Avigail T. , Triolo Matthew , Hood David A. 
Published: September 2018

Abstractp53 plays an important role in regulating mitochondrial homeostasis. However, it is unknown whether p53 is required for the physiological and mitochondrial adaptations with exercise training. Furthermore, it is also unknown whether impairments in the absence of p53 are a result of its loss in skeletal muscle, or a secondary effect due to its deletion in alternative tissues. Thus, we investigated the role of p53 in regulating mitochondria both basally, and under the influence of exercise, by subjecting C57Bl/6J whole-body (WB) and muscle-specific p53 knockout (mKO) mice to a 6-week training program. Our results confirm that p53 is important for regulating mitochondrial content and function, as well as proteins within the autophagy and apoptosis pathways. Despite an increased proportion of phosphorylated p53 (Ser15) in the mitochondria, p53 is not required for training-induced adaptations in exercise capacity or mitochondrial content and function. In comparing mouse models, similar directional alterations were observed in basal and exercise-induced signaling modifications in WB and mKO mice, however the magnitude of change was less pronounced in the mKO mice. Our data suggest that p53 is required for basal mitochondrial maintenance in skeletal muscle, but is not required for the adaptive responses to exercise training.
Spatial Characterization of Soybean Yield and Quality (Amino Acids, Oil, and Protein) for United States
Authors: Assefa Y. , Bajjalieh N. , Archontoulis S. , Casteel S. , Davidson D. , Kovács P. , Naeve S. , Ciampitti Ignacio A. 
Published: September 2018

AbstractContinued economic relevancy of soybean is a function of seed quality. The objectives of this study were to: (i) assess the spatial association between soybean yield and quality across major US soybean producing regions, (ii) investigate the relationship between protein, oil, and yield with amino acids (AAs) composition, and (iii) study interrelationship among essential AAs in soybean seed. Data from soybean testing programs conducted across 14 US states from 2012 to 2016 period (n = 35,101 data points) were analyzed. Results indicate that for each Mg ha−1 yield increase, protein yield increased by 0.35 Mg protein ha−1 and oil yield improved by 0.20 Mg oil ha−1. Essential AA concentrations exhibit a spatial autocorrelation and there was a negative relationship between concentration of AA, protein, and oil, with latitude. There was a positive interrelationship with different degree of strength among all AAs, and the correlation between Isoleucine and Valine was the strongest (r = 0.93) followed by the correlation among Arginine, Leucine, Lysine, and Threonine (0.71 < r < 0.88). We concluded that the variability in genotype (G) x management (M) x environment (E) across latitudes influencing yield also affected soybean quality; AA, protein, and oil content in a similar manner.
Increased TIMP-3 expression alters the cellular secretome through dual inhibition of the metalloprotease ADAM10 and ligand-binding of the LRP-1 receptor
Authors: Scilabra Simone D. , Pigoni Martina , Pravatá Veronica , Schätzl Tobias , Müller Stephan A. , Troeberg Linda , Lichtenthaler Stefan F. 
Published: September 2018

AbstractThe tissue inhibitor of metalloproteinases-3 (TIMP-3) is a major regulator of extracellular matrix turnover and protein shedding by inhibiting different classes of metalloproteinases, including disintegrin metalloproteinases (ADAMs). Tissue bioavailability of TIMP-3 is regulated by the endocytic receptor low-density-lipoprotein receptor-related protein-1 (LRP-1). TIMP-3 plays protective roles in disease. Thus, different approaches have been developed aiming to increase TIMP-3 bioavailability, yet overall effects of increased TIMP-3in vivohave not been investigated. Herein, by using unbiased mass-spectrometry we demonstrate that TIMP-3-overexpression in HEK293 cells has a dual effect on shedding of transmembrane proteins and turnover of soluble proteins. Several membrane proteins showing reduced shedding are known as ADAM10 substrates, suggesting that exogenous TIMP-3 preferentially inhibits ADAM10 in HEK293 cells. Additionally identified shed membrane proteins may be novel ADAM10 substrate candidates. TIMP-3-overexpression also increased extracellular levels of several soluble proteins, including TIMP-1, MIF and SPARC. Levels of these proteins similarly increased upon LRP-1 inactivation, suggesting that TIMP-3 increases soluble protein levels by competing for their binding to LRP-1 and their subsequent internalization. In conclusion, our study reveals that increased levels of TIMP-3 induce substantial modifications in the cellular secretome and that TIMP-3-based therapies may potentially provoke undesired, dysregulated functions of ADAM10 and LRP-1.
Atorvastatin provides a new lipidome improving early regeneration after partial hepatectomy in osteopontin deficient mice
Authors: Nuñez-Garcia Maitane , Gomez-Santos Beatriz , Saenz de Urturi Diego , Mestre Daniela , Gonzalez-Romero Francisco , Buque Xabier , Gutiérrez-de Juan Virginia , Martinez-Chantar María Luz , Syn Wing-Kin , Fresnedo Olatz , Aspichueta Patricia 
Published: September 2018

AbstractOsteopontin (OPN), a multifunctional cytokine that controls liver glycerolipid metabolism, is involved in activation and proliferation of several liver cell types during regeneration, a condition of high metabolic demands. Here we investigated the role of OPN in modulating the liver lipidome during regeneration after partial-hepatectomy (PH) and the impact that atorvastatin treatment has over regeneration in OPN knockout (KO) mice. The results showed that OPN deficiency leads to remodeling of phosphatidylcholine and triacylglycerol (TG) species primarily during the first 24 h after PH, with minimal effects on regeneration. Changes in the quiescent liver lipidome in OPN-KO mice included TG enrichment with linoleic acid and were associated with higher lysosome TG-hydrolase activity that maintained 24 h after PH but increased in WT mice. OPN-KO mice showed increased beta-oxidation 24 h after PH with less body weight loss. In OPN-KO mice, atorvastatin treatment induced changes in the lipidome 24 h after PH and improved liver regeneration while no effect was observed 48 h post-PH. These results suggest that increased dietary-lipid uptake in OPN-KO mice provides the metabolic precursors required for regeneration 24 h and 48 h after PH. However, atorvastatin treatment offers a new metabolic program that improves early regeneration when OPN is deficient.
A novel ulvan lyase family with broad-spectrum activity from the ulvan utilisation loci of Formosa agariphila KMM 3901
Authors: Konasani Venkat Rao , Jin Chunsheng , Karlsson Niclas G. , Albers Eva 
Published: September 2018

AbstractUlvan, which is one of the major structural polysaccharides of the cell walls of green macroalgae, is degraded by ulvan lyases via the β-elimination mechanism with the release of oligosaccharides that have unsaturated 4-deoxy-L-threo-hex-4-enopyranosiduronic acid (∆) at the non-reducing end. These ulvan lyases belong to the PL24 or PL25 or PL28 family in the CAZy database. In this study, we identify and biochemically characterise a periplasmic novel broad-spectrum ulvan lyase from Formosa agariphila KMM 3901. The lyase was overexpressed in Escherichia coli, and the purified recombinant enzyme depolymerised ulvan in an endolytic manner with a Km of 0.77 mg/ml, and displayed optimum activity at 40 °C and pH 8. This lyase also degraded heparan sulphate and chondroitin sulphate. Detailed analyses of the end-products of the enzymatic degradation of ulvan using 1H- and 13C-NMR and LC-MS revealed an unsaturated disaccharide (∆Rha3S) and a tetrasaccharide (∆Rha3S-Xyl-Rha) as the principal end-products. In contrast to the previously described ulvan lyases, this novel lyase is mostly composed of α-helices that form an (α/α)6 incomplete toroid domain and displays a remarkably broad-spectrum activity. This novel lyase is the first member of a new family of ulvan lyases.
Counterfactual Bell-State Analysis
Authors: Zaman Fakhar , Jeong Youngmin , Shin Hyundong 
Published: September 2018

AbstractThe Bell-state analysis to distinguish between the four maximally entangled Bell states requires the joint measurement on entangled particles. However, spatially separated parties cannot perform the joint measurement. In this paper, we present a counterfactual Bell-state analysis based on the chained quantum Zeno effect. This counterfactual analysis not only enables us to perform a complete Bell-state analysis, but also enables spatially separated parties to distinguish between the four Bell states without transmitting any physical particle over the channel.
Angiogenic Properties of ‘Leukocyte- and Platelet-Rich Fibrin’
Authors: Ratajczak Jessica , Vangansewinkel Tim , Gervois Pascal , Merckx Greet , Hilkens Petra , Quirynen Marc , Lambrichts Ivo , Bronckaers Annelies 
Published: September 2018

AbstractLeukocyte- and Platelet-Rich Fibrin (L-PRF) is an autologous platelet concentrate, consisting of a fibrin matrix enriched with platelets, leukocytes and a plethora of cytokines and growth factors. Since L-PRF is produced bedside from whole blood without the use of an anti-coagulant, it is becoming a popular adjuvant in regenerative medicine. While other types of platelet concentrates have been described to stimulate blood vessel formation, little is known about the angiogenic capacities of L-PRF. Therefore, this study aimed to fully characterize the angiogenic potential of L-PRF. With an antibody array, the growth factors released by L-PRF were determined and high levels of CXC chemokine receptor 2 (CXCR-2) ligands and epidermal growth factor (EGF) were found. L-PRF induced in vitro key steps of the angiogenic process: endothelial proliferation, migration and tube formation. In addition, we could clearly demonstrate that L-PRF is able to induce blood vessel formation in vivo, the chorioallantoic membrane assay. In conclusion, we could demonstrate the angiogenic capacity of L-PRF both in vitro and in vivo, underlying the clinical potential of this easy-to-use platelet concentrate.
Chromatin architecture changes and DNA replication fork collapse are critical features in cryopreserved cells that are differentially controlled by cryoprotectants
Authors: Falk Martin , Falková Iva , Kopečná Olga , Bačíková Alena , Pagáčová Eva , Šimek Daniel , Golan Martin , Kozubek Stanislav , Pekarová Michaela , Follett Shelby E. , Klejdus Bořivoj , Elliott K. Wade , Varga Krisztina , Teplá Olga , Kratochvílová Irena 
Published: September 2018

AbstractIn this work, we shed new light on the highly debated issue of chromatin fragmentation in cryopreserved cells. Moreover, for the first time, we describe replicating cell-specific DNA damage and higher-order chromatin alterations after freezing and thawing. We identified DNA structural changes associated with the freeze-thaw process and correlated them with the viability of frozen and thawed cells. We simultaneously evaluated DNA defects and the higher-order chromatin structure of frozen and thawed cells with and without cryoprotectant treatment. We found that in replicating (S phase) cells, DNA was preferentially damaged by replication fork collapse, potentially leading to DNA double strand breaks (DSBs), which represent an important source of both genome instability and defects in epigenome maintenance. This induction of DNA defects by the freeze-thaw process was not prevented by any cryoprotectant studied. Both in replicating and non-replicating cells, freezing and thawing altered the chromatin structure in a cryoprotectant-dependent manner. Interestingly, cells with condensed chromatin, which was strongly stimulated by dimethyl sulfoxide (DMSO) prior to freezing had the highest rate of survival after thawing. Our results will facilitate the design of compounds and procedures to decrease injury to cryopreserved cells.
A systems biology approach to explore the impact of maple tree dormancy release on sap variation and maple syrup quality
Authors: N’guyen Guillaume Quang , Martin Nathalie , Jain Mani , Lagacé Luc , Landry Christian R. , Filteau Marie 
Published: September 2018

AbstractMaple sap is a complex nutrient matrix collected during spring to produce maple syrup. The characteristics of sap change over the production period and its composition directly impacts syrup quality. This variability could in part be attributed to changes in tree metabolism following dormancy release, but little is known about these changes in deciduous trees. Therefore, understanding the variation in sap composition associated with dormancy release could help pinpoint the causes of some defects in maple syrup. In particular, a defect known as “buddy”, is an increasing concern for the industry. This off-flavor appears around the time of bud break, hence its name. To investigate sap variation related to bud break and the buddy defect, we monitored sap variation with respect to a dormancy release index (Sbb) and syrup quality. First, we looked at variation in amino acid content during this period. We observed a shift in amino acid relative proportions associated with dormancy release and found that most of them increase rapidly near the point of bud break, correlating with changes in syrup quality. Second, we identified biological processes that respond to variation in maple sap by performing a competition assay using the barcoded Saccharomyces cerevisiae prototroph deletion collection. This untargeted approach revealed that the organic sulfur content may be responsible for the development of the buddy off-flavor, and that dormancy release is necessary for the appearance of the defect, but other factors such as microbial activity may also be contributing.
The imprinted gene Pw1/Peg3 regulates skeletal muscle growth, satellite cell metabolic state, and self-renewal
Authors: Correra Rosa Maria , Ollitrault David , Valente Mariana , Mazzola Alessia , Adalsteinsson Bjorn T. , Ferguson-Smith Anne C. , Marazzi Giovanna , Sassoon David A. 
Published: September 2018

AbstractPw1/Peg3 is an imprinted gene expressed from the paternally inherited allele. Several imprinted genes, including Pw1/Peg3, have been shown to regulate overall body size and play a role in adult stem cells. Pw1/Peg3 is expressed in muscle stem cells (satellite cells) as well as a progenitor subset of muscle interstitial cells (PICs) in adult skeletal muscle. We therefore examined the impact of loss-of-function of Pw1/Peg3 during skeletal muscle growth and in muscle stem cell behavior. We found that constitutive loss of Pw1/Peg3 function leads to a reduced muscle mass and myofiber number. In newborn mice, the reduction in fiber number is increased in homozygous mutants as compared to the deletion of only the paternal Pw1/Peg3 allele, indicating that the maternal allele is developmentally functional. Constitutive and a satellite cell-specific deletion of Pw1/Peg3, revealed impaired muscle regeneration and a reduced capacity of satellite cells for self-renewal. RNA sequencing analyses revealed a deregulation of genes that control mitochondrial function. Consistent with these observations, Pw1/Peg3 mutant satellite cells displayed increased mitochondrial activity coupled with accelerated proliferation and differentiation. Our data show that Pw1/Peg3 regulates muscle fiber number determination during fetal development in a gene-dosage manner and regulates satellite cell metabolism in the adult.
Single shot femtosecond laser nano-ablation of CVD monolayer graphene
Authors: Gil-Villalba A. , Meyer R. , Giust R. , Rapp L. , Billet C. , Courvoisier F. 
Published: September 2018

AbstractWe investigate ablation of CVD monolayer graphene by femtosecond pulses in the single shot regime. We show that the ablation probability of flat graphene drastically reduces for small illumination diameters even if the ablation threshold is exceeded. However, the presence of graphene wrinkles enhances the ablation probability. This is interpreted in terms of electron and energy diffusion within the graphene layer. This differentiated behavior is a drawback for single shot laser nanopatterning. The morphology of the holes with minimal diameter depends on the fluence distribution at ablation threshold. Strong fluence gradients due to strong focussing produce an explosive folding of graphene during ablation.
Microgravity induces autophagy via mitochondrial dysfunction in human Hodgkin’s lymphoma cells
Authors: Jeong Ae Jin , Kim Yoon Jae , Lim Min Hyuk , Lee Haeri , Noh Kumhee , Kim Byung-Hak , Chung Jin Woong , Cho Chung-Hyun , Kim Sungwan , Ye Sang-Kyu 
Published: September 2018

AbstractGravitational forces can impose physical stresses on the human body as it functions to maintain homeostasis. It has been reported that astronauts exposed to microgravity experience altered biological functions and many subsequent studies on the effects of microgravity have therefore been conducted. However, the anticancer mechanisms of simulated microgravity remain unclear. We previously showed that the proliferation of human Hodgkin’s lymphoma (HL) cells was inhibited when these cells were cultured in time-averaged simulated microgravity (taSMG). In the present study, we investigated whether taSMG produced an anticancer effect. Exposure of human HL cells to taSMG for 2 days increased their reactive oxygen species (ROS) production and NADPH oxidase family gene expression, while mitochondrial mass, ATPase, ATP synthase, and intracellular ATP levels were decreased. Furthermore, human HL cells exposed to taSMG underwent autophagy via AMPK/Akt/mTOR and MAPK pathway modulation; such autophagy was inhibited by the ROS scavenger N-acetylcysteine (NAC). These results suggest an innovative therapeutic approach to HL that is markedly different from conventional chemotherapy and radiotherapy.
Contrast-enhanced ultrasound tractography for 3D vascular imaging of the prostate
Authors: van Sloun Ruud J. G. , Demi Libertario , Schalk Stefan G. , Caresio Cristina , Mannaerts Christophe , Postema Arnoud W. , Molinari Filippo , van der Linden Hans C. , Huang Pingtong , Wijkstra Hessel , Mischi Massimo 
Published: September 2018

AbstractDiffusion tensor tractography (DTT) enables visualization of fiber trajectories in soft tissue using magnetic resonance imaging. DTT exploits the anisotropic nature of water diffusion in fibrous structures to identify diffusion pathways by generating streamlines based on the principal diffusion vector. Anomalies in these pathways can be linked to neural deficits. In a different field, contrast-enhanced ultrasound is used to assess anomalies in blood flow with the aim of locating cancer-induced angiogenesis. Like water diffusion, blood flow and transport of contrast agents also shows a principal direction; however, this is now determined by the local vasculature. Here we show how the tractographic techniques developed for magnetic resonance imaging DTT can be translated to contrast-enhanced ultrasound, by first estimating contrast flow velocity fields from contrast-enhanced ultrasound acquisitions, and then applying tractography. We performed 4D in-vivo contrast-enhanced ultrasound of three human prostates, proving the feasibility of the proposed approach with clinically acquired datasets. By comparing the results to histopathology after prostate resection, we observed qualitative agreement between the contrast flow tracts and typical markers of cancer angiogenic microvasculature: higher densities and tortuous geometries in tumor areas. The method can be used in-vivo using a standard contrast-enhanced ultrasound protocol, opening up new possibilities in the area of vascular characterization for cancer diagnostics.
The intracellular proteome of African swine fever virus
Authors: Keßler Catharina , Forth Jan H. , Keil Günther M. , Mettenleiter Thomas C. , Blome Sandra , Karger Axel 
Published: September 2018

AbstractAfrican swine fever (ASF) is a viral disease that affects members of the Suidae family such as African bush pigs, warthogs, but also domestic pigs, and wild boar. It is transmitted by direct contact of naïve with infected animals, by soft ticks of the Ornithodoros genus, or indirectly by movement of infected animals, improper disposal of contaminated animal products or other sources related to human activity. The recent spread of ASF into Eastern and Central European countries is currently threatening the European pig industry. The situation is aggravated as to-date no efficient vaccine is available. African swine fever virus (ASFV) is a large enveloped ds DNA-virus encoding at least 150 open reading frames. Many of the deduced gene products have not been described, less functionally characterized. We have analysed ASFV protein expression in three susceptible mammalian cell lines representing a susceptible host (wild boar) and two non-susceptible species (human and green monkey) by mass spectrometry and provide first evidence for the expression of 23 so far uncharacterized ASFV ORFs. Expression levels of several newly identified ASFV proteins were remarkably high indicating importance in the viral replication cycle. Moreover, expression profiles of ASFV proteins in the three cell lines differed markedly.