bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological inhibition of Notch signaling regresses pre-established abdominal aortic aneurysm
Authors: Sharma Neekun , Dev Rishabh , Ruiz-Rosado Juan de Dios , Partida-Sanchez Santiago , Guerau-de-Arellano Mireia , Dhakal Pramod , Kuivaniemi Helena , Hans Chetan P. 
Published: September 2019

AbstractAbdominal aortic aneurysm (AAA) is characterized by transmural infiltration of myeloid cells at the vascular injury site. Previously, we reported preventive effects of Notch deficiency on the development of AAA by reduction of infiltrating myeloid cells. In this study, we examined if Notch inhibition attenuates the progression of pre-established AAA and potential implications. Pharmacological Notch inhibitor (N-[N-(3,5-difluorophenacetyl)-L-alanyl]-(S)-phenylglycine t-butyl ester; DAPT) was administered subcutaneously three times a week starting at day 28 of angiotensin II (AngII) infusion. Progressive increase in pulse wave velocity (PWV), maximal intra-luminal diameter (MILD) and maximal external aortic diameter (MEAD) were observed at day 56 of the AngII. DAPT prevented such increase in MILD, PWV and MEAD (P < 0.01). Histologically, the aortae of DAPT-treated Apoe−/− mice had significant reduction in inflammatory response and elastin fragmentation. Naked collagen microfibrils and weaker banded structure observed in the aortae of Apoe−/− mice in response to AngII, were substantially diminished by DAPT. A significant decrease in the proteolytic activity in the aneurysmal tissues and vascular smooth muscle cells (vSMCs) was observed with DAPT (P < 0.01). In human and mouse AAA tissues, increased immunoreactivity of activated Notch signaling correlated strongly with CD38 expression (R2 = 0.61). Collectively, we propose inhibition of Notch signaling as a potential therapeutic target for AAA progression.
Potent modulation of the CepR quorum sensing receptor and virulence in a Burkholderia cepacia complex member using non-native lactone ligands
Authors: Slinger Betty L. , Deay Jacqueline J. , Chandler Josephine R. , Blackwell Helen E. 
Published: September 2019

AbstractThe Burkholderia cepacia complex (Bcc) is a family of closely related bacterial pathogens that are the causative agent of deadly human infections. Virulence in Bcc species has been shown to be controlled by the CepI/CepR quorum sensing (QS) system, which is mediated by an N-acyl L-homoserine lactone (AHL) signal (C8-AHL) and its cognate LuxR-type receptor (CepR). Chemical strategies to block QS in Bcc members would represent an approach to intercept this bacterial communication process and further delineate its role in infection. In the current study, we sought to identify non-native AHLs capable of agonizing or antagonizing CepR, and thereby QS, in a Bcc member. We screened a library of AHL analogs in cell-based reporters for CepR, and identified numerous highly potent CepR agonists and antagonists. These compounds remain active in a Bcc member, B. multivorans, with one agonist 250-fold more potent than the native ligand C8-AHL, and can affect QS-controlled motility. Further, the CepR antagonists prolong C. elegans survival in an infection model. These AHL analogs are the first reported non-native molecules that both directly modulate CepR and impact QS-controlled phenotypes in a Bcc member, and represent valuable chemical tools to assess the role of QS in Bcc infections.
TBK1 Limits mTORC1 by Promoting Phosphorylation of Raptor Ser877
Authors: Antonia Ricardo J. , Castillo Johnny , Herring Laura E. , Serafin D. Stephen , Liu Pengda , Graves Lee M. , Baldwin Albert S. , Hagan Robert S. 
Published: September 2019

AbstractWhile best known for its role in the innate immune system, the TANK-binding kinase 1 (TBK1) is now known to play a role in modulating cellular growth and autophagy. One of the major ways that TBK1 accomplishes this task is by modulating the mechanistic Target of Rapamycin (mTOR), a master regulator that when activated promotes cell growth and inhibits autophagy. However, whether TBK1 promotes or inhibits mTOR activity is highly cell type and context dependent. To further understand the mechanism whereby TBK1 regulates mTOR, we tested the hypothesis that TBK1 phosphorylates a key component of the mTOR complex 1 (mTORC1), Raptor. Using kinase assays coupled with mass spectrometry, we mapped the position of the TBK1 dependent phosphorylation sites on Raptor in vitro. Among the sites identified in vitro, we found that TBK1 promotes Raptor Ser877 phosphorylation in cells both basally and in response to pathogen-associated molecules known to induce TBK1 activity. The levels of Raptor Ser877 phosphorylation were inversely correlated with the levels of mTOR activity. Expression of a mutant Raptor that could not be phosphorylated at Ser877 led to an increase in mTORC1 activity. We conclude that TBK1 limits mTORC1 activity by promoting Raptor Ser877 phosphorylation.
EDX-analysis of fluoride precipitation on human enamel
Authors: Scholz Konstantin Johannes , Federlin Marianne , Hiller Karl-Anton , Ebensberger Helga , Ferstl Gerlinde , Buchalla Wolfgang 
Published: September 2019

AbstractOne mechanism of action for the anticaries effect of topical fluoridation is through precipitation of CaF2. In this in vitro study energy-dispersive x-ray spectroscopy (EDX) is used as a semiquantitative method to detect enamel fluoride-precipitation under the influence of acidic and neutral pH-value and absence or presence of a salivary pellicle. Crowns of 30 human caries-free third molars were quartered into four specimens and the enamel surface ground flat and polished. Two specimens each were stored in human saliva (120 minutes pellicle formation). Teeth were randomly allocated into 6 treatment groups: NaF_a (experimental acidic sodium fluoride; 12500 ppmF−, pH 4.75); NaF_n (experimental neutral sodium fluoride; 12500 ppmF−, pH 7.0); GB_a (acidic gel base; 0 ppmF−, pH 4.75); GB_n (neutral gel base; 0 ppmF−, pH 7.0); AmF-NaF_a (experimental acidic amine/sodium fluoride; 12500 ppmF−, pH 4.75); EG_a (acidic amine/sodium fluoride; Elmex Geleé, CP-GABA GmbH; 12500 ppmF−, pH 4.75). Each gel was applied for 60 seconds to one specimen with and one specimen without pellicle. Two specimens served as controls (no gel, without/with pellicle). Atomic percent (At%) of O, F, Na, Mg, P, Ca was measured by EDX. ∆At% and Ca/P-ratios were calculated. EDX could semi-quantify superficial enamel fluoride-precipitation. Only specimens treated with acidic fluoride gels showed fluoride-precipitation, a salivary pellicle tended to decrease At%F.
A Bone Morphogenetic Protein (BMP)-derived Peptide Based on the Type I Receptor-binding Site Modifies Cell-type Dependent BMP Signalling
Authors: Tong Zhen , Guo Jingxu , Glen Robert C. , Morrell Nicholas W. , Li Wei 
Published: September 2019

AbstractBone morphogenetic proteins (BMPs) are multifunctional cytokines of the transforming growth factor β (TGFβ) superfamily with potential therapeutic applications due to their broad biological functionality. Designing BMP mimetics with specific activity will contribute to the translational potential of BMP-based therapies. Here, we report a BMP9 peptide mimetic, P3, designed from the type I receptor binding site, which showed millimolar binding affinities for the type I receptor activin receptor like kinase 1 (ALK1), ALK2 and ALK3. Although showing no baseline activity, P3 significantly enhanced BMP9-induced Smad1/5 phosphorylation as well as ID1, BMPR2, HEY1 and HEY2 gene expression in pulmonary artery endothelial cells (hPAECs), and this activity is dependent on its alpha helix propensity. However, in human dermal microvascular endothelial cells, P3 did not affect BMP9-induced Smad1/5 phosphorylation, but potently inhibited ALK3-dependent BMP4-induced Smad1/5 phosphorylation and gene expression. In C2C12 mouse myoblast cells, P3 had no effect on BMP9-induced osteogenic signalling, which is primarily mediated by ALK2. Interestingly, a previously published peptide from the knuckle region of BMP9 was found to inhibit BMP4-induced Smad1/5 phosphorylation. Together, our data identify a BMP9-derived peptide that can selectively enhance ALK1-mediated BMP9 signalling in hPAECs and modulate BMP9 and BMP4 signalling in a cell type-specific manner.
Same species, different prerequisites: investigating body condition and foraging success in young reef sharks between an atoll and an island system
Authors: Weideli Ornella C. , Bouyoucos Ian A. , Papastamatiou Yannis P. , Mescam Gauthier , Rummer Jodie L. , Planes Serge 
Published: September 2019

AbstractAcquiring and storing energy is vital to sharks of all age-classes. Viviparous shark embryos receive endogenous maternal energy reserves to sustain the first weeks after birth. Then, in order to maintain body condition, sharks must start foraging. Our goal was to understand whether maternal energy investments vary between blacktip reef sharks (Carcharhinus melanopterus) from two populations and to what extent body condition and the initiation of foraging might be affected by presumably variable maternal investments. A total of 546 young sharks were captured at St. Joseph atoll (Seychelles) and Moorea (French Polynesia) between 2014 and 2018, and indices of body condition and percentage of stomachs containing prey were measured. Maternal investment was found to be site-specific, with significantly larger, heavier, and better conditioned individuals in Moorea. Despite these advantages, as time progressed, Moorea sharks exhibited significant decreases in body condition and were slower to initiate foraging. We suggest that the young sharks’ foraging success is independent of the quality of maternal energy resources, and that other factors, such as prey availability, prey quality, and/or anthropogenic stressors are likely responsible for the observed differences across sites. Insights into intraspecific variations in early life-stages may further support site-specific management strategies for young sharks from nearshore habitats.
The interactive effects of mowing and N addition did not weaken soil net N mineralization rates in semi-arid grassland of Northern China
Authors: Luo Yükun , Wang Changhui , Shen Yan , Sun Wei , Dong Kuanhu 
Published: September 2019

AbstractAs the largest portion of the terrestrial ecosystems, the arid and semi-arid grassland ecosystem is relatively sensitive and vulnerable to nitrogen (N) deposition. Mowing, the main management in Inner Mongolia grassland also has deep direct and indirect effect on N transformation by removing the nutrient from soils. However, the interaction effect of N addition and mowing on N transformation is still unclear, especially in semi-arid grassland. Here, we conducted a field-manipulated experiment to assess N addition (10 g N m−2 y−1) and mowing (in the middle of August) effects on soil net N mineralization rate across 4 growing seasons (2006–2009) in a semi-arid grassland in Inner Mongolia of northern China. We found that N addition with or without mowing led to significant effect on soil ammonification rate and net N mineralization rate, but had no significant effect on nitrification rates. Furthermore, mowing had no significant effect on soil net N mineralization, ammonification and nitrification rates. N addition and Mowing decreased microbial respiration and metabolic quotient, whereas the interaction of N addition and mowing had no significant effect on microbial respiration and metabolic quotient. Our results indicated that the effects of mowing and N addition did not interactively weaken soil net N mineralization rates in a semi-arid grassland of Northern China. Therefore, the anthropic management (i.e. mowing for hay once a year) with N addition may be a sustainable approach for restoration and reconstruction of vegetation in the abandoned grassland of Northern China.
Identification, Functional Characterization, and Pharmacological Analysis of Two Sulfakinin Receptors in the Medically-Important Insect Rhodnius prolixus
Authors: Bloom Mark , Lange Angela B. , Orchard Ian 
Published: September 2019

AbstractThe chordate gastrin/cholecystokinin and ecdysozoan sulfakinin (SK)-signaling systems are functionally and structurally homologous. In the present study, we isolated the cDNA sequences encoding the SK receptors in Rhodnius prolixus (Rhopr-SKR-1 and Rhopr-SKR-2). The Rhopr-SKRs have been functionally characterized and their intracellular signaling pathways analysed via a functional receptor assay. Both Rhopr-SKRs are exclusively activated via the two native R. prolixus sulfakinins, Rhopr-SK-1 and Rhopr-SK-2, but not via nonsulfated Rhopr-SK-1. The Rhopr-SKRs are each linked to the intracellular Ca2+ second messenger pathway, and not to the cyclic AMP pathway. Spatial transcript expression analyses revealed that each Rhopr-SKR is predominantly expressed in the central nervous system with lower expression throughout peripheral tissues. The critical importance of the SK-signaling pathway in the blood-feeding behaviour of R. prolixus was demonstrated by knockdown of the transcripts for Rhopr-SKs and Rhopr-SKRs, which results in an increase in the mass of blood meal taken. The parasite causing Chagas disease is transmitted to the host after R. prolixus has taken a blood meal, and characterization of the SKRs provides further understanding of the coordination of feeding and satiation, and ultimately the transmission of the parasite.
Estimating dyskinesia severity in Parkinson’s disease by using a waist-worn sensor: concurrent validity study
Authors: Rodríguez-Molinero Alejandro , Pérez-López Carlos , Samà Albert , Rodríguez-Martín Daniel , Alcaine Sheila , Mestre Berta , Quispe Paola , Giuliani Benedetta , Vainstein Gabriel , Browne Patrick , Sweeney Dean , Quinlan Leo R. , Arostegui J. Manuel Moreno , Bayes Àngels , Lewy Hadas , Costa Alberto , Annicchiarico Roberta , Counihan Timothy , Laighin Gearòid Ò. , Cabestany Joan 
Published: September 2019

AbstractOur research team previously developed an accelerometry-based device, which can be worn on the waist during daily life activities and detects the occurrence of dyskinesia in patients with Parkinson’s disease. The goal of this study was to analyze the magnitude of correlation between the numeric output of the device algorithm and the results of the Unified Dyskinesia Rating Scale (UDysRS), administered by a physician. In this study, 13 Parkinson’s patients, who were symptomatic with dyskinesias, were monitored with the device at home, for an average period of 30 minutes, while performing normal daily life activities. Each patient’s activity was simultaneously video-recorded. A physician was in charge of reviewing the recorded videos and determining the severity of dyskinesia through the UDysRS for every patient. The sensor device yielded only one value for dyskinesia severity, which was calculated by averaging the recorded device readings. Correlation between the results of physician’s assessment and the sensor output was analyzed with the Spearman’s correlation coefficient. The correlation coefficient between the sensor output and UDysRS result was 0.70 (CI 95%: 0.33–0.88; p = 0.01). Since the sensor was located on the waist, the correlation between the sensor output and the results of the trunk and legs scale sub-items was calculated: 0.91 (CI 95% 0.76–0.97: p < 0.001). The conclusion is that the magnitude of dyskinesia, as measured by the tested device, presented good correlation with that observed by a physician.
Increased abundance of proteobacteria in aggressive Crohn’s disease seven years after diagnosis
Authors: Vester-Andersen M. K. , Mirsepasi-Lauridsen H. C. , Prosberg M. V. , Mortensen C. O. , Träger C. , Skovsen K. , Thorkilgaard T. , Nøjgaard C. , Vind I. , Krogfelt K. A. , Sørensen N. , Bendtsen F. , Petersen A. M. 
Published: September 2019

AbstractIntestinal dysbiosis in inflammatory bowel disease (IBD) patients depend on disease activity. We aimed to characterize the microbiota after 7 years of follow-up in an unselected cohort of IBD patients according to disease activity and disease severity. Fifty eight Crohn’s disease (CD) and 82 ulcerative colitis (UC) patients were included. Disease activity was assessed by the Harvey-Bradshaw Index for CD and Simple Clinical Colitis Activity Index for UC. Microbiota diversity was assessed by 16S rDNA MiSeq sequencing. In UC patients with active disease and in CD patients with aggressive disease the richness (number of OTUs, p = 0.018 and p = 0.013, respectively) and diversity (Shannons index, p = 0.017 and p = 0.023, respectively) were significantly decreased. In the active UC group there was a significant decrease in abundance of the phylum Firmicutes (p = 0.018). The same was found in CD patients with aggressive disease (p = 0.05) while the abundance of Proteobacteria phylum showed a significant increase (p = 0.03) in CD patients. We found a change in the microbial abundance in UC patients with active disease and in CD patients with aggressive disease. These results suggest that dysbiosis of the gut in IBD patients is not only related to current activity but also to the course of the disease.
Role of Clathrin Assembly Protein-2 Beta Subunit during White Spot Syndrome Virus Infection in Black Tiger Shrimp Penaeus monodon
Authors: Jatuyosporn Thapanan , Laohawutthichai Pasunee , Supungul Premruethai , Sotelo-Mundo Rogerio R. , Ochoa-Leyva Adrian , Tassanakajon Anchalee , Krusong Kuakarun 
Published: September 2019

AbstractWhite spot syndrome virus (WSSV) is one of the most lethal viruses severely affecting shrimp industry. This disease can cause 100% mortality of farmed shrimp within a week. This work aims to characterize clathrin assembly proteins in Penaeus monodon and investigate their roles in WSSV entry. In general, clathrin assembly proteins form complexes with specific receptors and clathrins, leading to clathrin-mediated endocytosis. Adaptor protein 2 (AP-2), which is responsible for endocytosis at plasma membrane, consists of four subunits including α, β2, μ2 and σ2. Knockdown of clathrin coat AP17, or σ subunit of AP-2 dramatically reduced WSSV infectivity. Similar results were observed, when shrimp were pre-treated with chlorpromazine (CPZ), an inhibitor of clathrin-dependent endocytosis. The complete open reading frames of AP-2β and μ subunits of P. monodon are reported. PmAP-2 β was up-regulated about 4-fold at 6 and 36 h post-WSSV infection. Knockdown of PmAP-2β delayed shrimp mortality during WSSV infection, of which WSSV intermediate early 1 gene expression was also down-regulated. Immunogold-labelling and transmission electron microscopy revealed that PmAP-2β co-localized with WSSV particles at plasma membrane. In addition, PmAP-2β-silencing significantly affected the expression levels of PmSTAT, PmDOME, PmDorsal and ALFPm3 during WSSV infection. It is possible that PmAP-2β is associated with the JAK/STAT and the Toll pathway.
Molecular diversity and selective sweeps in maize inbred lines adapted to African highlands
Authors: Wegary Dagne , Teklewold Adefris , Prasanna Boddupalli M. , Ertiro Berhanu T. , Alachiotis Nikolaos , Negera Demewez , Awas Geremew , Abakemal Demissew , Ogugo Veronica , Gowda Manje , Semagn Kassa 
Published: September 2019

AbstractLittle is known on maize germplasm adapted to the African highland agro-ecologies. In this study, we analyzed high-density genotyping by sequencing (GBS) data of 298 African highland adapted maize inbred lines to (i) assess the extent of genetic purity, genetic relatedness, and population structure, and (ii) identify genomic regions that have undergone selection (selective sweeps) in response to adaptation to highland environments. Nearly 91% of the pairs of inbred lines differed by 30–36% of the scored alleles, but only 32% of the pairs of the inbred lines had relative kinship coefficient <0.050, which suggests the presence of substantial redundancy in allelic composition that may be due to repeated use of fewer genetic backgrounds (source germplasm) during line development. Results from different genetic relatedness and population structure analyses revealed three different groups, which generally agrees with pedigree information and breeding history, but less so by heterotic groups and endosperm modification. We identified 944 single nucleotide polymorphic (SNP) markers that fell within 22 selective sweeps that harbored 265 protein-coding candidate genes of which some of the candidate genes had known functions. Details of the candidate genes with known functions and differences in nucleotide diversity among groups predicted based on multivariate methods have been discussed.
Quantifying the potential for bluetongue virus transmission in Danish cattle farms
Authors: Haider Najmul , Kjær Lene Jung , Skovgård Henrik , Nielsen Søren Achim , Bødker Rene 
Published: September 2019

AbstractWe used a mechanistic transmission model to estimate the number of infectious bites (IBs) generated per bluetongue virus (BTV) infected host (cattle) using estimated hourly microclimatic temperatures at 22,004 Danish cattle farms for the period 2000–2016, and Culicoides midge abundance based on 1,453 light-trap collections during 2007–2016. We used a range of published estimates of the duration of the hosts’ infectious period and equations for the relationship between temperature and four key transmission parameters: extrinsic incubation period, daily vector survival rate, daily vector biting rate and host-to-vector transmission rate resulting in 147,456 combinations of daily IBs. More than 82% combinations of the parameter values predicted > 1 IBs per host. The mean IBs (10–90th percentiles) for BTV per infectious host were 59 (0–73) during the transmission period. We estimated a maximum of 14,954 IBs per infectious host at some farms, while a best-case scenario suggested transmission was never possible at some farms. The use of different equations for the vector survival rate and host-to-vector transmission rates resulted in large uncertainty in the predictions. If BTV is introduced in Denmark, local transmission is very likely to occur. Vectors infected as late as mid-September (early autumn) can successfully transmit BTV to a new host until mid-November (late autumn).
Comparative evaluation of RNA-Seq library preparation methods for strand-specificity and low input
Authors: Sarantopoulou Dimitra , Tang Soon Yew , Ricciotti Emanuela , Lahens Nicholas F. , Lekkas Damien , Schug Jonathan , Guo Xiaofeng S. , Paschos Georgios K. , FitzGerald Garret A. , Pack Allan I. , Grant Gregory R. 
Published: September 2019

AbstractLibrary preparation is a key step in sequencing. For RNA sequencing there are advantages to both strand specificity and working with minute starting material, yet until recently there was no kit available enabling both. The Illumina TruSeq stranded mRNA Sample Preparation kit (TruSeq) requires abundant starting material while the Takara Bio SMART-Seq v4 Ultra Low Input RNA kit (V4) sacrifices strand specificity. The SMARTer Stranded Total RNA-Seq Kit v2 - Pico Input Mammalian (Pico) by Takara Bio claims to overcome these limitations. Comparative evaluation of these kits is important for selecting the appropriate protocol. We compared the three kits in a realistic differential expression analysis. We prepared and sequenced samples from two experimental conditions of biological interest with each of the three kits. We report differences between the kits at the level of differential gene expression; for example, the Pico kit results in 55% fewer differentially expressed genes than TruSeq. Nevertheless, the agreement of the observed enriched pathways suggests that comparable functional results can be obtained. In summary we conclude that the Pico kit sufficiently reproduces the results of the other kits at the level of pathway analysis while providing a combination of options that is not available in the other kits.