bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic differentiation and intercontinental population structure of mosquito vectors Culex pipiens pipiens and Culex pipiens molestus
Authors: Yurchenko Andrey A. , Masri Reem A. , Khrabrova Natalia V. , Sibataev Anuarbek K. , Fritz Megan L. , Sharakhova Maria V. 
Published: May 2020

AbstractUnderstanding the population structure and mechanisms of taxa diversification is important for organisms responsible for the transmission of human diseases. Two vectors of West Nile virus,Culex pipiens pipiensandCx. p. molestus, exhibit epidemiologically important behavioral and physiological differences, but the whole-genome divergence between them was unexplored. The goal of this study is to better understand the level of genomic differentiation and population structures ofCx. p. pipiensandCx. p. molestusfrom different continents. We sequenced and compared the whole genomes of 40 individual mosquitoes from two locations in Eurasia and two in North America. Principal Component, ADMIXTURE, and neighbor joining analyses of the nuclear genomes identified two major intercontinental, monophyletic clusters ofCx. p. pipiensandCx. p. molestus. The level of genomic differentiation between the subspecies was uniform along chromosomes. The ADMIXTURE analysis determined signatures of admixture inCx. p. pipenspopulations but not inCx. p. molestuspopulations. Comparison of mitochondrial genomes among the specimens showed a paraphyletic origin of the major haplogroups between the subspecies but a monophyletic structure between the continents. Thus, our study identified thatCx. p. molestusandCx. p. pipiensrepresent different evolutionary units with monophyletic origin that have undergone incipient ecological speciation.
Using aircraft location data to estimate current economic activity
Authors: Miller Sam , Moat Helen Susannah , Preis Tobias 
Published: May 2020

AbstractAviation is a key sector of the economy, contributing at least 3% to gross domestic product (GDP) in the UK and the US. Currently, airline performance statistics are published with a three month delay. However, aircraft now broadcast their location in real-time using the Automated Dependent Surveillance Broadcast system (ADS-B). In this paper, we analyse a global dataset of flights since July 2016. We first show that it is possible to accurately estimate airline flight volumes using ADS-B data, which is available immediately. Next, we demonstrate that real-time knowledge of flight volumes can be a leading indicator for aviation’s direct contribution to GDP in both the UK and the US. Using ADS-B data could therefore help move us towards real-time estimates of GDP, which would equip policymakers with the information to respond to shocks more quickly.
Toward neuroprosthetic real-time communication from in silico to biological neuronal network via patterned optogenetic stimulation
Authors: Mosbacher Yossi , Khoyratee Farad , Goldin Miri , Kanner Sivan , Malakai Yenehaetra , Silva Moises , Grassia Filippo , Simon Yoav Ben , Cortes Jesus , Barzilai Ari , Levi Timothée , Bonifazi Paolo 
Published: May 2020

AbstractRestoration of the communication between brain circuitry is a crucial step in the recovery of brain damage induced by traumatic injuries or neurological insults. In this work we present a study of real-time unidirectional communication between a spiking neuronal network (SNN) implemented on digital platform and an in-vitro biological neuronal network (BNN), generating similar spontaneous patterns of activity both spatial and temporal. The communication between the networks was established using patterned optogenetic stimulation via a modified digital light projector (DLP) receiving real-time input dictated by the spiking neurons’ state. Each stimulation consisted of a binary image composed of 8 × 8 squares, representing the state of 64 excitatory neurons. The spontaneous and evoked activity of the biological neuronal network was recorded using a multi-electrode array in conjunction with calcium imaging. The image was projected in a sub-portion of the cultured network covered by a subset of the all electrodes. The unidirectional information transmission (SNN to BNN) is estimated using the similarity matrix of the input stimuli and output firing. Information transmission was studied in relation to the distribution of stimulus frequency and stimulus intensity, both regulated by the spontaneous dynamics of the SNN, and to the entrainment of the biological networks. We demonstrate that high information transfer from SNN to BNN is possible and identify a set of conditions under which such transfer can occur, namely when the spiking network synchronizations drive the biological synchronizations (entrainment) and in a linear regime response to the stimuli. This research provides further evidence of possible application of miniaturized SNN in future neuro-prosthetic devices for local replacement of injured micro-circuitries capable to communicate within larger brain networks.
Transcriptome profiling reveals insertional mutagenesis suppressed the expression of candidate pathogenicity genes in honeybee fungal pathogen, Ascosphaera apis
Authors: Getachew Awraris , Abejew Tessema Aynalem , Wu Jiangli , Xu Jin , Yu Huimin , Tan Jing , Wu Pengjie , Tu Yangyang , Kang Weipeng , Wang Zheng , Xu Shufa 
Published: May 2020

AbstractChalkbrood disease is caused by Ascosphaera apis which severely affects honeybee brood. Spore inoculation experiments shown pathogenicity varies among different strains and mutants, however, the molecular mechanism of pathogenicity is unclear. We sequenced, assembled and annotated the transcriptomes of wild type (SPE1) and three mutants (SPE2, SPE3 and SPE4) with reduced pathogenicity that were constructed in our previous study. Illumina sequencing generated a total of 394,910,604 clean reads and de novo Trinity-based assembled into 12,989 unigenes, among these, 9,598 genes were successfully annotated to known proteins in UniProt database. A total of 172, 3,996, and 650 genes were up-regulated and 4,403, 2,845, and 3,016 genes were down-regulated between SPE2-SPE1, SPE3-SPE1, and SPE4-SPE1, respectively. Overall, several genes with a potential role in fungal pathogenicity were detected down-regulated in mutants including 100 hydrolytic enzymes, 117 transcriptional factors, and 47 cell wall related genes. KEGG pathway enrichment analysis reveals 216 genes involved in nine pathways were down-regulated in mutants compared to wild type. The down-regulation of more pathways involved in pathogenicity in SPE2 and SPE4 than SPE3 supports their lower pathogenicity during in-vitro bioassay experiment. Expression of 12 down-regulated genes in mutants was validated by quantitative real time PCR. This study provides valuable information on transcriptome variation caused by mutation for further functional validation of candidate pathogenicity genes in A. apis.
Models suggest pathogen risks to wild fish can be mitigated by acquired immunity in freshwater aquaculture systems
Authors: Teixeira Alves Mickael , Taylor Nick G. H. 
Published: May 2020

AbstractThe interaction of pathogens between wild and farmed aquatic animal populations is a concern that remains unclear and controversial.Ichthyophthirius multifiliis, a ciliated protozoan parasite, is a pathogen of freshwater finfish species with geographic and host range that causes significant economic losses in aquaculture. Flow-through farming systems may facilitate the transfer of such a parasite with free-living stages between farmed and wild stocks. Here, experimental and field study infection data are used to describe the infection dynamics ofIchthyophthirius multifiliisin rainbow trout using a simple macroparasite model by including host resistance. The study considered flow-through farming systems with a single or two age-class compartments and simulated the transfer of the parasite between farmed and wild fish populations. Results suggest that aquaculture can promote the prevalence of the resistance in wild stocks by increasing the parasite population in the wild environment. At the same time, acquired resistance in the farmed fish population may protect the wild fish population from lethal effects of the parasite by reducing the total parasite population. This study offers a promising mathematical basis for understanding the effects of freshwater aquaculture in disease spread in wildlife, developing risk assessment modeling, and exploring new ways of aquaculture management.
The calcitonin-like system is an ancient regulatory system of biomineralization
Authors: Cardoso João C. R. , Félix Rute C. , Ferreira Vinícius , Peng MaoXiao , Zhang Xushuai , Power Deborah M. 
Published: May 2020

AbstractBiomineralization is the process by which living organisms acquired the capacity to accumulate minerals in tissues. Shells are the biomineralized exoskeleton of marine molluscs produced by the mantle but factors that regulate mantle shell building are still enigmatic. This study sought to identify candidate regulatory factors of molluscan shell mineralization and targeted family B G-protein coupled receptors (GPCRs) and ligands that include calcium regulatory factors in vertebrates, such as calcitonin (CALC). In molluscs, CALC receptor (CALCR) number was variable and arose through lineage and species-specific duplications. The Mediterranean mussel (Mytilus galloprovincialis) mantle transcriptome expresses six CALCR-like and two CALC-precursors encoding four putative mature peptides. Mussel CALCR-like are activated in vitro by vertebrate CALC but only receptor CALCRIIc is activated by the mussel CALCIIa peptide (EC50 = 2.6 ×10−5 M). Ex-vivo incubations of mantle edge tissue and mantle cells with CALCIIa revealed they accumulated significantly more calcium than untreated tissue and cells. Mussel CALCIIa also significantly decreased mantle acid phosphatase activity, which is associated with shell remodelling. Our data indicate the CALC-like system as candidate regulatory factors of shell mineralization. The identification of the CALC system from molluscs to vertebrates suggests it is an ancient and conserved calcium regulatory system of mineralization.
Predictive engines based on pharmacokinetics modelling for tacrolimus personalized dosage in paediatric renal transplant patients
Authors: Prado-Velasco Manuel , Borobia Alberto , Carcas-Sansuan Antonio 
Published: May 2020

AbstractThe development of predictive engines based on pharmacokinetic-physiological mathematical models for personalised dosage recommendations is an immature field. Nevertheless, these models are extensively applied during the design of new drugs. This study presents new advances in this subject, through a stable population of patients who underwent kidney transplantation and were prescribed tacrolimus. We developed 2 new population pharmacokinetic models based on a compartmental approach, with one following the physiologically based pharmacokinetic approach and both including circadian modulation of absorption and clearance variables. One of the major findings was an improved predictive capability for both models thanks to the consideration of circadian rhythms, both in estimating the population and in Bayesian individual customisation. This outcome confirms a plausible mechanism suggested by other authors to explain circadian patterns of tacrolimus concentrations. We also discovered significant intrapatient variability in tacrolimus levels a week after the conversion from a fast-release (Prograf) to a sustained-release formulation (Advagraf) using adaptive optimisation techniques, despite high adherence and controlled conditions. We calculated the intrapatient variability through parametric intrapatient variations, which provides a method for quantifying the mechanisms involved. We present a first application for the analysis of bioavailability changes in formulation conversion. The 2 pharmacokinetic models have demonstrated their capability as predictive engines for personalised dosage recommendations, although the physiologically based pharmacokinetic model showed better predictive behaviour.
Comprehensive analysis of posttranslational protein modifications in aging of subcellular compartments
Authors: Baldensperger Tim , Eggen Michael , Kappen Jonas , Winterhalter Patrick R. , Pfirrmann Thorsten , Glomb Marcus A. 
Published: May 2020

AbstractEnzymatic and non-enzymatic posttranslational protein modifications by oxidation, glycation and acylation are key regulatory mechanisms in hallmarks of aging like inflammation, altered epigenetics and decline in proteostasis. In this study a mouse cohort was used to monitor changes of posttranslational modifications in the aging process. A protocol for the extraction of histones, cytosolic and mitochondrial proteins from mouse liver was developed and validated. In total, 6 lysine acylation structures, 7 advanced glycation endproducts, 6 oxidative stress markers, and citrullination were quantitated in proteins of subcellular compartments using HPLC-MS/MS. Methionine sulfoxide, acetylation, formylation, and citrullination were the most abundant modifications. Histone proteins were extraordinary high modified and non-enzymatic modifications accumulated in all subcellular compartments during the aging process. Compared to acetylation of histone proteins which gave between 350 and 305 µmol/mol leucine equivalents in young and old animals, modifications like acylation, glycation, and citrullination raised to 43%, 20%, and 18% of acetylation, respectively. On the other hand there was an age related increase of selected oxidative stress markers by up to 150%. The data and patterns measured in this study are mandatory for further studies and will strongly facilitate understanding of the molecular mechanisms in aging.
An elevated neutrophil-to-lymphocyte ratio associates with weight loss and cachexia in cancer
Authors: Barker Tyler , Fulde Gail , Moulton Bryce , Nadauld Lincoln D. , Rhodes Terence 
Published: May 2020

AbstractSystemic inflammation is present during and serves as a diagnostic tool for cancer-associated cachexia and is detrimental to serum 25-hydroxyvitamin D (25(OH)D) concentrations in non-cancer conditions. The neutrophil-to-lymphocyte ratio (NLR) is a desirable measure of systemic inflammation because it is easily calculated from a routine complete blood cell count with differentials. We sought to determine if an elevation in the NLR associates with greater weight loss, cachexia, and lower serum 25-hydroxyvitamin D (25(OH)D) concentrations in patients with advanced cancer. Advanced colon, lung, and prostate cancer patients (stages III/IV; n = 50) were retrospectively studied and separated into one of two groups: 1) Above (n = 25) or 2) Below (n = 25) the median NLR of 3.15 determined at diagnosis. Around the time of diagnosis, serum 25(OH)D and body weight were assessed, while body weight was assessed again at a later date. Weight loss and cachexia were significantly (both p < 0.05) greater and there was a trend (p < 0.10) for lower serum 25(OH)D concentrations in the Above group. We conclude that an elevation in the NLR associates with greater weight loss and cachexia, and potentially, a lower serum 25(OH)D concentration in patients with advanced colon, lung, or prostate cancer.
Tumor grafts grown on the chicken chorioallantoic membrane are distinctively characterized by MRI under functional gas challenge
Authors: Waschkies Conny F. , Pfiffner Fatma Kivrak , Heuberger Dorothea M. , Schneider Marcel A. , Tian Yinghua , Wolint Petra , Calcagni Maurizio , Giovanoli Pietro , Buschmann Johanna 
Published: May 2020

AbstractRecently, a tumor model based on the chorioallantoic membrane (CAM) was characterized structurally with Magnetic Resonance Imaging (MRI). Yet, capability of MRI to assess vascular functional reserve and potential of oxygenation-sensitive MRI remain largely unexplored in this model. For this purpose, we compared MC-38 colon and A549 lung adenocarcinoma cell grafts grown on the CAM, using quantitative T1 and T2* MRI readouts as imaging markers. These are associated with vascular functionality and oxygenation status when compared between periods of air and carbogen exposure. Our data show that in A549 lung adenocarcinoma cell grafts T2* values increased significantly upon carbogen exposure (p < 0.004, Wilcoxon test; no change in T1), while MC-38 grafts displayed no changes in T1 and T2*), indicating that the grafts differ in their vascular response. Heterogeneity with regard to T1 and T2* distribution within the grafts was noted. MC-38 grafts displayed larger T1 and T2* in the graft centre, while in A549 they were distributed more towards the graft surface. Finally, qualitative assessment of gadolinium-enhancement suggests that A549 grafts display more prominent enhancement compared to MC-38 grafts. Furthermore, MC-38 grafts had 65% larger volumes than A549 grafts. Histology revealed distinct underlying phenotypes of the two tumor grafts, pertaining to the proliferative status (Ki-67) and cellularity (H&E). In sum, a functional gas challenge with carbogen is feasible through gas exchange on the CAM, and it affects MRI signals associated with vascular reactivity and oxygenation status of the tumor graft planted on the CAM. Different grafts based on A549 lung adenocarcinoma and MC-38 colon carcinoma cell lines, respectively, display distinct phenotypes that can be distinguished and characterized non-invasively in ovo using MRI in the living chicken embryo.
Endothelial Twist1-PDGFB signaling mediates hypoxia-induced proliferation and migration of αSMA-positive cells
Authors: Mammoto Akiko , Hendee Kathryn , Muyleart Megan , Mammoto Tadanori 
Published: May 2020

AbstractRemodeling of distal pulmonary arterioles (PAs) associated with marked accumulation of pulmonary artery smooth muscle cells (PASMCs) represents one of the major pathologic features of pulmonary hypertension (PH). We have reported that the transcription factor Twist1 mediates hypoxia-induced PH. However, the mechanism by which endothelial Twist1 stimulates SMC accumulation to distal PAs in PH remains unclear. Here, we have demonstrated that Twist1 overexpression increases the expression of platelet-derived growth factor (PDGFB) in human pulmonary arterial endothelial (HPAE) cells. Hypoxia upregulates the levels of Twist1 and PDGFB in HPAE cells. When we implant hydrogel supplemented with endothelial cells (ECs) on the mouse lung, these ECs form vascular lumen structures and hypoxia upregulates PDGFB expression and stimulates accumulation of αSMA–positive cells in the gel, while knockdown of endothelial Twist1 suppresses the effects. The levels of Twist1 and PDGFB are higher in PAE cells isolated from idiopathic pulmonary arterial hypertension (IPAH) patients compared to those from healthy controls. IPAH patient-derived PAE cells stimulate accumulation of αSMA–positive cells in the implanted gel, while Twist1 knockdown in PAE cells inhibits the effects. Endothelial Twist1-PDGFB signaling plays a key role in αSMA–positive cell proliferation and migration in PH.
Effective bifidogenic growth factors cyclo-Val-Leu and cyclo-Val-Ile produced by Bacillus subtilis C-3102 in the human colonic microbiota model
Authors: Hatanaka Misaki , Morita Hiroto , Aoyagi Yumi , Sasaki Kengo , Sasaki Daisuke , Kondo Akihiko , Nakamura Teppei 
Published: May 2020

AbstractBifidobacterium species are known to fulfill important functions within the human colon. Thus, stimulating the activity of bifidobacteria is important to maintain host health. We revealed that culture supernatants of Bacillus subtilis C-3102 (referred to as C-3102) stimulated the growth of Bifidobacterium species. In this study, we isolated and identified six bifidogenic growth factors, which were cyclo (D-Val-D-Ile), cyclo (L-Val-D-Ile), cyclo (D-Val-L-Ile), cyclo (L-Val-L-Ile), cyclo (D-Val-L-Leu) and cyclo (L-Val-L-Leu). These six cyclic dipeptides increased the growth of Bifidobacterium species and had no effect on potentially harmful gut organisms. Moreover, supplementation with a mixture of these six cyclic dipeptides significantly increased the abundance of microorganisms related to the genus Bifidobacterium in a human colonic microbiota model culture system, although supplementation with a single type of dipeptide had no effect. These results show that cyclic dipeptides containing Val-Leu and Val-Ile produced by C-3102 could serve as bifidogenic growth factors in the gut microbial community.
High gamma response tracks different syntactic structures in homophonous phrases
Authors: Artoni Fiorenzo , d’Orio Piergiorgio , Catricalà Eleonora , Conca Francesca , Bottoni Franco , Pelliccia Veronica , Sartori Ivana , Russo Giorgio Lo , Cappa Stefano F. , Micera Silvestro , Moro Andrea 
Published: May 2020

AbstractSyntax is a species-specific component of human language combining a finite set of words in a potentially infinite number of sentences. Since words are by definition expressed by sound, factoring out syntactic information is normally impossible. Here, we circumvented this problem in a novel way by designing phrases with exactly the same acoustic content but different syntactic structures depending on the other words they occur with. In particular, we used phrases merging an article with a noun yielding a Noun Phrase (NP) or a clitic with a verb yielding a Verb Phrase (VP). We performed stereo-electroencephalographic (SEEG) recordings in epileptic patients. We measured a different electrophysiological correlates of verb phrases vs. noun phrases in multiple cortical areas in both hemispheres, including language areas and their homologous in the non-dominant hemisphere. The high gamma band activity (150-300 Hz frequency), which plays a crucial role in inter-regional cortical communications, showed a significant difference during the presentation of the homophonous phrases, depending on whether the phrase was a verb phrase or a noun phrase. Our findings contribute to the ultimate goal of a complete neural decoding of linguistic structures from the brain.
Iridium Corroles Exhibit Weak Near-Infrared Phosphorescence but Efficiently Sensitize Singlet Oxygen Formation
Authors: Thomassen Ivar K. , McCormick-McPherson Laura J. , Borisov Sergey M. , Ghosh Abhik 
Published: May 2020

AbstractSix-coordinate iridium(III) triarylcorrole derivatives, Ir[TpXPC)]L2, where TpXPC = tris(para-X-phenyl)corrole (X = CF3, H, Me, and OCH3) and L = pyridine (py), trimethylamine (tma), isoquinoline (isoq), 4-dimethylaminopyridine (dmap), and 4-picolinic acid (4pa), have been examined, with a view to identifying axial ligands most conducive to near-infrared phosphorescence. Disappointingly, the phosphorescence quantum yield invariably turned out to be very low, about 0.02 – 0.04% at ambient temperature, with about a two-fold increase at 77 K. Phosphorescence decay times were found to be around ~5 µs at 295 K and ~10 µs at 77 K. Fortunately, two of the Ir[TpCF3PC)]L2 derivatives, which were tested for their ability to sensitize singlet oxygen formation, were found to do so efficiently with quantum yields Φ(1O2) = 0.71 and 0.38 for L = py and 4pa, respectively. Iridium corroles thus may hold promise as photosensitizers in photodynamic therapy (PDT). The possibility of varying the axial ligand and of attaching biotargeting groups at the axial positions makes iridium corroles particularly exciting as PDT drug candidates.