bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oscillatory shear potentiates latent TGF-β1 activation more than steady shear as demonstrated by a novel force generator
Authors: Kouzbari Karim , Hossan Mohammad R. , Arrizabalaga Julien H. , Varshney Rohan , Simmons Aaron D. , Gostynska Sandra , Nollert Matthias U. , Ahamed Jasimuddin 
Published: April 2019

AbstractCardiovascular mechanical stresses trigger physiological and pathological cellular reactions including secretion of Transforming Growth Factor β1 ubiquitously in a latent form (LTGF-β1). While complex shear stresses can activate LTGF-β1, the mechanisms underlying LTGF-β1 activation remain unclear. We hypothesized that different types of shear stress differentially activate LTGF-β1. We designed a custom-built cone-and-plate device to generate steady shear (SS) forces, which are physiologic, or oscillatory shear (OSS) forces characteristic of pathologic states, by abruptly changing rotation directions. We then measured LTGF-β1 activation in platelet releasates. We modeled and measured flow profile changes between SS and OSS by computational fluid dynamics (CFD) simulations. We found a spike in shear rate during abrupt changes in rotation direction. OSS activated TGF-β1 levels significantly more than SS at all shear rates. OSS altered oxidation of free thiols to form more high molecular weight protein complex(es) than SS, a potential mechanism of shear-dependent LTGF-β1 activation. Increasing viscosity in platelet releasates produced higher shear stress and higher LTGF-β1 activation. OSS-generated active TGF-β1 stimulated higher pSmad2 signaling and endothelial to mesenchymal transition (EndoMT)-related genes PAI-1, collagen, and periostin expression in endothelial cells. Overall, our data suggest variable TGF-β1 activation and signaling occurs with competing blood flow patterns in the vasculature to generate complex shear stress, which activates higher levels of TGF-β1 to drive vascular remodeling.
In situ response of Antarctic under-ice primary producers to experimentally altered pH
Authors: Cummings Vonda J. , Barr Neill G. , Budd Rod G. , Marriott Peter M. , Safi Karl A. , Lohrer Andrew M. 
Published: April 2019

AbstractElevated atmospheric CO2 concentrations are contributing to ocean acidification (reduced seawater pH and carbonate concentrations), with potentially major ramifications for marine ecosystems and their functioning. Using a novel in situ experiment we examined impacts of reduced seawater pH on Antarctic sea ice-associated microalgal communities, key primary producers and contributors to food webs. pH levels projected for the following decades-to-end of century (7.86, 7.75, 7.61), and ambient levels (7.99), were maintained for 15 d in under-ice incubation chambers. Light, temperature and dissolved oxygen within the chambers were logged to track diurnal variation, with pH, O2, salinity and nutrients assessed daily. Uptake of CO2 occurred in all treatments, with pH levels significantly elevated in the two extreme treatments. At the lowest pH, despite the utilisation of CO2 by the productive microalgae, pH did not return to ambient levels and carbonate saturation states remained low; a potential concern for organisms utilising this under-ice habitat. However, microalgal community biomass and composition were not significantly affected and only modest productivity increases were noted, suggesting subtle or slightly positive effects on under-ice algae. This in situ information enables assessment of the influence of future ocean acidification on under-ice community characteristics in a key coastal Antarctic habitat.
Ectopic miR-975 induces CTP synthase directed cell proliferation and differentiation in Drosophila melanogaster
Authors: Woo Wai Kan , Dzaki Najat , Thangadurai Shallinie , Azzam Ghows 
Published: April 2019

AbstractCTP synthase (CTPSyn) is an essential metabolic enzyme, synthesizing precursors required for nucleotides and phospholipids production. Previous studies have also shown that CTPSyn is elevated in various cancers. In many organisms, CTPSyn compartmentalizes into filaments called cytoophidia. In Drosophila melanogaster, only its isoform C (CTPSynIsoC) forms cytoophidia. In the fruit fly’s testis, cytoophidia are normally seen in the transit amplification regions close to its apical tip, where the stem-cell niche is located, and development is at its most rapid. Here, we report that CTPSynIsoC overexpression causes the lengthening of cytoophidia throughout the entirety of the testicular body. A bulging apical tip is found in approximately 34% of males overexpressing CTPSynIsoC. Immunostaining shows that this bulged phenotype is most likely due to increased numbers of both germline cells and spermatocytes. Through a microRNA (miRNA) overexpression screen, we found that ectopic miR-975 concurrently increases both the expression levels of CTPSyn and the length of its cytoophidia. The bulging testes phenotype was also recovered at a penetration of approximately 20%. However, qPCR assays reveal that CTPSynIsoC and miR-975 overexpression each provokes a differential response in expression of a number of cancer-related genes, indicating that the shared CTPSyn upregulation seen in either case is likely the cause of observed testicular overgrowth. This study presents the first instance of consequences of miRNA-asserted regulation upon CTPSyn in D. melanogaster, and further reaffirms the enzyme’s close ties to germline cells overgrowth.
Individual play patterns stimulated by a familiar object are group-driven
Authors: Zupan Manja , Rehn Therese , de Oliveira Daiana , Malovrh Špela , Keeling Linda 
Published: April 2019

AbstractThis study investigates the dynamics of play behaviour within groups of four juvenile pigs and uses a novel clustering and statistical modelling approach to describe new details in how individuals play with a familiar object (toy rope). We examined complex state sequence data collected during a 30 min home pen play test, using the package TraMineR, where the states were defined as object play, locomotor/social play and no play. From behavioural observations, and based on the relative proportion of the different types of object play observed, each individual was later categorised as an initiator or joiner type of player. Initiators were found to be more solitary and to show more object play whereas joiners were more social and showed less object play. The majority of groups did not have an initiator type of player, yet on average they played more. Despite strong group and type of player effects, we identified three general individual play patterns. On a group level, our results demonstrate differences in how a period of playing develops, that playing with the object simultaneously occurs more often in groups than expected by chance and that the number of pigs playing together is stable over time.
Heritability and genome-wide association study of benign prostatic hyperplasia (BPH) in the eMERGE network
Authors: Hellwege Jacklyn N. , Stallings Sarah , Torstenson Eric S. , Carroll Robert , Borthwick Kenneth M. , Brilliant Murray H. , Crosslin David , Gordon Adam , Hripcsak George , Jarvik Gail P. , Linneman James G. , Devi Parimala , Peissig Peggy L. , Sleiman Patrick A. M. , Hakonarson Hakon , Ritchie Marylyn D. , Verma Shefali Setia , Shang Ning , Denny Josh C. , Roden Dan M. , Velez Edwards Digna R. , Edwards Todd L. 
Published: April 2019

AbstractBenign prostatic hyperplasia (BPH) results in a significant public health burden due to the morbidity caused by the disease and many of the available remedies. As much as 70% of men over 70 will develop BPH. Few studies have been conducted to discover the genetic determinants of BPH risk. Understanding the biological basis for this condition may provide necessary insight for development of novel pharmaceutical therapies or risk prediction. We have evaluated SNP-based heritability of BPH in two cohorts and conducted a genome-wide association study (GWAS) of BPH risk using 2,656 cases and 7,763 controls identified from the Electronic Medical Records and Genomics (eMERGE) network. SNP-based heritability estimates suggest that roughly 60% of the phenotypic variation in BPH is accounted for by genetic factors. We used logistic regression to model BPH risk as a function of principal components of ancestry, age, and imputed genotype data, with meta-analysis performed using METAL. The top result was on chromosome 22 in SYN3 at rs2710383 (p-value = 4.6 × 10−7; Odds Ratio = 0.69, 95% confidence interval = 0.55–0.83). Other suggestive signals were near genes GLGC, UNCA13, SORCS1 and between BTBD3 and SPTLC3. We also evaluated genetically-predicted gene expression in prostate tissue. The most significant result was with increasing predicted expression of ETV4 (chr17; p-value = 0.0015). Overexpression of this gene has been associated with poor prognosis in prostate cancer. In conclusion, although there were no genome-wide significant variants identified for BPH susceptibility, we present evidence supporting the heritability of this phenotype, have identified suggestive signals, and evaluated the association between BPH and genetically-predicted gene expression in prostate.
Epsilon-Near-Zero Grids for On-chip Quantum Networks
Authors: Vertchenko Larissa , Akopian Nika , Lavrinenko Andrei V. 
Published: April 2019

AbstractRealization of an on-chip quantum network is a major goal in the field of integrated quantum photonics. A typical network scalable on-chip demands optical integration of single photon sources, optical circuitry and detectors for routing and processing of quantum information. Current solutions either notoriously experience considerable decoherence or suffer from extended footprint dimensions limiting their on-chip scaling. Here we propose and numerically demonstrate a robust on-chip network based on an epsilon-near-zero (ENZ) material, whose dielectric function has the real part close to zero. We show that ENZ materials strongly protect quantum information against decoherence and losses during its propagation in the dense network. As an example, we model a feasible implementation of an ENZ network and demonstrate that information can be reliably sent across a titanium nitride grid with a coherence length of 434 nm, operating at room temperature, which is more than 40 times larger than state-of-the-art plasmonic analogs. Our results facilitate practical realization of large multi-node quantum photonic networks and circuits on-a-chip.
Effects of a phytogenic, alone and associated with potassium diformate, on tilapia growth, immunity, gut microbiome and resistance against francisellosis
Authors: Suphoronski S. A. , Chideroli R. T. , Facimoto C. T. , Mainardi R. M. , Souza F. P. , Lopera-Barrero N. M. , Jesus G. F. A. , Martins M. L. , Di Santis G. W. , de Oliveira A. , Gonçalves G. S. , Dari R. , Frouel S. , Pereira U. P. 
Published: April 2019

AbstractThis work evaluated the effects of dietary supplementation of A-Live (phytogenic) either individually or in combination with Aquaform (potassium diformate, acidifier) on juvenile Nile tilapia (Oreochromis niloticus) growth performance, innate immune parameters, gut microbiome, and resistance against Francisella noatunensis subsp. orientalis challenge. Each experimental group contained 140 fishes (34.3 ± 0.33) in two 150L tanks. The experimental design consisted of five groups: a negative control; treated groups (G1, G2, G3) supplemented with different concentrations of A-Live and Aquaform in the feed; and a positive control (PC) for pathogen infection. Groups G1, G2, G3, and PC were challenged with Francisella spp. after 15 days. After infection, the mortality was significantly lower in groups G1, G2, and G3 (p < 0.01). Furthermore, these groups showed significant increase (p < 0.05) in daily weight gain, feed conversion rate, and specific growth rate. The PC group presented increase (p < 0.05) in the leukocytes and neutrophils number. Innate immunity parameters showed no difference between treatments after infection. Microbiome analysis revealed an increased number of bacteria belonging to the Vibrionaceae family after pathogen infection suggesting a secondary pathogen function of these bacteria. These results validate the beneficial effects of these products in tilapia farming.
An overview of the oil-brine interfacial behavior and a new surface complexation model
Authors: Bonto María , Eftekhari Ali A. , Nick Hamidreza M. 
Published: April 2019

AbstractThe few existing surface complexation models (SCM) for the brine-oil interface have important limitations: the chemistry of each crude oil is not considered, they cannot capture the water/non-polar hydrocarbons surface charge, the interactions between Na+ and the acid sites are not included, and the equilibrium constants for the adsorption reactions are not validated against experimental data. We address the aforementioned constraints by proposing an improved diffuse-layer SCM for the oil-brine interface. The new model accounts for the chemistry of crude oils by considering surface sites linearly dependent on the TAN (total acid number) and TBN (total base number). We define weak sites to account for the negative surface charge observed for non-polar hydrocarbons in water. We optimize the parameters of our model by fitting the model to reported zeta potential measurements of oil in aqueous solutions. When we validate the optimized model against different experimental data sets, it generally shows a good performance in predicting the surface charge of oil in different brines with different pHs. We show that the acid and base numbers are only useful as a qualitative estimation of the distribution of polar groups at the oil surface, and more sophisticated analysis is necessary to quantify the chemistry of the oil-brine interface.
Different effects of prenatal MAM vs. perinatal THC exposure on regional cerebral blood perfusion detected by Arterial Spin Labelling MRI in rats
Authors: Drazanova Eva , Ruda-Kucerova Jana , Kratka Lucie , Stark Tibor , Kuchar Martin , Maryska Michal , Drago Filippo , Starcuk Zenon , Micale Vincenzo 
Published: April 2019

AbstractClinical studies consistently report structural impairments (i.e.: ventricular enlargement, decreased volume of anterior cingulate cortex or hippocampus) and functional abnormalities including changes in regional cerebral blood flow in individuals suffering from schizophrenia, which can be evaluated by magnetic resonance imaging (MRI) techniques. The aim of this study was to assess cerebral blood perfusion in several schizophrenia-related brain regions using Arterial Spin Labelling MRI (ASL MRI, 9.4 T Bruker BioSpec 94/30USR scanner) in rats. In this study, prenatal exposure to methylazoxymethanol acetate (MAM, 22 mg/kg) at gestational day (GD) 17 and the perinatal treatment with Δ-9-tetrahydrocannabinol (THC, 5 mg/kg) from GD15 to postnatal day 9 elicited behavioral deficits consistent with schizophrenia-like phenotype, which is in agreement with the neurodevelopmental hypothesis of schizophrenia. In MAM exposed rats a significant enlargement of lateral ventricles and perfusion changes (i.e.: increased blood perfusion in the circle of Willis and sensorimotor cortex and decreased perfusion in hippocampus) were detected. On the other hand, the THC perinatally exposed rats did not show differences in the cerebral blood perfusion in any region of interest. These results suggest that although both pre/perinatal insults showed some of the schizophrenia-like deficits, these are not strictly related to distinct hemodynamic features.
Influence of childhood trauma and brain-derived neurotrophic factor Val66Met polymorphism on posttraumatic stress symptoms and cortical thickness
Authors: Jin Min Jin , Jeon Hyeonjin , Hyun Myoung Ho , Lee Seung-Hwan 
Published: April 2019

AbstractInteraction between childhood trauma and genetic factors influences the pathophysiology of posttraumatic stress disorder (PTSD). This study examined the interaction effect of childhood trauma and brain-derived neurotrophic factor (BDNF) Val66Met polymorphism on PTSD symptoms and brain cortical thickness. A total of 216 participants (133 healthy volunteers and 83 PTSD patients) were recruited. T1-weighted structural magnetic resonance imaging, BDNF rs6265 genotyping through blood sampling, and clinical assessments including the childhood trauma questionnaire (CTQ) and posttraumatic stress disorder Checklist (PCL) were performed. A moderated regression analysis, two-way multivariate analysis of covariance, and correlation analysis were conducted. An interaction between the CTQ and the BDNF polymorphism significantly influenced PTSD symptom severity. In fact, people with rs6265 Val/Val genotype and higher CTQ scores showed higher PCL scores. Additionally, this interaction was significant on both left fusiform and transverse temporal gyri thickness. Furthermore, the thickness of both brain regions was significantly correlated with psychological symptoms including depression, anxiety, rumination, and cognitive emotion regulation methods; yet this was mainly observed in people with the Val/Val genotype. The interaction between childhood trauma and BDNF polymorphism significantly influences both PTSD symptoms and cortical thickness and the Val/Val genotype may increase the risk in Korean population.
Stage-specific transcriptome of Bursaphelenchus xylophilus reveals temporal regulation of effector genes and roles of the dauer-like stages in the lifecycle
Authors: Tanaka Suguru E. , Dayi Mehmet , Maeda Yasunobu , Tsai Isheng J. , Tanaka Ryusei , Bligh Mark , Takeuchi-Kaneko Yuko , Fukuda Kenji , Kanzaki Natsumi , Kikuchi Taisei 
Published: April 2019

AbstractThe pine wood nematode Bursaphelenchus xylophilus is the causal agent of pine wilt disease, one of the most devastating forest diseases in East Asian and West European countries. The lifecycle of B. xylophilus includes four propagative larval stages and gonochoristic adults which are involved in the pathogenicity, and two stages of dispersal larvae involved in the spread of the disease. To elucidate the ecological roles of each developmental stage in the pathogenic life cycle, we performed a comprehensive transcriptome analysis using RNA-seq generated from all developmental stages of B. xylophilus and compared transcriptomes between stages. We found more than 9000 genes are differentially expressed in at least one stage of the life cycle including genes involved in general nematode biology such as reproduction and moulting but also effector genes likely to be involved in parasitism. The dispersal-stage transcriptome revealed its analogy to C. elegans dauer and the distinct roles of the two larval stages from each other regarding survival and transmission. This study provides important insights and resources to understand B. xylophilus parasitic biology.
Repeat domain-associated O-glycans govern PMEL fibrillar sheet architecture
Authors: Graham Morven , Tzika Athanasia C. , Mitchell Susan M. , Liu Xinran , Leonhardt Ralf M. 
Published: April 2019

AbstractPMEL is a pigment cell-specific protein that forms a functional amyloid matrix in melanosomes. The matrix consists of well-separated fibrillar sheets on which the pigment melanin is deposited. Using electron tomography, we demonstrate that this sheet architecture is governed by the PMEL repeat (RPT) domain, which associates with the amyloid as an accessory proteolytic fragment. Thus, the RPT domain is dispensable for amyloid formation as such but shapes the morphology of the matrix, probably in order to maximize the surface area available for pigment adsorption. Although the primary amino acid sequence of the RPT domain differs vastly among various vertebrates, we show that it is a functionally conserved, interchangeable module. RPT domains of all species are predicted to be very highly O-glycosylated, which is likely the common defining feature of this domain. O-glycosylation is indeed essential for RPT domain function and the establishment of the PMEL sheet architecture. Thus, O-glycosylation, not amino acid sequence, appears to be the major factor governing the characteristic PMEL amyloid morphology.
CEP120 interacts with C2CD3 and Talpid3 and is required for centriole appendage assembly and ciliogenesis
Authors: Tsai Jhih-Jie , Hsu Wen-Bin , Liu Jia-Hua , Chang Ching-Wen , Tang Tang K. 
Published: April 2019

AbstractCentrosomal protein 120 (CEP120) was originally identified as a daughter centriole-enriched protein that participates in centriole elongation. Recent studies showed that CEP120 gene mutations cause complex ciliopathy phenotypes in humans, including Joubert syndrome and Jeune asphyxiating thoracic dystrophy, suggesting that CEP120 plays an additional role in ciliogenesis. To investigate the potential roles of CEP120 in centriole elongation and cilia formation, we knocked out the CEP120 gene in p53-deficient RPE1 cells using the CRISPR/Cas9 editing system, and performed various analyses. We herein report that loss of CEP120 produces short centrioles with no apparent distal and subdistal appendages. CEP120 knockout was also associated with defective centriole elongation, impaired recruitment of C2CD3 and Talpid3 to the distal ends of centrioles, and consequent defects in centriole appendage assembly and cilia formation. Interestingly, wild-type CEP120 interacts with C2CD3 and Talpid3, whereas a disease-associated CEP120 mutant (I975S) has a low affinity for C2CD3 binding and perturbs cilia assembly. Together, our findings reveal a novel role of CEP120 in ciliogenesis by showing that it interacts with C2CD3 and Talpid3 to assemble centriole appendages and by illuminating the molecular mechanism through which the CEP120 (I975S) mutation causes complex ciliopathies.
Gene expression profile in patients with Gaucher disease indicates activation of inflammatory processes
Authors: Ługowska Agnieszka , Hetmańczyk-Sawicka Katarzyna , Iwanicka-Nowicka Roksana , Fogtman Anna , Cieśla Jarosław , Purzycka-Olewiecka Joanna Karolina , Sitarska Dominika , Płoski Rafał , Filocamo Mirella , Lualdi Susanna , Bednarska-Makaruk Małgorzata , Koblowska Marta 
Published: April 2019

AbstractGaucher disease (GD) is a rare inherited metabolic disease caused by pathogenic variants in the GBA1 gene. So far, the pathomechanism of GD was investigated mainly in animal models. In order to delineate the molecular changes in GD cells we analysed gene expression profile in cultured skin fibroblasts from GD patients, control individuals and, additionally, patients with Niemann-Pick type C disease (NPC). We used expression microarrays with subsequent validation by qRT-PCR method. In the comparison GD patients vs. controls, the most pronounced relative fold change (rFC) in expression was observed for genes IL13RA2 and IFI6 (up-regulated) and ATOH8 and CRISPLD2 (down-regulated). Products of up-regulated and down-regulated genes were both enriched in genes associated with immune response. In addition, products of down-regulated genes were associated with cell-to-cell and cell-to-matrix interactions, matrix remodelling, PI3K-Akt signalling pathway and a neuronal survival pathway. Up-regulation of PLAU, IFIT1, TMEM158 and down-regulation of ATOH8 and ISLR distinguished GD patients from both NPC patients and healthy controls. Our results emphasize the inflammatory character of changes occurring in human GD cells indicating that further studies on novel therapeutics for GD should consider anti-inflammatory agents.