bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased FUS levels in astrocytes leads to astrocyte and microglia activation and neuronal death
Authors: Ajmone-Cat Maria Antonietta , Onori Angela , Toselli Camilla , Stronati Eleonora , Morlando Mariangela , Bozzoni Irene , Monni Emanuela , Kokaia Zaal , Lupo Giuseppe , Minghetti Luisa , Biagioni Stefano , Cacci Emanuele 
Published: March 2019

AbstractMutations of Fused in sarcoma (FUS), a ribonucleoprotein involved in RNA metabolism, have been found associated with both familial and sporadic cases of amyotrophic lateral sclerosis (ALS). Notably, besides mutations in the coding sequence, also mutations into the 3′ untranslated region, leading to increased levels of the wild-type protein, have been associated with neuronal death and ALS pathology, in ALS models and patients. The mechanistic link between altered FUS levels and ALS-related neurodegeneration is far to be elucidated, as well as the consequences of elevated FUS levels in the modulation of the inflammatory response sustained by glial cells, a well-recognized player in ALS progression. Here, we studied the effect of wild-type FUS overexpression on the responsiveness of mouse and human neural progenitor-derived astrocytes to a pro-inflammatory stimulus (IL1β) used to mimic an inflammatory environment. We found that astrocytes with increased FUS levels were more sensitive to IL1β, as shown by their enhanced expression of inflammatory genes, compared with control astrocytes. Moreover, astrocytes overexpressing FUS promoted neuronal cell death and pro-inflammatory microglia activation. We conclude that overexpression of wild-type FUS intrinsically affects astrocyte reactivity and drives their properties toward pro-inflammatory and neurotoxic functions, suggesting that a non-cell autonomous mechanism can support neurodegeneration in FUS-mutated animals and patients.
Detection and characterisation of canine astrovirus, canine parvovirus and canine papillomavirus in puppies using next generation sequencing
Authors: Bhatta Tarka Raj , Chamings Anthony , Vibin Jessy , Alexandersen Soren 
Published: March 2019

AbstractGastroenteritis in young animals is a clinical presentation with many infectious and non- infectious aetiologies. We used next generation sequencing (NGS) to investigate the possible infectious causes of gastroenteritis in puppies from a dog kennel in Victoria, Australia. The near complete genome of a canine astrovirus was obtained from pooled faecal samples, and was found to be 94.7% identical with a canine astrovirus detected in the United Kingdom in 2012. The phylogenetic analysis of the capsid gene found similarities to those of canine astroviruses identified in Italy in 2005 and in UK and Hungary in 2012, but distant from that of a canine astrovirus previously identified in Australia in 2012. Thus, different serotypes of canine astrovirus are likely circulating in Australia. The close relationship to European astroviruses also suggested that there had been recent movements of ancestor canine astroviruses between Australia and Europe. NGS also detected other infections in the puppies including several canine papillomaviruses and a canine parvovirus (vaccine strain) as well as a very low level of campylobacter. Canine astrovirus was the probable cause of diarrhoea in these puppies, with the possible involvement of campylobacter bacteria. NGS was effective as a non-targeted method to determine the likely infectious cause of gastroenteritis.
Association of symptoms of attention deficit-hyperactivity disorder and impulsive-aggression with severity of suicidal behavior in adult attempters
Authors: Conejero I. , Jaussent I. , Lopez R. , Guillaume S. , Olié E. , Hebbache C. , Cohen R. F. , Kahn J. P. , Leboyer M. , Courtet P. , Lopez-Castroman J. 
Published: March 2019

AbstractLiterature emphasizes the relationship between attention deficit-hyperactivity disorder (ADHD) and suicidal behavior (SB). However, the link between ADHD and the severity of SB is yet to be determined. We investigated the association between a probable diagnosis of ADHD and the severity of SB in 539 hospitalized suicide attempters, and determined the role of comorbid psychiatric diagnoses. The severity of SB was defined as the number of suicide attempts, age at first suicide attempt, seriousness and violence of suicide attempts. A diagnosis of probable adult ADHD (probable ADHD) was defined as the presence of both current ADHD symptoms and ADHD symptoms in childhood. We evaluated the combined effect of high impulsive-aggression levels and probable ADHD. Probable ADHD was not associated with early or frequent suicide attempts after adjustment for psychiatric disorders and treatment intake. High levels of impulsive-aggression increased the risk of an early suicide attempt, particularly in patients with ADHD symptoms, and independently of other clinical factors. The association between serious suicide attempts and probable ADHD remained significant after adjustment. Although ADHD is involved in suicidal vulnerability, psychiatric comorbidities and impulsive-aggression appear to largely explain the severity of SB in adult attempters with ADHD symptoms.
Steroidogenic Factor 1 (Nr5a1) is Required for Sertoli Cell Survival Post Sex Determination
Authors: Anamthathmakula Prashanth , Miryala Chandra Suma Johnson , Moreci Rebecca S. , Kyathanahalli Chandrashekara , Hassan Sonia S. , Condon Jennifer C. , Jeyasuria Pancharatnam 
Published: March 2019

AbstractThe elevated level of Steroidogenic Factor 1 (Nr5a1, Sf-1) expression in the male gonadal development pathway, post sex determination, implies a vital role in testis gonadal differentiation. In this study we generated Sertoli cell-specific Nr5a1 KO mice (SC-SF-1−/−) at E14.5, which coincides with testis development post sex determination, using the Amh-Cre mouse model. Analysis of SC-SF-1−/− (Sertoli cell specific Nr5a1 knockout) testes demonstrated apoptosis as early as E15. Further analysis revealed that SC-SF-1−/− gonads displayed lower MDM2 levels resulting in elevated TP53 levels, which we believe may lead to apoptosis of the Sertoli cell population, inferring the possibility that NR5A1 directly regulates MDM2 expression. By E15.5, the Sertoli cell and germ cell population declined in SC-SF-1−/− mice resulting in the disruption of seminiferous cords with limited cord structure remaining at E18.5. Due to the loss of Sertoli and germ cells, the testis weights of SC-SF-1−/− mice at 6-weeks were much reduced; however, SC-SF-1−/− seminal vesicles weights were comparable suggesting intact Leydig cell androgen production. We conclude that NR5A1 regulates the TP53 pathway during development, is essential for fetal Sertoli cell survival and controls the cell cycle of Sertoli cells during differentiation.
Assessment of arterial stiffness variables in patients with rheumatoid arthritis: A mediation analysis
Authors: Taverner Delia , Paredes Silvia , Ferré Raimon , Masana Lluís , Castro Antoni , Vallvé Joan-Carles 
Published: March 2019

AbstractWe aimed to study arterial stiffness variables in patients with rheumatoid arthritis (RA), specifically considering their associations with path model mediation analysis. We examined arterial stiffness expressed by the pulse wave velocity (PVW), augmentation index (AIx), distensibility, and clinical and biochemical characteristics in a cohort of 214 RA patients. Variable associations were analysed using multivariate linear regression analysis. We also used path model mediation analysis for PWV variable. Our results indicate that age, systolic blood pressure (SBP), and body mass index (BMI) were significantly associated with PWV, and collectively accounted for 32% of PWV variability. The parallel mediation analysis showed that SBP and BMI accounted for 21% and 7% (a total of 28%) of the total effect of age on PWV, respectively, indicating a partial mediation effect. The associated variables with AIx were age and tender joint count, while those with distensibility were BMI and sex, overall accounting for 16.5% and 4.7% of the variation in AIx and distensibility, respectively. We observed no associations of arterial stiffness with inflammatory variables, disease activity and duration, or cholesterol levels. In conclusion, in our population of RA patients, age is the most important variable that determines the increase in PWV. We have also shown that a significant proportion of the negative effects of age on PWV occurs through increases in SBP and BMI. In our study, lipid and inflammation variables were not associated with an increase in arterial stiffness.
Tracking Decitabine Incorporation into Malignant Myeloid Cell DNA in vitro and in vivo by LC-MS/MS with Enzymatic Digestion
Authors: Chilakala Sujatha , Feng Ye , Li Lan , Mahfouz Reda , Quteba Ebrahem , Saunthararajah Yogen , Xu Yan 
Published: March 2019

AbstractThe DNA hypomethylating agents decitabine and 5-azacytidine are the only two drugs approved for treatment of all subtypes of the myeloid malignancy myelodysplastic syndromes (MDS). The key to drug activity is incorporation into target cell DNA, however, a practical method to measure this incorporation is un-available. Here, we report a sensitive and specific LC-MS/MS method to simultaneously measure decitabine incorporation and DNA hypomethylation. A stable heavy isotope of 2′-deoxycytidine was used as an internal standard and one-step multi-enzyme digestion was used to release the DNA bound drug. Enzyme-released decitabine along with other mononucleosides were separated by a reverse-phase C18column and quantified by mass spectrometry using multiple-reaction-monitoring (MRM) mode, with a lower limit of quantitation at 1.00 nM.In vitrostudies demonstrated dosage and time-dependent incorporation of decitabine into myeloid leukemia cell DNA that correlated with extent of DNA hypomethylation. When applied to clinical samples serially collected from MDS patients treated with decitabine, the method again demonstrated correlation between decitabine DNA-incorporation and DNA hypomethylation. This novel assay to measure the intended molecular pharmacodynamic effect of decitabine therapy can therefore potentially provide insights into mechanisms underlying sensitivity versus resistance to therapy.
Serum lipidomic analysis from mixed neutron/X-ray radiation fields reveals a hyperlipidemic and pro-inflammatory phenotype
Authors: Laiakis Evagelia C. , Canadell Monica Pujol , Grilj Veljko , Harken Andrew D. , Garty Guy Y. , Astarita Giuseppe , Brenner David J. , Smilenov Lubomir , Fornace Albert J. 
Published: March 2019

AbstractHeightened threats for nuclear terrorism using improvised nuclear devices (IND) necessitate the development of biodosimetry assays that could rapidly assess thousands of individuals. However, the radiation exposures from an IND may be complex due to mixed fields of neutrons and photons (γ-rays), shielding from buildings, and proximity to the epicenter among others. In this study we utilized lipidomics to analyze serum samples from mice exposed to various percentages of neutrons and X-rays to a total dose of 3 Gy. Triacylglycerides, phosphatidylserines, lysophosphatidylethanolamines, lysophosphatidylcholines (LPCs), sphingolipids, and cholesteryl esters all showed delayed increases at day 7 compared to day 1 after irradiation, while diacylglycerides decreased in mixed field exposures and phosphatidylcholines (PCs) remained largely unchanged. Individual lipid molecules with a high degree of unsaturation exhibited the highest fold changes in mixed fields compared to photons alone. More importantly, the increased ratio of LPCs to PCs of each irradiation group compared to control could be used as a radiation biomarker and highlights the existence of a pro-inflammatory phenotype. The results showed that even a small percentage of neutrons in a mixed field can lead to high biological responses with implications for accurate biodosimetry, triage and medical managements of exposed populations.
Pharmacokinetic and pharmacodynamic actions of clozapine-N-oxide, clozapine, and compound 21 in DREADD-based chemogenetics in mice
Authors: Jendryka Martin , Palchaudhuri Monika , Ursu Daniel , van der Veen Bastiaan , Liss Birgit , Kätzel Dennis , Nissen Wiebke , Pekcec Anton 
Published: March 2019

AbstractMuscarinic Designer Receptors Exclusively Activated by Designer Drugs (DREADD) gated by clozapine-N-oxide (CNO) allow selective G-protein cascade activation in genetically specified cell-types in vivo. Here we compare the pharmacokinetics, off-target effects and efficacy of CNO, clozapine (CLZ) and compound 21 (Cmpd-21) at the inhibitory DREADD human Gi-coupled M4 muscarinic receptor (hM4Di). The half maximal effective concentration (EC50) of CLZ was substantially lower (0.42 nM) than CNO (8.1 nM); Cmpd-21 was intermediate (2.95 nM). CNO was back-converted to CLZ in mice, and CLZ accumulated in brain tissue. However, CNO itself also entered the brain, and free cerebrospinal fluid (CSF) levels were within the range to activate hM4Di directly, while free (CSF) CLZ levels remained below the detection limit. Furthermore, directly injected CLZ was strongly converted to its pharmacologically active metabolite, norclozapine. Cmpd-21 showed a superior brain penetration and long-lasting presence. Although we identified a wide range of CNO and Cmpd-21 off-targets, there was hardly any nonspecific behavioural effects among the parameters assessed by the 5-choice-serial-reaction-time task. Our results suggest that CNO (3–5 mg/kg) and Cmpd-21 (0.4–1 mg/kg) are suitable DREADD agonists, effective at latest 15 min after intraperitoneal application, but both require between-subject controls for unspecific effects.
Lyme Disease Patient Trajectories Learned from Electronic Medical Data for Stratification of Disease Risk and Therapeutic Response
Authors: Ichikawa Osamu , Glicksberg Benjamin S. , Genes Nicholas , Kidd Brian A. , Li Li , Dudley Joel T. 
Published: March 2019

AbstractLyme disease (LD) is the most common tick-borne illness in the United States. Although appropriate antibiotic treatment is effective for most cases, up to 20% of patients develop post-treatment Lyme disease syndrome (PTLDS). There is an urgent need to improve clinical management of LD using precise understanding of disease and patient stratification. We applied machine-learning to electronic medical records to better characterize the heterogeneity of LD and developed predictive models for identifying medications that are associated with risks of subsequent comorbidities. For broad disease categories, we identified 3, 16, and 17 comorbidities within 2, 5, and 10 years of diagnosis, respectively. At a higher resolution of ICD-9 codes, we identified known associations with LD including chronic pain and cognitive disorders, as well as particular comorbidities on a timescale that matched PTLDS symptomology. We identified 7, 30, and 35 medications associated with risks of these comorbidities within 2, 5, and 10 years, respectively. For instance, the first-line antibiotic doxycycline exhibited a consistently protective association for typical symptoms of LD, including backache. Our approach and findings may suggest new hypotheses for more personalized treatments regimens for LD patients.
Morphological changes of telocytes in camel efferent ductules in response to seasonal variations during the reproductive cycle
Authors: Abdel-Maksoud Fatma M. , Abd-Elhafeez Hanan H. , Soliman Soha A. 
Published: March 2019

AbstractTelocytes (TCs) are a distinct stromal cell type described in many organs. The present study investigated the existence of TCs within the efferent ductules in camel and the changes that occur in their morphology and activity during active and inactive reproductive seasons. TCs in the camel had a cell body and multiple telopodes (TPs), and most TCs had indented nuclei that exhibited prominent intranucleolar chromatin. TCs exhibited seasonal differences which were evaluated by histochemistry, immunohistochemistry (IHC), Transimition electron microscopy (TEM) and scanning electron microscopy (SEM). The presence of TCs in camel efferent ductules has been confirmed by CD34 positive immunostaing. In addition to the expression of the vascular endothelial growth factor (VEGF) which was stronger in the summer season. TCs exhibited stronger immunoreactivity for progesterone and oestrogen alpha receptors (ESR1) in the spring than in the summer. In addition, TCs showed strong positive immunostaining for both vimentin and androgen receptor (AR). Several ultrastructural changes were observed in TCs during the two seasons. TPs in the summer season had delicate ramifications whereas, in the spring, TPs displayed fine arborization and became more corrugated. TCs acquired signs of exaggerated secretory activities in the spring; TPs became expanded and packed with secretory vesicles. Thus, we conclude that, hormonal alterations during the reproductive cycle impact the morphology and secretory behavior of TCs.
Retinotopic and topographic analyses with gaze restriction for steady-state visual evoked potentials
Authors: Zhang Nannan , Liu Yadong , Yin Erwei , Deng Baosong , Cao Lu , Jiang Jun , Zhou Zongtan , Hu Dewen 
Published: March 2019

AbstractAlthough the mechanisms of steady-state visual evoked potentials (SSVEPs) have been well studied, none of them have been implemented with strictly experimental conditions. Our objective was to create an ideal observer condition to exploit the features of SSVEPs. We present here an electroencephalographic (EEG) eye tracking experimental paradigm that provides biofeedback for gaze restriction during the visual stimulation. Specifically, we designed an EEG eye tracking synchronous data recording system for successful trial selection. Forty-six periodic flickers within a visual field of 11.5° were successively presented to evoke SSVEP responses, and online biofeedback based on an eye tracker was provided for gaze restriction. For eight participants, SSVEP responses in the visual field and topographic maps from full-brain EEG were plotted and analyzed. The experimental results indicated that the optimal visual flicking arrangement to boost SSVEPs should include the features of circular stimuli within a 4–6° spatial distance and increased stimulus area below the fixation point. These findings provide a basis for determining stimulus parameters for neural engineering studies, e.g. SSVEP-based brain-computer interface (BCI) designs. The proposed experimental paradigm could also provide a precise framework for future SSVEP-related studies.
Transcriptomic and lipidomic analysis of an EPA-containing Nannochloropsis sp. PJ12 in response to nitrogen deprivation
Authors: Liang Jibei , Wen Fang , Liu Jianhua 
Published: March 2019

AbstractTo understand genes involved in neutral lipid accumulation upon nitrogen deprivation (ND) in a novel isolate of Nannochloropsis sp. PJ12, we performed comparative transcriptomic and lipidomic analyses of cells under ND and NR (nitrogen replete) conditions. Transcriptomic profiling indicated that, while enzymes involved in TCA cycle in PJ12 under ND condition were upregulated compared to that under NR condition, those involved in Calvin cycle and glycolysis under ND condition were downregulated. Furthermore, we showed that enzymes involved in fatty acid synthesis and glycerolipid synthesis were downregulated but not β-oxidation. Lipidomic profiling indicated that, while the level of neutral lipids in ND cells was increased compared to that of NR cells, level of photosynthetic membrane-lipids DGDG and PG was decreased. Taken together, our analysis indicated that TAG accumulation is attributed to the modification of membrane lipids derived primarily from “prokaryotic” pathway and secondarily from “eukaryotic” pathway based on the 16:X or 18:X fatty acid at the sn2 position of the glycerol backbone. We propose that two-phase (NR-ND) growth is ideal for biomass and biofuel production because ND reduces cell growth rate due to the loss of photosynthetic membrane and decreased quantum yield.
Evaluation of a new lymphocyte proliferation assay based on cyclic voltammetry; an alternative method
Authors: Nikbakht Mohammad , Pakbin Babak , Nikbakht Brujeni Gholamreza 
Published: March 2019

AbstractLymphocyte proliferation assays are widely used to assess the cell-mediated immunity. Current in vitro testing methods that are being used have extensive applications but still more problematic, due to the technical complexity and the needs for specialized equipment and reagents. Electrochemical methods such as cyclic voltammetry represent a very promising tool for the development of label-free in vitro assays of cell proliferation and viability. Here, a novel procedure based on voltammetric behaviours of proliferating cells was fabricated. Results indicated that proliferation in cell cultures and whole blood can be monitored electrochemically using cyclic voltammetry. In the comparison with colorimetric (MTT) assay, cyclic voltammetry gave the best correlation with cell count data over a range of 1200–300,000 cells/well of a microplate. Besides the advantages of short assay duration (4 hours) and the rapidness, the possibility use of fresh blood without further processing, would give more accurate results because cells are monitoring in an intact environment. Cyclic voltammetry assay is an efficient analytical method, which can provide a simple platform for the electrochemical study of lymphocyte proliferation.
What Arouses Evangelicals? Cultural Schemas, Interpretive Prisms, and Evangelicals’ Divergent Collective Responses to Pornography and Masturbation
Authors: Perry Samuel L 
Published: March 2019

AbstractThis study elucidates the puzzle of evangelical grievance selection by comparing evangelicals’ divergent collective responses to pornography use and solo-masturbation. Drawing on eighty in-depth interviews and content analyses of fifty-five evangelical monographs, I show how internal and external influences shape evangelicals’ evaluations of and responses to the two issues. Internally, evangelical cultural schemas of biblicism and pietistic idealism necessitate that grievances be connected directly to the Bible and believers’ “hearts.” Pornography is more aptly linked to explicit biblical proscriptions against heart-lust and consequently perceived collectively as a moral threat, compared with masturbation, which is neither directly addressed in the Bible nor unambiguously connected to lust. Externally, the growing influence of psychology within evangelicalism heightened concern about pornography’s harms while debunking myths associating masturbation with mental illness. These cultural influences provide “interpretive prisms” through which evangelicals differentially perceive the two issues, resulting in fervent anti-pornography activism and relative ambivalence toward masturbation.