Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of Flap Structure-Specific Endonuclease 1 as a Factor Involved in Long-Term Memory Formation of Aversive Learning

We previously proposed that DNA recombination/repair processes play a role in memory formation. Here, we examined the possible role of the fen-1 gene, encoding a flap structure-specific endonuclease, in memory consolidation of conditioned taste aversion (CTA). Quantitative real-time PCR showed that amygdalar fen-1 mRNA induction was associated to the central processing of the illness experience related to CTA and to CTA itself, but not to the central processing resulting from the presentation of a novel flavor. CTA also increased expression of the Fen-1 protein in the amygdala, but not the insular cortex. In addition, double immunofluorescence analyses showed that amygdalar Fen-1 expression is mostly localized within neurons. Importantly, functional studies demonstrated that amygdalar antisense knockdown of fen-1 expression impaired consolidation, but not short-term memory, of CTA. Overall, these studies define the fen-1 endonuclease as a new DNA recombination/repair factor involved in the formation of long-term memories.
Toxicology and Carcinogenesis Study of Senna in C3B6.129F1-Trp53 tm1Brd N12 Haploinsufficient Mice

Senna is a pod or leaf of Senna alexandrina P. Mill and is used as a stimulant laxative. In the large intestine, bacterial enzymes reduce sennosides to rhein-9-anthrone, the active form for the laxative effect. To determine the potential toxic effects of senna, a 5-week dose range finding study in the C57BL/6N mouse and a 40-week toxicology and carcinogenesis study in the C3B6.129F1-Trp53 tm1Brd N12 haploinsufficient (p53+/−) mouse were conducted. In the 5-week study, C57BL/6N mice were exposed to up to 10,000 ppm senna in feed. Increased incidences of epithelial hyperplasia of the cecum and colon were observed in males and females exposed to 5,000 or 10,000 ppm senna. These intestinal lesions were not considered to be of sufficient severity to cause mortality and, thus, in the p53+/− mouse 40-week study, the high dose of 10,000 ppm was selected. Significant increases in the incidences of epithelial hyperplasia of the colon and cecum were observed at 10,000 ppm in p53+/− males and females, and the incidence of hyperplasia of the colon was significantly increased at 3,000 ppm in females. In conclusion, the large intestine was the major target of senna-induced toxicity in both wild-type and the p53+/− mouse model. There was no neoplastic change when senna was administered to p53+/− mouse.
Quantitative urine confirmatory testing for synthetic cannabinoids in randomly collected urine specimens.

Synthetic cannabinoid intake is an ongoing health issue worldwide, with new compounds continually emerging, making drug testing complex. Parent synthetic cannabinoids are rarely detected in urine, the most common matrix employed in workplace drug testing. Optimal identification of synthetic cannabinoid markers in authentic urine specimens and correlation of metabolite concentrations and toxicities would improve synthetic cannabinoid result interpretation. We screened 20 017 randomly collected US military urine specimens between July 2011 and June 2012 with a synthetic cannabinoid immunoassay yielding 1432 presumptive positive specimens. We analyzed all presumptive positive and 1069 negative specimens with our qualitative synthetic cannabinoid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, which confirmed 290 positive specimens. All 290 positive and 487 randomly selected negative specimens were quantified with the most comprehensive urine quantitative LC-MS/MS method published to date; 290 specimens confirmed positive for 22 metabolites from 11 parent synthetic cannabinoids. The five most predominant metabolites were JWH-018 pentanoic acid (93%), JWH-N-hydroxypentyl (84%), AM2201 N-hydroxypentyl (69%), JWH-073 butanoic acid (69%), and JWH-122 N-hydroxypentyl (45%) with 11.1 (0.1-2,434), 5.1 (0.1-1,239), 2.0 (0.1-321), 1.1 (0.1-48.6), and 1.1 (0.1-250) µg/L median (range) concentrations, respectively. Alkyl hydroxy and carboxy metabolites provided suitable biomarkers for 11 parent synthetic cannabinoids; although hydroxyindoles were also observed. This is by far the largest data set of synthetic cannabinoid metabolites urine concentrations from randomly collected workplace drug testing specimens rather than acute intoxications or driving under the influence of drugs. These data improve the interpretation of synthetic cannabinoid urine test results and suggest suitable urine markers of synthetic cannabinoid intake.
Behavior therapy versus clomipramine for the treatment of obsessive-compulsive disorder in children and adolescents.

OBJECTIVE To compare, via a pilot study, the effectiveness of behavior therapy and of drug treatment in children and adolescents with obsessive-compulsive disorder. METHOD Twenty-two children aged between 8 and 18 years were randomly assigned to behavior therapy (n = 12) or open clomipramine (n = 10) in a parallel design lasting 12 weeks. Behavior therapy included exposure and response prevention administered in weekly sessions. The mean dosage of clomipramine was 2.5 mg/kg (range = 1.4-3.3 mg/kg). The main outcome variables were the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) and the Leyton Obsessional Inventory-Child Version (LOI-CV). RESULTS Significant improvement was obtained in both treatment conditions. Behavior therapy produced stronger therapeutic changes than clomipramine on the CY-BOCS (p < .05), whereas on the LOI-CV no significant differences between the results of the two treatments were found. Five of the nine initial nonresponders showed significant changes after extension of treatment for another 12 weeks. CONCLUSION Behavior therapy is shown to be a good alternative for drug treatment and deserves further study in larger samples of children with obsessive-compulsive disorder.
Precipitation of Cerium Sulfate Converted from Cerium Oxide in Sulfuric Acid Solutions and the Conversion Kinetics

acid solutions (C/S), and particle size on the conversion process were investigated. All experiments were carried out in the range of 8­14 mol/dm 3 for sulfuric acid concentration, 105­135°C for reaction temperature, 0.04­0.28mol/dm 3 for C/S, and 2.5­112.5µm for average particle size. The conversion process involves the dissolution of cerium (IV) oxide and the precipitation of cerium (IV) sulfate. Cerium (IV) oxide reacted with sulfuric acid very slowly and then dissolved cerium (IV) in a saturated condition directly formed cerium (IV) sulfate indicating that the conversion rate was controlled by the dissolution rate of cerium (IV) oxide. Increases in sulfuric acid concentration and reaction temperature increased the dissolution rate, whereas increase in particle size decreased it. However, the C/S had no effect on the dissolution rate. In terms of the yield of precipitated cerium (IV) sulfate after reaction equilibrium, increases in sulfuric acid concentration and C/S increased the yield. However, the particle size and the reaction temperature had no effect on the yield of precipitated cerium (IV) sulfate. The kinetics of cerium (IV) oxide dissolution, under various conditions of sulfuric acid concentration, reaction temperature, C/S, and particle size, was interpreted by a shrinking core model with chemical reaction. The variation of rate constant upon dissolution with temperature obeyed the Arrhenius equation with an activation energy of 123kJ/mol. [doi:10.2320/matertrans.M-M2012826]
Curcumin prevents adriamycin-induced nephropathy MCP-1 expression through blocking histone acetylation

Objective: To investigate the anti-MCP-1 expression effect of curcumin in kidney disease model and the possible mechanisms associated with histone acetylation. Methods: ADR nephropathy was induced in male SD rats by twice intravenous injections of ADR at day 0 (5 mg·kg-1) and 1 week later (2.5 mg·kg-1). Curcumin treatment was started at week 6. EP300 and MCP-1 mRNA transcription were assessed by real-time PCR. The acetylation levels of the histones H3 and H4 in the promoters of MCP-1 were detected by ChIP-qPCR. And mouse podocytes were cultured to investigate the effect of curcumin against ADR-induced injury. Results: In animal model, curcumin intervention attenuated renal glomerulosclerosis and partially decreased transcription of EP300 and MCP-1 (P < 0.05) mRNA. Also, curcumin prevented an increase of acetylation of MCP-1 promoters H3 and H4 in ADR-nephropathy. In vitro cultured podocytes, compared with the untreated ADR group, pretreatment with low concentration of curcumin preserved podocyte cytoskeleton. Curcumin significantly reduced EP300 and MCP-1 mRNA (P < 0.01). Besides, curcumin prevented ADR-induced MCP-1 promoter hyper-acetylation in ADR injured podocytes by ChIP-qPCR. Conclusion: Curcumin prevents kidney fibrosis and decreases MCP-1 expression through modification of histone acetylation, and could be used as a therapy for patients with kidney disease.
IgG transport across trophoblast‐derived BeWo cells: a model system to study IgG transport in the placenta

In primates, prenatal transfer of IgG from mother to offspring occurs predominantly across the placenta. Although a number of Fcγ‐receptors and IgG binding proteins have been detected in human placental tissue, an involvement of any of these receptors in IgG transport across the syncytiotrophoblast remains to be demonstrated. Therefore, we investigated the mechanism of IgG transcytosis in trophoblast‐derived BeWo cells. BeWo cells were not only found to express the MHC class I‐related IgG Fc receptor, human FcRn, but also specifically bound fluorescein isothiocyanate (FITC)‐labeled human IgG (FITC‐hIgG) at the apical surface at mildly acidic pH. The cells preferentially transcytosed FITC‐hIgG from the apical to the basolateral side when compared to the fluid‐phase marker FITC‐dextran and to FITC‐hIgG transcytosis in the opposite direction. However, endocytosis of FITC‐hIgG at the apical plasma membrane at physiological pH required the continuous presence of FITC‐hIgG at concentrations similar to those present in the maternal circulation. These results suggest a mechanism by which IgG is internalized by BeWo cells via fluid‐phase endocytosis. Tight binding of IgG to hFcRn may then occur in acidic endosomes, followed by selective sorting into the transcytotic pathway. Thus, the main function of this receptor is to prevent entry of IgG into the degradative pathway in lysosomes.
Post‐transcriptional regulation of transcript abundance by a conserved member of the tristetraprolin family in Candida albicans

Members of the tristetraprolin (TTP) family of CCCH tandem zinc finger proteins bind to AU‐rich regions in target mRNAs, leading to their deadenylation and decay. Family members in Saccharomyces cerevisiae influence iron metabolism, whereas the single protein expressed in Schizosaccharomyces pombe, Zfs1, regulates cell–cell interactions. In the human pathogen Candida albicans, deep sequencing of mutants lacking the orthologous protein, Zfs1, revealed significant increases (> 1.5‐fold) in 156 transcripts. Of these, 113 (72%) contained at least one predicted TTP family member binding site in their 3′UTR, compared with only 3 of 56 (5%) down‐regulated transcripts. The zfs1Δ/Δ mutant was resistant to 3‐amino‐1,2,4‐triazole, perhaps because of increased expression of the potential target transcript encoded by HIS3. Sequences of the proteins encoded by the putative Zfs1 targets were highly conserved among other species within the fungal CTG clade, while the predicted Zfs1 binding sites in these mRNAs often ‘disappeared’ with increasing evolutionary distance from the parental species. C. albicans Zfs1 bound to the ideal mammalian TTP binding site with high affinity, and Zfs1 was associated with target transcripts after co‐immunoprecipitation. Thus, the biochemical activities of these proteins in fungi are highly conserved, but Zfs1‐like proteins may target different transcripts in each species.
Expression of Epstein-Barr virus-encoded small RNA (by the EBER-1 gene) in liver specimens from transplant recipients with post-transplantation lymphoproliferative disease.

BACKGROUND Epstein-Barr virus (EBV)-associated post-transplantation lymphoproliferative disease (PTLD) develops in 1 to 10 percent of transplant recipients, in whom it can be treated by a reduction in the level of immunosuppression. We postulated that the tissue expression of the small RNA transcribed by the EBER-1 gene during latent EBV infection would identify patients at risk for PTLD. METHODS We studied EBER-1 gene expression in liver specimens obtained from 24 patients 2 days to 22 months before the development of PTLD, using in situ hybridization with an oligonucleotide probe. Control specimens were obtained from 20 recipients of allografts with signs of injury due to organ retrieval, acute graft rejection, or viral hepatitis in whom PTLD had not developed 9 to 71 months after the biopsy. RESULTS Of the 24 patients with PTLD, 17 (71 percent) had specimens in which 1 to 40 percent of mononuclear cells were positive for the EBER-1 gene. In addition, 10 of these 17 patients (59 percent) had specimens with histopathological changes suggestive of EBV hepatitis. In every case, EBER-1-positive cells were found within the lymphoproliferative lesions identified at autopsy. Only 2 of the 20 controls (10 percent) had specimens with EBER-1-positive cells (P < 0.001), and such cells were rare. CONCLUSIONS EBER-1 gene expression in liver tissue precedes the occurrence of clinical and histologic PTLD. The possibility of identifying patients at risk by the method we describe here and preventing the occurrence of PTLD by a timely reduction of immunosuppression needs to be addressed by future prospective studies.
Particulate matter air pollution and liver cancer survival

Particulate matter (PM) air pollution exposure has been associated with cancer incidence and mortality especially with lung cancer. The liver is another organ possibly affected by PM due to its role in detoxifying xenobiotics absorbed from PM. Various studies have investigated the mechanistic pathways between inhaled pollutants and liver damage, cancer incidence, and tumor progression. However, little is known about the effects of PM on liver cancer survival. Twenty thousand, two hundred and twenty‐one California Cancer Registry patients with hepatocellular carcinoma (HCC) diagnosed between 2000 and 2009 were used to examine the effect of exposure to ambient PM with diameter <2.5 μm (PM2.5) on HCC survival. Cox proportional hazards models were used to estimate hazard ratios (HRs) relating PM2.5 to all‐cause and liver cancer‐specific mortality linearly and nonlinearly—overall and stratified by stage at diagnosis (local, regional and distant)—adjusting for potential individual and geospatial confounders.PM2.5 exposure after diagnosis was statistically significantly associated with HCC survival. After adjustment for potential confounders, the all‐cause mortality HR associated with a 1 standard deviation (5.0 µg/m3) increase in PM2.5 was 1.18 (95% CI: 1.16–1.20); 1.31 (95% CI:1.26–1.35) for local stage, 1.19 (95% CI:1.14–1.23) for regional stage, and 1.05 (95% CI:1.01–1.10) for distant stage. These associations were nonlinear, with substantially larger HRs at higher exposures. The associations between liver cancer‐specific mortality and PM2.5 were slightly attenuated compared to all‐cause mortality, but with the same patterns.Exposure to elevated PM2.5 after the diagnosis of HCC may shorten survival, with larger effects at higher concentrations.
Creativity, diversity, and integration: Radical change in the bachelor of music curriculum

During 2013–2014, the Task Force on the Undergraduate Music Major of the USA’s College Music Society prepared a report entitled Transforming Music Study from its Foundations: A Manifesto for Progressive Change in the Undergraduate Preparation of Music Majors. The report is a call for increased relevance in undergraduate music studies that prepare students for leadership, adaptability, and initiative in advancing the values of music and musicians in a techno-global society. Specifically, the task force recommends that curricula derive from the three pillars of creativity, diversity, and integration, arguing that composition, improvisation, performance, and theoretical-cultural-historic music studies be taught holistically and in ways authentic to the art and practice of music itself. In addition, the report calls for greater participation by students in planning degree programs that provide trajectories in keeping with their goals and interests, and for greater nimbleness that enhances curricular adaptations on an ongoing basis.
Fields of Definition for Representations of Associative Algebras

Abstract We examine situations, where representations of a finite-dimensional F-algebra A defined over a separable extension field K/F, have a unique minimal field of definition. Here the base field F is assumed to be a field of dimension ≼1. In particular, F could be a finite field or k(t) or k((t)), where k is algebraically closed. We show that a unique minimal field of definition exists if (a) K/F is an algebraic extension or (b) A is of finite representation type. Moreover, in these situations the minimal field of definition is a finite extension of F. This is not the case if A is of infinite representation type or F fails to be of dimension ≼1. As a consequence, we compute the essential dimension of the functor of representations of a finite group, generalizing a theorem of Karpenko, Pevtsova and the second author.
Maternal depression and trajectories of adolescent depression: The role of stress responses in youth risk and resilience

Abstract This study examined the independent and interactive contributions of maternal depression and youth stress responses to trajectories of youth depression in adolescence. Youths (n = 165, M age = 12.43, SD = 1.18) and their maternal caregivers participated in a 4-year longitudinal study. Mothers and youths were administered diagnostic interviews assessing depression, and youths provided reports of their responses to peer stress. Consistent with an interactive model, adaptive responses to stress (high effortful engagement and low involuntary disengagement) buffered the effect of maternal depression on initial levels and trajectories of youth depression, with gender differences emerging. Consistent with a dual-risk model, maternal depression and maladaptive responses to stress (high effortful disengagement and involuntary engagement) contributed additive risks such that youths displayed the highest levels of depression when they were exposed to maternal depression and showed maladaptive stress responses. This research provides novel evidence that responses to stress contribute to individual differences in depression among offspring of depressed mothers, and suggests that responses to stress are an important target for efforts to promote resilience in at-risk youth.
Exogenous Microparticles of Iron Oxide Bind to Activated Endothelial Cells but, Unlike Monocytes, Do Not Trigger an Endothelial Response

Targeting particles to sites of inflammation is of considerable interest for applications relating to molecular imaging and drug delivery. We and others have described micron-sized particles of iron oxide (MPIO) that can be directed using specific ligands (e.g. antibodies, peptides and oligosaccharides) to bind to mediators of vascular inflammation in vivo. Since leukocyte binding to these molecules can induce changes in the target cell, an outstanding question has been whether the binding of imaging particles to these mediators induces biologically significant changes in the endothelial cells, potentially initiating or propagating inflammation. Here, we address these questions by looking for changes in endothelial cells following binding of contrast agent. Specifically, we have quantified calcium flux, rearrangement of the actin cytoskeleton, production of reactive oxygen species (ROS), apoptosis and potential secondary changes, such as changes in gene and protein expression follow binding events to primary endothelial cells in vitro. Although leukocytes induced changes to endothelial cell function, we did not see any significant changes to endothelial calcium flux, cytoskeletal organisation, production of ROS or induction of apoptosis in response to antibody-MPIO binding. Furthermore, there were no changes to gene expression monitored via real-time RT-PCR or presentation of protein on the cell surface measured using flow cytometry. Our experiments demonstrate that whilst antibody-targeted microparticles mimic the binding capability of leukocytes to inflamed endothelium, they do not trigger the same cellular responses and do not appear to initiate or compound inflammation. These properties are desirable for targeted therapeutic and diagnostic agents.
Stueckelberg interferometry using periodically driven spin-orbit-coupled Bose-Einstein condensates

We study the single-particle dispersion of a spin-orbit coupled (SOC) Bose-Einstein condensate (BEC) under the periodical modulation of the Raman coupling. This modulation introduces a further coupling of the SOC dressed eigenlevels, thus creating a second generation of modulation-dressed eigenlevels. Theoretical calculations show that these modulation-dressed eigenlevels feature a pair of avoided crossings and a richer spin-momentum locking, which we observe using BEC transport measurements. Furthermore, we use the pair of avoided crossings to engineer a tunable Stueckelberg interferometer that gives interference fringes in the spin polarization of BECs.
Correlation Network Analysis Reveals Relationships between MicroRNAs, Transcription Factor T-bet, and Deregulated Cytokine/Chemokine-Receptor Network in Pulmonary Sarcoidosis

Sarcoidosis is an inflammatory granulomatous disease with unknown etiology driven by cytokines and chemokines. There is limited information regarding the regulation of cytokine/chemokine-receptor network in bronchoalveolar lavage (BAL) cells in pulmonary sarcoidosis, suggesting contribution of miRNAs and transcription factors. We therefore investigated gene expression of 25 inflammation-related miRNAs, 27 cytokines/chemokines/receptors, and a Th1-transcription factor T-bet in unseparated BAL cells obtained from 48 sarcoidosis patients and 14 control subjects using quantitative RT-PCR. We then examined both miRNA-mRNA expressions to enrich relevant relationships. This first study on miRNAs in sarcoid BAL cells detected deregulation of miR-146a, miR-150, miR-202, miR-204, and miR-222 expression comparing to controls. Subanalysis revealed higher number of miR-155, let-7c transcripts in progressing (n = 20) comparing to regressing (n = 28) disease as assessed by 2-year follow-up. Correlation network analysis revealed relationships between microRNAs, transcription factor T-bet, and deregulated cytokine/chemokine-receptor network in sarcoid BAL cells. Furthermore, T-bet showed more pronounced regulatory capability to sarcoidosis-associated cytokines/chemokines/receptors than miRNAs, which may function rather as “fine-tuners” of cytokine/chemokine expression. Our correlation network study implies contribution of both microRNAs and Th1-transcription factor T-bet to the regulation of cytokine/chemokine-receptor network in BAL cells in sarcoidosis. Functional studies are needed to confirm biological relevance of the obtained relationships.