Miracle-dz/UniFAR-FTUs huggingface dataset:
Interleukin‐1β represses MRP2 gene expression through inactivation of interferon regulatory factor 3 in HepG2 cells

The human multidrug resistance protein 2 (MRP2/ABCC2), expressed on the bile canalicular membrane, mediates the multispecific efflux of several organic anions, including conjugates of glucuronate, sulfate, and glutathione. Expression of MRP2 can be altered in response to environmental stimuli such as cholestasis and jaundice. We previously reported that MRP2 mRNA expression levels are decreased in the nontumorous part of hepatitis C virus‐infected human liver tissues, and that inflammatory cytokines inhibit MRP2 expression in human hepatic (HepG2) cells. We investigated the molecular mechanisms by which inflammatory cytokines modulate MRP2 gene expression in hepatic cells. Treatment of human hepatic cells with interleukin‐1β (IL‐1β) or tumor necrosis factor α resulted in a decrease in the protein and mRNA levels of MRP2. IL‐1β inhibited the transcriptional activity of MRP2 promoter constructs by 40%, and this inhibition of MRP2 promoter activity was mediated through the interferon stimulatory response element (ISRE). Electrophoretic mobility shift assays with IL‐1β‐treated nuclear extracts showed a decrease in the formation of DNA protein complexes, specifically those including interferon regulatory factor 3 (IRF3). Expression of recombinant human IRF3 increased MRP2 promoter activity. Treatment with a specific extracellular signal‐regulated kinase inhibitor relieved IL‐1β‐induced MRP2 mRNA downregulation and abrogated the binding of IRF3 to the ISRE element. In conclusion, IL‐1β induces downregulation of the MRP2 gene by inactivating IRF3 binding to ISRE on the MRP2 promoter in human hepatic cells; this inactivation is accomplished via interference with the extracellular signal‐regulated kinase pathway. (HEPATOLOGY 2004;39:1574–1582.)
Affinity purification of transcription factor IIA from HeLa cell nuclear extracts.

One of the general transcription factors, TFIIA, was purified to homogeneity from HeLa cell nuclear extracts by yeast TFIID affinity chromatography. Human TFIIA had a molecular weight of approximately 38 kd. It was able to associate with the complex formed by yeast TFIID and the TATA elements of the adenovirus E4 and ML promoters, and the HSP70 promoter. The association extended the protected region on each TATA element by yeast TFIID from DNase I digestion. Affinity‐purified TFIIA was also able to stimulate transcription from the E4 and ML promoters in in vitro reconstituted systems.
A graph-based approach enhancing correctness and speed of web services composition through explicit specification of functional semantics

Since most of studies on the automated composition of web services do not consider the functional semantics of services, unsatisfied results may be generated against users' intentions. Their time complexity is very high since every possible combination of available services must be considered. To enhance the correctness and speed of the composition of services, we propose a graph-based composition method, which explicitly specifies and uses the functional semantics of web services. A representative action, which represents what a service actually does, is identified. Data dependencies among available services are organised and stored as an AND/OR graph, on which service composition is performed. Rules are devised to map a service onto an appropriate action and to combine service actions. Effective pruning rules are also proposed. The experimental results demonstrate the superiority of the proposed method in terms of the correctness and speed of service composition.
Targeting Norovirus: Strategies for the Discovery of New Antiviral Drugs

Gastroenteritis is globally responsible for great morbidity and mortality among all ages. In the developing countries, it still represents one of the top causes of death for children <5 years of age, resulting in 1,8 million fatalities every year (Boschi-Pinto et al., 2008; Bryce et al., 2005). Viruses are responsible for the majority of cases of gastroenteritis with rotaviruses and noroviruses being the major pathogens.
Diagnostic value of bone‐turnover metabolites in the diagnosis of bone metastases in patients with lung carcinoma

Several biochemical markers of bone formation and bone resorption have been developed recently. The authors evaluated the usefulness of new biomarkers, such as urinary deoxypyridinoline (D‐PYD), serum pyridinoline cross‐linked C‐telopeptides of Type I collagen (1CTP), and urinary pyridinoline cross‐linked N‐telopeptides of Type I collagen (NTx), in the assessment of bone metastases in patients with lung carcinoma.
Are IL-10+ regulatory Th17 cells implicated in the sustained response to glucocorticoid treatment in patients with giant cell arteritis? Comment on the paper of Espigol-Frigole et al

We have read with interest the recently published paper of Espigol-Frigole et al 1 in which the authors confirmed that interleukin (IL)-17 is highly expressed in giant cell arteritis (GCA) lesions.1–3 They also demonstrated for the first time that IL-17 expression in temporal artery biopsies (TABs) was correlated with a better outcome. Among other interesting results, the identification of Foxp3+IL-17+ T cells by confocal microscopy in TAB made the authors to hypothesize that these cells could be induced regulatory T cells (Treg) that may facilitate the remission of the disease under steroid therapy. …
Vasodilatory effect of arginine vasopressin is mediated by nitric oxide in human forearm vessels.

Arginine vasopressin (AVP) causes biphasic changes in vascular resistance in human forearms; vasoconstriction at lower doses and vasodilation at higher doses. Vasoconstriction is mediated by the V1 receptor. However, the mechanism of AVP-induced vasodilation is not known. We investigated whether AVP-induced vasodilation is mediated by nitric oxide (NO) in human forearms by examining the effects of L-arginine (a precursor of NO) and NG-monomethyl-L-arginine (L-NMMA, a blocker of NO synthase) on AVP-induced vasodilation. AVP was infused intraarterially at doses of 0.05, 0.1, 0.2, 0.5, and 1.0 ng/kg per min (n = 8). The lower doses of AVP (< or = 0.1 ng/kg per min) increased, whereas the higher doses of AVP (> or = 0.5 ng/kg per min) decreased forearm vascular resistance (FVR) (P < 0.01). Intraarterially infused L-arginine at 10 mg/min did not alter arterial pressure, baseline FVR, or heart rate. L-arginine did not alter the magnitude of AVP-induced vasoconstriction at the lower doses, but L-arginine augmented the magnitude of AVP-induced vasodilation at doses of 0.2 (P < 0.05), 0.5 (P < 0.01), and 1.0 (P < 0.05) ng/kg per min. In another group (n = 6), intraarterially infused L-NMMA (4 mumol/min for 5 min) increased baseline FVR without systemic effects, and inhibited acetylcholine-induced vasodilation (P < 0.01). L-NMMA at this dose inhibited AVP-induced vasodilation (P < 0.01) but did not affect vasoconstriction. L-arginine reversed the inhibitory effect of L-NMMA. Our results suggest that the vasodilatory effect of AVP may be mediated by NO in human forearms.
Commentary: dissecting the PNPLA3 association with liver fat and stiffness, and interaction with diet – authors’ reply

1. Shen J, Wong GL-H, Chan HL-Y, et al. PNPLA3 gene polymorphism accounts for fatty liver in community subjects without metabolic syndrome. Aliment Pharmacol Ther 2014; 39: 532–9. 2. Romeo S, Sentinelli F, Dash S, et al. Morbid obesity exposes the association between PNPLA3 I148M (rs738409) and indices of hepatic injury in individuals of European descent. Int J Obes (Lond) 2010; 34: 190–4. 3. Giudice EM, Grandone A, Cirillo G, et al. The association of PNPLA3 variants with liver enzymes in childhood obesity is driven by the interaction with abdominal fat. PLoS ONE 2011; 6: e27933. 4. Davis JN, Le KA, Walker RW, et al. Increased hepatic fat in overweight Hispanic youth influenced by interaction between genetic variation in PNPLA3 and high dietary carbohydrate and sugar consumption. Am J Clin Nutr 2010; 92: 1522–7. 5. Santoro N, Savoye M, Kim G, et al. Hepatic fat accumulation is modulated by the interaction between the rs738409 variant in the PNPLA3 gene and the dietary omega6/omega3 PUFA intake. PLoS ONE 2012; 7: e37827. 6. Loomba R, Rao F, Zhang L, et al. Genetic covariance between gamma-glutamyl transpeptidase and fatty liver riskk factors: role of beta2-adrenergic receptor genetic variation in twins. Gastroenterology 2010; 139: 836–45, 845.e1. 7. Noureddin M, Lam J, Peterson MR, et al. Utility of magnetic resonance imaging versus histology for quantifying changes in liver fat in nonalcoholic fatty liver disease trials. Hepatology 2013; 58: 1930–40. 8. Petersen KF, Dufour S, Feng J, et al. Increased prevalence of insulin resistance and nonalcoholic fatty liver disease in AsianIndian men. Proc Natl Acad Sci USA 2006; 103: 18273–7. 9. Romeo S, Kozlitina J, Xing C, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 2008; 40: 1461–5. 10. Rotman Y, Koh C, Zmuda JM, et al. The association of genetic variability in patatin-like phospholipase domain-containing protein 3 (PNPLA3) with histological severity of nonalcoholic fatty liver disease. Hepatology 2010; 52: 894–903.
Vitamin D receptor (VDR) localization in human promyelocytic leukemia cells

Although vitamin D analogs are known to induce the differentiation of the HL-60 promyelocytic leukemia cells, the effect of vitamin D analogs on the distribution of vitamin D receptor (VDR) in these cells is not well studied. This report showed, by confocal microscopy, that VDR mainly resided in the cytoplasm in the absence of VDR ligands. When cells were treated with 19-nor-1α,25-(OH)2D2 or 1,25(OH)2D3, VDR moved from the cytoplasm into the nucleus in a time-dependent manner. VDR could be observed in the nucleus as early as 6 h after drug treatment and was still observed in the nucleus 3 days after one single addition of 100 nm 19-nor-1α,25-(OH)2D2 or 1,25(OH)2D3. The VDR protein level was significantly increased by 19-nor-1α,25-(OH)2D2 or 1,25(OH)2D3 in a dose-dependent manner, while the VDR mRNA level was not affected by either compound. These results suggest that binding of vitamin D analogs to VDR induced receptor translocation into the nucleus, which stabilizes the receptor, resulting in an accumulation of the VDR protein.
Is estimated cardiovascular risk higher in HIV-infected patients than in the general population?

Cardiovascular disease (CVD) is an increasing concern for human immunodeficiency virus (HIV)-infected patients, and risk assessment is recommended in routine HIV care. The absolute cardiovascular risk in an individual is determined by several factors, and various algorithms may be applied. To date, few comparisons of HIV patients with persons of the same age from the general population have been conducted. We hypothesized that the calculated risk of CVD may be increased in HIV patients. The probability for acute coronary events within 10 y (Framingham Risk Score) and the probability for fatal cardiovascular disease (SCORE algorithm) were assessed in 403 consecutive HIV-positive subjects free from overt cardiovascular disease, as well as in 96 age- and gender-matched control subjects drawn from the general population living in the same geographical area. The average 10-y risk for acute coronary events (Framingham Risk Score) was 7.0%±5% in HIV subjects and 6.3%±5% in the control group (p =0.32). The 10-y estimated risk for cardiovascular mortality (SCORE algorithm) was 1.23%±2.3% and 0.83%±0.9%, respectively (p =0.01). The main contributor to the increased CVD risk was the high proportion of smokers, but not an increase in cholesterol level. In conclusion, a limited increase in estimated risk of CVD was found in HIV-infected patients compared to the general population. In HIV-infected individuals other factors of less value in the general population and not included in any cardiovascular algorithm might be important. In our patients intervention to modify traditional risk factors should be addressed primarily towards modifying smoking habits.
With a little help from my assistant: buffering the negative effects of emotional dissonance on dentist performance.

OBJECTIVE In this study, we hypothesized that dentist' interpersonal resources (good cooperation with one's assistant) together with their personal resources (optimism) buffer the negative effects of emotional dissonance (a demand that occurs when there is a difference between felt and displayed emotions) on job performance (in-role and extra-role performance) over time. METHOD We carried out Hierarchical Regression Modeling on a sample of 1954 Finnish dentists who participated in a two-wave 4-year longitudinal study. RESULTS Results showed that good cooperation with dental assistants buffered the negative effects of emotional dissonance on both in-role and extra-role performance among the dentists in the long term. However, unexpectedly, dentists' high optimism did not buffer their in-role nor extra-role performance over time under conditions of experiencing high emotional dissonance. CONCLUSIONS We conclude that interpersonal job resources such as good cooperation with one's colleagues may buffer the negative effect of emotional dissonance on dentists' job performance even in the long term, whereas the role of personal resources (e.g., optimism) may be less important for maintaining high job performance under conditions of emotional dissonance. The study novelties include the test of the negative effects of emotional dissonance on long-term performance in dentistry and the identification of the job rather than personal resources as the buffers against the negative effects of emotional dissonance on long-term performance.
Detection of endogenous iron deposits in the injured mouse spinal cord through high‐resolution ex vivo and in vivo MRI

The main aim of this study was to employ high‐resolution MRI to investigate the spatiotemporal development of pathological features associated with contusive spinal cord injury (SCI) in mice. Experimental mice were subjected to either sham surgery or moderate contusive SCI. A 16.4‐T small‐animal MR system was employed for nondestructive imaging of post‐mortem, fixed spinal cord specimens at the subacute (7 days) and more chronic (28–35 days) stages post‐injury. Routine histological techniques were used for subsequent investigation of the observed neuropathology at the microscopic level. The central core of the lesion appeared as a dark hypo‐intense area on MR images at all time points investigated. Small focal hypo‐intense spots were also observed spreading through the dorsal funiculi proximal and distal to the site of impact, an area that is known to undergo gliosis and Wallerian degeneration in response to injury. Histological examination revealed these hypo‐intense spots to be high in iron content as determined by Prussian blue staining. Quantitative image analysis confirmed the increased presence of iron deposits at all post‐injury time points investigated (p < 0.05). Distant iron deposits were also detectable through live imaging without the use of contrast‐enhancing agents, enabling the longitudinal investigation of this pathology in individual animals. Further immunohistochemical evaluation showed that intracellular iron deposits localised to macrophages/microglia, astrocytes and oligodendrocytes in the subacute phase of SCI, but predominantly to glial fibrillary acidic protein‐positive, CC‐1‐positive astrocytes at later stages of recovery. Progressive, widespread intracellular iron accumulation is thus a normal feature of SCI in mice, and high‐resolution MRI can be effectively used to detect and monitor these neuropathological changes with time. Copyright © 2012 John Wiley & Sons, Ltd.
Preparation of Epithelial and Mesenchymal Stem Cells from Murine Mammary Gland

The mammary gland is a complex organ consisting of multiple cell types that undergo extensive remodeling during pregnancy and involution, cyclical changes that suggest the existence of a resident stem cell population that is responsible for remarkable tissue regeneration. The basic functional unit of the mammary gland is the terminal duct lobular unit, which invades the stromal tissue (fat, connective tissue, blood vessels, etc.). Luminal epithelial cells line the ducts while outer myoepithelial cells secrete the basal lamina that separates the mammary gland parenchyma from the mesenchymal cells of the stroma. Within the epithelial cell population of the ducts resides the mammary gland stem cells and it is believed that this population is the origin of the mammary gland cancer stem cells as well. In the mouse, epithelial stem cells can be separated from mesenchymal cells on the basis of CD24, CD44, and CD49f expression. This allows for the determination of both normal and cancer stem cell potential of these two populations and permits investigation into their interaction in tumor development. Curr. Protoc. Toxicol. 50:22.3. 1‐22.3. 15. © 2011 by John Wiley & Sons, Inc.
Prophylactic Stabilization of Vertebral Body Metastasis at Risk of Imminent Fracture Using Balloon Kyphoplasty

Study Design. Case report. Objective. Presentation of the previously unreported technique of balloon kyphoplasty being used to prophylactically stabilize a vertebral body metastasis at risk of imminent fracture. Summary of Background Data. Many patients with spinal metastases are not suitable for a total en bloc resection. Untreated these metastases may fracture, with the risk of cord compression. Methods. We present the case of a 53-year-old gentleman with an isolated T10 renal cell metastasis. This gentleman presented with back pain, and was deemed to be at risk of imminent fracture. The metastasis was prophylactically stabilized using balloon kyphoplasty. Results. Lasting pain relief and spinal stability were achieved following treatment with balloon kyphoplasty. He remains pain free 14-months post treatment. Conclusion. This is the first reported case of balloon kyphoplasty being used to prophylactically stabilize a vertebral body containing a metastasis, achieving both mechanical stability and pain relief.
Modular permanent magnet machine based on soft magnetic composite

With the improvement of soft magnetic composite (SMC) material, electric machine design is no longer limited to the traditional iron lamination technology. The single extrusion fabrication process of the SMC material simplifies construction of machine armature core. Moreover, the isotropic material property can be exploited for various machine structure design, compared with the 2D flux distribution of typical iron laminations. In this paper, a drive system based on a novel multi phase modular permanent magnet machine is proposed. The concentric winding structure simplifies the stator structure with the benefit of less end winding loss, which also offers the potential of fault tolerant capability. The performance of the drive system is analyzed and discussed with the simulation results provided.
Survival probability of drug resistant mutants in malaria parasites

This study predicts the ultimate probability of survival of a newly arisen drug resistant mutant in a population of malaria parasites, with a view to understanding what conditions favour the evolution of drug resistance. Using branching process theory and a population genetics transmission model, the probabilities of survival of one- and two-locus new mutants are calculated as functions of the degree of drug pressure, the mean and variation in transmission rate, and the degree of natural selection against the mutant. Probability of survival increases approximately linearly with drug pressure, the slope of the line increasing with mean transmission rate. Thus increased drug pressure, especially in combination with high transmission rates, strongly favours the evolution of drug resistance. These conclusions also hold for the case of multiple drug resistance where it is coded for by two unlinked loci: the greater effective recombination breakdown in high transmission areas is counteracted by greater effective selection so that the net effect of higher transmission rates is to favour the evolution of multiple drug resistance. High variability in transmission rate and natural selection against the mutants are unfavourable to mutant survival, though these are relatively weak forces.
Mechanisms of Ovarian Atresia Induced by Xenobiotic Exposures

The focus of this chapter is the mechanisms of apoptosis that occur during “normal” (physiologically-induced) or “abnormal” (chemicalor pathology-induced) attrition of ovarian oocytes. One of the primary functions of the ovary is development and maturation of oocytes, which occur within a follicular structure. During fetal development of the ovary, primordial germ cells (oogonia) are formed and become oocytes when they stop dividing, and are arrested at the diplotene stage (prophase) of the first meiotic division. At this stage the oocyte is surrounded by a single layer of flattened somatic cells (pre-granulosa cells) and a basement membrane to form primordial follicles (Hirshfield, 1991), the most immature follicular stage of development. As a result, the lifetime supply of oocytes is set at the time of birth, and is irreplaceable. Association of the granulosa cells with the oocyte is critical for maintenance of oocyte viability and follicle development (Buccione et al., 1990). Development and progression of a recruited follicle also requires the appropriate expression of numerous factors, including critical members of the transforming growth factor β superfamily, such as growth differentiation factor 9 (GDF9) and bone morphogenic protein (BMP15) (Paulini and Melo 2011). Characterization of GDF9 function has a demonstrated a required role in promoting somatic cells of the follicle to undergo mitosis and initiates paracrine signaling between the oocyte and the follicular cells surrounding it (Carabatsos et al. 1998; Hreinsson et al. 2002; Nilsson and Skinner 2002). The impaired fertility in GDF9 mice appears to primarily be a result of loss of function in somatic cells since oocytes of GDF knockout mice remain capable of undergoing in vitro maturation and progressing to metaphase II of meiosis (Carabatsos et al. 1998).
A contraction approach for efficient regulation of networked systems

We present a computationally efficient method for designing regulatory controllers for networked systems using only local information. Using a contraction approach, we derive a connection between a system’s intra-dynamics and its neighboring systems. We then show that the design of regulatory controllers is equivalent to a linear feasibility problem on the order of the number of systems. We illustrate our main result using a disturbance mitigation problem, where the goal is to design controllers at a subset of nodes to drive the global nodal values to a particular value in the presence of destabilizing forces. We note that our main result is especially applicable to networks that exhibit interconnection variability and intermittent subsystem faults, like energy grids.