Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibitory Effect of Selaginellins from Selaginella tamariscina (Beauv.) Spring against Cytochrome P450 and Uridine 5′-Diphosphoglucuronosyltransferase Isoforms on Human Liver Microsomes

Selaginella tamariscina (Beauv.) has been used for traditional herbal medicine for treatment of cancer, hepatitis, and diabetes in the Orient. Numerous bioactive compounds including alkaloids, flavonoids, lignans, and selaginellins have been identified in this medicinal plant. Among them, selaginellins having a quinone methide unit and an alkylphenol moiety have been known to possess anticancer, antidiabetic, and neuroprotective activity. Although there have been studies on the biological activities of selaginellins, their modulatory potential of cytochrome P450 (P450) and uridine 5′-diphosphoglucuronosyltransferase (UGT) activities have not been previously evaluated. In this study, we investigated the drug interaction potential of two selaginellins on ten P450 isoforms (CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 2J2 and 3A) and six UGT isoforms (UGT1A1, 1A3, 1A4, 1A6, 1A9 and 2B7) using human liver microsomes and liquid chromatography-tandem mass spectrometry. Selaginellin and selaginellin M had high inhibitory potential for CYP2C8-mediated amodiaquine O-demethylation with IC50 values of 0.5 and 0.9 μM, respectively. Selaginellin and selaginellin M also showed medium inhibitory potential against CYP2C9, CYP2J2, UGT1A1, and UGT1A3 (1 μM < IC50 < 5 μM). These two selaginellins had low inhibitory potential against CYP1A2, CYP2A6, CYP2E1, and UGT1A6 (IC50 > 25 μM). This information might be helpful to predict possible drug interaction potential of between selaginellins and co-administered drugs.
P2Y12 Receptor on the Verge of a Neuroinflammatory Breakdown

In the CNS, neuroinflammation occurring during pathologies as amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) is the consequence of an intricate interplay orchestrated by various cell phenotypes. Among the molecular cues having a role in this process, extracellular nucleotides are responsible for intercellular communication and propagation of inflammatory stimuli. This occurs by binding to several receptor subtypes, defined P2X/P2Y, which are widespread in different tissues and simultaneously localized on multiple cells. For instance, the metabotropic P2Y12 subtype is found in the CNS on microglia, affecting activation and chemotaxis, on oligodendrocytes, possessing a hypothesized role in myelination, and on astrocytes. By comparative analysis, we have established here that P2Y12 receptor immunolabelled by antibodies against C-terminus or second intracellular loop, is, respectively, distributed and modulated under neuroinflammatory conditions on ramified microglia or myelinated fibers, in primary organotypic cerebellar cultures, tissue slices from rat striatum and cerebellum, spinal cord sections from symptomatic/end stage SOD1-G93A ALS mice, and finally autoptic cortical tissue from progressive MS donors. We suggest that modulation of P2Y12 expression might play a dual role as analytic marker of branched/surveillant microglia and demyelinating lesions, thus potentially acquiring a predictive value under neuroinflammatory conditions as those found in ALS and MS.
Electoral Bias and Policy Choice: Theory and Evidence

This paper develops an approach to studying how bias in favor of one party due to the pattern of electoral districting affects policy choice. We tie a commonly used measure of electoral bias to the theory of party competition and show how this affects party strategy in theory. The usefulness of the approach is illustrated using data on local government in England. The results suggest that reducing electoral bias leads parties to moderate their policies.
Habitat-specific adaptation of immune responses of stickleback (Gasterosteus aculeatus) lake and river ecotypes

Freshwater populations of three-spined sticklebacks (Gasterosteus aculeatus) in northern Germany are found as distinct lake and river ecotypes. Adaptation to habitat-specific parasites might influence immune capabilities of stickleback ecotypes. Here, naive laboratory-bred sticklebacks from lake and river populations were exposed reciprocally to parasite environments in a lake and a river habitat. Sticklebacks exposed to lake conditions were infected with higher numbers of parasite species when compared with the river. River sticklebacks in the lake had higher parasite loads than lake sticklebacks in the same habitat. Respiratory burst, granulocyte counts and lymphocyte proliferation of head kidney leucocytes were increased in river sticklebacks exposed to lake when compared with river conditions. Although river sticklebacks exposed to lake conditions showed elevated activation of their immune system, parasites could not be diminished as effectively as by lake sticklebacks in their native habitat. River sticklebacks seem to have reduced their immune-competence potential due to lower parasite diversity in rivers.
Efficacies of uterine artery embolization for symptomatic uterine fibroids using gelatin sponge: a single-center experience and literature review

Aim The aim of this study was to retrospectively analyze the efficacies of uterine artery embolization (UAE) using gelatin sponge for symptomatic uterine fibroids. Methods A series of 60 consecutive premenopausal women underwent UAE using gelatin sponge particles or porous gelatin particles. Patients were routinely followed up at 1, 3, 6, and 12 months after the procedure and asked to report any procedure-related complications. At each follow-up, an original clinical questionnaire was completed by the patients to evaluate changes in fibroid-related symptoms. Pelvic magnetic resonance imaging was performed before and at 3 and 12 months after the procedure, and the changes in volume of the dominant fibroid were calculated. Results Bilateral UAE was successfully performed in all the patients. Median age was 45 years (range 34–53 years), and median follow-up period was 25.2 months (range 1–116 months). At the 3- and 12-month follow-up, the dominant fibroid volumes were found to be significantly decreased by 33.4% (95% confidence interval [CI]: 24.9–41.1) and 48.4% (95% CI: 40.7–56.1) compared to baseline volumes, respectively. Excluding patients not having menorrhagia or bulk-related symptoms, at 12 months 49 of 50 (98%) women showed improvement in menorrhagia, and 45 of 47 (95.7%) women showed improvement in bulk-related symptoms. During the follow-up period, ten patients (16.7%) required further interventions including two patients who had undergone hysterectomy. No sequelae were experienced by any of the patients. Conclusion UAE using gelatin sponge was associated with a high clinical success rate and good fibroid volume reduction compared to UAE using other embolic agents.
Pulmonary , gastrointestinal and urogenital pharmacology Protective effect of 2-hydroxy-4-methoxy benzoic acid on testosterone induced benign prostatic hyperplasia in Wister rats

Oxidative stress is one of the major causative factors for development of benign prostatic hyperplasia (BPH). The aim of the present study is to evaluate the effect of 2-hydroxy-4-methoxy benzoic acid (HMBA), a potential antioxidant on testosterone induced BPH in rats. Male Wistar rats were divided into five groups (n1⁄46), Group I—received saline, Group II—received testosterone (3 mg/kg/s.c.), Group III—received testosteroneþfinasteride (5 mg/kg/oral), Group IV and V received testosteroneþHMBA (200 and 400 mg/kg/i.p.), respectively, for 21 days. Animals were weighed before and after the study period. On 22nd day, animals were humanly killed by cervical dislocation. Prostates were excised and weighed, and used for biochemical and histological studies. As a result, testosterone treated rats showed increased prostate weight; prostatic index accompanied with depleted antioxidant enzymes levels, elevated lipid peroxides and total nitrite and associated histology disruption. HMBA treatment at 200 mg/kg/i.p. and 400 mg/kg/i.p. significantly restored (Po0.05) antioxidant enzyme levels, lipid peroxide and total nitrite when compared to disease control animals. It also ameliorated the testosterone induced histological changes. The present study suggests the protective role of HMBA on testosterone induced BPH by virtue of its antioxidant potential. & 2012 Elsevier B.V. All rights reserved.
A FACTOR ANALYSIS APPROACH IN PERFORMANCE ANALYSIS OF T-20 CRICKET

This paper investigates the systematic covariation among various dimensions pertaining to batting and bowling capabilities of T20 cricket using the advanced statistical technique of factor analysis. The real dataset of 85 batsmen and 85 bowlers has been considered from Indian Premier League (IPL) 2012 for analysis purpose. The findings of this study show that batting capability dominates over bowling capability. This conclusion coincides with the general opinion of several cricketing enthusiasts and experts; however till date, there is no research study, to the best of the author’s knowledge that provides statistical evidence to support this notion.
Helminth parasites of the rare endemic catfish, Liobagrus reini, in Japan.

Examinations of 29 specimens of the catfish Liobagrus reini Hilgendorf (Siluriformes: Amblycipitidae), a species endemic to Japan, collected from the Sho River, Toyama Prefecture, in central Honshu, revealed the presence of four species of helminth parasites: Plagioporus honshuensis sp. n. (Trematoda), Rhabdochona coronacauda Belouss, 1965, R. japonica Moravec, 1975 and Mexiconema liobagri sp. n. (all Nematoda). The new opecoelid trematode P. honshuensis is characterized mainly by the extent of vitelline follicles, the size ratio of the suckers (1 : 1.7-2.1), the situation of testes near the middle of the body and by the structure, size and shape of the cirrus sac. Allopodocotyle Pritchard, 1966 is considered a junior synonym of Plagioporus Stafford, 1904. The males of R. japonica are described for the first time and conspecific females are redescribed; this species is a specific parasite of L. reini. The principle hosts of R. coronacauda are cyprinids and, therefore, its finding in the catfish may indicate an accidental infection; L. reini represents a new host record. M. liobagri (only females were found) from the host's abdominal cavity is the second known species of this dracunculoid genus, being characterized by the position of the excretory pore and the number (1) of caudal processes in the female. The recorded helminths are briefly described and illustrated and problems of their systematic status are discussed.
Heterogeneous Background Risks and Portfolio Choice: Evidence from Micro-Level Data

We construct a set of household‐level background risk variables to capture the covariance structure of three nonfinancial assets and two financial assets. These risks are in general statistically significant and economically important for a household's stock market participation and stockholdings. A one‐standard‐deviation increase in background risks reduces the participation probability by 11% and the stockholdings‐to‐wealth ratio by 4%. The volatilities of labor income, housing value, and business income reduce a household's participation and stockholdings. A household with labor income highly correlated with stock (bond) returns is less (more) likely to invest in stock.
Resveratrol Induces Differentiation Markers Expression in Anaplastic Thyroid Carcinoma via Activation of Notch1 Signaling and Suppresses Cell Growth

Anaplastic thyroid carcinoma (ATC) is an extremely aggressive malignancy with undifferentiated features, for which conventional treatments, including radioactive iodine ablation, are usually not effective. Recent evidence suggests that the Notch1 pathway is important in the regulation of thyroid cancer cell growth and expression of thyrocyte differentiation markers. However, drug development targeting Notch1 signaling in ATC remains largely underexplored. Previously, we have identified resveratrol out of over 7,000 compounds as the most potent Notch pathway activator using a high-throughput screening method. In this study, we showed that resveratrol treatment (10–50 μmol/L) suppressed ATC cell growth in a dose-dependent manner for both HTh7 and 8505C cell lines via S-phase cell-cycle arrest and apoptosis. Resveratrol induced functional Notch1 protein expression and activated the pathway by transcriptional regulation. In addition, the expression of thyroid-specific genes including TTF1, TTF2, Pax8, and sodium iodide symporter (NIS) was upregulated in both ATC cell lines with resveratrol treatment. Notch1 siRNA interference totally abrogated the induction of TTF1 and Pax8 but not of TTF2. Moreover, Notch1 silencing by siRNA decreased resveratrol-induced NIS expression. In summary, our data indicate that resveratrol inhibits cell growth and enhances redifferentiation in ATC cells dependent upon the activation of Notch1 signaling. These findings provide the first documentation for the role of resveratrol in ATC redifferentiation, suggesting that activation of Notch1 signaling could be a potential therapeutic strategy for patients with ATC and thus warrants further clinical investigation. Mol Cancer Ther; 12(7); 1276–87. ©2013 AACR.
Overlapping functions of myosin-I isoforms?

S INCE the discovery of myosin-I (MI) 1 in Acanthamoeba (32), DNA cloning and/or biochemical purification have established the presence of multiple MI isoforms in nearly every eukaryotic cell examined. Despite intensive study, the physiological role of these actin-based, molecular motors has remained a mystery, in large part, because cells express several isoforms of MI with similar biochemical properties. The main questions have been: what are the cellular and molecular functions of MI? Are any isoforms essential for life? Do any isoforms perform unique functions? Recent molecular genetic experiments from the laboratories of M.A. Titus (Duke University, Durham, NC) (27) and J.A. Hammer (National Institutes of Health, Bethesda, MD) (19; this issue) provide important help in untangling the roles of four of the MI isoforms in the cellular slime mold, Dictyostelium. MI's are single-headed, low molecular weight members of the myosin superfamily (Fig. 1). Similar physical characteristics and conserved features of the sequences of their NH2-terminal motor domains set all of the MI's apart from the ten other families of myosin (5, 14, 26). This NH2-terminal domain couples the hydrolysis of ATP to movement along actin filaments. Although MI's move actin filaments more slowly than muscle myosins (26, 33), the mechanism of actin-activated ATP hydrolysis by Acanthamoeba MI is almost identical (28) to the mechanism of myosin-II (23). Therefore, the basic chemistry of the energy transducing process has been conserved since the times of the earliest eukaryotes, and unlike kinesin, low numbers of MI molecules cannot support processive movement (28). MI tail sequences have diverged much more than the sequences of the heads, so the tails probably hold the secret to the existence of multiple MI isoforms and their specialized functions (35). Immunolocalization, cell fractionation, and in vitro motility assays (26, 33) suggest that MI participates in actin-dependent membrane-based motility, as well as more conventional contraction of actin filament networks. MI tails bind membranes (2, 8, 24) and actin filaments (22), providing the mechanical connections required for these postulated movements. Dictyostelium is a good system to examine MI function because one can inhibit MI using molecular genetics tech-
Comparison of Tenofovir, Zidovudine, or Stavudine as Part of First-Line Antiretroviral Therapy in a Resource-Limited-Setting: A Cohort Study

Background Tenofovir (TDF) is part of the WHO recommended first-line antiretroviral therapy (ART); however, there are limited data comparing TDF to other nucleoside reverse transcriptase inhibitors in resource-limited-settings. Using a routine workplace and community-based ART cohort in South Africa, we assessed single drug substitution, HIV RNA suppression, CD4 count increase, loss-from-care, and mortality between TDF, stavudine (d4T) 30 mg dose, and zidovudine (AZT). Methods In a prospective cohort study we included ART naïve patients aged ≥17 years-old who initiated ART containing TDF, d4T, or AZT between 2007 and 2009. For analysis of single drug substitutions we used a competing-risks time-to-event analysis; for loss-from-care, mixed-effect Poisson modeling; for HIV RNA suppression, competing-risks logistic regression; for CD4 count slope, mixed-effects linear regression; and for mortality, proportional hazards modeling. Results Of 6,196 patients, the initial drug was TDF for 665 (11%), d4T for 4,179 (68%), and AZT for 1,352 (22%). During the first 6 months of ART, the adjusted hazard ratio for a single drug substitution was 2.3 for d4T (95% confidence interval [CI]: 0.27, 19) and 5.2 for AZT (95% CI: 1.1, 23), compared to TDF; whereas, after 6 months, it was 10 (95% CI: 5.8, 18) and 4.4 (95% CI: 2.5, 7.8) for d4T and AZT, respectively. Virologic suppression was similar by agent; however, CD4 count rise was lowest for AZT. The adjusted hazard ratio for loss-from-care, when compared to TDF, was 1.5 (95% CI: 1.1, 1.9) for d4T and 1.2 (95% CI: 1.1, 1.4) for AZT. The adjusted hazard ratio for mortality, when compared to TDF, was 2.7 (95% CI: 2.0, 3.5) and 1.4 (95% CI: 1.3, 1.5) and for d4T and AZT, respectively. Discussion In routine care, TDF appeared to perform better than either d4T or AZT, most notably with less drug substitution and mortality than for either other agent.
Friction and visco-elasticity effects in tendon-based transmission systems

In this paper, the characterization of the force distribution along a tendon sliding on a curved pathway, subject to friction and visco-elastic effects, is investigated. In order to have a better understanding of the system behavior, a specific setup able to measure tension forces in different points along the tendon's path has been built. Experimental data collected by measuring the tendon tension forces during both the pulling and the release phase are presented, and theoretical models reproducing the tendon behavior with increasing fidelity are proposed. In particular, the friction arising from the interaction between the tendon pathway and the tendon itself is characterized by means of a LuGre-like dynamic friction model. The introduction of a dynamic friction model allows to reproduce in simulation some effects arising during experimental activities that cannot be reproduced employing an equivalent static friction model. Moreover, the adoption of tendons made by polymeric fibers introduces hysteresis in the tendon transmission characteristic due to the plasticity and creep phenomena typical of these materials. With the aim of reproducing this behavior, a visco-elastic model is used for modeling the tendon compliance.
THE DETERMINATION OF LYSOZYME

Since the discovery of lysozyme by Fleming (1922) several authors have proposed different methods for determining the activity of various preparations containing this enzyme. Most of these methods were based upon the clearing of dense suspensions of a susceptible organism without concern for accurate quantitative results. The isolation of highly purified crystalline lysozyme by Alderton and Fevold (1946) suggested the possibility of a method for assaying lysozyme. The procedure described here provides for the rapid and accurate microbiological assay of materials that show lytic activity considered to be due to lysozyme. Fleming (1922), in his original work, observed the lytic activity of lysozyme either as clear zones on agar plates seeded with Micrococcus lysodeikticus or as a clearing of a suspension of the same organism. Sandow (1926) used serial dilutions of egg white in meat infusion broth inoculated with various species of organisms. After incubation these mixtures were observed for growth, as evidenced by the turbidity of the tubes. This procedure was applied to a study of the different organisms affected by lysozyme, the dilution of egg white capable of producing inhibition or sterilization being noted. Goldsworthy and Florey (1930) devised a scheme of assay which consisted of washing an 18-hour culture of M. lysodeikticus with saline and adjusting the opacity of that suspension to that of Brown's barium sulfate standard no. 4. Lysozyme was serially diluted so that each succeeding dilution contained only half as much of the enzyme as the one previous. Then 0.5 ml of each dilution was mixed with an equal quantity of cell suspension. The mixtures were allowed to incubate at 38 C for 1 hour. A unit was defined as the least amount of lysozyme necessary to produce complete lysis. Rosenthal and Lieberman (1931) in determining the lysozyme content of infant stools mixed a susceptible sarcina with stool extracts. Visual observations of the mixture were made under the microscope. A disappearance of the sarcina cells indicated lysozyme activity. Boasson (1938) developed a technique involving the use of optical measurements of turbidity. A phenol-killed suspension of the test organism was mixed with various dilutions of lysozyme. The amount and rate of clearing was carefully measured in a Moll extinctometer and correlated with the concentration of lysozyme. Since the activity for the known concentration could be observed accurately, it was possible to compare the extent of activity of an unknown and in this manner to determine the amount of lysozyme present.
Compartmentalization within the nucleus: discovery of a novel subnuclear region

Antibodies to a set of structurally related autoantigens (p23-25) bind to a previously uncharacterized, large structural domain in the nucleus of a variety of human cell types. This subnuclear domain is visible by phase contrast alone as a region of decreased density after several different fixation protocols. The morphology of this region changes dramatically during the cell cycle and we have given it the name PIKA (for polymorphic interphase karyosomal association) based on preliminary evidence that the PIKA proteins may be associated with chromatin. The function of the PIKA is not yet known, but our immunolocalization data indicate that it is unlikely to be associated with regions of ongoing DNA replication, heterogeneous nuclear RNA storage, or mRNA processing. The discovery of the PIKA provides evidence supporting an emerging model of nuclear structure. It now appears that the nucleus is organized into distinct domains which include not only the nucleolus, but also previously unidentified regions such as the PIKAs. Furthermore, structural rearrangements undergone by the nucleolus and the PIKAs may be indicative of a broad tendency for nuclear organization to change in a cell cycle-specific fashion.
Coupling between the Circadian Clock and Cell Cycle Oscillators: Implication for Healthy Cells and Malignant Growth

Uncontrolled cell proliferation is one of the key features leading to cancer. Seminal works in chronobiology have revealed that disruption of the circadian timing system in mice, either by surgical, genetic, or environmental manipulation, increased tumor development. In humans, shift work is a risk factor for cancer. Based on these observations, the link between the circadian clock and cell cycle has become intuitive. But despite identification of molecular connections between the two processes, the influence of the clock on the dynamics of the cell cycle has never been formally observed. Recently, two studies combining single live cell imaging with computational methods have shed light on robust coupling between clock and cell cycle oscillators. We recapitulate here these novel findings and integrate them with earlier results in both healthy and cancerous cells. Moreover, we propose that the cell cycle may be synchronized or slowed down through coupling with the circadian clock, which results in reduced tumor growth. More than ever, systems biology has become instrumental to understand the dynamic interaction between the circadian clock and cell cycle, which is critical in cellular coordination and for diseases such as cancer.