Miracle-dz/UniFAR-FTUs huggingface dataset:
Sox9 and p300 Cooperatively Regulate Chromatin-mediated Transcription*

Chromatin structure is a fundamental component of gene regulation, expression, and cellular differentiation. We have previously reported that the multifunctional coactivator p300 is a member of the Sox9 (Sry-type high mobility group box 9)-related transcriptional apparatus and activates Sox9-dependent transcription during chondrogenesis. However, the mechanism of synergy between Sox9 and p300 in chromatin-mediated transcription has not been elucidated. In the present study we investigated the activity of Sox9 and p300 on chromatinized templates in vitro. Recombinant Sox9 was shown to be associated with several transcriptional cofactors including p300. In vitro transcription assays revealed that p300 potentiated Sox9-dependent transcription on chromatinized DNA and, importantly, was associated with hyperacetylated histones. Consistent with these results, the histone deacetylase inhibitor trichostatin A stimulated the expression of Sox9-regulated cartilage matrix genes and induced histone acetylation around the enhancer region of the collagen α1 (II) gene in chondrocytes. These findings suggest that Sox9 interacts with chromatin and activates transcription via regulation of chromatin modification.
A Note on Population Pharmacokinetic Studies With a Single Sampling Design

The choice of sampling time point in a population pharmacokinetic study with severe limitation on the number of samples per study subject (single sampling design) is critical in obtaining reliable parameter estimates. The authors have investigated the relationship between the timing as well as the degree of distribution of a sampling point among study subjects and the reliability of the estimates of pharmacokinetic parameters in a population pharmacokinetic study. This was achieved through a simulation, assuming an intravenously administered drug whose pharmacokinetic profile follows a 1-compartment model. The convergence rate of the NLMIXED procedure as well as the values of bias and MSE for the estimated parameters showed great variability depending on the sampling schedules. The results indicate that, in the case of a single sampling design, the sampling points should be distributed as widely as possible over a time range along the concentration-time profile to obtain reliable parameter estimates.
Lipid excipients Peceol and Gelucire 44/14 decrease P-glycoprotein mediated efflux of rhodamine 123 partially due to modifying P-glycoprotein protein expression within Caco-2 cells.

PURPOSE The objective of this study was to determine the influence of two lipid excipients, Peceol(c) and Gelucire(c) 44/14 on P-glycoprotein (Pgp) activity and protein expression in human colon adenocarcinoma cells (Caco-2). Lipid excipients are increasingly used as drug delivery systems for hydrophobic drugs to increase their bioavailability by overcoming the barrier of low absorption. This study will probe a novel mechanism by which lipid excipients reduce Pgp-mediated efflux and thereby increase bioavailability of orally administered therapeutics. METHODS Non-cytotoxic concentrations of Peceol(c) and Gelucire(c) 44/14 were determined for 24-hour treatments of Caco-2 cells using integrity of the cell membranes and mitochondrial respiration as markers. Pgp activity after treatment with non-cytotoxic concentrations of Peceol(c) and Gelucire(c) 44/14 was measured with a fluorescent Pgp substrate, rhodamine 123 (Rh123). The activity of Pgp was ascertained by measuring accumulation and the directional flux of Rh123 using the Transwell(c) semi-permeable cell culture support system. To assess the effect of Peceol(c) and Gelucire(c) 44/14 on Pgp protein expression, Western blotting with a specific Pgp antibody was performed. RESULTS. The two assays for cytotoxicity were in agreement and showed that concentrations of less than 0.5% (v/v) Peceol(c) and less than 0.02% (w/v) Gelucire(c) 44/14 were not toxic to Caco-2 cells. Rh123 accumulation was increased up to 3-fold in cells treated with sub-toxic concentrations of the excipients. The flux of Rh123 across the cell monolayer was unaffected by treatment in the absorptive (apical to basolateral) direction but the efflux transport was reduced after treatment with Peceol(c), Gelucire(c) 44/14 or the positive control , 100microM verapamil. Some of the reduction in Pgp efflux activity can be explained by the reduction in protein expression after treatment with the lipid excipients; treatment with 0.25% (v/v) and 0.5% (v/v) Peceol(c) reduced Pgp protein levels to 62.4% and 68.4% of the control respectively while Gelucire(c) 44/14 treatments of 0.01% (w/v) and 0.02% (w/v) reduced Pgp to 64.5% and 51.8% respectively. CONCLUSION In this study we utilized established methodologies to assess the inhibitory effect of the excipients on the Pgp-mediated efflux of the probe, Rh123 and tested the hypothesis that long-term treatment of Caco-2 cells with the lipid excipients, Peceol(c) and Gelucire(c) 44/14, decreased Pgp protein expression. The results suggest a new mechanism which may contribute to the improved bioavailability seen for drugs formulated with lipid-based excipients.
Uncontrolled Donors with Controlled Reperfusion after Sixty Minutes of Asystole: A Novel Reliable Resource for Kidney Transplantation

Background Organ shortage leads to usage of kidneys from donors after sudden cardiac death, or uncontrolled donors (UDCD). Ischemic injury due to cessation of circulation remains a crucial problem that limits adoption of UDCD. Our clinical investigation was to determine the applicability of kidneys obtained from UDCD and resuscitated by extracorporeal perfusion in situ after 60 minutes of asystole. Methods In 2009–2011, organ procurement service of St. Petersburg, obtained kidneys from 22 UDCD with critically expanded warm ischemic time (WIT). No patients were considered as potential organ donors initially. All donors died after sudden irreversible cardiac arrest. Mean WIT was 61.4±4.5 minutes. For kidney resuscitation, the subnormothermic extracorporeal abdominal perfusion with thrombolytics and leukocyte depletion was employed. Grafts were transplanted into 44 recipients. The outcomes of transplantation of resuscitated kidneys were compared to outcomes of 87 KTx from 74 brain death donors (BDDs). Results Immediate functioning of kidney grafts was observed in 21 of the 44 recipients, with no cases of primary non function. By the end of the first post-transplant year there was an acute rejection rate of 9.1% (4 episodes of rejection) in the UDCD group versus 14.2% (13 episodes of rejection) in the BDD group. The actual 1-year graft survival rate was 95.5% (n = 42) in UDCD group, and 94.6% (n = 87) in BDD group. Creatinine levels at the end of the first year were 0.116±0.008 and 0.115±0.004 mmol/l in UDCD and BDD groups, respectively. Conclusions UDCD kidneys with critically expanded WIT could be succefully used for transplantation if in situ organ “resuscitation” perfusion is included into procurement protocol. The results of 1-year follow-up meet the generally accepted criteria for graft survival and function. In situ reperfusion may exert a therapeutic effect on grafts before procurement. This approach could substantially expand the organ donors' pool.
Space-Efficient Identity Based EncryptionWithout Pairings

Identity Based Encryption (IBE) systems are often constructed using bilinear maps (a.k.a. pairings) on elliptic curves. One exception is an elegant system due to Cocks which builds an IBE based on the quadratic residuosity problem modulo an RSA composite N. The Cocks system, however, produces long ciphertexts. Since the introduction of the Cocks system in 2001 it has been an open problem to construct a space efficient IBE system without pairings. In this paper we present an IBE system in which ciphertext size is short: an encryption of an f. -bit message consists of a single element in Z/NZ plus lscr + 1 additional bits. Security, as in the Cocks system, relies on the quadratic residuosity problem. The system is based on the theory of ternary quadratic forms and as a result, encryption and decryption are slower than in the Cocks system.
Robust Temporal Processing of News

We introduce an annotation scheme for temporal expressions, and describe a method for resolving temporal expressions in print and broadcast news. The system, which is based on both hand-crafted and machine-learnt rules, achieves an 83.2% accuracy (F-measure) against hand-annotated data. Some initial steps towards tagging event chronologies are also described.
Systematic review of genetic association studies involving histologically confirmed non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease has an increasing prevalence in Western countries, affecting up to 20% of the population. Objective The aim of this project was to systematically review and summarise the genetic association studies that investigate possible genetic influences that confer susceptibility to non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Design The MEDLINE and SCOPUS databases were searched to identify candidate gene studies on histologically diagnosed non-alcoholic fatty liver disease. Results A total of 85 articles have been summarised and categorised on the basis of the general pathway each candidate gene is involved in, including lipid metabolism, lipoprotein processing, cholesterol synthesis, glucose homoeostasis, inflammatory response, protection against oxidative stress and whole body metabolism. Conclusions The main findings demonstrate a small but consistent association of PNPLA3 with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Genetic association studies have investigated general disease susceptibility, histological characteristics, severity and progression. However, further study is required to better elucidate the genetic factors influencing fatty liver disease.
Significance of serum magnesium levels in critically ill-patients

Background: Magnesium is one of the major electrolytes, deficiency of which is frequently overlooked in critical illness, leading to an adverse clinical outcome if not monitored regularly. Settings and Design: Single center prospective observational study of 2 years duration. Materials and Methods: The subjects studied were monitored for serum magnesium levels 2 times: Day 1 and day 4 of intensive care unit (ICU) admission. Patients were divided into normomagnesemic and hypomagnesemic groups and compared for various parameters. Results: Out of 70 critically ill-patients, 50 patients (71.43%) were normomagnesemic, 17 patients (24.29%) were hypomagnesemic and three patients were hypermagnesemic. The stay of the patients in ICU (P > 0.05), Acute Physiology and Chronic Health Evaluation-II (APACHE-II) scoring (P = 0.34) and co-morbidity (P = 0.360) showed an insignificant variation between the two groups. Associated electrolyte abnormalities in hypomagnesemic patients were hypokalemia (58.82%), hyponatremia (47.05%), hypocalcemia (70.58%) and hypophosphatemia (29.41%). About 76.47% of hypomagnesemic population was on magnesium lowering drugs while as 46% of normomagnesemic population was on magnesium lowering drugs (P = 0.030). Mortality of hypomagnesemic group was 74.47% while that of normomagnesemic group was 36% (P = 0.004). Conclusion: Hypomagnesemia is a significant electrolyte abnormality in critically ill-patients. Critically ill hypomagnesemic patients have higher mortality than the normomagnesemic patients.
Autism and the extraction of emotion from briefly presented facial expressions: stumbling at the first step of empathy.

Identification of other people's emotion from quickly presented stimuli, including facial expressions, is fundamental to many social processes, including rapid mimicry and empathy. This study examined extraction of valence from brief emotional expressions in adults with autism spectrum disorder (ASD), a condition characterized by impairments in understanding and sharing of emotions. Control participants were individuals with reading disability and typical individuals. Participants were shown images for durations in the range of microexpressions (15 ms and 30 ms), thus reducing the reliance on higher level cognitive skills. Participants detected whether (a) emotional faces were happy or angry, (b) neutral faces were male or female, and (c) neutral images were animals or objects. Individuals with ASD performed selectively worse on emotion extraction, with no group differences for gender or animal? object tasks. The emotion extraction deficit remains even when controlling for gender, verbal ability, and age and is not accounted for by speed-accuracy tradeoffs. The deficit in rapid emotional processing may contribute to ASD difficulties in mimicry, empathy, and related processes. The results highlight the role of rapid early emotion processing in adaptive social? emotional functioning.
Brachypodium distachyon as a new model system for understanding iron homeostasis in grasses: phylogenetic and expression analysis of Yellow Stripe-Like (YSL) transporters.

BACKGROUND AND AIMS Brachypodium distachyon is a temperate grass with a small stature, rapid life cycle and completely sequenced genome that has great promise as a model system to study grass-specific traits for crop improvement. Under iron (Fe)-deficient conditions, grasses synthesize and secrete Fe(III)-chelating agents called phytosiderophores (PS). In Zea mays, Yellow Stripe1 (ZmYS1) is the transporter responsible for the uptake of Fe(III)-PS complexes from the soil. Some members of the family of related proteins called Yellow Stripe-Like (YSL) have roles in internal Fe translocation of plants, while the function of other members remains uninvestigated. The aim of this study is to establish brachypodium as a model system to study Fe homeostasis in grasses, identify YSL proteins in brachypodium and maize, and analyse their expression profiles in brachypodium in response to Fe deficiency. METHODS The YSL family of proteins in brachypodium and maize were identified based on sequence similarity to ZmYS1. Expression patterns of the brachypodium YSL genes (BdYSL genes) were determined by quantitative RT-PCR under Fe-deficient and Fe-sufficient conditions. The types of PS secreted, and secretion pattern of PS in brachypodium were analysed by high-performance liquid chromatography. KEY RESULTS Eighteen YSL family members in maize and 19 members in brachypodium were identified. Phylogenetic analysis revealed that some YSLs group into a grass-specific clade. The Fe status of the plant can regulate expression of brachypodium YSL genes in both shoots and roots. 3-Hydroxy-2'-deoxymugineic acid (HDMA) is the dominant type of PS secreted by brachypodium, and its secretion is diurnally regulated. CONCLUSIONS PS secretion by brachypodium parallels that of related crop species such as barley and wheat. A single grass species-specific YSL clade is present, and expression of the BdYSL members of this clade could not be detected in shoots or roots, suggesting grass-specific functions in reproductive tissues. Finally, the Fe-responsive expression profiles of several YSLs suggest roles in Fe homeostasis.
Postsynaptic calcium is necessary for the induction of LTP and LTD of monosynaptic EPSPs in prefrontal neurons: An in vitro study in the rat

In the prefrontal (PrF) cortex of the rat, tetanic stimulation of layers 1-11 induces either long-term potentiation (LTP) or depression (LTD) of monosynaptic EPSPs recorded from pyramidal cells in layer V (Hirsch and Crepel, 1990). In agreement with earlier results in the hippocampus (Collinridge et al., 1983) and neocortex (see review by Bindman et al., 1991), we have recently found that blockade of N-methyl-D-aspartate (NMDA) receptors prevents the induction of LTP in PrF neurons (Hirsch and Crepel, 1991). By contrast, in the same study we observed that blockade of NMDA receptors not only fails to suppress LTD, but increases its probability of occurrence. Similar results were obtained in the visual cortex (Artola and Singer, 1990). In several brain regions, the biochemical mechanisms that initiate both LTP and LTD appear to be dependent on a rise of cytosolic calcium (Ca") in the postsynaptic cell. For example, it is well established that in area CA1 of the hippocampus, opening of NMDA receptor-gated channels produces a postsynaptic influx of Ca2+ that is essential for the induction of LTP (Lynch et al., 1983; Malenka et al., 1988); in the cerebellum, activation of voltage-dependent Ca2+ channels induces LTD of synaptic transmission at parallel fiber-Purkinje cell synapses (Sakurai, 1990; Crepel and Jaillard, 1990,1991). In the present study we have tested whether LTP and LTD are still induced in PrF neurons when the elevation of cytosolic Ca2+ associated with tetanus is prevented by intracellular injections of BAPTA into the postsynaptic cell. Coronal slices (400 km thick) from rat frontal poles (Sprague-Dawley, 20-30 days old) were prepared and maintained at 33°C in a submerged chamber as previously described (Hirsch and Crepel, 1990). In all experiments the artificial cerebrospinal fluid (ACSF) contained the GABAA receptor antagonist bicuculline methiodide (0.5 FM). Control cells (N = 50) were recorded with K acetate or K acetate-QX314 filled micropipettes (3 M K acetate,
Comparison between Sequence Analysis and a Line Probe Assay for Testing Genotypic Resistance of Human Immunodeficiency Virus Type 1 to Antiretroviral Drugs

ABSTRACT The purpose of this study was to compare a line probe assay (LiPA) with sequence analysis for the detection of mutations conferring resistance to nucleoside and non-nucleoside inhibitors in human immunodeficiency reverse transcriptase and protease inhibitors. The limitations for interpreting LiPA make it unacceptable for routine clinical practice.
Resistance of Hepatitis C Virus to Inhibitors: Complexity and Clinical Implications

Selection of inhibitor-resistant viral mutants is universal for viruses that display quasi-species dynamics, and hepatitis C virus (HCV) is no exception. Here we review recent results on drug resistance in HCV, with emphasis on resistance to the newly-developed, directly-acting antiviral agents, as they are increasingly employed in the clinic. We put the experimental observations in the context of quasi-species dynamics, in particular what the genetic and phenotypic barriers to resistance mean in terms of exploration of sequence space while HCV replicates in the liver of infected patients or in cell culture. Strategies to diminish the probability of viral breakthrough during treatment are briefly outlined.
Effect of montmorillonite content in nanocomposites of segmented polyurethanes with poly(2-alkyl-2-oxazoline) sequences

A series of polyurethane/montmorillonite (PU/MMT) nanocomposites, based on poly(tetramethyleneglycol) (PTMG), α,ω-dihydroxylated poly(2-alkyl-2-oxazoline) (PROZO), [4,4’-methylenebis-(phenyl isocyanate)] (MDI) or [4,4’-methylenebis-(cyclohexyl isocyanate)] (H12MDI) and montmorillonite (MMT), were investigated. The amount of added clay ranged from 3 up to 10% by weight. The influence of the MMT weight fraction in the polymer matrix on the morphology and thermal, dynamic mechanical and tensile properties was characterized by scanning electron microscopy, X-ray diffraction analysis, Fourier-transform infrared spectrophotometry, differential scanning callorimetry, thermogravimetric analysis and dynamic—mechanical analysis. The results of the investigations were used to rank the nanocomposites according to their properties in relation to the polyurethane matrix structure and MMT content. It was evidenced that the silicate layers were preferentially, but not exclusively, attracted to the hydrophilic polar PROZO domains, their level of dispersion being controlled through specific intermolecular interactions and the filler loading amount. Introducing clay in the polyurethane matrix resulted in an increase of both tensile strength and thermal stability. Their non-monotonic dependence on clay content was explained by considering that concomitant and contrasting effects develop as the clay amount increases: an improvement of the filler—matrix interactions and a reduction of the matrix labile physical crosslinking degree by hydrogen bonding coupled with a lower dispersion homogeneity. For high inorganic filler amount aggregated clay particles together with regions with mixture of exfoliated and intercalated morphologies were revealed.
Pre- and postharvest management of aflatoxin in maize: an African perspective.

Preand postharvest contamination of aflatoxin in maize is a major health deterrent for people in Africa where maize production has increased dramatically. This chapter highlights management options for preand postharvest toxin contamination in maize. Sound crop management practices are an effective way of avoiding, or at least diminishing, infection by Aspergillus jlavus and subsequent aflatoxin production. Preand postharvest practices that reduced aflatoxin contamination include: the use of resistant cultivars, harvesting at maturity, rapid drying on platforms to avoid contact with soil, appropriate shelling methods to reduce grain damage, sorting, use of clean and aerated storage structures, controlling insect damage, and avoiding long storage periods. These contamination reducing management practices are being tested in collaboration with farmers. Work continues on food basket surveys, the bio-ecology of aflatoxin production, developing biological control through a competitive exclusion strategy, reducing the impact of postharvest management practices on human blood toxin levels, and breeding to reduce the impact of mycotoxins on trade.
Congestion phenomena on complex networks

We define a minimal model of traffic flows in complex networks in order to study the trade-off between topological-based and traffic-based routing strategies. The resulting collective behavior is obtained analytically for an ensemble of uncorrelated networks and summarized in a rich phase diagram presenting second-order as well as first-order phase transitions between a free-flow phase and a congested phase. We find that traffic control improves global performance, enlarging the free-flow region in parameter space only in heterogeneous networks. Traffic control introduces nonlinear effects and, beyond a critical strength, may trigger the appearance of a congested phase in a discontinuous manner. The model also reproduces the crossover in the scaling of traffic fluctuations empirically observed on the Internet.